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Zhou J, Lei Y, Zhang S, Liu Y, Yi D. Panaxadiol Attenuates Neuronal Oxidative Stress and Apoptosis in Cerebral Ischemia/Reperfusion Injury via Regulation of the JAK3/STAT3/HIF-1α Signaling Pathway. CNS Neurosci Ther 2025; 31:e70233. [PMID: 39957706 PMCID: PMC11831195 DOI: 10.1111/cns.70233] [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: 11/07/2024] [Revised: 01/06/2025] [Accepted: 01/13/2025] [Indexed: 02/18/2025] Open
Abstract
BACKGROUND Cerebral ischemic stroke (CIS) is a debilitating neurological condition lacking specific treatments. Cerebral ischemia/reperfusion injury (CIRI) is a critical pathological process in CIS. PURPOSE This study aimed to explore the protective effects of panaxadiol (PD) against oxidative stress-induced neuronal apoptosis in CIS/CIRI and its underlying mechanisms. METHOD An MCAO mouse model was established to investigate the therapeutic effects of PD in vivo. Network pharmacology and molecular docking techniques were used to predict PD's anti-CIS targets. The protective effects of PD were further validated in vitro using oxygen-glucose deprivation/reoxygenation (OGD/R)-treated HT22 cells. Finally, core targets were verified through combined in vivo and in vitro experiments to elucidate the mechanisms of PD in treating CIS. RESULT PD exhibited significant neuroprotective activity, demonstrated by restoration of behavioral performance, reduced infarct volume, and decreased neuronal apoptosis in mice. Network pharmacology analysis identified 24 overlapping target genes between PD and CIS-related targets. The hub genes, PTGS2, SERPINE1, ICAM-1, STAT3, MMP3, HMOX1, and NOS3, were associated with the HIF-1α pathway, which may play a crucial role in PD's anti-CIS effects. Molecular docking confirmed the stable binding of PD to these hub genes. Both in vitro and in vivo experiments further confirmed that PD significantly mitigates neuronal apoptosis and oxidative stress induced by CIS/CIRI. CONCLUSION PD significantly counteracts CIS/CIRI by modulating the JAK3/STAT3/HIF-1α signaling pathway, making it a promising therapeutic agent for treating CIS/CIRI.
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Affiliation(s)
- Jiabin Zhou
- Department of Neurosurgery, Union Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei ProvincePeople's Republic of China
- Wuhan UniversityWuhanHubei ProvincePeople's Republic of China
| | - Yu Lei
- Wuhan UniversityWuhanHubei ProvincePeople's Republic of China
| | - Shilin Zhang
- Naval Aviation University of Chinese People's Liberation ArmyYantaiShandong ProvincePeople's Republic of China
| | - Yuhan Liu
- Department of GastroenterologyHubei Provincial Hospital of Integrated Chinese and Western MedicineWuhanHubei ProvincePeople's Republic of China
| | - Dongye Yi
- Department of Neurosurgery, Union Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei ProvincePeople's Republic of China
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Oh JW, Muthu M, Pushparaj SSC, Gopal J. Anticancer Therapeutic Effects of Green Tea Catechins (GTCs) When Integrated with Antioxidant Natural Components. Molecules 2023; 28:molecules28052151. [PMID: 36903395 PMCID: PMC10004647 DOI: 10.3390/molecules28052151] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2023] [Revised: 02/20/2023] [Accepted: 02/21/2023] [Indexed: 03/02/2023] Open
Abstract
After decades of research and development concerning cancer treatment, cancer is still at large and very much a threat to the global human population. Cancer remedies have been sought from all possible directions, including chemicals, irradiation, nanomaterials, natural compounds, and the like. In this current review, we surveyed the milestones achieved by green tea catechins and what has been accomplished in cancer therapy. Specifically, we have assessed the synergistic anticarcinogenic effects when green tea catechins (GTCs) are combined with other antioxidant-rich natural compounds. Living in an age of inadequacies, combinatorial approaches are gaining momentum, and GTCs have progressed much, yet there are insufficiencies that can be improvised when combined with natural antioxidant compounds. This review highlights that there are not many reports in this specific area and encourages and recommends research attention in this direction. The antioxidant/prooxidant mechanisms of GTCs have also been highlighted. The current scenario and the future of such combinatorial approaches have been addressed, and the lacunae in this aspect have been discussed.
