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Cai PJ, Chen SY, Chen YF, Yen GC. 6-Shogaol inhibits the cell motility of prostate cancer cells by suppressing the PI3K/AKT/mTOR and Ras/Raf/MAPK pathways with comparable effects to paclitaxel treatment. Food Funct 2025. [PMID: 40397499 DOI: 10.1039/d5fo00798d] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/22/2025]
Abstract
Prostate cancer ranks among the top causes of cancer-related deaths in men, with a substantial number of fatalities occurring in metastatic cases. Although paclitaxel (PTX) is used as a first-line treatment, its effectiveness is hindered by side effects and drug resistance, which complicate the therapy and contribute to the progression of metastasis. Research has shown that phytochemicals can induce cancer cell death and inhibit metastasis without significantly harming normal cells, suggesting a potential alternative strategy for suppressing metastatic prostate cancer. 6-Shogaol (6-S), a pungent constituent of ginger, has been demonstrated to inhibit metastasis in renal cancer cells, human endometrial carcinoma, and lung and breast cancers by downregulating the PI3K/Akt/mTOR and Ras/Raf/MAPK pathways. However, the anti-metastatic effects of 6-S on prostate cancer remain unclear. Accordingly, this study was aimed at investigating how 6-S suppresses the metastatic capacity of human prostate cancer cells PC-3 and DU145. Results showed that 6-S inhibited cell migration and invasion in both cell lines in a dose-dependent manner, and no cytotoxicity was observed in the normal human prostate cell RWPE-1. Mechanistically, 6-S upregulated PTEN and suppressed the activation of the CXCL12/CXCR4, PI3K/AKT/mTOR, and Ras/Raf/MAPK pathways, which in turn affected the expression of transcription factors Snail and Twist, leading to increased E-cadherin levels and reduced expression of N-cadherin, vimentin, MMP-2, and MMP-9. This limited the cell motility and showed comparable effects to paclitaxel treatment. In summary, 6-S demonstrates significant potential against the metastatic characteristics of prostate cancer cells and could serve as a potential candidate for adjuvant therapy after further clinical evaluations.
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Affiliation(s)
- Pei-Jhen Cai
- Department of Food Science and Biotechnology, National Chung Hsing University, 145 Xingda Road, Taichung 40227, Taiwan.
| | - Sheng-Yi Chen
- Department of Food Science and Biotechnology, National Chung Hsing University, 145 Xingda Road, Taichung 40227, Taiwan.
| | - Yi-Fan Chen
- Department of Food Science and Biotechnology, National Chung Hsing University, 145 Xingda Road, Taichung 40227, Taiwan.
| | - Gow-Chin Yen
- Department of Food Science and Biotechnology, National Chung Hsing University, 145 Xingda Road, Taichung 40227, Taiwan.
- Advanced Plant and Food Crop Biotechnology Center, National Chung Hsing University, Taichung 40227, Taiwan
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Naidu D, Althaf Umar KP, Muhsina K, Augustine S, Jeengar MK, S K K. Zingiberaceae in Cardiovascular Health: A review of adipokine modulation and endothelial protection via adipocyte-endothelial crosstalk mechanism. Curr Nutr Rep 2025; 14:66. [PMID: 40366476 DOI: 10.1007/s13668-025-00656-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/28/2025] [Indexed: 05/15/2025]
Abstract
PURPOSE OF THE REVIEW Although adipose tissue controls metabolism and protects vital organs, its importance to general health is being highlighted by the rise in type 2 diabetes and cardiovascular disease. Adipokines produced by adipose cells are essential regulators of metabolism, glucose homeostasis, and inflammatory response. It also protects vascular endothelial cells for its potential implications for cardiovascular protection. Understanding its intricate involvement in adipose tissue-endothelial communication is critical in developing targeted therapeutics to treat cardiovascular conditions linked with obesity and metabolic dysregulation. Spices from the Zingiberaceae family, such as cardamom, turmeric, and ginger, have anti-inflammatory and anti-oxidant properties that help reduce oxidative stress, vascular dysfunction, and adipocyte-endothelial crosstalk which are all linked to the etiology of CVD. Comprehensive molecular insights into how they modulate adipokine signalling, inflammatory pathways, and ROS-induced adipocyte-vascular interactions remain unexplored, demanding additional translational and clinical validation. With an emphasis on patients with obesity and metabolic dysregulation, the investigation aims to elucidate the mechanisms by which the spice as whole/bioactive constituents of the Zingiberaceae family may provide protection against CVD by integrating previous studies. RECENT FINDINGS Current research continues to support the use of spices from the Zingiberaceae family, such as ginger, turmeric, cardamom, and pepper, as potential therapeutic agents for addressing metabolic complications like obesity, type II diabetes, and CVDs. These natural remedies may modulate adipocyte-endothelial crosstalk and inflammation by modulating important signalling pathways such as AMPK, AKT, PPAR, and NF-κB.. CONCLUSION This review provides a complete summary of existing knowledge, opening the way for future research and prospective therapeutic applications of Zingiberaceae spices in cardiovascular health management.
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Affiliation(s)
- Disha Naidu
- Department of Pharmacology, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, Kochi, 682041, Kerala, India
| | - K P Althaf Umar
- Department of Pharmacology, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, Kochi, 682041, Kerala, India
| | - K Muhsina
- Department of Pharmacology, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, Kochi, 682041, Kerala, India
| | - Sanu Augustine
- Department of Pharmacology, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, Kochi, 682041, Kerala, India
| | - Manish Kumar Jeengar
- Department of Pharmacology, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, Kochi, 682041, Kerala, India.
| | - Kanthlal S K
- Department of Pharmacology, Sree Krishna College of Pharmacy and Research Centre, Parassala, Thiruvananthapuram, Kerala, 695502, India.
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Imtiaz I, Schloss J, Bugarcic A. Interplay Between Traditional and Scientific Knowledge: Phytoconstituents and Their Roles in Lung and Colorectal Cancer Signaling Pathways. Biomolecules 2025; 15:380. [PMID: 40149916 PMCID: PMC11940637 DOI: 10.3390/biom15030380] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2025] [Revised: 02/27/2025] [Accepted: 02/27/2025] [Indexed: 03/29/2025] Open
Abstract
Natural plant products have been used for cancer treatment since ancient times and continue to play a vital role in modern anticancer drug development. However, only a small fraction of identified medicinal plants has been thoroughly investigated, particularly for their effects on cellular pathways in lung and colorectal cancers, two under-researched cancers with poor prognostic outcomes (lung cancers). This review focuses on the lung and colorectal cancer signaling pathways modulated by bioactive compounds from eleven traditional medicinal plants: Curcuma longa, Astragalus membranaceus, Glycyrrhiza glabra, Althaea officinalis, Echinacea purpurea, Sanguinaria canadensis, Codonopsis pilosula, Hydrastis canadensis, Lobelia inflata, Scutellaria baicalensis, and Zingiber officinale. These plants were selected based on their documented use in traditional medicine and modern clinical practice. Selection criteria involved cross-referencing herbs identified in a scoping review of traditional cancer treatments and findings from an international survey on herbal medicine currently used for lung and colorectal cancer management by our research group and the availability of existing literature on their anticancer properties. The review identifies several isolated phytoconstituents from these plants that exhibit anticancer properties by modulating key signaling pathways such as PI3K/Akt/mTOR, RAS/RAF/MAPK, Wnt/β-catenin, and TGF-β in vitro. Notable constituents include sanguinarine, berberine, hydrastine, lobeline, curcumin, gingerol, shogaol, caffeic acid, echinacoside, cichoric acid, glycyrrhizin, 18-β-glycyrrhetinic acid, astragaloside IV, lobetyolin, licochalcone A, baicalein, baicalin, wogonin, and glycyrol. Curcumin and baicalin show preclinical effectiveness but face bioavailability challenges, which may be overcome by combining them with piperine or using oral extracts to enhance gut microbiome conversion, integrating traditional knowledge with modern strategies for improved outcomes. Furthermore, herbal extracts from Echinacea, Glycyrrhiza, and Codonopsis, identified in traditional knowledge, are currently in clinical trials. Notably, curcumin and baicalin also modulate miRNA pathways, highlighting a promising intersection of modern science and traditional medicine. Thus, the development of anticancer therapeutics continues to benefit from the synergy of traditional knowledge, scientific innovation, and technological advancements.
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Affiliation(s)
| | | | - Andrea Bugarcic
- National Centre for Naturopathic Medicine, Faculty of Health, Southern Cross University, Military Road, Lismore, NSW 2480, Australia; (I.I.); (J.S.)
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El Alaa R, Al-Jaber H, Chokor FAZ, Shaito AA, Al-Mansoori L. Ethnobotanical survey of medicinal plants used in management of breast cancers in Qatar. Heliyon 2025; 11:e42541. [PMID: 40028611 PMCID: PMC11869100 DOI: 10.1016/j.heliyon.2025.e42541] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2024] [Revised: 02/03/2025] [Accepted: 02/06/2025] [Indexed: 03/05/2025] Open
Abstract
Breast cancer is a global health concern, including in Qatar, where it impacts women significantly. The complexity of breast cancer requires diverse treatment approaches influenced by tumor characteristics and biology. Despite advancements, current treatments still fall short of providing definitive solutions, particularly for triple-negative breast cancer. Complementary and Alternative Medicine (CAM), including herbal remedies, is increasingly popular among cancer patients, including those in Qatar. In Qatar, herbal medicine is widely used by the population, including breast cancer patients, yet preserving this knowledge faces significant challenges. This study aimed to document herbalists' ethnobotanical practices concerning breast cancer treatment in Qatar and corroborate any identified plant remedies' anticancer use with the literature. Thirteen herbalists were identified in Doha, Qatar, and surveyed using an ethnobotanical questionnaire between October and November 2022. Herbalists' demographic data and their herbal recommendations for breast cancer treatment were collected through structured interviews. Descriptive statistics and the Relative Frequency Citation (RFC) were employed for data analysis. The current study aimed to document herbalists' practices for breast cancer management in Qatar and validate the anticancer potential of the identified plants through existing literature. The present study documented the ethnobotanical knowledge of 13 herbalists in Qatar regarding breast cancer treatment, revealing the use of various plant species from ten different families. Saussurea costus (Falc.) Lipsch. (Al Qist Al Hindi), Zingiber officinale Roscoe (Ginger) (zanjabel) and Nigella sativa L. (Black seeds) (habit elbaraka) were the most recommended plants. Literature searches revealed that many of these plants possess compounds with potential anticancer properties as sesquiterpenes, flavonoids, thymoquinone, volatile terpenic compounds and anthocyanin. The sources of these plants were primarily India and Iran due to their historical trade relations with Qatar. Herbalists predominantly use plant underground parts but could consider integrating leaves with proven anticancer properties. Each reported plant was scrutinized for its anticancer potential, by collecting the published research about its anticancer uses, revealing significant cytotoxicity against breast cancer cells. The literature survey also uncovered that most plants are reported to induce apoptosis through specific pathways, while others showed chemo-sensitization effects and cancer-induced mutation prevention. Moreover, some of the recommended plants have advanced to clinical studies. Beyond cancer, these plants displayed promise in addressing diabetes and inflammation. In conclusion, our study on herbalists' recommendations for breast cancer documents the traditional practices for patient therapy in Qatar. Saussurea costus (Falc.) Lipsch. (Al Qist Al Hindi) emerged as a commonly prescribed plant, with the roots being predominantly used. Overall, our findings describe the current traditional practices for handling breast cancer in Qatar and offer insights into integrating traditional practices with modern medicine for enhanced breast cancer management.
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Affiliation(s)
| | - Hend Al-Jaber
- Biomedical Research Center (BRC), QU Health, Qatar University, Qatar
| | | | | | - Layla Al-Mansoori
- Biomedical Research Center (BRC), QU Health, Qatar University, Qatar
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Kim TW, Lee HG. Anti-Inflammatory 8-Shogaol Mediates Apoptosis by Inducing Oxidative Stress and Sensitizes Radioresistance in Gastric Cancer. Int J Mol Sci 2024; 26:173. [PMID: 39796030 PMCID: PMC11719885 DOI: 10.3390/ijms26010173] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2024] [Revised: 12/21/2024] [Accepted: 12/27/2024] [Indexed: 01/13/2025] Open
Abstract
Radiotherapy is a powerful tumor therapeutic strategy for gastric cancer patients. However, radioresistance is a major obstacle to kill cancer cells. Ginger (Zingiber officinale Roscoe) exerts a potential function in various cancers and is a noble combined therapy to overcome radioresistance in gastric cancer radiotherapy. In this study, we suggested that 8-shogaol, a monomethoxybenzene compound extracted from Zingiber officinale Roscoe, has an anti-cancer and anti-inflammatory activity. In lipopolysaccharide (LPS)-induced inflammatory murine models in vivo and in vitro, 8-shogaol suppressed LPS-mediated cytokine production, including COX-2, TNFα, IL-6, and IL-1β. In xenograft mouse models of AGS gastric cancer cell lines, 8-shogaol reduced tumor volume. In gastric cancer cell lines AGS and NCI-N87, 8-shogaol reduced cell viability and increased caspase-3 activity and cytotoxicity LDH. However, combined with Z-VAD-FMK, 8-shogaol blocked caspase-dependent apoptotic cell death. 8-Shogaol induced intracellular reactive oxygen species (ROS) production, intracellular calcium (Ca2+) release, and endoplasmic reticulum (ER) stress response via the PERK-CHOP signaling pathway. Thapsigargin (TG), an ER stressor, mediated synergistic apoptosis and cell death in 8-shogaol-treated AGS and NCI-N87 cell lines. Nevertheless, loss of PERK or CHOP function suppressed ER-stress-induced apoptosis and cell death in 8-shogaol-treated AGS and NCI-N87 cell lines. 8-Shogaol-induced NADPH oxidase 4 (NOX4) activation is related to ROS generation. However, NOX4 knockdown and ROS inhibitors DPI or NAC blocked ER-stress-induced apoptosis by suppressing the inhibition of cell viability and the enhance of caspase-3 activity, intracellular ROS activity, and cytotoxicity LDH in 8-shogaol-treated AGS and NCI-N87 cell lines. Radioresistant gastric cancer models (AGSR and NCI-N87R) were developed and combined with 8-shogaol and radiation (2 Gy) to overcome radioresistance via the upregulation of N-cadherin and vimentin and the downregulation of E-cadherin. Therefore, these results indicated that 8-shogaol is a novel combined therapeutic strategy in gastric cancer radiotherapy.
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Affiliation(s)
- Tae Woo Kim
- Department of Biopharmaceutical Engineering, Dongguk University-WISE, Gyeongju 38066, Republic of Korea;
| | - Hee Gu Lee
- Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Yuseong-gu, Daejeon 34141, Republic of Korea
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Matin M, Matin FB, Ksepka N, Wysocki K, Mickael ME, Wieczorek M, Horbańczuk JO, Jóźwik A, Atanasov AG. The Clinical Research on Ginger (Zingiber officinale): Insights from ClinicalTrials.gov analysis. PLANTA MEDICA 2024; 90:834-843. [PMID: 38944033 DOI: 10.1055/a-2357-7064] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/01/2024]
Abstract
Ginger (Zingiber officinale) has a rich history of traditional medicinal use and has attracted a global interest in its health benefits. This study aims to provide insights into the clinical research landscape on ginger, focusing on its pharmacological effects and studied health-related outcomes. The study design involves systematic analysis of data from clinical trials available on ClinicalTrials.gov and discussion of findings in the context of the existing scientific knowledge. A comprehensive analysis of clinical trials registered on ClinicalTrials.gov related to ginger was first conducted, and the scientific background related to specific ginger clinical research avenues was further evaluated through PubMed searches. A variety of trial designs were identified, including treatment, prevention, and supportive care objectives. A total of 188 studies were identified on ClinicalTrials.gov, of which 89 met the inclusion criteria. Among the 89 trials, treatment objectives were predominant (47.2%), and dietary supplements (40.4%) and drugs (27%) were the most prevalent intervention types. These trials covered various health outcomes, such as antiemetic activity, analgesic function, effects on health-related quality of life, blood pressure variation, energy expenditure, and reduction in xerostomia. This study analysis provides a comprehensive overview of the clinical trials landscape on ginger, focusing on its broad spectrum of potential health benefits. While individual trials show promising results, a significant gap in the available data with a low reporting rate of final results is identified, underscoring the need for further research to establish conclusive evidence of ginger's therapeutic potentials.