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Affiliation(s)
- Jae-Wook Oh
- Department of Stem Cell and Regenerative Biology, Konkuk University, Seoul 05029, Republic of Korea
| | - Manikandan Muthu
- Department of Research and Innovation, Saveetha School of Engineering, Saveetha Institute of Medical and Technical Sciences (SIMATS), Thandalam, Chennai 602105, India
| | - Suraj Shiv Charan Pushparaj
- Department of Research and Innovation, Saveetha School of Engineering, Saveetha Institute of Medical and Technical Sciences (SIMATS), Thandalam, Chennai 602105, India
| | - Judy Gopal
- Department of Research and Innovation, Saveetha School of Engineering, Saveetha Institute of Medical and Technical Sciences (SIMATS), Thandalam, Chennai 602105, India
- Correspondence: ; Tel.: +91-44-66726677; Fax: +91-44-2681-1009
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Han L, Li T, Miao D, Lee J, Xiao S, Piao H, Zhao Y. Design, Synthesis and Cytotoxicity Evaluation of Novel Indole Derivatives of Panaxadiol. Chem Biodivers 2022; 19:e202200372. [PMID: 35938749 DOI: 10.1002/cbdv.202200372] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2022] [Accepted: 07/18/2022] [Indexed: 11/05/2022]
Abstract
Based on the well-known cytotoxicity of indole compounds, we used the 'Fisher indole synthesis' method to introduce appropriately substituted indole rings into panaxadiol (PD), generating eighteen novel Panaxadiol indole derivatives. Six human cancer cell lines (A549, HepG-2, HCT-116, SGC-7901, MDA-MB-231, PC-3 cells) and one normal ovarian cell lines (IOSE144) were designed to evaluate the anti-proliferative activity of the PD derivatives. The results showed that the majority of PD derivatives showed enhanced anti-proliferative activity, when compared with PD, with P-Methylindolo-PD exhibiting the highest cytotoxicity. In A549 cells, IC50 value was 5.01±0.87 μM, which is roughly 12 times higher than the activity of PD and 5 times that of 5-FU. Moreover, cell morphology analysis and Annexin V-FITC/PI assays exhibited that P-Methylindolo-PD could induce A549 cell apoptosis (55.7 % of apoptotic cells at 20 μM). Moreover, molecular docking experiments were performed to explore the molecular mechanism underlining the binding of P-Methylindolo-PD to the active site of EGFR. The results support that P-Methylindolo-PD might be a promising lead compound for further studies.
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Affiliation(s)
- Linlin Han
- Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Yanbian University, Yanji, 133002, P. R. China
| | - Tao Li
- Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Yanbian University, Yanji, 133002, P. R. China
| | - Dongyu Miao
- Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Yanbian University, Yanji, 133002, P. R. China
| | - Jungjoon Lee
- Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Yanbian University, Yanji, 133002, P. R. China
| | - Shengnan Xiao
- Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Yanbian University, Yanji, 133002, P. R. China
| | - Huri Piao
- Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Yanbian University, Yanji, 133002, P. R. China
| | - Yuqing Zhao
- Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Yanbian University, Yanji, 133002, P. R. China
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Encapsulation of EGCG by Zein-Gum Arabic Complex Nanoparticles and In Vitro Simulated Digestion of Complex Nanoparticles. Foods 2022; 11:foods11142131. [PMID: 35885374 PMCID: PMC9317346 DOI: 10.3390/foods11142131] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2022] [Revised: 07/15/2022] [Accepted: 07/17/2022] [Indexed: 11/18/2022] Open
Abstract
Epigallocatechin gallate (EGCG) has many excellent qualities such as its antitumor, antiradiation and anti-oxidation properties, but its application is limited because its oral bioavailability is low and stability is poor. In this paper, zein and gum arabic (GA) were used as wall materials to prepare Zein-GA complex nanoparticles for encapsulating and protecting the EGCG. The particle size of Zein-GA-EGCG complex nanoparticles ranged from 128.03–221.23 nm, and the EGCG encapsulation efficiency reached a maximum of 75.23% when the mass ratio of zein to GA was 1:1. The FTIR and XRD results illustrated that the components of the Zein-GA-EGCG complex nanoparticles interacted by electrostatic, hydrogen bonding, and hydrophobic interactions. The EGCG release rate of Zein-GA-EGCG nanoparticles (16.42%) was lower than that of Zein-EGCG (25.52%) during gastric digestion, and a large amount of EGCG was released during intestinal digestion, suggesting that the Zein-GA-EGCG nanoparticles could achieve the sustained release of EGCG during in vitro digestion. Hence, using Zein-GA complexes to encapsulate EGCG effectively increased the encapsulation efficiency of EGCG and realized the purpose of sustained release during simulated gastrointestinal digestion.