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Affiliation(s)
- Maima Matin
- Institute of Genetics and Animal Biotechnology of the Polish Academy of Sciences, Jastrzebiec, Magdalenka, Poland
| | - Farhan Bin Matin
- Department of Pharmacy, East West University, Aftabnagar, Dhaka, Bangladesh
| | - Natalia Ksepka
- Institute of Genetics and Animal Biotechnology of the Polish Academy of Sciences, Jastrzebiec, Magdalenka, Poland
| | - Kamil Wysocki
- Institute of Genetics and Animal Biotechnology of the Polish Academy of Sciences, Jastrzebiec, Magdalenka, Poland
| | - Michel-Edwar Mickael
- Institute of Genetics and Animal Biotechnology of the Polish Academy of Sciences, Jastrzebiec, Magdalenka, Poland
| | - Marek Wieczorek
- Department of Neurobiology, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland
| | - Jarosław Olav Horbańczuk
- Institute of Genetics and Animal Biotechnology of the Polish Academy of Sciences, Jastrzebiec, Magdalenka, Poland
| | - Artur Jóźwik
- Institute of Genetics and Animal Biotechnology of the Polish Academy of Sciences, Jastrzebiec, Magdalenka, Poland
| | - Atanas G Atanasov
- Institute of Genetics and Animal Biotechnology of the Polish Academy of Sciences, Jastrzebiec, Magdalenka, Poland
- Ludwig Boltzmann Institute Digital Health and Patient Safety, Medical University of Vienna, Vienna, Austria
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Chen GQ, Nan Y, Huang SC, Ning N, Du YH, Lu DD, Yang YT, Meng FD, Yuan L. Research progress of ginger in the treatment of gastrointestinal tumors. World J Gastrointest Oncol 2023; 15:1835-1851. [DOI: 10.4251/wjgo.v15.i11.1835] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2023] [Revised: 09/15/2023] [Accepted: 09/27/2023] [Indexed: 11/15/2023] Open
Abstract
Cancer seriously endangers human health. Gastrointestinal cancer is the most common and major malignant tumor, and its morbidity and mortality are gradually increasing. Although there are effective treatments such as radiotherapy and chemotherapy for gastrointestinal tumors, they are often accompanied by serious side effects. According to the traditional Chinese medicine and food homology theory, many materials are both food and medicine. Moreover, food is just as capable of preventing and treating diseases as medicine. Medicine and food homologous herbs not only have excellent pharmacological effects and activities but also have few side effects. As a typical medicinal herb with both medicinal and edible uses, some components of ginger have been shown to have good efficacy and safety against cancer. A mass of evidence has also shown that ginger has anti-tumor effects on digestive tract cancers (such as gastric cancer, colorectal cancer, liver cancer, laryngeal cancer, and pancreatic cancer) through a variety of pathways. The aim of this study is to investigate the mechanisms of action of the main components of ginger and their potential clinical applications in treating gastrointestinal tumors.
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Affiliation(s)
- Guo-Qing Chen
- College of Pharmacy, Ningxia Medical College, Yinchuan 750004, Ningxia Hui Autonomous Region, China
| | - Yi Nan
- Key Laboratory of Ningxia Ethnomedicine Modernization, Ministry of Education, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
- Traditional Chinese Medicine College, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
| | - Shi-Cong Huang
- College of Pharmacy, Ningxia Medical College, Yinchuan 750004, Ningxia Hui Autonomous Region, China
| | - Na Ning
- College of Pharmacy, Ningxia Medical College, Yinchuan 750004, Ningxia Hui Autonomous Region, China
| | - Yu-Hua Du
- College of Pharmacy, Ningxia Medical College, Yinchuan 750004, Ningxia Hui Autonomous Region, China
| | - Dou-Dou Lu
- School of Clinical Medicine College, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
| | - Ya-Ting Yang
- Traditional Chinese Medicine College, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
| | - Fan-Di Meng
- Traditional Chinese Medicine College, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
| | - Ling Yuan
- College of Pharmacy, Ningxia Medical College, Yinchuan 750004, Ningxia Hui Autonomous Region, China
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Hasan N, Nadaf A, Imran M, Jiba U, Sheikh A, Almalki WH, Almujri SS, Mohammed YH, Kesharwani P, Ahmad FJ. Skin cancer: understanding the journey of transformation from conventional to advanced treatment approaches. Mol Cancer 2023; 22:168. [PMID: 37803407 PMCID: PMC10559482 DOI: 10.1186/s12943-023-01854-3] [Citation(s) in RCA: 70] [Impact Index Per Article: 35.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2023] [Accepted: 08/30/2023] [Indexed: 10/08/2023] Open
Abstract
Skin cancer is a global threat to the healthcare system and is estimated to incline tremendously in the next 20 years, if not diagnosed at an early stage. Even though it is curable at an early stage, novel drug identification, clinical success, and drug resistance is another major challenge. To bridge the gap and bring effective treatment, it is important to understand the etiology of skin carcinoma, the mechanism of cell proliferation, factors affecting cell growth, and the mechanism of drug resistance. The current article focusses on understanding the structural diversity of skin cancers, treatments available till date including phytocompounds, chemotherapy, radiotherapy, photothermal therapy, surgery, combination therapy, molecular targets associated with cancer growth and metastasis, and special emphasis on nanotechnology-based approaches for downregulating the deleterious disease. A detailed analysis with respect to types of nanoparticles and their scope in overcoming multidrug resistance as well as associated clinical trials has been discussed.
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Affiliation(s)
- Nazeer Hasan
- Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, 110062, India
| | - Arif Nadaf
- Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, 110062, India
| | - Mohammad Imran
- Frazer Institute, Faculty of Medicine, University of Queensland, Brisbane, 4102, Australia
| | - Umme Jiba
- Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, 110062, India
| | - Afsana Sheikh
- Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, 110062, India
| | - Waleed H Almalki
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Umm Al-Qura University, 24381, Makkah, Saudi Arabia
| | - Salem Salman Almujri
- Department of Pharmacology, College of Pharmacy, King Khalid University, 61421, Asir-Abha, Saudi Arabia
| | | | - Prashant Kesharwani
- Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, 110062, India.
- Center for Global Health Research, Saveetha Medical College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Kuthambakkam, India.
| | - Farhan Jalees Ahmad
- Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, 110062, India.
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Zhang S, Fasina Y, Dosu G, Sang S. Absorption and Metabolism of Ginger Compounds in Broiler Chicks. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2023; 71:13757-13767. [PMID: 37691237 DOI: 10.1021/acs.jafc.3c01857] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/12/2023]
Abstract
Bioavailability is critical in ensuring bioefficacy of ginger compounds, which have not been studied in chicks. In this study, day-old chicks were treated with ginger root extract at 0.0, 0.4, 0.8, 1.5, and 3.0% for 42 days. The gingerols and shogaols in chick samples were analyzed by liquid chromatography-mass spectrometry. The primary phase-I metabolic pathway for gingerols and shogaols was the reduction of ketone groups into hydroxyl groups. Shogaols were also metabolized through thiol conjugation and hydrogenation of double-bond pathways. Within the bloodstream, gingerols and their metabolites predominantly existed as glucuronidate or sulfate conjugates. However, the levels of the free form and conjugates were comparable for shogaols. In breast meat, the quantities of both the free form and conjugates for all compounds were similar. In plasma, more than 50% of absorbed 6-gingerol (6G) and 90% of absorbed 6-shogaol underwent reduction to their respective metabolites. However, in breast meat, the percentage of reduction for absorbed 6G was less than 50%, and for absorbed 6-shogaol, it was less than 60%. Ginger compounds were absorbed into chick plasma ranging from 1.4 to 8.5 μg/mL and breast meat ranging from 7.1 to 114.6 μg/100 g across the 0.4-3.0% dose range in a dose-dependent manner.
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Affiliation(s)
- Shuwei Zhang
- Laboratory for Functional Foods and Human Health, Center for Excellence in Post-Harvest Technologies, North Carolina Agricultural and Technical State University, North Carolina Research Campus, Kannapolis, North Carolina 28081, United States
| | - Yewande Fasina
- Department of Animal Sciences, North Carolina A&T State University, Greensboro, North Carolina 27411, United States
| | - George Dosu
- Department of Animal Sciences, North Carolina A&T State University, Greensboro, North Carolina 27411, United States
| | - Shengmin Sang
- Laboratory for Functional Foods and Human Health, Center for Excellence in Post-Harvest Technologies, North Carolina Agricultural and Technical State University, North Carolina Research Campus, Kannapolis, North Carolina 28081, United States
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Kim HR, Noh EM, Kim SY. Anti-inflammatory effect and signaling mechanism of 8-shogaol and 10-shogaol in a dextran sodium sulfate-induced colitis mouse model. Heliyon 2023; 9:e12778. [PMID: 36647352 PMCID: PMC9840358 DOI: 10.1016/j.heliyon.2022.e12778] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2022] [Revised: 12/23/2022] [Accepted: 12/30/2022] [Indexed: 01/06/2023] Open
Abstract
Ethnopharmacological relevance Ginger (Zingiber officinale Roscoe) has been used for food and applied in Ayurvedic medicine in India for thousands of years. With a reputation for strong anti-inflammatory properties, it has been used for to treat colds, migraines, nausea, arthritis, and high blood pressure in China and Southeast Asia. The physiological activity of ginger is attributed to its functional components, including gingerol and shogaol, and their derivatives. Aim of the study We aimed to investigate the effects of 8- and 10-shogaol and their bioactive signaling mechanisms in a dextran sodium sulfate (DSS)-induced colitis mouse model. The anti-colitis efficacy of 6-, 8-, and 10-derivatives of gingerol and shogaol was comparatively analyzed. Materials and methods Colitis was induced by providing mice with drinking water containing 5% DSS (w/v) for 8 days. The 6-, 8-, and 10-derivatives of gingerol and shogaol were orally administered for two weeks at a dose of 30 mg/kg. Changes in body weight and disease activity index were measured. The levels of pro-inflammatory cytokines, iNOS and COX-2, as well as the phosphorylation of NF-κB were analyzed using ELISA, PCR, or western blotting. Mucin expression and mRNA levels were measured using alcian blue staining and PCR, respectively. The tight-junction-associated proteins occludin and ZO-1 were assessed using immunohistological staining. Results The 6-, 8-, and 10-derivatives of gingerol and shogaol exhibited anti-inflammatory effects by regulating NF-κB signaling. Among the compounds administered, 10-shogaol was the most effective against DSS-induced inflammation. Comparative analysis of the chemical structure showed that shogaol, a dehydrated analog of gingerol, was more effective. 6- and 10-shogaol showed similar effects on DSS-induced morphological changes in the colonic mucus layer, mucin expression, and tight junction proteins. Conclusions 6-, 8-, and 10-Gingerol and 6-, 8-, and 10-shogaol significantly improved the clinical symptoms and intestinal epithelial barrier damage in DSS-induced colitis in mice. The derivatives effectively inhibited DSS-induced inflammation through the regulation of NF-κB signaling. Moreover, 10-shogaol showed the most potent anti-inflammatory effect among the six compounds used in this study. The results indicate that 8- and 10-shogaol, both main ingredients in ginger, may serve as therapeutic candidates for the treatment of colitis.
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Affiliation(s)
| | - Eun-Mi Noh
- Corresponding author. Jeonju AgroBio-Materials Institute, 111-27 Wonjangdong-gil, Deokjin-gu, Jeonju, 54810, Republic of Korea.
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Salinas-Arellano ED, Castro-Dionicio IY, Jeyaraj JG, Mirtallo Ezzone NP, Carcache de Blanco EJ. Phytochemical Profiles and Biological Studies of Selected Botanical Dietary Supplements Used in the United States. PROGRESS IN THE CHEMISTRY OF ORGANIC NATURAL PRODUCTS 2023; 122:1-162. [PMID: 37392311 DOI: 10.1007/978-3-031-26768-0_1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/03/2023]
Abstract
Based on their current wide bioavailability, botanical dietary supplements have become an important component of the United States healthcare system, although most of these products have limited scientific evidence for their use. The most recent American Botanical Council Market Report estimated for 2020 a 17.3% increase in sales of these products when compared to 2019, for a total sales volume of $11,261 billion. The use of botanical dietary supplements products in the United States is guided by the Dietary Supplement Health and Education Act (DSHEA) from 1994, enacted by the U.S. Congress with the aim of providing more information to consumers and to facilitate access to a larger number of botanical dietary supplements available on the market than previously. Botanical dietary supplements may be formulated for and use only using crude plant samples (e.g., plant parts such as the bark, leaves, or roots) that can be processed by grinding into a dried powder. Plant parts can also be extracted with hot water to form an "herbal tea." Other preparations of botanical dietary supplements include capsules, essential oils, gummies, powders, tablets, and tinctures. Overall, botanical dietary supplements contain bioactive secondary metabolites with diverse chemotypes that typically are found at low concentration levels. These bioactive constituents usually occur in combination with inactive molecules that may induce synergy and potentiation of the effects observed when botanical dietary supplements are taken in their different forms. Most of the botanical dietary supplements available on the U.S. market have been used previously as herbal remedies or as part of traditional medicine systems from around the world. Their prior use in these systems also provides a certain level of assurance in regard to lower toxicity levels. This chapter will focus on the importance and diversity of the chemical features of bioactive secondary metabolites found in botanical dietary supplements that are responsible for their applications. Many of the active principles of botanical dietary substances are phenolics and isoprenoids, but glycosides and some alkaloids are also present. Biological studies on the active constituents of selected botanical dietary supplements will be discussed. Thus, the present chapter should be of interest for both members of the natural products scientific community, who may be performing development studies of the products available, as well as for healthcare professionals who are directly involved in the analysis of botanical interactions and evaluation of the suitability of botanical dietary supplements for human consumption.
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Affiliation(s)
- Eric D Salinas-Arellano
- Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, 500 West 12th Avenue, Columbus, OH, 43210, USA
| | - Ines Y Castro-Dionicio
- Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, 500 West 12th Avenue, Columbus, OH, 43210, USA
| | - Jonathan G Jeyaraj
- Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, 500 West 12th Avenue, Columbus, OH, 43210, USA
| | - Nathan P Mirtallo Ezzone
- Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, 500 West 12th Avenue, Columbus, OH, 43210, USA
| | - Esperanza J Carcache de Blanco
- Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, 500 West 12th Avenue, Columbus, OH, 43210, USA.
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12
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Wang R, Lee YG, Dhandapani S, Baek NI, Kim KP, Cho YE, Xu X, Kim YJ. 8-paradol from ginger exacerbates PINK1/Parkin mediated mitophagy to induce apoptosis in human gastric adenocarcinoma. Pharmacol Res 2023; 187:106610. [PMID: 36521573 DOI: 10.1016/j.phrs.2022.106610] [Citation(s) in RCA: 24] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2022] [Revised: 11/28/2022] [Accepted: 12/10/2022] [Indexed: 12/14/2022]
Abstract
Gastric cancer (GC) occurs in the gastric mucosa, and its high morbidity and mortality make it an international health crisis. Therefore, novel drugs are needed for its treatment. The use of natural products and their components in cancer treatments has shown promise. Therefore, this study aimed to evaluate the effect of 8-paradol, a phenolic compound isolated from ginger (Zingiber officinale Roscoe), on GC and determine its underlying mechanisms of action. In this study, repeated column chromatography was conducted on ginger EtOH extract to isolate gingerol and its derivatives. The cytotoxicity of the eight ginger compounds underwent a (3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyltetrazolium bromide) tetrazolium reduction (MTT) assay. 8-paradol showed the most potent cytotoxicity effect among the isolated ginger compounds. The underlying mechanism by which 8-paradol regulated specific proteins in AGS cells was evaluated by proteomic analysis. To validate the predicted mechanisms, AGS cells and thymus-deficient nude mice bearing AGS xenografts were used as in vitro and in vivo models of GC, respectively. The results showed that the 8-paradol promoted PINK1/Parkin-associated mitophagy, mediating cell apoptosis. Additionally, the inhibition of mitophagy by chloroquine (CQ) ameliorated 8-paradol-induced mitochondrial dysfunction and apoptosis, supporting a causative role for mitophagy in the 8-paradol-induced anticancer effect. Molecular docking results revealed the molecular interactions between 8-paradol and mitophagy-/ apoptosis-related proteins at the atomic level. Our study provides strong evidence that 8-paradol could act as a novel potential therapeutic agent to suppress the progression of GC by targeting mitophagy pathway.
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Affiliation(s)
- Rongbo Wang
- Graduate School of Biotechnology, and College of Life Science, Kyung Hee University, Yongin-si 17104, Gyeonggi-do, Republic of Korea
| | - Yeong-Geun Lee
- Graduate School of Biotechnology, and College of Life Science, Kyung Hee University, Yongin-si 17104, Gyeonggi-do, Republic of Korea
| | - Sanjeevram Dhandapani
- Graduate School of Biotechnology, and College of Life Science, Kyung Hee University, Yongin-si 17104, Gyeonggi-do, Republic of Korea
| | - Nam-In Baek
- Graduate School of Biotechnology, and College of Life Science, Kyung Hee University, Yongin-si 17104, Gyeonggi-do, Republic of Korea
| | - Kwang-Pyo Kim
- Department of Applied Chemistry, Institute of Natural Science, Global Center for Pharmaceutical Ingredient Materials, Kyung Hee University, Yongin-si 17104, Gyeonggi-do, Republic of Korea
| | - Yeong-Eun Cho
- Department of Applied Chemistry, Institute of Natural Science, Global Center for Pharmaceutical Ingredient Materials, Kyung Hee University, Yongin-si 17104, Gyeonggi-do, Republic of Korea
| | - Xingyue Xu
- Graduate School of Biotechnology, and College of Life Science, Kyung Hee University, Yongin-si 17104, Gyeonggi-do, Republic of Korea; Beijing Key Laboratory of Traditional Chinese Medicine Basic Research on Prevention and Treatment for Major Diseases, Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing 100700, China.
| | - Yeon-Ju Kim
- Graduate School of Biotechnology, and College of Life Science, Kyung Hee University, Yongin-si 17104, Gyeonggi-do, Republic of Korea.
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13
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Ballester P, Cerdá B, Arcusa R, Marhuenda J, Yamedjeu K, Zafrilla P. Effect of Ginger on Inflammatory Diseases. Molecules 2022; 27:7223. [PMID: 36364048 PMCID: PMC9654013 DOI: 10.3390/molecules27217223] [Citation(s) in RCA: 69] [Impact Index Per Article: 23.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2022] [Revised: 10/17/2022] [Accepted: 10/21/2022] [Indexed: 08/13/2023] Open
Abstract
Ulcerative colitis, Crohn's disease, rheumatoid arthritis, psoriasis, and lupus erythematosus are some of common inflammatory diseases. These affections are highly disabling and share signals such as inflammatory sequences and immune dysregulation. The use of foods with anti-inflammatory properties such as ginger (Zingiber officinale Roscoe) could improve the quality of life of these patients. Ginger is a plant widely used and known by its bioactive compounds. There is enough evidence to prove that ginger possesses multiple biological activities, especially antioxidant and anti-inflammatory capacities. In this review, we summarize the current knowledge about the bioactive compounds of ginger and their role in the inflammatory process and its signaling pathways. We can conclude that the compounds 6-shoagol, zingerone, and 8-shoagol display promising results in human and animal models, reducing some of the main symptoms of some inflammatory diseases such as arthritis. For lupus, 6-gingerol demonstrated a protective attenuating neutrophil extracellular trap release in response to phosphodiesterase inhibition. Ginger decreases NF-kβ in psoriasis, and its short-term administration may be an alternative coadjuvant treatment. Ginger may exert a function of supplementation and protection against cancer. Furthermore, when receiving chemotherapy, ginger may reduce some symptoms of treatment (e.g., nausea).
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Affiliation(s)
| | - Begoña Cerdá
- Nutrition, Oxidative Stress and Bioavailability Group, Degree in Pharmacy, Faculty of Health Sciences, Catholic University of San Antonio de Murcia, 30107 Murcia, Spain
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14
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Esquivel-Alvarado D, Zhang S, Hu C, Zhao Y, Sang S. Using Metabolomics to Identify the Exposure and Functional Biomarkers of Ginger. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2022; 70:12029-12040. [PMID: 36099064 PMCID: PMC9699694 DOI: 10.1021/acs.jafc.2c05117] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/25/2023]
Abstract
Liquid chromatography-mass spectrometry (LC-MS)-based metabolomics has become an important tool to increase our understanding of how diet affects human health. However, public and commercial mass spectral libraries of dietary metabolites are limited, resulting in the greatest challenge in converting mass spectrometry data into biological insights. In this study, we constructed an LC-MS/MS ginger library as an example to demonstrate the importance of dietary libraries for discovering food biomarkers. The functional and exposure biomarkers of ginger were investigated using plasma samples from mice treated with control and ginger extract diets. Our results showed clear discrimination between the metabolome of mice on normal and ginger extract diets. Using the in-house ginger library, we identified 20 ginger metabolites that can be used as exposure biomarkers of ginger. However, without the LC-MS/MS ginger library, none of the ginger metabolites could be accurately identified based on online mass databases. In addition, ginger treatment significantly impacts the endogenous metabolome, especially the purine metabolism and phenylalanine, tyrosine, and tryptophan biosynthesis. Overall, we demonstrated that the construction of LC-MS/MS spectra dietary libraries would enhance the ability to identify potential dietary biomarkers and correlate potential health benefits associated with food consumption.
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Affiliation(s)
- Daniel Esquivel-Alvarado
- Laboratory for Functional Foods and Human Health, Center for Excellence in Post-Harvest Technologies, North Carolina Agricultural and Technical State University, Kannapolis, North Carolina 28081, United States
| | - Shuwei Zhang
- Laboratory for Functional Foods and Human Health, Center for Excellence in Post-Harvest Technologies, North Carolina Agricultural and Technical State University, Kannapolis, North Carolina 28081, United States
| | - Changling Hu
- Laboratory for Functional Foods and Human Health, Center for Excellence in Post-Harvest Technologies, North Carolina Agricultural and Technical State University, Kannapolis, North Carolina 28081, United States
| | - Yantao Zhao
- Laboratory for Functional Foods and Human Health, Center for Excellence in Post-Harvest Technologies, North Carolina Agricultural and Technical State University, Kannapolis, North Carolina 28081, United States
| | - Shengmin Sang
- Laboratory for Functional Foods and Human Health, Center for Excellence in Post-Harvest Technologies, North Carolina Agricultural and Technical State University, Kannapolis, North Carolina 28081, United States
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15
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Liu M, Yang Y, Zhang M, Xue Y, Zheng B, Zhang Y, Liu Y, Chu X, Sun Z, Han X. Inhibition of human ether-à-go-go-related gene K+ currents expressed in HEK293 cells by three gingerol components from ginger. J Pharm Pharmacol 2022; 74:1133-1139. [PMID: 35511715 DOI: 10.1093/jpp/rgac029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2021] [Accepted: 04/04/2022] [Indexed: 11/13/2022]
Abstract
OBJECTIVES Gingerols are bioactive compounds derived from ginger, our experiment investigates the effects of 6-, 8- and 10-Gin on the human ether-à-go-go-related gene (hERG) K+ channels by using patch clamp technology. KEY FINDINGS hERG K+ currents were suppressed by 6-, 8- and 10-Gin in a concentration-dependent manner. The IC50 values of 6-, 8- and 10-Gin were 41.5, 16.1 and 86.5 μM for the hERG K+ currents, respectively. The maximum inhibitory effects caused by 6-, 8- and 10-Gin were 44.3% ± 2.0%, 88.6% ± 1.3% and 63.1% ± 1.1%, respectively, and the effects were almost completely reversible. CONCLUSION These findings suggest that 8-Gin is the most potent hERG K+ channel inhibitor among gingerol components and may offer a new approach for understanding and treating cancer.
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Affiliation(s)
- Miaomaio Liu
- School of Pharmacy, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China
| | - Yakun Yang
- School of Pharmacy, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China
| | - Muqing Zhang
- School of Pharmacy, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China
| | - Yucong Xue
- School of Pharmacy, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China
| | - Bin Zheng
- School of Pharmacy, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China
| | - Yuanyuan Zhang
- School of Pharmacy, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China
| | - Yu Liu
- School of Pharmacy, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China
| | - Xi Chu
- The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
| | - Zhenqing Sun
- Qingdao Hospital of Traditional Chinese Medicine (Qingdao Hiser hospital), Qingdao, Shandong, China
| | - Xue Han
- Affiliated Hospital, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China
- Hebei Key Laboratory of Integrative Medicine on Liver-Kidney Patterns, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China
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16
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Zhang S, DiMango E, Zhu Y, Saroya TK, Emala CW, Sang S. Pharmacokinetics of Gingerols, Shogaols, and Their Metabolites in Asthma Patients. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2022; 70:9674-9683. [PMID: 35916113 PMCID: PMC9654594 DOI: 10.1021/acs.jafc.2c03150] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/20/2023]
Abstract
6-Gingerol and 6-shogaol are the most abundant gingerols and shogaols in ginger root and have been shown to reduce the asthmatic phenotype in murine models of asthma. Several studies have described the pharmacokinetics of gingerols and shogaols in humans following the oral ingestion of ginger, while little was known about the metabolism of these components in humans, particularly in patients with asthma. In this study, a dietary supplement of 1.0 g of ginger root extract was administered to asthma patients twice daily for 56 days and serum samples were drawn at 0.5-8 h on days 0, 28, and 56. The metabolic profiles of gingerols and shogaols in human plasma and the kinetic changes of gingerols, shogaols, and their metabolites in asthma patients collected on the three different visits were analyzed using liquid chromatography-mass spectrometry (LC-MS). Ketone reduction was the major metabolic pathway of both gingerols and shogaols. Gingerdiols were identified as the major metabolites of 6-, 8-, and 10-gingerols. M11 and M9 were identified as the double-bond reduction and both the double-bond and ketone reduction metabolites of 6-shogaol, respectively. Cysteine conjugation was another major metabolic pathway of 6-shogaol in asthma patients, and two cysteine-conjugated 6-shogaol, M1 and M2, were identified as the major metabolites of 6-shogaol. Furthermore, gingerols, shogaols, and their metabolites were quantitated in the human serum collected at different time points during each of the three visits using a very sensitive high-resolution LC-MS method. The results showed that one-third of 6-gingerol was metabolized to produce its reduction metabolites, 6-gingerdiols, and more than 90% of 6-shogaol was metabolized to its phase I and cysteine-conjugated metabolites, suggesting the importance of considering the contribution of these metabolites to the bioavailability and health beneficial effects of gingerols and shogaols. All gingerols, shogaols, and their metabolites reached their peak concentrations in less than 2 h, and their half-lives (t1/2) were from 0.6 to 2.4 h. Furthermore, long-term treatment of ginger supplements, especially after 56 days of treatment, increases the absorption of ginger compounds and their metabolites in asthma patients.
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Affiliation(s)
- Shuwei Zhang
- Laboratory for Functional Foods and Human Health, Center for Excellence in Post-Harvest Technologies, North Carolina Agricultural and Technical State University, North Carolina Research Campus, Kannapolis, North Carolina 28081, United States
| | - Emily DiMango
- Department of Medicine (Pulmonology, Allergy and Critical Care), Columbia University, New York, New York 10027-6902, United States
| | - Yingdong Zhu
- Laboratory for Functional Foods and Human Health, Center for Excellence in Post-Harvest Technologies, North Carolina Agricultural and Technical State University, North Carolina Research Campus, Kannapolis, North Carolina 28081, United States
| | - Tarnjot K Saroya
- Department of Medicine (Pulmonology, Allergy and Critical Care), Columbia University, New York, New York 10027-6902, United States
| | - Charles W Emala
- Department of Anesthesiology, Columbia University, New York, New York 10027-6902, United States
| | - Shengmin Sang
- Laboratory for Functional Foods and Human Health, Center for Excellence in Post-Harvest Technologies, North Carolina Agricultural and Technical State University, North Carolina Research Campus, Kannapolis, North Carolina 28081, United States
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17
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Bioactive Compounds from the Zingiberaceae Family with Known Antioxidant Activities for Possible Therapeutic Uses. Antioxidants (Basel) 2022; 11:antiox11071281. [PMID: 35883772 PMCID: PMC9311506 DOI: 10.3390/antiox11071281] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2022] [Revised: 06/18/2022] [Accepted: 06/21/2022] [Indexed: 02/04/2023] Open
Abstract
The Zingiberaceae family is a rich source of diverse bioactive phytochemicals. It comprises about 52 genera and 1300 species of aromatic flowering perennial herbs with characteristic creeping horizontal or tuberous rhizomes. Notable members of this family include ginger (Zingiber officinale Roscoe), turmeric (Curcuma longa L.), Javanese ginger (Curcuma zanthorrhiza Roxb.), and Thai ginger (Alpinia galanga L.). This review focuses on two main classes of bioactive compounds: the gingerols (and their derivatives) and the curcuminoids. These compounds are known for their antioxidant activity against several maladies. We highlight the centrality of their antioxidant activities with notable biological activities, including anti-inflammatory, antidiabetic, hepatoprotective, neuroprotective, antimicrobial, and anticancer effects. We also outline various strategies that have been applied to enhance these activities and make suggestions for research areas that require attention.
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18
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Liu X, Wang Y, Zheng Y, Duan D, Dai F, Zhou B. Michael acceptor-dependent pro-oxidative intervention against angiogenesis by [6]-dehydroshogaol, a pungent constituent of ginger. Eur J Pharmacol 2022; 925:174990. [PMID: 35500643 DOI: 10.1016/j.ejphar.2022.174990] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2022] [Revised: 04/23/2022] [Accepted: 04/26/2022] [Indexed: 11/30/2022]
Abstract
Accumulating evidence suggests that ginger and its pungent constituents harbor a wealth of biological activities including cancer chemopreventive activity. However, relatively few researches focus on [6]-dehydroshogaol (6-DHS) compared with other ginger pungent constituents such as [6]-shogaol (6S). In this work, we selected three ginger compounds, 6-DHS, 6S and [6]-paradol (6P) differentiated by the presence and number of the Michael acceptor units, to probe structural basis and mechanism of 6-DHS in inhibiting angiogenesis, a key step for tumor growth and metastasis. It was found that their antiangiogenic activity is significantly dependent on the presence and number of Michael acceptor units. Benefiting from its two Michael acceptor units, 6-DHS is the most potent inhibitor of thioredoxin reductase and depletor of glutathione, thereby being the most active generator of reactive oxygen species, which is responsible for its strongest ability to inhibit angiogenesis. This work highlights 6-DHS being a Michael acceptor-dependent pro-oxidative angiogenesis inhibitor.
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Affiliation(s)
- Xuefeng Liu
- State Key Laboratory of Applied Organic Chemistry, Lanzhou University, 222 Tianshui Street S., Lanzhou, Gansu, 730000, China; School of Pharmacy, Lanzhou University, 222 Tianshui Street S., Lanzhou, Gansu, 730000, China
| | - Yihua Wang
- State Key Laboratory of Applied Organic Chemistry, Lanzhou University, 222 Tianshui Street S., Lanzhou, Gansu, 730000, China
| | - Yalong Zheng
- State Key Laboratory of Applied Organic Chemistry, Lanzhou University, 222 Tianshui Street S., Lanzhou, Gansu, 730000, China
| | - Dechen Duan
- State Key Laboratory of Applied Organic Chemistry, Lanzhou University, 222 Tianshui Street S., Lanzhou, Gansu, 730000, China
| | - Fang Dai
- State Key Laboratory of Applied Organic Chemistry, Lanzhou University, 222 Tianshui Street S., Lanzhou, Gansu, 730000, China
| | - Bo Zhou
- State Key Laboratory of Applied Organic Chemistry, Lanzhou University, 222 Tianshui Street S., Lanzhou, Gansu, 730000, China.