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Zhao L, Zhang Y, Li Y, Li C, Shi K, Zhang K, Liu N. Therapeutic effects of ginseng and ginsenosides on colorectal cancer. Food Funct 2022; 13:6450-6466. [PMID: 35661189 DOI: 10.1039/d2fo00899h] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Colorectal cancer (CRC) is among the most common malignant diseases with high morbidity and mortality rates. Ginseng and its major extracts, ginsenosides, have been used in medical fields for thousands of years. In particular, their huge anti-cancer potential has drawn a great deal of attention in recent years. There is a large body of evidence that has shown that ginseng and its extracts could significantly inhibit tumor development and progression by suppressing cell proliferation, tumor growth, invasion and metastasis, inducing tumor cell apoptosis, regulating tumor-associated immune responses, and improving the therapeutic effect of chemotherapy. Notably, different subtypes of ginsenosides, even those extracted from the same ginseng, have exhibited distinct anti-cancer functions through different mechanisms. Over the past few years, a large number of studies have focused on how ginseng or various ginsenosides influence CRC development. Therefore, the roles and the potential of ginseng and ginsenosides in the treatment of CRC are summarized in this review. In addition, the biochemical properties of ginseng and ginsenosides are also briefly described.
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Affiliation(s)
- Linxian Zhao
- Department of General Surgery, The Second Hospital of Jilin University, Changchun, Jilin, 130041, China.
| | - Yueming Zhang
- Department of Pharmacy, the First Hospital of Jilin University, Changchun, China
| | - Yajuan Li
- Jilin Provincial Key Laboratory of Nutrition and Functional Food and College of Food Science and Engineering, Jilin University, Changchun, Jilin, 130062, China
| | - Chen Li
- Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, Jilin University, Changchun, Jilin, 130062, China
| | - Kai Shi
- Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, Jilin University, Changchun, Jilin, 130062, China
| | - Kai Zhang
- Department of General Surgery, The Second Hospital of Jilin University, Changchun, Jilin, 130041, China.
| | - Ning Liu
- Department of Central Laboratory, The Second Hospital of Jilin University, Changchun, Jilin, 130041, China.
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Liu C, Lv N, Ren G, Wu R, Wang B, Cao Z, Xie H. Explore the interaction mechanism between zein and EGCG using multi-spectroscopy and molecular dynamics simulation methods. Food Hydrocoll 2021. [DOI: 10.1016/j.foodhyd.2021.106906] [Citation(s) in RCA: 104] [Impact Index Per Article: 26.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
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Inhibition of JAK2/STAT3 signaling pathway by panaxadiol limits the progression of pancreatic cancer. Aging (Albany NY) 2021; 13:22830-22842. [PMID: 34623971 PMCID: PMC8544303 DOI: 10.18632/aging.203575] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2021] [Accepted: 08/18/2021] [Indexed: 11/25/2022]
Abstract
Pancreatic cancer is the fourth leading cause of cancer-related death with the characteristics of chemoresistance and early metastasis. Panaxadiol, a triterpenoid saponin extracted from the roots of American ginseng, has been proved to display anti-tumor activity in colon cancer. In this study, we found panaxadiol significantly inhibited proliferation, and induced apoptosis in human pancreatic cancer cell lines PANC-1 and Patu8988 in a dose-dependent manner. Furthermore, the expression of apoptosis-related proteins (Bax, Bcl2, Cleaved-caspase3) was detected via western blot and immunofluorescence staining. In addition, panaxadiol was also found to inhibit the migration of pancreatic cancer cells by wound healing and transwell assays. In vivo, the growth of xenograft pancreatic cancer models was also notably suppressed by panaxadiol compared to the control group. Moreover, the down-regulation of JAK2-STAT3 signaling pathway was responsible for the underlying pro-apoptosis mechanism of panaxadiol, and this result was in good agreement with molecular docking analysis between panaxadiol and STAT3. In conclusion, our work comprehensively explored the anti-tumor ability in PANC-1 and Patu8988 cells of panaxadiol and provided a potential choice for the clinical treatment of pancreatic cancer patients.
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Hussain Y, Luqman S, Meena A. Research Progress in Flavonoids as Potential Anticancer Drug Including Synergy with Other Approaches. Curr Top Med Chem 2021; 20:1791-1809. [PMID: 32357817 DOI: 10.2174/1568026620666200502005411] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2019] [Revised: 03/13/2020] [Accepted: 03/31/2020] [Indexed: 12/13/2022]
Abstract
BACKGROUND In chemotherapy for cancer, conventional drugs aim to target the rapidly growing and dividing cells at the early stages. However, at an advanced stage, cancer cells become less susceptible because of the multidrug resistance and the recruitment of alternative salvage pathways for their survival. Besides, owing to target non-selectivity, healthy proliferating cells also become vulnerable to the damage. The combination therapies offered using flavonoids to cure cancer not only exert an additive effect against cancer cells by targetting supplementary cell carnage pathways but also hampers the drug resistance mechanisms. Thus, the review aims to discuss the potential and pharmacokinetic limitations of flavonoids in cancer treatment. Further successful synergistic studies reported using flavonoids to treat cancer has been described along with potential drug delivery systems. METHODS A literature search was done by exploring various online databases like Pubmed, Scopus, and Google Scholar with the specific keywords like "Anticancer drugs", "flavonoids", "oncology research", and "pharmacokinetics". RESULTS Dietary phytochemicals, mainly flavonoids, hinder cell signalling responsible for multidrug resistance and cancer progression, primarily targeting cancer cells sparing normal cells. Such properties establish flavonoids as a potential candidate for synergistic therapy. However, due to low absorption and high metabolism rates, the bioavailability of flavonoids becomes a challenge. Such challenges may be overcome using novel approaches like derivatization, and single or co-delivery nano-complexes of flavonoids with conventional drugs. These new approaches may improve the pharmacokinetic and pharmacodynamic of flavonoids. CONCLUSION This review highlights the application of flavonoids as a potential anticancer phytochemical class in combination with known anti-cancer drugs/nanoparticles. It also discusses flavonoid's pharmacokinetics and pharmacodynamics issues and ways to overcome such issues. Moreover, it covers successful methodologies employed to establish flavonoids as a safe and effective phytochemical class for cancer treatment.
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Affiliation(s)
- Yusuf Hussain
- Molecular Bioprospection Department of Biotechnology Division, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow-226015, Uttar Pradesh, India
| | - Suaib Luqman
- Molecular Bioprospection Department of Biotechnology Division, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow-226015, Uttar Pradesh, India
| | - Abha Meena
- Molecular Bioprospection Department of Biotechnology Division, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow-226015, Uttar Pradesh, India
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Dombe S, Shirote P. Nanosponges Encapsulated Phytochemicals for Targeting Cancer: A Review. Curr Drug Targets 2021; 22:443-462. [PMID: 33045959 DOI: 10.2174/1389450121999201012201455] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2020] [Revised: 08/16/2020] [Accepted: 09/02/2020] [Indexed: 11/22/2022]
Abstract
Cancer is the most ruinous disease globally. Natural products have impressive characteristics, such as exceptional chemical versatility, chemical and biological properties of macromolecular specificity and less toxicity which make them good leads in finding novel drugs. The phytochemicals not only help to prevent but also treat chronic cancerous conditions. The present review attempts to put forth some selected anticancer phytochemicals that had reported omics characteristic and specifically suppressed cancer with in vitro and in vivo activity. Certain issues pertaining to anticancer phytochemicals like delivery to target site in the body and achieving controlled release in order to prevent overdoses have been a major concern for medical researchers worldwide. The most conventional chemotherapy protocols for the treatment of cancer lead to adverse effects that limit biological efficacy and compromise patient outcomes. In order to defeat incompetency of current and upcoming natural anticancer agents and to attain targeted drug delivery with good efficacy and fewer side effects, there is a special focus on novel nanostructured particles and nano approaches consisting of carrier system. Recent studies have led to the discovery of mesoporous and nanoporous drug delivery mechanisms, such as inorganic or organic-based nanosponges. The metal based inorganic systems have exhibited toxicity and non-biodegradable character in vivo. As a result of problems related to inorganic systems, major shift of research from inorganic to organic nanosystems has occurred. About decades ago, researchers developed organic nanosponges to control the limitation of drug delivery and cancer therapies. This review article discusses the development and application of nanosponges encapsulated phytochemicals for cancer therapy.