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Nasti R, Bassanini I, Ferrandi EE, Linguardo F, Bertuletti S, Vanoni M, Riva S, Verotta L, Monti D. Stereoselective Biocatalyzed Reductions of Ginger Active Components Recovered from Industrial Wastes. Chembiochem 2022; 23:e202200105. [PMID: 35188325 PMCID: PMC9314113 DOI: 10.1002/cbic.202200105] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2022] [Indexed: 11/30/2022]
Abstract
Ginger is among the most widespread and widely consumed traditional medicinal plants around the world. Its beneficial effects, which comprise e. g. anticancer and anti-inflammatory activities as well as gastrointestinal regulatory effects, are generally attributed to a family of non-volatile compounds characterized by an arylalkyl long-chained alcohol, diol, or ketone moiety. In this work, ginger active components have been successfully recovered from industrial waste biomass of fermented ginger. Moreover, their recovery has been combined with the first systematic study of the stereoselective reduction of gingerol-like compounds by isolated alcohol dehydrogenases (ADHs), obtaining the enantioenriched sec-alcohol derivatives via a sustainable biocatalytic path in up to >99 % conversions and >99 % enantiomeric/diastereomeric excesses.
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Affiliation(s)
- Rita Nasti
- Department of Environmental Science and PolicyUniversità degli Studi di MilanoVia Celoria 2Milano20133Italy
| | - Ivan Bassanini
- Istituto di Scienze e Tecnologie Chimiche “Giulio Natta”Consiglio Nazionale delle RicercheVia Mario Bianco 9Milano20131Italy
| | - Erica Elisa Ferrandi
- Istituto di Scienze e Tecnologie Chimiche “Giulio Natta”Consiglio Nazionale delle RicercheVia Mario Bianco 9Milano20131Italy
| | - Federica Linguardo
- Istituto di Scienze e Tecnologie Chimiche “Giulio Natta”Consiglio Nazionale delle RicercheVia Mario Bianco 9Milano20131Italy
| | - Susanna Bertuletti
- Istituto di Scienze e Tecnologie Chimiche “Giulio Natta”Consiglio Nazionale delle RicercheVia Mario Bianco 9Milano20131Italy
| | - Marta Vanoni
- Istituto di Scienze e Tecnologie Chimiche “Giulio Natta”Consiglio Nazionale delle RicercheVia Mario Bianco 9Milano20131Italy
| | - Sergio Riva
- Istituto di Scienze e Tecnologie Chimiche “Giulio Natta”Consiglio Nazionale delle RicercheVia Mario Bianco 9Milano20131Italy
| | - Luisella Verotta
- Department of Environmental Science and PolicyUniversità degli Studi di MilanoVia Celoria 2Milano20133Italy
| | - Daniela Monti
- Istituto di Scienze e Tecnologie Chimiche “Giulio Natta”Consiglio Nazionale delle RicercheVia Mario Bianco 9Milano20131Italy
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20
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Wang J, Li D, Zhao B, Kim J, Sui G, Shi J. Small Molecule Compounds of Natural Origin Target Cellular Receptors to Inhibit Cancer Development and Progression. Int J Mol Sci 2022; 23:ijms23052672. [PMID: 35269825 PMCID: PMC8911024 DOI: 10.3390/ijms23052672] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2022] [Revised: 02/16/2022] [Accepted: 02/25/2022] [Indexed: 01/03/2023] Open
Abstract
Receptors are macromolecules that transmit information regulating cell proliferation, differentiation, migration and apoptosis, play key roles in oncogenic processes and correlate with the prognoses of cancer patients. Thus, targeting receptors to constrain cancer development and progression has gained widespread interest. Small molecule compounds of natural origin have been widely used as drugs or adjuvant chemotherapeutic agents in cancer therapies due to their activities of selectively killing cancer cells, alleviating drug resistance and mitigating side effects. Meanwhile, many natural compounds, including those targeting receptors, are still under laboratory investigation for their anti-cancer activities and mechanisms. In this review, we classify the receptors by their structures and functions, illustrate the natural compounds targeting these receptors and discuss the mechanisms of their anti-cancer activities. We aim to provide primary knowledge of mechanistic regulation and clinical applications of cancer therapies through targeting deregulated receptors.
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Affiliation(s)
| | | | | | | | - Guangchao Sui
- Correspondence: (G.S.); (J.S.); Tel.: +86-451-82191081 (G.S. & J.S.)
| | - Jinming Shi
- Correspondence: (G.S.); (J.S.); Tel.: +86-451-82191081 (G.S. & J.S.)
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21
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Bischoff-Kont I, Primke T, Niebergall LS, Zech T, Fürst R. Ginger Constituent 6-Shogaol Inhibits Inflammation- and Angiogenesis-Related Cell Functions in Primary Human Endothelial Cells. Front Pharmacol 2022; 13:844767. [PMID: 35281937 PMCID: PMC8914105 DOI: 10.3389/fphar.2022.844767] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2021] [Accepted: 01/31/2022] [Indexed: 12/15/2022] Open
Abstract
Rhizomes from Zingiber officinale Roscoe are traditionally used for the treatment of a plethora of pathophysiological conditions such as diarrhea, nausea, or rheumatoid arthritis. While 6-gingerol is the pungent principle in fresh ginger, in dried rhizomes, 6-gingerol is dehydrated to 6-shogaol. 6-Shogaol has been demonstrated to exhibit anticancer, antioxidative, and anti-inflammatory actions more effectively than 6-gingerol due to the presence of an electrophilic Michael acceptor moiety. In vitro, 6-shogaol exhibits anti-inflammatory actions in a variety of cell types, including leukocytes. Our study focused on the effects of 6-shogaol on activated endothelial cells. We found that 6-shogaol significantly reduced the adhesion of leukocytes onto lipopolysaccharide (LPS)-activated human umbilical vein endothelial cells (HUVECs), resulting in a significantly reduced transmigration of THP-1 cells through an endothelial cell monolayer. Analyzing the mediators of endothelial cell–leukocyte interactions, we found that 30 µM of 6-shogaol blocked the LPS-triggered mRNA and protein expression of cell adhesion molecules. In concert with this, our study demonstrates that the LPS-induced nuclear factor κB (NFκB) promoter activity was significantly reduced upon treatment with 6-shogaol. Interestingly, the nuclear translocation of p65 was slightly decreased, and protein levels of the LPS receptor Toll-like receptor 4 remained unimpaired. Analyzing the impact of 6-shogaol on angiogenesis-related cell functions in vitro, we found that 6-shogaol attenuated the proliferation as well as the directed and undirected migration of HUVECs. Of note, 6-shogaol also strongly reduced the chemotactic migration of endothelial cells in the direction of a serum gradient. Moreover, 30 µM of 6-shogaol blocked the formation of vascular endothelial growth factor (VEGF)-induced endothelial sprouts from HUVEC spheroids and from murine aortic rings. Importantly, this study shows for the first time that 6-shogaol exhibits a vascular-disruptive impact on angiogenic sprouts from murine aortae. Our study demonstrates that the main bioactive ingredient in dried ginger, 6-shogaol, exhibits beneficial characteristics as an inhibitor of inflammation- and angiogenesis-related processes in vascular endothelial cells.
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Affiliation(s)
- Iris Bischoff-Kont
- Institute of Pharmaceutical Biology, Goethe University Frankfurt, Frankfurt, Germany
| | - Tobias Primke
- Institute of Pharmaceutical Biology, Goethe University Frankfurt, Frankfurt, Germany
| | - Lea S. Niebergall
- Institute of Pharmaceutical Biology, Goethe University Frankfurt, Frankfurt, Germany
| | - Thomas Zech
- Institute of Pharmaceutical Biology, Goethe University Frankfurt, Frankfurt, Germany
| | - Robert Fürst
- Institute of Pharmaceutical Biology, Goethe University Frankfurt, Frankfurt, Germany
- LOEWE Center for Translational Biodiversity Genomics (LOEWE-TBG), Frankfurt, Germany
- *Correspondence: Robert Fürst,
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22
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Zhang S, Kou X, Zhao H, Mak KK, Balijepalli MK, Pichika MR. Zingiber officinale var. rubrum: Red Ginger's Medicinal Uses. Molecules 2022; 27:775. [PMID: 35164040 PMCID: PMC8840670 DOI: 10.3390/molecules27030775] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2021] [Revised: 01/18/2022] [Accepted: 01/18/2022] [Indexed: 11/17/2022] Open
Abstract
Zingiber officinale var. rubrum (red ginger) is widely used in traditional medicine in Asia. Unlike other gingers, it is not used as a spice in cuisines. To date, a total of 169 chemical constituents have been reported from red ginger. The constituents include vanilloids, monoterpenes, sesquiterpenes, diterpenes, flavonoids, amino acids, etc. Red ginger has many therapeutic roles in various diseases, including inflammatory diseases, vomiting, rubella, atherosclerosis, tuberculosis, growth disorders, and cancer. Scientific evidence suggests that red ginger exhibits immunomodulatory, antihypertensive, antihyperlipidemic, antihyperuricemic, antimicrobial, and cytotoxic activities. These biological activities are the underlying causes of red ginger's therapeutic benefits. In addition, there have been few reports on adverse side effects of red ginger. This review aims to provide insights in terms the bioactive constituents and their biosynthesis, biological activities, molecular mechanisms, pharmacokinetics, and qualitative and quantitative analysis of red ginger.
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Affiliation(s)
- Shiming Zhang
- School of Postgraduate Studies, International Medical University, Kuala Lumpur 57000, Malaysia; (S.Z.); (K.-K.M.)
| | - Xuefang Kou
- Experimental Centre, Shandong University of Traditional Chinese Medicine, Jinan 250355, China;
| | - Hui Zhao
- School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China;
| | - Kit-Kay Mak
- School of Postgraduate Studies, International Medical University, Kuala Lumpur 57000, Malaysia; (S.Z.); (K.-K.M.)
- Pharmaceutical Chemistry Department, School of Pharmacy, International Medical University, Kuala Lumpur 57000, Malaysia
- Centre for Bioactive Molecules and Drug Delivery, Institute for Research, Development & Innovation (IRDI), International Medical University, Kuala Lumpur 57000, Malaysia
| | - Madhu Katyayani Balijepalli
- Department of Pharmacology, Faculty of Medicine and Health Sciences, MAHSA University, Selangor 42610, Malaysia;
| | - Mallikarjuna Rao Pichika
- Pharmaceutical Chemistry Department, School of Pharmacy, International Medical University, Kuala Lumpur 57000, Malaysia
- Centre for Bioactive Molecules and Drug Delivery, Institute for Research, Development & Innovation (IRDI), International Medical University, Kuala Lumpur 57000, Malaysia
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23
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Lai W, Yang S, Lin X, Zhang X, Huang Y, Zhou J, Fu C, Li R, Zhang Z. Zingiber officinale: A Systematic Review of Botany, Phytochemistry and Pharmacology of Gut Microbiota-Related Gastrointestinal Benefits. THE AMERICAN JOURNAL OF CHINESE MEDICINE 2022; 50:1007-1042. [PMID: 35729087 DOI: 10.1142/s0192415x22500410] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
Ginger (Zingiber officinale Rosc.) is a traditional edible medicinal herb with a wide range of uses and long cultivation history. Fresh ginger (Zingiberis Recens Rhizoma; Sheng Jiang in Chinese, SJ) and dried ginger (Zingiberis Rhizoma; Gan Jiang in Chinese, GJ) are designated as two famous traditional Chinese herbal medicines, which are different in plant cultivation, appearances and functions, together with traditional applications. Previous researches mainly focused on the differences in chemical composition between them, but there was no systematical comparison on the similarity concerning research achievements of the two herbs. Meanwhile, ginger has traditionally been used for the treatment of gastrointestinal disorders, but so far, the possible interaction with human gut microbiota has hardly been considered. This review comprehensively presents similarities and differences between SJ and GJ retrospectively, particularly proposing them the significant differences in botany, phytochemistry and ethnopharmacology, which can be used as evidence for clinical application of SJ and GJ. Furthermore, the pharmacology of gut microbiota-related gastrointestinal benefits has also been discussed in order to explore better ways to prevent and treat gastrointestinal disorders, which can be used as a reference for further research.
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Affiliation(s)
- Wenjing Lai
- State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy College, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, P. R. China
| | - Shasha Yang
- State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy College, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, P. R. China
| | - Xia Lin
- State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy College, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, P. R. China
| | - Xing Zhang
- State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy College, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, P. R. China
| | - You Huang
- State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy College, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, P. R. China
| | - Jingwei Zhou
- State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy College, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, P. R. China
| | - Chaomei Fu
- State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy College, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, P. R. China
| | - Rui Li
- State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy College, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, P. R. China
| | - Zhen Zhang
- State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy College, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, P. R. China
- Key Laboratory of Quality Control and Efficacy Evaluation of Traditional Chinese Medicine Formula Granules, Sichuan New Green Medicine Science and Technology Development Co., Ltd., Pengzhou 610081, P. R. China
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Luković E, Perez-Zoghbi JF, Zhang Y, Zhu Y, Sang S, Emala CW. Ginger metabolites and metabolite-inspired synthetic products modulate intracellular calcium and relax airway smooth muscle. Am J Physiol Lung Cell Mol Physiol 2021; 321:L912-L924. [PMID: 34549600 PMCID: PMC8616613 DOI: 10.1152/ajplung.00271.2021] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2021] [Revised: 09/10/2021] [Accepted: 09/17/2021] [Indexed: 11/22/2022] Open
Abstract
Asthma affects millions of people worldwide and its prevalence is increasing. It is characterized by chronic airway inflammation, airway remodeling, and pathologic bronchoconstriction, and it poses a continuous treatment challenge with very few new therapeutics available. Thus, many asthmatics turn to plant-based complementary products, including ginger, for better symptom control, indicating an unmet need for novel therapies. Previously, we demonstrated that 6-shogaol (6S), the primary bioactive component of ginger, relaxes human airway smooth muscle (hASM) likely by inhibition of phosphodiesterases (PDEs) in the β-adrenergic (cyclic nucleotide PDEs), and muscarinic (phospholipase C, PLC) receptor pathways. However, oral 6S is extensively metabolized and it is unknown if the resulting metabolites remain bioactive. Here, we screened all the known human metabolites of 6S and several metabolite-based synthetic derivatives to better understand their mechanism of action and structure-function relationships. We demonstrate that several metabolites and metabolite-based synthetic derivatives are able to prevent Gq-coupled stimulation of intracellular calcium [Ca2+]i and inositol trisphosphate (IP3) synthesis by inhibiting PLC, similar to the parent compound 6S. We also show that these compounds prevent recontraction of ASM after β-agonist relaxation likely by inhibiting PDEs. Furthermore, they potentiate isoproterenol-induced relaxation. Importantly, moving beyond cell-based assays, metabolites also retain the functional ability to relax Gq-coupled-contractions in upper (human) and lower (murine) airways. The current study indicates that, although oral ginger may be metabolized rapidly, it retains physiological activity through its metabolites. Moreover, we are able to use naturally occurring metabolites as inspiration to develop novel therapeutics for brochoconstrictive diseases.