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Affiliation(s)
- Shailaja Dombe
- Department of Pharmaceutics, Arvind Gavali College of Pharmacy, Satara, Shivaji University, Satara-415004, India
| | - Pramodkumar Shirote
- Department of Pharmaceutical Chemistry, Arvind Gavali College of Pharmacy, Satara, Shivaji University, Satara- 415004, India
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Alami Merrouni I, Elachouri M. Anticancer medicinal plants used by Moroccan people: Ethnobotanical, preclinical, phytochemical and clinical evidence. JOURNAL OF ETHNOPHARMACOLOGY 2021; 266:113435. [PMID: 33022340 DOI: 10.1016/j.jep.2020.113435] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/21/2020] [Revised: 09/23/2020] [Accepted: 09/26/2020] [Indexed: 05/18/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Cancer is a major health problem worldwide. Drugs' side effects and high cost of treatment remain the main limitations of conventional therapy. Nowadays, developing new therapeutic strategies is necessary. Therefore, medicinal plants can be used to promote novel, safe, and potent anticancer drugs through their natural compounds. AIM OF THE STUDY This review aims to provide scientific evidence related to the anticancer activities of medicinal plants used by Moroccan people as well as approving their efficiency as an alternative cancer therapy. METHODS An ethnopharmacological review approach was conducted by analyzing Moroccan published ethnobotanical surveys from 1991 to 2019 and consulting peer-reviewed articles worldwide to investigate the pharmacological, phytochemical, and clinical effects related to the anticancer activities. Plants with anticancer proprieties were classified into four groups: (a) plants only cited as anticancer, (b) plants pharmacologically investigated, (c) plants with bioactive compounds tested as anticancer, and (d) plants clinically investigated. RESULTS A total of 103 plant species belonging to 47 botanical families used by Moroccans to treat cancer have been recorded. Aristolochia fontanesii Boiss. & Reut, Marrubium vulgare L., and Allium sativum L. are the most referred species in Morocco. Medicinal plants used for cancer treatment were classified into four groups: 48 species were used traditionally as anticancer (group a), 41 species pharmacologically investigated for their anticancer activities (group b), 32 plants with bioactive compounds tested against cancer (group c), and eight plants were clinically investigated for their anticancer effects (group d). Out of 82 plants' extracts pharmacologically tested (from plants of group b), only 24 ones show a significant cytotoxic effect. A total of seventy-seven compounds are isolated from plants of group (c). However, only six ones were clinically evaluated, and most of them exhibit a beneficial effect on cancerous patients with few side effects. CONCLUSION Medicinal plants can be a promising candidate for alternative cancer therapy. Nevertheless, it is critical to increasing the clinical trials to confirm their beneficial effect on patients with cancer. Overall, this review can serve as a database for further studies.
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Affiliation(s)
- Ilyass Alami Merrouni
- Laboratory of Physiology, Genetics, and Ethnopharmacology, Faculty of Sciences, Mohammed First University, Oujda, Morocco.
| | - Mostafa Elachouri
- Laboratory of Physiology, Genetics, and Ethnopharmacology, Faculty of Sciences, Mohammed First University, Oujda, Morocco.
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Li F, Qasim S, Li D, Dou QP. Updated review on green tea polyphenol epigallocatechin-3-gallate as a cancer epigenetic regulator. Semin Cancer Biol 2021; 83:335-352. [PMID: 33453404 DOI: 10.1016/j.semcancer.2020.11.018] [Citation(s) in RCA: 44] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2020] [Revised: 11/26/2020] [Accepted: 11/26/2020] [Indexed: 02/06/2023]
Abstract
In-depth insights in cancer biology over the past decades have highlighted the important roles of epigenetic mechanisms in the initiation and progression of tumorigenesis. The cancer epigenome usually experiences multiple alternations, including genome-wide DNA hypomethylation and site-specific DNA hypermethylation, various histone posttranslational modifications, and dysregulation of non-coding RNAs (ncRNAs). These epigenetic changes are plastic and reversible, and could potentially occur in the early stage of carcinogenesis preceding genetic mutation, offering unique opportunities for intervention therapies. Therefore, targeting the cancer epigenome or cancer epigenetic dysregulation with some selected agents (called epi-drugs) represents an evolving and promising strategy for cancer chemoprevention and therapy. Phytochemicals, as a class of pleiotropic molecules, have manifested great potential in modulating different cancer processes through epigenetic machinery, of which green tea polyphenol epigallocatechin-3-gallate (EGCG) is one of the most extensively studied. In this review, we first summarize epigenetic events involved in the pathogenesis of cancer, including DNA/RNA methylations, histone modifications and ncRNAs' dysregulations. We then focus on the recently discovered roles of phytochemicals, with a special emphasis on EGCG, in modulating different cancer processes through regulating epigenetic machinery. We finally discuss limitations of EGCG as an epigenetic modulator for cancer chemoprevention and treatment and offer potential strategies to overcome the shortcomings.
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Affiliation(s)
- Feng Li
- College of Food Science and Engineering, Shandong Agricultural University, Tainan, 271018, China
| | - Syeda Qasim
- Departments of Oncology, Pharmacology & Pathology, School of Medicine, Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, MI, 48201, USA; Ryerson University, Toronto, Ontario, M5B 2K3, Canada
| | - Dapeng Li
- College of Food Science and Engineering, Shandong Agricultural University, Tainan, 271018, China
| | - Q Ping Dou
- Departments of Oncology, Pharmacology & Pathology, School of Medicine, Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, MI, 48201, USA.
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Varlamova EG, Zaripov OG. Beta-lactoglobulin-nutrition allergen and nanotransporter of different nature ligands therapy with therapeutic action. Res Vet Sci 2020; 133:17-25. [PMID: 32919234 DOI: 10.1016/j.rvsc.2020.08.014] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2020] [Revised: 08/08/2020] [Accepted: 08/28/2020] [Indexed: 02/06/2023]
Abstract
β-lactoglobulin is one of the nutrition allergens present in the milk of many mammals, with the exception of human. This protein belongs to the family of lipocalins, consisting of nine antiparallel β-strands (β-A to β-I) and one α-helix. This structure allows it to serve as a nanotransporter of various nature ligands in a pH dependent manner, which allows us to confidently consider it as a reliable carrier of drugs directly into the intestine, bypassing the destructive acidic environment of the stomach. Based on the latest data, this review describes the currently known methods of reducing the allergenicity of beta-lactoglobulin, as well as the mechanisms and methods of forming complexes of this protein with ligands, which emphasizes its importance and versatility and explains the growing interest in studying its properties in recent decades, and also opens up prospects for its practical application in medicine and pharmaceuticals.
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Affiliation(s)
- E G Varlamova
- Federal State Institution of Science Institute of Cell Biophysics, Russian Academy of Sciences, Institutskaya st. 3, 142290, Pushchino, Moscow Region, Russia.
| | - O G Zaripov
- Federal Science Center for Animal Husbandry named after Academy Member L.K. Ernst, Dubrovitsy village, house 60, 142132, Moscow region, Podolsky city district, Russia
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Pires F, Magalhães-Mota G, Geraldo VPN, Ribeiro PA, Oliveira ON, Raposo M. The impact of blue light in monolayers representing tumorigenic and nontumorigenic cell membranes containing epigallocatechin-3-gallate. Colloids Surf B Biointerfaces 2020; 193:111129. [PMID: 32502833 DOI: 10.1016/j.colsurfb.2020.111129] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2019] [Revised: 04/21/2020] [Accepted: 05/11/2020] [Indexed: 02/08/2023]
Abstract
Natural products such as epigallocatechin-3-gallate (EGCG) have been suggested for complementary treatments of cancer, since they lower toxic side effects of anticancer drugs, and possess anti-inflammatory and antioxidant properties that inhibit carcinogenesis. Their effects on cancer cells depend on interactions with the membrane, which is the motivation to investigate Langmuir monolayers as simplified membrane models. In this study, EGCG was incorporated in zwitterionic dipalmitoyl phosphatidyl choline (DPPC) and anionic dipalmitoyl phosphatidyl serine (DPPS) Langmuir monolayers to simulate healthy and cancer cells membranes, respectively. EGCG induces condensation in surface pressure isotherms for both DPPC and DPPS monolayers, interacting mainly via electrostatic forces and hydrogen bonding with the choline and phosphate groups of the phospholipids, according to data from polarization-modulated infrared reflection absorption spectroscopy (PM-IRRAS). Both monolayers become more compressible upon interaction with EGCG, which may be correlated to the synergy between EGCG and anticancer drugs reported in the literature. The interaction with EGCG is stronger for DPPC, leading to stronger morphological changes in Brewster angle microscopy (BAM) images and higher degree of condensation in the surface pressure isotherms. The changes induced by blue irradiation on DPPC and DPPS monolayers were largely precluded when EGCG was incorporated, thus confirming its antioxidant capacity for both types of membrane.
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Affiliation(s)
- Filipa Pires
- CEFITEC, Departamento de Física, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, Caparica, Portugal
| | - Gonçalo Magalhães-Mota
- CEFITEC, Departamento de Física, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, Caparica, Portugal
| | | | - Paulo A Ribeiro
- CEFITEC, Departamento de Física, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, Caparica, Portugal
| | | | - Maria Raposo
- CEFITEC, Departamento de Física, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, Caparica, Portugal.
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Chang CC, You HL, Huang ST. Catechin inhibiting the H1N1 influenza virus associated with the regulation of autophagy. J Chin Med Assoc 2020; 83:386-393. [PMID: 32132384 DOI: 10.1097/jcma.0000000000000289] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023] Open
Abstract
BACKGROUND The influenza virus is a highly infectious disease, with a notably rapid transmission rate. Autophagy is triggered by viral infection and is a survival mechanism exerted to maintain cellular homeostasis. Catechin is a representative phenolic acid which exerts anti-inflammatory responses against influenza A virus infection. The aim of this study is to explore the anti-H1N1 influenza virus effects by catechin associated with the restoration of autophagy. METHODS XTT assay was used to detect cellular viability. The inhibitory effects on the H1N1 influenza virus were assessed by hemagglutination assay, neuraminidase activity, and quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The protein levels of H1N1 influenza virulence and autophagic markers were detected by Western blot. RESULTS We herein demonstrated that catechin had no cytotoxic effect on both infected and noninfected A549 cells and exerted protective effects on infected A549 cells. The results of the hemagglutination assay, neuraminidase activity, and qRT-PCR to examine viral load demonstrated that catechin effectively inhibited the replication of the H1N1 influenza virus. The virulent M2 protein and viral nucleoprotein were also inhibited after treatment with catechin. As for the autophagic markers, the LC3B protein was notably decreased by catechin in a dose-dependent manner, while the amount of autophagic vacuoles in H1N1 influenza virus-infected cells also decreased after catechin treatment in a dose-dependent manner. CONCLUSION Collectively, the autophagy activated by the H1N1 influenza virus could be reversed after catechin treatment. This study indicates that catechin effectively inhibits H1N1 viral proliferation and thus may be applied as an adjuvant in future clinical application.