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Affiliation(s)
- Elvedin Luković
- Department of Anesthesiology, Columbia University, New York, New York
| | | | - Yi Zhang
- Department of Anesthesiology, Columbia University, New York, New York
| | - Yingdong Zhu
- Laboratory for Functional Foods and Human Health, Center for Excellence in Post-Harvest Technologies, North Carolina Agricultural and Technical State University, North Carolina Research Campus, Kannapolis, North Carolina
| | - Shengmin Sang
- Laboratory for Functional Foods and Human Health, Center for Excellence in Post-Harvest Technologies, North Carolina Agricultural and Technical State University, North Carolina Research Campus, Kannapolis, North Carolina
| | - Charles W Emala
- Department of Anesthesiology, Columbia University, New York, New York
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25
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Cömertpay S, Gül A, Delibaş M, Tekin Turhan MS. Investigating the Efficacy of Zingerone on Mesothelioma and the Role of TRPV1 in This Effect. Nutr Cancer 2021; 74:2174-2183. [PMID: 34533076 DOI: 10.1080/01635581.2021.1980592] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
Mesothelioma is a highly lethal cancer developing in the lung, heart, and abdominal membranes. Zingerone, a capsaicin-like bioactive compound, has been shown to have anticancer properties. Transient Receptor Potential Vanilloid 1 (TRPV1) is an ion channel involving in the cytotoxicity of capsaicin. In the present study, we aimed at determining the cytotoxicity of zingerone on a mesothelioma cell line and to evaluate the role of TRPV1 in this effect. For this purpose, H2452 was used as the mesothelioma cell line and MTS was performed to calculate zingerone cytotoxicity. Moreover, TRPV1 was inhibited by capsazepeine while TRPV1 production was reduced through shRNA treatment. Besides, wound healing and clonogenic assays were performed to measure the migration and colony forming abilities, respectively. As a result, IC50 value of zingerone was calculated as 11.49 mM. Capsazepine treatment or lowered TRPV1 gene expression did not appear to affect zingerone cytotoxicity (p > 0.05) even though the migration rate and colony forming abilities of the zingerone treated cells decreased significantly compared to the control (p < 0.05). Therefore, we concluded that zingerone was less cytotoxic to H2452 cells than the most cancer types and TRPV1 did not seem to have a role in its cytotoxicity.
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Affiliation(s)
- Sabahattin Cömertpay
- Agriculture Faculty, Agricultural Biotechnology Department, Kahramanmaras Sutcu Imam University, Kahramanmaras, Turkey
| | - Abdülmecit Gül
- Agriculture Faculty, Agricultural Biotechnology Department, Kahramanmaras Sutcu Imam University, Kahramanmaras, Turkey
| | - Mehmet Delibaş
- Agriculture Faculty, Agricultural Biotechnology Department, Kahramanmaras Sutcu Imam University, Kahramanmaras, Turkey
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26
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Bischoff-Kont I, Fürst R. Benefits of Ginger and Its Constituent 6-Shogaol in Inhibiting Inflammatory Processes. Pharmaceuticals (Basel) 2021; 14:ph14060571. [PMID: 34203813 PMCID: PMC8232759 DOI: 10.3390/ph14060571] [Citation(s) in RCA: 63] [Impact Index Per Article: 15.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2021] [Revised: 06/10/2021] [Accepted: 06/11/2021] [Indexed: 12/18/2022] Open
Abstract
Ginger (Zingiber officinale Roscoe) is widely used as medicinal plant. According to the Committee on Herbal Medicinal Products (HMPC), dried powdered ginger rhizome can be applied for the prevention of nausea and vomiting in motion sickness (well-established use). Beyond this, a plethora of pre-clinical studies demonstrated anti-cancer, anti-oxidative, or anti-inflammatory actions. 6-Shogaol is formed from 6-gingerol by dehydration and represents one of the main bioactive principles in dried ginger rhizomes. 6-Shogaol is characterized by a Michael acceptor moiety being reactive with nucleophiles. This review intends to compile important findings on the actions of 6-shogaol as an anti-inflammatory compound: in vivo, 6-shogaol inhibited leukocyte infiltration into inflamed tissue accompanied with reduction of edema swelling. In vitro and in vivo, 6-shogaol reduced inflammatory mediator systems such as COX-2 or iNOS, affected NFκB and MAPK signaling, and increased levels of cytoprotective HO-1. Interestingly, certain in vitro studies provided deeper mechanistic insights demonstrating the involvement of PPAR-γ, JNK/Nrf2, p38/HO-1, and NFκB in the anti-inflammatory actions of the compound. Although these studies provide promising evidence that 6-shogaol can be classified as an anti-inflammatory substance, the exact mechanism of action remains to be elucidated. Moreover, conclusive clinical data for anti-inflammatory actions of 6-shogaol are largely lacking.
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Affiliation(s)
- Iris Bischoff-Kont
- Institute of Pharmaceutical Biology, Goethe University Frankfurt, 60438 Frankfurt, Germany;
| | - Robert Fürst
- Institute of Pharmaceutical Biology, Goethe University Frankfurt, 60438 Frankfurt, Germany;
- LOEWE Center for Translational Biodiversity Genomics (LOEWE-TBG), 60325 Frankfurt, Germany
- Correspondence:
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27
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Najafi Dorcheh S, Rahgozar S, Talei D. 6-Shogaol induces apoptosis in acute lymphoblastic leukaemia cells by targeting p53 signalling pathway and generation of reactive oxygen species. J Cell Mol Med 2021; 25:6148-6160. [PMID: 33939282 PMCID: PMC8406487 DOI: 10.1111/jcmm.16528] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2020] [Revised: 03/22/2021] [Accepted: 03/24/2021] [Indexed: 12/22/2022] Open
Abstract
Combination therapies, using medicinal herbs, are broadly recommended to attenuate the chemotherapy adverse effects. Based on our previous findings considering the anti-leukaemic effects of ginger extract on acute lymphoblastic leukaemia (ALL) cells, the present study was aimed to investigate the anti-cancer role of this pharmaceutical plant on ALL mice models. Moreover, we worked towards identifying the most anti-leukaemic derivative of ginger and the mechanism through which it may exert its cytotoxic impact. In vivo experiments were performed using five groups of six C57BL/6 nude mice, and the anti-leukaemic activity of ginger extract alone or in combination with methotrexate (MTX) was examined. Results showed increased survival rate and reduced damages in mice brain and liver tissues. Subsequently, MTT assay demonstrated synergistic growth inhibitory effect of 6-shogaol (6Sh) and MTX on ALL cell lines and patients primary cells. Eventually, the molecular anti-neoplastic mechanism of 6Sh was evaluated using Bioinformatics. Flow cytometry illustrated 6Sh-mediated apoptosis in Nalm-6 cells confirmed by Western blotting and RT-PCR assays. Further analyses exhibited the generation of reactive oxygen species (ROS) through 6Sh. The current study revealed the in vivo novel anti-leukaemic role of ginger extract, promoted by MTX. Moreover, 6-shogaol was introduced as the major player of ginger cytotoxicity through inducing p53 activity and ROS generation.
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Affiliation(s)
| | | | - Daryush Talei
- Medicinal Plants Research CenterShahed UniversityTehranIran
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28
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Zivarpour P, Nikkhah E, Maleki Dana P, Asemi Z, Hallajzadeh J. Molecular and biological functions of gingerol as a natural effective therapeutic drug for cervical cancer. J Ovarian Res 2021; 14:43. [PMID: 33706784 PMCID: PMC7953815 DOI: 10.1186/s13048-021-00789-x] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2021] [Accepted: 02/22/2021] [Indexed: 12/12/2022] Open
Abstract
Cervical cancer is one of the most common and important gynecological cancers, which has a global concern with an increasing number of patients and mortality rates. Today, most women in the world who suffer from cervical cancer are developing advanced stages of the disease. Smoking and even exposure to secondhand smoke, infections caused by the human papillomavirus, immune system dysfunction and high-risk individual-social behaviors are among the most important predisposing factors for this type of cancer. In addition, papilloma virus infection plays a more prominent role in cervical cancer. Surgery, chemotherapy or radical hysterectomy, and radiotherapy are effective treatments for this condition, the side effects of these methods endanger a person's quality of life and cause other problems in other parts of the body. Studies show that herbal medicines, including taxol, camptothecin and combretastatins, have been shown to be effective in treating cervical cancer. Ginger (Zingiber officinale, Zingiberaceae) is one of the plants with valuable compounds such as gingerols, paradols and shogoals, which is a rich source of antioxidants, anti-cancer and anti-inflammatory agents. Numerous studies have reported the therapeutic effects of this plant through various pathways in cervical cancer. In this article, we look at the signaling mechanisms and pathways in which ginger is used to treat cervical cancer.
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Affiliation(s)
- Parinaz Zivarpour
- Department of Biological sciences, Faculty of Basic Sciences, Higher Education Institute of Rab-Rashid, Tabriz, Iran
| | - Elhameh Nikkhah
- Medicinal Plants Research Cent Maragheh University of Medical Sciences, Maragheh, Iran
| | - Parisa Maleki Dana
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
| | - Zatollah Asemi
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
| | - Jamal Hallajzadeh
- Department of Biochemistry and Nutrition, Research Center for Evidence-Based Health Management, Maragheh University of Medical Sciences, Maragheh, Iran
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29
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Sang S, Snook HD, Tareq FS, Fasina Y. Precision Research on Ginger: The Type of Ginger Matters. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2020; 68:8517-8523. [PMID: 32663000 DOI: 10.1021/acs.jafc.0c03888] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/11/2023]
Abstract
Ginger is a widely consumed spice and possesses numerous pharmacological properties. However, studies addressing the efficacy of ginger in humans have been inconsistent. Many confounding factors need to be considered when evaluating the health effects from ginger against chronic diseases, especially the levels of bioactive components in the ginger formulations used in human trials. Gingerols, the major compounds in fresh ginger, are liable to dehydrate and convert to shogaols, the major compounds in dried ginger, as a result of the instability of β-hydroxyl ketone when exposed to heat and/or acidic conditions. As a result of various heating and processing methods, the concentrations of gingerols and shogaols in ginger products vary significantly. Increasing evidence has shown that gingerols and shogaols have different bioactivities, molecular targets, and metabolic pathways, suggesting the importance of identifying the optimal oral ginger composition for a specific disease. In this perspective, we highlighted differences in the composition between fresh ginger and dry ginger, bioactivities, molecular targets, and metabolic pathways of gingerols and shogaols as well as future perspectives regarding precision research on ginger.
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Affiliation(s)
- Shengmin Sang
- Laboratory for Functional Foods and Human Health, Center for Excellence in Post-Harvest Technologies, North Carolina Agricultural and Technical State University, North Carolina Research Campus, 500 Laureate Way, Kannapolis, North Carolina 28081, United States
| | - Hunter D Snook
- Laboratory for Functional Foods and Human Health, Center for Excellence in Post-Harvest Technologies, North Carolina Agricultural and Technical State University, North Carolina Research Campus, 500 Laureate Way, Kannapolis, North Carolina 28081, United States
| | - Fakir Shahidullah Tareq
- Laboratory for Functional Foods and Human Health, Center for Excellence in Post-Harvest Technologies, North Carolina Agricultural and Technical State University, North Carolina Research Campus, 500 Laureate Way, Kannapolis, North Carolina 28081, United States
| | - Yewande Fasina
- Department of Animal Sciences, North Carolina Agricultural and Technical State University, 1601 East Market Street, Greensboro, North Carolina 27411, United States
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30
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Ahmad R, Khan MA, Srivastava A, Gupta A, Srivastava A, Jafri TR, Siddiqui Z, Chaubey S, Khan T, Srivastava AK. Anticancer Potential of Dietary Natural Products: A Comprehensive Review. Anticancer Agents Med Chem 2020; 20:122-236. [DOI: 10.2174/1871520619666191015103712] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2018] [Revised: 06/21/2019] [Accepted: 07/02/2019] [Indexed: 02/07/2023]
Abstract
Nature is a rich source of natural drug-like compounds with minimal side effects. Phytochemicals
better known as “Natural Products” are found abundantly in a number of plants. Since time immemorial, spices
have been widely used in Indian cuisine as flavoring and coloring agents. Most of these spices and condiments
are derived from various biodiversity hotspots in India (which contribute 75% of global spice production) and
form the crux of India’s multidiverse and multicultural cuisine. Apart from their aroma, flavor and taste, these
spices and condiments are known to possess several medicinal properties also. Most of these spices are mentioned
in the Ayurveda, the indigenous system of medicine. The antimicrobial, antioxidant, antiproliferative,
antihypertensive and antidiabetic properties of several of these natural products are well documented in
Ayurveda. These phytoconstituemts are known to act as functional immunoboosters, immunomodulators as well
as anti-inflammatory agents. As anticancer agents, their mechanistic action involves cancer cell death via induction
of apoptosis, necrosis and autophagy. The present review provides a comprehensive and collective update
on the potential of 66 commonly used spices as well as their bioactive constituents as anticancer agents. The
review also provides an in-depth update of all major in vitro, in vivo, clinical and pharmacological studies done
on these spices with special emphasis on the potential of these spices and their bioactive constituents as potential
functional foods for prevention, treatment and management of cancer.
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Affiliation(s)
- Rumana Ahmad
- Department of Biochemistry, Era’s Lucknow Medical College & Hospital, Era University, Sarfarazganj, Lucknow-226003, UP, India
| | - Mohsin A. Khan
- Chancellor, Era University, Sarfarazganj, Hardoi Road, Lucknow-226003, UP, India
| | - A.N. Srivastava
- Department of Pathology, Era’s Lucknow Medical College & Hospital, Era University, Sarfarazganj, Lucknow-226003, UP, India
| | - Anamika Gupta
- Department of Biochemistry, Era’s Lucknow Medical College & Hospital, Era University, Sarfarazganj, Lucknow-226003, UP, India
| | - Aditi Srivastava
- Department of Biochemistry, Era’s Lucknow Medical College & Hospital, Era University, Sarfarazganj, Lucknow-226003, UP, India
| | - Tanvir R. Jafri
- Department of Biochemistry, Era’s Lucknow Medical College & Hospital, Era University, Sarfarazganj, Lucknow-226003, UP, India
| | - Zainab Siddiqui
- Department of Pathology, Era’s Lucknow Medical College & Hospital, Era University, Sarfarazganj, Lucknow-226003, UP, India
| | - Sunaina Chaubey
- Department of Biochemistry, Era’s Lucknow Medical College & Hospital, Era University, Sarfarazganj, Lucknow-226003, UP, India
| | - Tahmeena Khan
- Department of Chemistry, Integral University, Dasauli, P.O. Bas-ha, Kursi Road, Lucknow 226026, UP, India
| | - Arvind K. Srivastava
- Department of Food and Nutrition, Era University, Sarfarazganj, Lucknow-226003, UP, India
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Rondanelli M, Riva A, Allegrini P, Faliva MA, Naso M, Peroni G, Nichetti M, Gasparri C, Spadaccini D, Iannello G, Infantino V, Fazia T, Bernardinelli L, Perna S. The Use of a New Food-Grade Lecithin Formulation of Highly Standardized Ginger ( Zingiber officinale) and Acmella oleracea Extracts for the Treatment of Pain and Inflammation in a Group of Subjects with Moderate Knee Osteoarthritis. J Pain Res 2020; 13:761-770. [PMID: 32368129 PMCID: PMC7183537 DOI: 10.2147/jpr.s214488] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2019] [Accepted: 02/25/2020] [Indexed: 11/23/2022] Open
Abstract
PURPOSE To evaluate the efficacy of a new food-grade lecithin formulation of standardized extracts of Zingiber officinale and Acmella oleracea on pain and inflammation. PATIENTS AND METHODS Pilot study with one-group pretest-posttest quasi-experimental design in which 50 subjects with moderate knee osteoarthritis (OA) (mean age: 62.46±8.45) were supplied for four weeks with two tablets/day. RESULTS Primary outcomes were 1) the evaluation of pain intensity, by a 30-day visual analogue scale (VAS) and 2) the assessment of knee function by WOMAC (Western Ontario and McMaster Universities Arthritis) Index and by Tegner Lysholm Knee Scoring collected at baseline, at 15 and 30 days after treatment. Secondary outcomes were 3) health-related quality of life, by the ShortForm36 (SF-36); 4) inflammation grade by C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR); and 5) body composition by dual-energy X-ray absorptiometry (DXA) measured at baseline and 30 days after treatment. Data showed significant effects of supplement intake for WOMAC (β=-3.27, p<0.0001), Lysholm (β=1.06, p=0.0003), CRP (β=-0.13, p=0.006), ESR (β=-3.09, p=0.004), physical activity (β=4.3, p=0.009) and fat-free mass (β=376.7, p=0.046). A significant VAS's decrease over time was observed in both knees (left: β=-0.08, p<0.0001; right: β=-0.07, p<0.0001). CONCLUSION The tested formulation seems to be effective and also free of side effects.