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Affiliation(s)
- Cheng-Chieh Chang
- Department of Chinese Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan, ROC
| | - Huey-Ling You
- Department of Laboratory Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan, ROC
- Department of Medical Laboratory Sciences and Biotechnology, Fooyin University, Kaohsiung, Taiwan, ROC
| | - Sheng-Teng Huang
- Department of Chinese Medicine, China Medical University Hospital, Taichung, Taiwan, ROC
- School of Chinese Medicine, China Medical University, Taichung, Taiwan, ROC
- An-Nan Hospital, China Medical University, Tainan, Taiwan, ROC
- Chinese Medicine Research Center, China Medical University, Taichung, Taiwan, ROC
- Research Center for Chinese Herbal Medicine, China Medical University, Taichung, Taiwan, ROC
- Department of Medical Research, Cancer Research Center for Traditional Chinese Medicine, China Medical University Hospital, Taichung, Taiwan, ROC
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16
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Wang M, Li H, Liu W, Cao H, Hu X, Gao X, Xu F, Li Z, Hua H, Li D. Dammarane-type leads panaxadiol and protopanaxadiol for drug discovery: Biological activity and structural modification. Eur J Med Chem 2020; 189:112087. [PMID: 32007667 DOI: 10.1016/j.ejmech.2020.112087] [Citation(s) in RCA: 44] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2019] [Revised: 12/14/2019] [Accepted: 01/20/2020] [Indexed: 12/13/2022]
Abstract
Based on the definite therapeutic benefits, such as neuroprotective, cardioprotective, anticancer, anti-diabetic and so on, the Panax genus which contains many valuable plants, including ginseng (Panax ginseng C.A. Meyer), notoginseng (Panax notoginseng) and American ginseng (Panax quinquefolius L.), attracts research focus. Actually, the biological and pharmacological effects of the Panax genus are mainly attributed to the abundant ginsenosides. However, the low membrane permeability and the gastrointestinal tract influence seriously limit the absorption and bioavailability of ginsenosides. The acid or base hydrolysates of ginsenosides, 20 (R,S)-panaxadiol and 20 (R,S)-protopanaxadiol showed improved bioavailability and diverse pharmacological activities. Moreover, relative stable skeletons and active hydroxyl group at C-3 position and other reactive sites are suitable for structural modification to improve biological activities. In this review, the pharmacological activities of panaxadiol, protopanaxadiol and their structurally modified derivatives are comprehensively summarized.
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Affiliation(s)
- Mingying Wang
- Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, And School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, PR China
| | - Haonan Li
- Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, And School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, PR China
| | - Weiwei Liu
- Wuya College of Innovation, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, PR China
| | - Hao Cao
- School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, PR China
| | - Xu Hu
- Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, And School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, PR China
| | - Xiang Gao
- Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, And School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, PR China
| | - Fanxing Xu
- Wuya College of Innovation, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, PR China
| | - Zhanlin Li
- Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, And School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, PR China
| | - Huiming Hua
- Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, And School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, PR China
| | - Dahong Li
- Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, And School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, PR China.
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17
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Wang ST, Cui WQ, Pan D, Jiang M, Chang B, Sang LX. Tea polyphenols and their chemopreventive and therapeutic effects on colorectal cancer. World J Gastroenterol 2020; 26:562-597. [PMID: 32103869 PMCID: PMC7029350 DOI: 10.3748/wjg.v26.i6.562] [Citation(s) in RCA: 73] [Impact Index Per Article: 14.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2019] [Revised: 12/30/2019] [Accepted: 01/11/2020] [Indexed: 02/06/2023] Open
Abstract
Colorectal cancer (CRC), a multifactorial disease, is usually induced and developed through complex mechanisms, including impact of diet and lifestyle, genomic abnormalities, change of signaling pathways, inflammatory response, oxidation stress, dysbiosis, and so on. As natural polyphenolic phytochemicals that exist primarily in tea, tea polyphenols (TPs) have been shown to have many clinical applications, especially as anticancer agents. Most animal studies and epidemiological studies have demonstrated that TPs can prevent and treat CRC. TPs can inhibit the growth and metastasis of CRC by exerting the anti-inflammatory, anti-oxidative or pro-oxidative, and pro-apoptotic effects, which are achieved by modulations at multiple levels. Many experiments have demonstrated that TPs can modulate several signaling pathways in cancer cells, including the mitogen-activated protein kinase pathway, phosphatidylinositol-3 kinase/Akt pathway, Wnt/β-catenin pathway, and 67 kDa laminin receptor pathway, to inhibit proliferation and promote cell apoptosis. In addition, novel studies have also suggested that TPs can prevent the growth and metastasis of CRC by modulating the composition of gut microbiota to improve immune system and decrease inflammatory responses. Molecular pathological epidemiology, a novel multidisciplinary investigation, has made great progress on CRC, and the further molecular pathological epidemiology research should be developed in the field of TPs and CRC. This review summarizes the existing in vitro and in vivo animal and human studies and potential mechanisms to examine the effects of tea polyphenols on CRC.