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Affiliation(s)
- Mariangela Rondanelli
- IRCCS Mondino Foundation, Pavia27100, Italy
- Department of Public Health, Experimental and Forensic Medicine, Unit of Human and Clinical Nutrition, University of Pavia, Pavia27100, Italy
| | - Antonella Riva
- Research and Development Unit, Indena, Milan20146, Italy
| | | | - Milena Anna Faliva
- Endocrinology and Nutrition Unit, Azienda di Servizi alla Persona “Istituto Santa Margherita”, University of Pavia, Pavia27100, Italy
| | - Maurizio Naso
- Endocrinology and Nutrition Unit, Azienda di Servizi alla Persona “Istituto Santa Margherita”, University of Pavia, Pavia27100, Italy
| | - Gabriella Peroni
- Endocrinology and Nutrition Unit, Azienda di Servizi alla Persona “Istituto Santa Margherita”, University of Pavia, Pavia27100, Italy
| | - Mara Nichetti
- Endocrinology and Nutrition Unit, Azienda di Servizi alla Persona “Istituto Santa Margherita”, University of Pavia, Pavia27100, Italy
| | - Clara Gasparri
- Endocrinology and Nutrition Unit, Azienda di Servizi alla Persona “Istituto Santa Margherita”, University of Pavia, Pavia27100, Italy
| | - Daniele Spadaccini
- Endocrinology and Nutrition Unit, Azienda di Servizi alla Persona “Istituto Santa Margherita”, University of Pavia, Pavia27100, Italy
| | - Giancarlo Iannello
- General Management, Azienda di Servizi alla Persona “Istituto Santa Margherita”, Pavia27100, Italy
| | - Vittoria Infantino
- Department of Biomedical Science and Human Oncology, University of Bari Aldo Moro, Bari70121, Italy
| | - Teresa Fazia
- Department of Brain and Behavioral Science, University of Pavia, Pavia, Italy
| | - Luisa Bernardinelli
- Department of Brain and Behavioral Science, University of Pavia, Pavia, Italy
| | - Simone Perna
- Department of Biology, College of Science, University of Bahrain, Sakhir Campus, Kingdom of Bahrain
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Aiello P, Sharghi M, Mansourkhani SM, Ardekan AP, Jouybari L, Daraei N, Peiro K, Mohamadian S, Rezaei M, Heidari M, Peluso I, Ghorat F, Bishayee A, Kooti W. Medicinal Plants in the Prevention and Treatment of Colon Cancer. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2019; 2019:2075614. [PMID: 32377288 PMCID: PMC7187726 DOI: 10.1155/2019/2075614] [Citation(s) in RCA: 79] [Impact Index Per Article: 13.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/08/2019] [Accepted: 07/03/2019] [Indexed: 01/04/2023]
Abstract
The standard treatment for cancer is generally based on using cytotoxic drugs, radiotherapy, chemotherapy, and surgery. However, the use of traditional treatments has received attention in recent years. The aim of the present work was to provide an overview of medicinal plants effective on colon cancer with special emphasis on bioactive components and underlying mechanisms of action. Various literature databases, including Web of Science, PubMed, and Scopus, were used and English language articles were considered. Based on literature search, 172 experimental studies and 71 clinical cases on 190 plants were included. The results indicate that grape, soybean, green tea, garlic, olive, and pomegranate are the most effective plants against colon cancer. In these studies, fruits, seeds, leaves, and plant roots were used for in vitro and in vivo models. Various anticolon cancer mechanisms of these medicinal plants include induction of superoxide dismutase, reduction of DNA oxidation, induction of apoptosis by inducing a cell cycle arrest in S phase, reducing the expression of PI3K, P-Akt protein, and MMP as well; reduction of antiapoptotic Bcl-2 and Bcl-xL proteins, and decrease of proliferating cell nuclear antigen (PCNA), cyclin A, cyclin D1, cyclin B1 and cyclin E. Plant compounds also increase both the expression of the cell cycle inhibitors p53, p21, and p27, and the BAD, Bax, caspase 3, caspase 7, caspase 8, and caspase 9 proteins levels. In fact, purification of herbal compounds and demonstration of their efficacy in appropriate in vivo models, as well as clinical studies, may lead to alternative and effective ways of controlling and treating colon cancer.
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Affiliation(s)
- Paola Aiello
- Council for Agricultural Research and Economics, Research Centre for Food and Nutrition, Via Ardeatina 546, 00178 Rome, Italy
- Department of Physiology and Pharmacology “V. Erspamer”, La Sapienza University of Rome, Rome, Italy
| | - Maedeh Sharghi
- Nursing and Midwifery School, Guilan University of Medical Sciences, Rasht, Iran
| | | | - Azam Pourabbasi Ardekan
- Lung Diseases and Allergy Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | - Leila Jouybari
- Nursing Research Center, Golestan University of Medical Sciences, Gorgan, Iran
| | - Nahid Daraei
- Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Khadijeh Peiro
- Department of Biology, Faculty of Sciences, Shahid Chamran University, Ahvaz, Iran
| | - Sima Mohamadian
- Faculty of Pharmacy and Pharmaceutical Sciences, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Mahdiyeh Rezaei
- Faculty of Pharmacy and Pharmaceutical Sciences, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Mahdi Heidari
- Lung Diseases and Allergy Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | - Ilaria Peluso
- Council for Agricultural Research and Economics, Research Centre for Food and Nutrition, Via Ardeatina 546, 00178 Rome, Italy
| | - Fereshteh Ghorat
- Traditional and Complementary Medicine Research Center, Sabzevar University of Medical Sciences, Sabzevar, Iran
| | - Anupam Bishayee
- Lake Erie College of Osteopathic Medicine, 5000 Lakewood Ranch Boulevard, Bradenton, FL 34211, USA
| | - Wesam Kooti
- Lung Diseases and Allergy Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran
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Omidvar S, Nasiri-Amiri F, Bakhtiari A, Begum K. Clinical trial for the management dysmenorrhea using selected spices. Complement Ther Clin Pract 2019; 36:34-38. [PMID: 31383440 DOI: 10.1016/j.ctcp.2019.04.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2018] [Revised: 04/03/2019] [Accepted: 04/10/2019] [Indexed: 10/26/2022]
Abstract
BACKGROUND Dysmenorrhea is the most common gynecologic complaint among adolescent and adult females. Some dysmenorrheic females do not respond to treatment with NSAIDs or oral contraceptives and exhibit contraindications to such medications. Therefore, alternative medication gained importance in management of dysmenorrhea. METHODS A comparative clinical trial was conducted on thirty-one dysmenorrheic subjects, who were randomly assigned to three groups. The dosage was 1gr/day, 3gr/day and 3gr/day for Ginger, Dill seeds, and Cumin, respectively. The girls in respective group consumed the spice for three days during each cycle for three consecutive cycles. RESULTS Dill seed was effective in reducing pain, followed by ginger wherein Cumin did not exhibit any effect. Cumin exhibited significant reduction in systemic responses like cold sweats, backache, fatigue and cramps. CONCLUSION Dill seeds were more effective in reducing pain. It was obvious from our study that reducing symptoms is also important in the overall management of dysmenorrhea.
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Affiliation(s)
- Shabnam Omidvar
- Social Determinants of Health Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran; Department of Midwifery, School of Nursing and Midwifery, Babol University of Medical Sciences, Babol, Iran
| | - Fatemeh Nasiri-Amiri
- Department of Midwifery, School of Nursing and Midwifery, Babol University of Medical Sciences, Babol, Iran; Infertility and Health Reproductive Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
| | - Afsaneh Bakhtiari
- Mobility Impairment Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran.
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Lechner JF, Stoner GD. Gingers and Their Purified Components as Cancer Chemopreventative Agents. Molecules 2019; 24:E2859. [PMID: 31394732 PMCID: PMC6719158 DOI: 10.3390/molecules24162859] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2019] [Revised: 07/29/2019] [Accepted: 08/05/2019] [Indexed: 12/17/2022] Open
Abstract
Chemoprevention by ingested substituents is the process through which nutraceuticals and/or their bioactive components antagonize carcinogenesis. Carcinogenesis is the course of action whereby a normal cell is transformed into a neoplastic cell. This latter action involves several steps, starting with initiation and followed by promotion and progression. Driving these stages is continued oxidative stress and inflammation, which in turn, causes a myriad of aberrant gene expressions and mutations within the transforming cell population and abnormal gene expressions by the cells within the surrounding lesion. Chemoprevention of cancer with bioreactive foods or their extracted/purified components occurs primarily via normalizing these inappropriate gene activities. Various foods/agents have been shown to affect different gene expressions. In this review, we discuss how the chemoprevention activities of gingers antagonize cancer development.
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Affiliation(s)
- John F Lechner
- Retired from Department of Medicine, Division of Medical Oncology, Ohio State University, Columbus 43210, OH, USA.
| | - Gary D Stoner
- Department of Microbiology and Immunology, Montana State University, Bozeman, MT 59717, USA
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Ariantari NP, Ancheeva E, Wang C, Mándi A, Knedel TO, Kurtán T, Chaidir C, Müller WEG, Kassack MU, Janiak C, Daletos G, Proksch P. Indole Diterpenoids from an Endophytic Penicillium sp. JOURNAL OF NATURAL PRODUCTS 2019; 82:1412-1423. [PMID: 31117519 DOI: 10.1021/acs.jnatprod.8b00723] [Citation(s) in RCA: 48] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/09/2023]
Abstract
A chemical investigation of the endophyte Penicillium sp. (strain ZO-R1-1), isolated from roots of the medicinal plant Zingiber officinale, yielded nine new indole diterpenoids (1-9), together with 13 known congeners (10-22). The structures of the new compounds were elucidated by 1D and 2D NMR analysis in combination with HRESIMS data. The absolute configuration of the new natural products 1, 3, and 7 was determined using the TDDFT-ECD approach and confirmed for 1 by single-crystal X-ray determination through anomalous dispersion. The isolated compounds were tested for cytotoxicity against L5178Y, A2780, J82, and HEK-293 cell lines. Compound 1 was the most active metabolite toward L5178Y cells, with an IC50 value of 3.6 μM, and an IC50 against A2780 cells of 8.7 μM. Interestingly, 1 features a new type of indole diterpenoid scaffold with a rare 6/5/6/6/6/6/5 heterocyclic system bearing an aromatic ring C, which is suggested to be important for the cytotoxic activity of this natural product against L5278Y and A2780 cells.
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Affiliation(s)
- Ni P Ariantari
- Institute of Pharmaceutical Biology and Biotechnology , Heinrich Heine University Düsseldorf , Universitätsstrasse 1 , 40225 Düsseldorf , Germany
- Department of Pharmacy, Faculty of Mathematic and Natural Sciences , Udayana University , 80361 Bali , Indonesia
| | - Elena Ancheeva
- Institute of Pharmaceutical Biology and Biotechnology , Heinrich Heine University Düsseldorf , Universitätsstrasse 1 , 40225 Düsseldorf , Germany
| | - Chenyin Wang
- Institute of Pharmaceutical and Medicinal Chemistry , Heinrich Heine University Düsseldorf , Universitätsstrasse 1 , 40225 Düsseldorf , Germany
| | - Attila Mándi
- Department of Organic Chemistry , University of Debrecen , P.O.B. 400, 4002 Debrecen , Hungary
| | - Tim-O Knedel
- Institute of Inorganic Chemistry and Structural Chemistry , Heinrich Heine University Düsseldorf , Universitätsstraße 1 , 40225 Düsseldorf , Germany
| | - Tibor Kurtán
- Department of Organic Chemistry , University of Debrecen , P.O.B. 400, 4002 Debrecen , Hungary
| | - Chaidir Chaidir
- Center for Pharmaceutical and Medical Technology , Agency for the Assessment and Application Technology , 10340 Jakarta , Indonesia
| | - Werner E G Müller
- Institute of Physiological Chemistry , Universitätsmedizin der Johannes Gutenberg-Universität Mainz , Duesbergweg 6 , 55128 Mainz , Germany
| | - Matthias U Kassack
- Institute of Pharmaceutical and Medicinal Chemistry , Heinrich Heine University Düsseldorf , Universitätsstrasse 1 , 40225 Düsseldorf , Germany
| | - Christoph Janiak
- Institute of Inorganic Chemistry and Structural Chemistry , Heinrich Heine University Düsseldorf , Universitätsstraße 1 , 40225 Düsseldorf , Germany
| | - Georgios Daletos
- Institute of Pharmaceutical Biology and Biotechnology , Heinrich Heine University Düsseldorf , Universitätsstrasse 1 , 40225 Düsseldorf , Germany
| | - Peter Proksch
- Institute of Pharmaceutical Biology and Biotechnology , Heinrich Heine University Düsseldorf , Universitätsstrasse 1 , 40225 Düsseldorf , Germany
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Fuzer AM, Martin AC, Becceneri AB, da Silva JA, Vieira PC, Cominetti MR. [10]-Gingerol Affects Multiple Metastatic Processes and Induces Apoptosis in MDAMB- 231 Breast Tumor Cells. Anticancer Agents Med Chem 2019; 19:645-654. [DOI: 10.2174/1871520618666181029125607] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2018] [Revised: 10/13/2018] [Accepted: 10/18/2018] [Indexed: 01/10/2023]
Abstract
Background:
Triple Negative Breast Cancer (TNBC) represents the approximately 15% of breast cancers
that lack expression of Estrogen (ER) and Progesterone Receptors (PR) and do not exhibit amplification of the human
epidermal growth factor receptor 2 (HER2) gene, imposing difficulties to treatment. Interactions between tumor
cells and their microenvironment facilitate tumor cell invasion in the surrounding tissues, intravasation through
newly formed vessels, and dissemination to form metastasis. To treat metastasis from breast and many other cancer
types, chemotherapy is one of the most extensively used methods. However, its efficacy and safety remain a primary
concern, as well as its toxicity and other side effects. Thus, there is increasing interest in natural antitumor agents.
In a previous work, we have demonstrated that [10]-gingerol is able to revert malignant phenotype in breast cancer
cells in 3D culture and, moreover, to inhibit the dissemination of TNBC to multiple organs including lung, bone and
brain, in spontaneous and experimental in vivo metastasis assays in mouse model.
Objective:
This work aims to investigate the in vitro effects of [10]-gingerol, using human MDA-MB-231TNBC
cells, in comparison to non-tumor MCF-10A breast cells, in order to understand the antitumor and antimetastatic
effects found in vivo and in a 3D environment.
Methods:
We investigated different steps of the metastatic process in vitro, such as cell migration, invasion, adhesion
and MMP activity. In addition, we analyzed the anti-apoptotic and genotoxic effects of [10]-gingerol using PEAnnexin,
DNA fragmentation, TUNEL and comet assays, respectively.
Results:
[10]-gingerol was able to inhibit cell adhesion, migration, invasion and to induce apoptosis more effectively in
TNBC cells, when compared to non-tumor cells, demonstrating that these mechanisms can be involved in the antitumor
and antimetastatic effects of [10]-gingerol, found both in 3D culture and in vivo.
Conclusion:
Taken together, results found here are complementary to previous studies of our group and others and
demonstrate that additional mechanisms, besides apoptotic cell death, is used by [10]-gingerol to accomplish its antitumor
and antimetastatic effects. Our results indicate a potential for this natural compound as an antitumor molecule or
as an adjuvant for chemotherapeutics already used in the clinic.
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Affiliation(s)
- Angelina M. Fuzer
- Department of de Gerontology, Federal University of Sao Carlos, Sao Carlos, SP, 13565-905, Brazil
| | - Ana C.B.M. Martin
- Department of de Gerontology, Federal University of Sao Carlos, Sao Carlos, SP, 13565-905, Brazil
| | - Amanda B. Becceneri
- Department of de Gerontology, Federal University of Sao Carlos, Sao Carlos, SP, 13565-905, Brazil
| | - James A. da Silva
- Department of Pharmacology, Federal University of Sergipe, Lagarto, SE 49100-000, Brazil
| | - Paulo C. Vieira
- Department of Chemistry, Federal University of Sao Carlos. Monjolinho, São Carlos, SP, 13565-905, Brazil
| | - Marcia R. Cominetti
- Department of de Gerontology, Federal University of Sao Carlos, Sao Carlos, SP, 13565-905, Brazil
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Zhang H, Wang Q, Sun C, Zhu Y, Yang Q, Wei Q, Chen J, Deng W, Adu-Frimpong M, Yu J, Xu X. Enhanced Oral Bioavailability, Anti-Tumor Activity and Hepatoprotective Effect of 6-Shogaol Loaded in a Type of Novel Micelles of Polyethylene Glycol and Linoleic Acid Conjugate. Pharmaceutics 2019; 11:pharmaceutics11030107. [PMID: 30845761 PMCID: PMC6470752 DOI: 10.3390/pharmaceutics11030107] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2018] [Revised: 03/01/2019] [Accepted: 03/01/2019] [Indexed: 12/20/2022] Open
Abstract
：6-shogaol is a promising anti-cancer and anti-inflammatory agent. However, the treatment effectiveness of 6-shogaol is limited by poor water solubility, poor oral absorption and rapid metabolism. Herein, 6-shogaol loaded in micelles (SMs) were designed to improve 6-shogaol's solubility and bioavailability. The micelles of a PEG derivative of linoleic acid (mPEG2k-LA) were prepared by the nanoprecipitation method with a particle size of 76.8 nm, and entrapment of 81.6 %. Intriguingly, SMs showed a slower release in phosphate buffer saline (PBS) (pH = 7.4) compared to free 6-shogaol while its oral bioavailability increased by 3.2⁻fold in vivo. More importantly, the in vitro cytotoxic effect in HepG2 cells of SMs was significantly higher than free 6-shogaol. Furthermore, SMs could significantly improve the tissue distribution of 6-shogaol, especially liver and brain. Finally, SMs showed a better hepatoprotective effect against carbon tetrachloride (CCl4)-induced hepatic injury in vivo than free 6-shogaol. These results suggest that the novel micelles could potentiate the activities of 6-shogaol in cancer treatment and hepatoprotection.
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Affiliation(s)
- Huiyun Zhang
- Center for Nano Drug/Gene Delivery and Tissue Engineering, Department of Pharmaceutics, School of Pharmacy, Jiangsu University, Zhenjiang 212013, China.
| | - Qilong Wang
- Center for Nano Drug/Gene Delivery and Tissue Engineering, Department of Pharmaceutics, School of Pharmacy, Jiangsu University, Zhenjiang 212013, China.
| | - Congyong Sun
- Center for Nano Drug/Gene Delivery and Tissue Engineering, Department of Pharmaceutics, School of Pharmacy, Jiangsu University, Zhenjiang 212013, China.
| | - Yuan Zhu
- Center for Nano Drug/Gene Delivery and Tissue Engineering, Department of Pharmaceutics, School of Pharmacy, Jiangsu University, Zhenjiang 212013, China.
| | - Qiuxuan Yang
- Center for Nano Drug/Gene Delivery and Tissue Engineering, Department of Pharmaceutics, School of Pharmacy, Jiangsu University, Zhenjiang 212013, China.
| | - Qiuyu Wei
- Center for Nano Drug/Gene Delivery and Tissue Engineering, Department of Pharmaceutics, School of Pharmacy, Jiangsu University, Zhenjiang 212013, China.
| | - Jiaxin Chen
- Center for Nano Drug/Gene Delivery and Tissue Engineering, Department of Pharmaceutics, School of Pharmacy, Jiangsu University, Zhenjiang 212013, China.
| | - Wenwen Deng
- Center for Nano Drug/Gene Delivery and Tissue Engineering, Department of Pharmaceutics, School of Pharmacy, Jiangsu University, Zhenjiang 212013, China.
| | - Michael Adu-Frimpong
- Center for Nano Drug/Gene Delivery and Tissue Engineering, Department of Pharmaceutics, School of Pharmacy, Jiangsu University, Zhenjiang 212013, China.
| | - Jiangnan Yu
- Center for Nano Drug/Gene Delivery and Tissue Engineering, Department of Pharmaceutics, School of Pharmacy, Jiangsu University, Zhenjiang 212013, China.
| | - Ximing Xu
- Center for Nano Drug/Gene Delivery and Tissue Engineering, Department of Pharmaceutics, School of Pharmacy, Jiangsu University, Zhenjiang 212013, China.
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Cao SY, Li Y, Meng X, Zhao CN, Li S, Gan RY, Li HB. Dietary natural products and lung cancer: Effects and mechanisms of action. J Funct Foods 2019. [DOI: 10.1016/j.jff.2018.11.004] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
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Ko MJ, Nam HH, Chung MS. Conversion of 6-gingerol to 6-shogaol in ginger (Zingiber officinale) pulp and peel during subcritical water extraction. Food Chem 2019; 270:149-155. [PMID: 30174028 DOI: 10.1016/j.foodchem.2018.07.078] [Citation(s) in RCA: 39] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2018] [Revised: 06/21/2018] [Accepted: 07/11/2018] [Indexed: 10/28/2022]
Abstract
Subcritical water extraction is an eco-friendly method for the extraction of less polar compounds without the use of organic solvents. This study determined the extraction conditions that maximize the contents of 6-gingerol and 6-shogaol obtained from ginger pulp and peel. The highest yields of 6-gingerol (0.68 ± 0.08 mg/g), and 6-shogaol (0.39 ± 0.03 mg/g) were obtained from ginger pulp at the extraction conditions of 130 °C/25 min, and 190 °C/15 min. 6-Shogaol content increased with the increasing extraction temperature and extraction time due to the conversion of 6-gingerol to 6-shogaol by thermal cracking. The antioxidant activity of ginger extracts were increased depending on the increasing of 6-shogaol content.
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Affiliation(s)
- Min-Jung Ko
- Department of Food Science and Engineering, Ewha Womans University, Seoul 120-750, South Korea.
| | - Hwa-Hyun Nam
- Department of Food Science and Engineering, Ewha Womans University, Seoul 120-750, South Korea.
| | - Myong-Soo Chung
- Department of Food Science and Engineering, Ewha Womans University, Seoul 120-750, South Korea.
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40
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He Z, Lei L, Kwek E, Zhao Y, Liu J, Hao W, Zhu H, Liang N, Ma KY, Ho HM, He WS, Chen ZY. Ginger attenuates trimethylamine-N-oxide (TMAO)-exacerbated disturbance in cholesterol metabolism and vascular inflammation. J Funct Foods 2019. [DOI: 10.1016/j.jff.2018.10.022] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/28/2022] Open
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Leoni A, Budriesi R, Poli F, Lianza M, Graziadio A, Venturini A, Broccoli M, Micucci M. Ayurvedic preparation of Zingiber officinale Roscoe: effects on cardiac and on smooth muscle parameters. Nat Prod Res 2018; 32:2139-2146. [PMID: 28846029 DOI: 10.1080/14786419.2017.1367779] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2017] [Accepted: 08/09/2017] [Indexed: 10/19/2022]
Abstract
The rhizome of the Zingiber officinale Roscoe, a biennial herb growing in South Asia, is commonly known as ginger. Ginger is used in clinical disorders, such as constipation, dyspepsia, diarrhoea, nausea and vomiting and its use is also recommended by the traditional medicine for cardiopathy, high blood pressure, palpitations and as a vasodilator to improve the circulation. The decoction of ginger rhizome is widely used in Ayurvedic medicine. In this papery by high-performance liquid chromatography, we have seen that its main phytomarkers were 6-gingerol, 8-gingerol and 6-shogaol and we report the effects of the decoction of ginger rhizome on cardiovascular parameters and on vascular and intestinal smooth muscle. In our experimental models, the decoction of ginger shows weak negative inotropic and chronotropic intrinsic activities but a significant intrinsic activity on smooth muscle with a potency on ileum is greater than on aorta: EC50 = 0.66 mg/mL versus EC50 = 1.45 mg/mL.
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Affiliation(s)
- Alberto Leoni
- a Department of Farmacy and Biotecnology , AlmaMater Studiorum- University of Bologna , Bologna , Italy
| | - Roberta Budriesi
- a Department of Farmacy and Biotecnology , AlmaMater Studiorum- University of Bologna , Bologna , Italy
| | - Ferruccio Poli
- a Department of Farmacy and Biotecnology , AlmaMater Studiorum- University of Bologna , Bologna , Italy
| | - Mariacaterina Lianza
- a Department of Farmacy and Biotecnology , AlmaMater Studiorum- University of Bologna , Bologna , Italy
| | - Alessandra Graziadio
- a Department of Farmacy and Biotecnology , AlmaMater Studiorum- University of Bologna , Bologna , Italy
| | - Alice Venturini
- b Educational Laboratory ex Lolli Hospital, School of Farmacy , Biotechnology and Sport Science , Imola , Italy
| | - Massimiliano Broccoli
- b Educational Laboratory ex Lolli Hospital, School of Farmacy , Biotechnology and Sport Science , Imola , Italy
| | - Matteo Micucci
- a Department of Farmacy and Biotecnology , AlmaMater Studiorum- University of Bologna , Bologna , Italy
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Du YT, Zheng YL, Ji Y, Dai F, Hu YJ, Zhou B. Applying an Electrophilicity-Based Strategy to Develop a Novel Nrf2 Activator Inspired from Dietary [6]-Shogaol. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2018; 66:7983-7994. [PMID: 29987924 DOI: 10.1021/acs.jafc.8b02442] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/08/2023]
Abstract
Activation of nuclear factor erythroid-2-related factor 2 (Nrf2) is a crucial cellular defense mechanisms against oxidative stress and also an effective means to decrease the risk of oxidative stress-related diseases including cancer. Thus, identifying novel Nrf2 activators is highly anticipated. Inspired from [6]-shogaol (6S), an active component of ginger, herein we developed a novel potent Nrf2 activator, (1E,4E)-1-(4-hydroxy-3-methoxyphenyl)-7-methylocta-1,4,6-trien-3-one (SA) by an electrophilicity-based strategy. Compared with the parent 6S, SA bearing a short but entirely conjugated unsaturated ketone chain manifested the improved electrophilicity and cytoprotection (cell viability for the 10 μM 6S- and SA-treated group being 48.9 ± 5.3% and 76.1 ± 3.2%, respectively) against tert-butylhydroperoxide ( t-BHP)-induced cell death (cell viability for the t-BHP-stimulated group being 42.4 ± 0.4%) of HepG2. Mechanistic study uncovers that SA works as a potent Nrf2 activator by inducing Keap1 modification, inhibiting Nrf2 ubiquitylation and phosphorylating ERK in a Michael acceptor-dependent fashion. Taking 6S as an example, this works illustrates the feasibility and importance of applying an electrophilicity-based strategy to develop Nrf2 activators with dietary molecules as an inspiration due to their low toxicity and extraordinarily diverse chemical scaffolds.
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Affiliation(s)
- Yu-Ting Du
- State Key Laboratory of Applied Organic Chemistry , Lanzhou University , 222 Tianshui Street South , Lanzhou , Gansu 730000 , China
| | - Ya-Long Zheng
- State Key Laboratory of Applied Organic Chemistry , Lanzhou University , 222 Tianshui Street South , Lanzhou , Gansu 730000 , China
| | - Yuan Ji
- State Key Laboratory of Applied Organic Chemistry , Lanzhou University , 222 Tianshui Street South , Lanzhou , Gansu 730000 , China
| | - Fang Dai
- State Key Laboratory of Applied Organic Chemistry , Lanzhou University , 222 Tianshui Street South , Lanzhou , Gansu 730000 , China
| | - Yong-Jing Hu
- State Key Laboratory of Applied Organic Chemistry , Lanzhou University , 222 Tianshui Street South , Lanzhou , Gansu 730000 , China
| | - Bo Zhou
- State Key Laboratory of Applied Organic Chemistry , Lanzhou University , 222 Tianshui Street South , Lanzhou , Gansu 730000 , China
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Ghasemzadeh A, Jaafar HZE, Baghdadi A, Tayebi-Meigooni A. Formation of 6-, 8- and 10-Shogaol in Ginger through Application of Different Drying Methods: Altered Antioxidant and Antimicrobial Activity. Molecules 2018; 23:E1646. [PMID: 29976903 PMCID: PMC6099745 DOI: 10.3390/molecules23071646] [Citation(s) in RCA: 39] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2018] [Revised: 06/26/2018] [Accepted: 06/28/2018] [Indexed: 01/12/2023] Open
Abstract
Gingerols and shogaols are compounds found in ginger (Zingiber officinale Roscoe); shogaols are found in lower concentration than gingerols but exhibit higher biological activities. This work studied the effects of different drying methods including open sun drying (OSD) solar tunnel drying (STD) and hot air drying (HAD) with various temperature on the formation of six main active compounds in ginger rhizomes, namely 6-, 8-, and 10-gingerols and 6-, 8-, and 10-shogaols, as well as essential oil content. Antioxidant and antimicrobial activity of dried ginger was also evaluated. High performance liquid chromatography (HPLC) analysis showed that after HAD with variable temperature (120, 150 and 180 °C), contents of 6-, 8-, and 10-gingerols decreased, while contents of 6-, 8-, and 10-shogaol increased. High formation of 6-, 8-, and 10-shogaol contents were observed in HAD (at 150 °C for 6 h) followed by STD and OSD, respectively. OSD exhibited high content of essential oil followed by STD and HAD method. Ginger-treated with HAD exhibited the highest DPPH (IC50 of 57.8 mg/g DW) and FRAP (493.8 µM of Fe(II)/g DM) activity, compared to STD and OSD method. HAD ginger exhibited potent antimicrobial activity with lower minimum inhibition concentration (MIC) value against bacteria strains followed by STD and OSD, respectively. Ginger extracts showed more potent antimicrobial activity against Gram positive bacteria than Gram negative bacteria strains. Result of this study confirmed that conversion of gingerols to shogaols was significantly affected by different drying temperature and time. HAD at 150 °C for 6 h, provides a method for enhancing shogaols content in ginger rhizomes with improving antioxidant and antimicrobial activities.
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Affiliation(s)
- Ali Ghasemzadeh
- Department of Crop Science, Faculty of Agriculture, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia.
| | - Hawa Z E Jaafar
- Department of Crop Science, Faculty of Agriculture, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia.
| | - Ali Baghdadi
- Department of Crop Science, Faculty of Agriculture, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia.
| | - Amin Tayebi-Meigooni
- Department of Food Science and Technology, Tehran North Branch, Islamic Azad University, Tehran 1987973133, Iran.
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Zammel N, Amri N, Chaabane R, Rebai T, Badraoui R. Proficiencies of Zingiber officinale against spine curve and vertebral damage induced by corticosteroid therapy associated with gonadal hormone deficiency in a rat model of osteoporosis. Biomed Pharmacother 2018; 103:1429-1435. [PMID: 29864927 DOI: 10.1016/j.biopha.2018.04.159] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2017] [Revised: 04/23/2018] [Accepted: 04/23/2018] [Indexed: 01/05/2023] Open
Abstract
This study was assessed to examine whether Zingiber officinale (ZO) can prevent spine disorder and trabecular microarchitecture disruption in osteoporotic murin model. Three groups of male rats were selected: Controls (CTRL), combined model of osteoporosis (CMO), in which rats were orchidectomized and treated with cortisol, and CMO treated with ZO (CMO + ZO). One month after the surgical procedures, the rats were sacrificed. Lumbar curve of the spine has been evaluated using the kyphotic method. The spines were submitted to histological and histomorphometric analysis and mineral (calcium and phosphorus) metabolism assessment. Compared to CTRL, the mean kyphotic angle (KA) was significantly higher in CMO rats. The spinal deconditioning associated decreased bone trabecular volume and a disrupted microarchitecture. A disorder was observed in the serum and bone levels of calcium and phosphorus in the combined severe osteopenia model. An increase in the level of TRAcP associated with an increase in osteoclast number and activity has been reported. These disturbances were reduced following the use of ZO in the CMO + ZO group. Finally, ginger might be an alternative therapeutic candidate for the treatment of severe osteopenia induced vertebral damage and spine curve disruption.
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Affiliation(s)
- Nourhène Zammel
- Laboratory of Histo-Embryology and Cytogenetics, Medicine Faculty of Sfax University, 3029, Sfax, Tunisia
| | - Nahed Amri
- Laboratory of Histo-Embryology and Cytogenetics, Medicine Faculty of Sfax University, 3029, Sfax, Tunisia
| | - Rim Chaabane
- Laboratory of Biochemistry, CHU Hédi Chaker of Sfax, 3029, Sfax, Tunisia
| | - Tarek Rebai
- Laboratory of Histo-Embryology and Cytogenetics, Medicine Faculty of Sfax University, 3029, Sfax, Tunisia
| | - Riadh Badraoui
- Laboratory of Histo-Embryology and Cytogenetics, Medicine Faculty of Sfax University, 3029, Sfax, Tunisia; Laboratory of Histology - Cytology, Medicine Faculty of Tunis, University of Tunis El Manar, 1007, La Rabta-Tunis, Tunisia.
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Jung MY, Lee MK, Park HJ, Oh EB, Shin JY, Park JS, Jung SY, Oh JH, Choi DS. Heat-induced conversion of gingerols to shogaols in ginger as affected by heat type (dry or moist heat), sample type (fresh or dried), temperature and time. Food Sci Biotechnol 2018; 27:687-693. [PMID: 30263794 PMCID: PMC6049668 DOI: 10.1007/s10068-017-0301-1] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2017] [Revised: 12/05/2017] [Accepted: 12/18/2017] [Indexed: 11/25/2022] Open
Abstract
The impact of heat type, sample type, temperature and time on the heat-induced conversion of gingerols to shogaols in ginger were studied by an UHPLC-ESI-MS/MS. Heat treatments greatly induced the conversion of gingerols to shogaols in ginger. As the temperature increased, the faster conversion of gingerols into shogaols were observed. However, the efficiency of the heat-induced conversion differed greatly with the heat types. Moist heat treatment induced significantly higher quantity of shogaols than dry heat treatment. The moist heat treatment at 120 °C for 360 min induced the highest conversion, reaching to 2991 mg 6-shogaol per kg ginger. In addition, dry-heat induced conversion was affected by the sample type. The dry-heat treatment on dried powder induced significantly higher quantity of shogaols than that on sliced fresh ginger. This represents the first systematic comparative study on the heat and sample types on the heat-induced conversion of gingerols into shogaols in ginger.
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Affiliation(s)
- Mun Yhung Jung
- Department of Food and Biotechnology, Graduate School, Woosuk University, Samnye-Eup, Wanju-Gun, Jeonbuk Province 55338 Republic of Korea
| | - Min Kyoung Lee
- Department of Food and Biotechnology, Graduate School, Woosuk University, Samnye-Eup, Wanju-Gun, Jeonbuk Province 55338 Republic of Korea
| | - Hee Jeong Park
- Department of Food and Biotechnology, Graduate School, Woosuk University, Samnye-Eup, Wanju-Gun, Jeonbuk Province 55338 Republic of Korea
| | - Eun-Bi Oh
- Department of Food and Biotechnology, Graduate School, Woosuk University, Samnye-Eup, Wanju-Gun, Jeonbuk Province 55338 Republic of Korea
| | - Je Young Shin
- Department of Food and Biotechnology, Graduate School, Woosuk University, Samnye-Eup, Wanju-Gun, Jeonbuk Province 55338 Republic of Korea
| | - Ji Su Park
- Department of Food and Biotechnology, Graduate School, Woosuk University, Samnye-Eup, Wanju-Gun, Jeonbuk Province 55338 Republic of Korea
- Food Analysis Center, Korea Food Research Institute, Wanju-Gun, Jeonbuk Province 55365 Republic of Korea
| | - Su Young Jung
- Healthy Local Food Branding Agency, Wanju, Jeonbuk Republic of Korea
| | - Jung-Hee Oh
- Healthy Local Food Branding Agency, Wanju, Jeonbuk Republic of Korea
| | - Dong-Seong Choi
- Department of Food and Biotechnology, Graduate School, Woosuk University, Samnye-Eup, Wanju-Gun, Jeonbuk Province 55338 Republic of Korea
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Kou X, Wang X, Ji R, Liu L, Qiao Y, Lou Z, Ma C, Li S, Wang H, Ho CT. Occurrence, biological activity and metabolism of 6-shogaol. Food Funct 2018; 9:1310-1327. [PMID: 29417118 DOI: 10.1039/c7fo01354j] [Citation(s) in RCA: 72] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2023]
Abstract
As one of the main bioactive compounds of dried ginger, 6-shogaol has been widely used to alleviate many ailments. It is also a major pungent flavor component, and its precursor prior to dehydration is 6-gingerol, which is reported to be responsible for the pungent flavor and biological activity of fresh ginger. Structurally, gingerols including 6-gingerol have a β-hydroxyl ketone moiety and is liable to dehydrate to generate an α,β-unsaturated ketone under heat and/or acidic conditions. The conjugation of the α,β-unsaturated ketone skeleton in the chemical structure of 6-shogaol explicates its higher potency and efficacy than 6-gingerol in terms of antioxidant, anti-inflammatory, anticancer, antiemetic and other bioactivities. Research on the health benefits of 6-shogaol has been conducted and results have been reported recently; however, scientific data are scattered due to a lack of systematic collection. In addition, action mechanisms of the preventive and/or therapeutic actions of 6-shogaol remain obscurely non-collective. Herein, we review the preparations, biological activity and mechanisms, and metabolism of 6-shogaol as well as the properties of 6-shogaol metabolites.
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Affiliation(s)
- Xingran Kou
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, People's Republic of China. and School of Food Science and Technology, Jiangnan University, Wuxi 214122, People's Republic of China and Department of Food Science, Rutgers University, 65 Dudley Road, New Brunswick, NJ 08901-8520, USA.
| | - Xiaoqi Wang
- Department of Food Science, Rutgers University, 65 Dudley Road, New Brunswick, NJ 08901-8520, USA.
| | - Ruya Ji
- Department of Food Science, Rutgers University, 65 Dudley Road, New Brunswick, NJ 08901-8520, USA.
| | - Lang Liu
- Department of Food Science, Rutgers University, 65 Dudley Road, New Brunswick, NJ 08901-8520, USA.
| | - Yening Qiao
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, People's Republic of China
| | - Zaixiang Lou
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, People's Republic of China. and School of Food Science and Technology, Jiangnan University, Wuxi 214122, People's Republic of China
| | - Chaoyang Ma
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, People's Republic of China. and School of Food Science and Technology, Jiangnan University, Wuxi 214122, People's Republic of China
| | - Shiming Li
- Department of Food Science, Rutgers University, 65 Dudley Road, New Brunswick, NJ 08901-8520, USA.
| | - Hongxin Wang
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, People's Republic of China. and National Engineering Research Center for Functional Food, Jiangnan University, Wuxi 214122, People's Republic of China and School of Food Science and Technology, Jiangnan University, Wuxi 214122, People's Republic of China
| | - Chi-Tang Ho
- Department of Food Science, Rutgers University, 65 Dudley Road, New Brunswick, NJ 08901-8520, USA.
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Comparison of Inhibitory Capacities of 6-, 8- and 10-Gingerols/Shogaols on the Canonical NLRP3 Inflammasome-Mediated IL-1β Secretion. Molecules 2018; 23:molecules23020466. [PMID: 29466287 PMCID: PMC6017621 DOI: 10.3390/molecules23020466] [Citation(s) in RCA: 38] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2018] [Revised: 02/13/2018] [Accepted: 02/20/2018] [Indexed: 11/17/2022] Open
Abstract
Endogenous noninfectious substances that mediate the nucleotide oligomerization domain (NOD)-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation and interleukin (IL)-1β secretion causes inappropriate sterile inflammation and is implicated in the pathogenesis of several chronic diseases, such as type 2 diabetes mellitus, gout, atherosclerosis and Alzheimer’s disease. Consequently, dietary phytochemicals exhibiting capacities to suppress canonical NLRP3 inflammasome-mediated IL-1β secretion can be a reliable supplement to prevent such diseases. The purpose of this study was to investigate and compare the inhibitory effects of ginger phytochemicals, including 6-, 8- and 10-gingerols/shogaols on the canonical NLRP3 inflammasome-mediated IL-1β secretion in THP-1 macrophages with ordered stimulations of lipopolysaccharide (LPS) and adenosine 5′-triphosphate (ATP). At 20 μM, the 10-gingerol and all the shogaols significantly inhibited canonical IL-1β secretion. The shogaols had a more potent inhibitory capacity than that of corresponding gingerols. Increase of alkyl chain length impacted negatively the inhibitory activity of shogaols. Additionally, these effective ginger phytochemicals not only inhibited the LPS-primed expression of pro-IL-1β and NLRP3, but also decreased ATP-activated caspase-1. The results demonstrated that ginger phytochemicals, especially the most potent, 6-shogaol, might be promising for developing as an inhibitor of the canonical NLRP3 inflammasome-mediated IL-1β secretion and further applied in prevention of NLRP3 inflammasome-associated diseases.
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48
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6-Shogaol induces caspase-independent paraptosis in cancer cells via proteasomal inhibition. Exp Cell Res 2018; 364:243-251. [PMID: 29462602 DOI: 10.1016/j.yexcr.2018.02.018] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2017] [Revised: 01/23/2018] [Accepted: 02/16/2018] [Indexed: 01/15/2023]
Abstract
An α, β-unsaturated carbonyl compound of ginger, 6-Shogaol (6S), induced extensive cytoplasmic vacuolation and cell death in breast cancer cell (MDA-MB-231) and non-small lung cancer (A549) cells. In the presence of autophagic inhibitors the cells continued to exhibit cytoplasmic vacuolation and cell death clearly distinguishing it from the classic autophagic process. 6S induced death did not exhibit the characteristic apoptotic features like caspase cleavage, phosphatidyl serine exposure and DNA fragmentation. The immunofluorescence with the Endoplasmic Reticulum (ER) resident protein, calreticulin indicated that the vacuoles were of ER origin, typical of paraptosis. This was supported by the increase in level of microtubule associated protein light chain 3B (LC3 I and LC3 II) and polyubiquitin binding protein, p62. The level of ER stress markers like polyubiquitinated proteins, Bip and CHOP also consistently increased. We have found that 6S inhibits the 26S proteasome. The proteasomal inhibitory activity was elucidated by a) molecular docking of 6S onto the active site of β5 subunit and b) reduced fluorescence by the fluorogenic substrate of the chymotrypsin-like subunit. In conclusion these studies demonstrate for the first time that proteasomal inhibition by 6S induces cell death via paraptosis. So 6-shogaol may act as a template for anti-cancer lead discovery against the apoptosis resistant cancer cells.
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49
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Kotowski U, Kadletz L, Schneider S, Foki E, Schmid R, Seemann R, Thurnher D, Heiduschka G. 6-shogaol induces apoptosis and enhances radiosensitivity in head and neck squamous cell carcinoma cell lines. Phytother Res 2018; 32:340-347. [PMID: 29168275 DOI: 10.1002/ptr.5982] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2017] [Revised: 09/26/2017] [Accepted: 10/18/2017] [Indexed: 01/14/2023]
Abstract
Ginger (Zingiber officinale Roscoe) is used for a wide array of conditions in traditional medicine in Asia, but little is known about the effect on head and neck cancer. In this study, the effect of two major pharmacologically active compounds of ginger, 6-gingerol and 6-shogaol, were studied on head and neck cancer cell lines. Furthermore, experiments in combination with established treatment methods for head and neck cancer were performed. Proliferation assays showed a dose-dependent reduction of cell viability. Flow cytometry analysis revealed the induction of apoptosis. Western blot analysis indicated that the antiapoptotic protein survivin was suppressed after treatment. Although a combination of 6-shogaol with cisplatin exhibited no synergistic effect, the combination with irradiation showed a synergistic reduction of clonogenic survival. In conclusion, ginger compounds have many noteworthy effects on head and neck cancer cell lines. In particular, the enhancement of radiosensitivity is remarkable.
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Affiliation(s)
- Ulana Kotowski
- Department of Otorhinolaryngology, Head and Neck Surgery, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria
| | - Lorenz Kadletz
- Department of Otorhinolaryngology, Head and Neck Surgery, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria
| | - Sven Schneider
- Department of Otorhinolaryngology, Head and Neck Surgery, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria
| | - Elisabeth Foki
- Department of Otorhinolaryngology, Head and Neck Surgery, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria
| | - Rainer Schmid
- Department of Radiotherapy, Medical University of Vienna, Waehringer Guertel, 18-20 1090, Vienna, Austria
| | - Rudolf Seemann
- Department of Cranio-, Maxillofacial- and Oral Surgery, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria
| | - Dietmar Thurnher
- Department of Otorhinolaryngology, Head and Neck Surgery, Medical University of Graz, Auenbruggerplatz 2, 8036, Graz, Austria
| | - Gregor Heiduschka
- Department of Otorhinolaryngology, Head and Neck Surgery, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria
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50
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Wu CY, Kong M, Zhang W, Long F, Zhou J, Zhou SS, Xu JD, Xu J, Li SL. Impact of sulphur fumigation on the chemistry of ginger. Food Chem 2018; 239:953-963. [PMID: 28873658 DOI: 10.1016/j.foodchem.2017.07.033] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2017] [Revised: 05/26/2017] [Accepted: 07/10/2017] [Indexed: 10/19/2022]
Abstract
Ginger (Zingiberis Rhizoma), a commonly-consumed food supplement, is often sulphur-fumigated during post-harvest handling, but it remains unknown if sulphur fumigation induces chemical transformations in ginger. In this study, the effects of sulphur fumigation on ginger chemicals were investigated by ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS/MS)-based metabolomics. The results showed that sulphur fumigation significantly altered the holistic chemical profile of ginger by triggering chemical transformations of certain original components. 6-Gingesulphonic acid, previously reported as a naturally-occurring component in ginger, was revealed to be a sulphur fumigation-induced artificial derivative, which was deduced to be generated by electrophilic addition of 6-shogaol to sulphurous acid. Using UHPLC-QTOF-MS/MS extracting ion analysis with 6-gingesulphonic acid as a characteristic chemical marker, all the commercial ginger samples inspected were determined to be sulphur-fumigated. The research outcomes provide a chemical basis for further comprehensive safety and efficacy evaluations of sulphur-fumigated ginger.
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Affiliation(s)
- Cheng-Ying Wu
- Department of Pharmaceutical Analysis, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, People's Republic of China
| | - Ming Kong
- Department of Pharmaceutical Analysis, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, People's Republic of China
| | - Wei Zhang
- Department of Metabolomics, Jiangsu Province Academy of Traditional Chinese Medicine and Jiangsu Branch of China Academy of Chinese Medical Sciences, Nanjing 210028, People's Republic of China
| | - Fang Long
- Department of Pharmaceutical Analysis, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, People's Republic of China
| | - Jing Zhou
- Department of Metabolomics, Jiangsu Province Academy of Traditional Chinese Medicine and Jiangsu Branch of China Academy of Chinese Medical Sciences, Nanjing 210028, People's Republic of China
| | - Shan-Shan Zhou
- Department of Pharmaceutical Analysis, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, People's Republic of China
| | - Jin-Di Xu
- Department of Metabolomics, Jiangsu Province Academy of Traditional Chinese Medicine and Jiangsu Branch of China Academy of Chinese Medical Sciences, Nanjing 210028, People's Republic of China
| | - Jun Xu
- Department of Metabolomics, Jiangsu Province Academy of Traditional Chinese Medicine and Jiangsu Branch of China Academy of Chinese Medical Sciences, Nanjing 210028, People's Republic of China; School of Chinese Medicine, Hong Kong Baptist University, Hong Kong.
| | - Song-Lin Li
- Department of Pharmaceutical Analysis, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, People's Republic of China; Department of Metabolomics, Jiangsu Province Academy of Traditional Chinese Medicine and Jiangsu Branch of China Academy of Chinese Medical Sciences, Nanjing 210028, People's Republic of China.
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