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Affiliation(s)
- Shi-Tong Wang
- Department of Cardiovascular Ultrasound, First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
| | - Wen-Qi Cui
- Department of Neurology, Shengjing Hospital, Affiliated Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
| | - Dan Pan
- Department of Geriatrics, First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
| | - Min Jiang
- Department of Gastroenterology, First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
| | - Bing Chang
- Department of Gastroenterology, First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
| | - Li-Xuan Sang
- Department of Geriatrics, First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
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18
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Molecular interaction of tea catechin with bovine β-lactoglobulin: A spectroscopic and in silico studies. Saudi Pharm J 2020; 28:238-245. [PMID: 32194324 PMCID: PMC7078544 DOI: 10.1016/j.jsps.2020.01.002] [Citation(s) in RCA: 54] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2019] [Accepted: 01/19/2020] [Indexed: 12/13/2022] Open
Abstract
Polyphenols has attained pronounced attention due to their beneficial values of health and found to prevent several chronic diseases. Here, we elucidated binding mechanism between frequently consumed polyphenol “tea catechin” and milk protein bovine beta-lactoglobulin (β-Lg). We investigated the conformational changes of β-Lg due to interaction with catechin using spectroscopic and in silico studies. Fluorescence quenching data (Stern-Volmer quenching constant) revealed that β-Lg interacted with catechin via dynamic quenching. Thermodynamic data revealed that the interaction between β-Lg and catechin is endothermic and spontaneously interacted mainly through hydrophobic interactions. The UV-Vis absorption and far-UV circular dichroism (CD) spectroscopy exhibited that the tertiary as well as secondary structure of β-Lg distorted after interaction with catechin. Molecular docking and simulation studies also confirm that catechin binds at the central cavity of β-Lg with high affinity (~105 M−1) and hydrophobic interactions play significant role in the formation of a stable β-Lg-catechin complex.
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19
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Chen Y, Al-Ghamdi AA, Elshikh MS, Shah MH, Al-Dosary MA, Abbasi AM. Phytochemical profiling, antioxidant and HepG2 cancer cells' antiproliferation potential in the kernels of apricot cultivars. Saudi J Biol Sci 2020; 27:163-172. [PMID: 31889831 PMCID: PMC6933278 DOI: 10.1016/j.sjbs.2019.06.013] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2019] [Revised: 05/17/2019] [Accepted: 06/17/2019] [Indexed: 01/01/2023] Open
Abstract
Phytochemical composition, in vitro antioxidant and antiproliferative activity against HepG2 cells were studied in the kernels of apricot cultivars grown in the northern areas of Pakistan. Relatively, the kernel of Habbi cultivar/AP-12 depicted significant potential to scavenge DPPH and ABTS+ free radicals as well as oxygen radical absorbance capacity along with highest contents of total flavonoids, phenolics, chlorogenic and syringic acids on dry weight basis. The average concentration of quercetin ranged 0.072-1.343 mg/100 g, and of EGCG from 0.713 to 6.521 mg/100 g with maximum concentration in Hulappa/AP-3 and Kho Chali-Khatta 3/AP-17, respectively. Amygdalin content was highest (1145 mg/100 g) in the kernel of Balaani/AP-14. Highest inhibition of HepG2 cells was found in the kernel of Waflu Chuli/AP-9 (EC50 = 15.70 ± 3.77 mg/mL). The PCA showed significant contributions of polyphenols and flavonoids towards biochemical assays, while CA revealed similarities and associations among various cultivars. Our study revealed that Habbi, Waflu Chuli, Thukdeena and Balaani kernels are rich sources of bioactive compounds and possess significant antioxidant and anticancer activity and can contribute considerably in the prevention and treatment of chronic health disorders.
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Affiliation(s)
- Yongsheng Chen
- Department of Food Science and Engineering, Jinan University, Guangzhou 510632, China
| | - Abdullah Ahmed Al-Ghamdi
- Department of Botany and Microbiology, Faculty of Sciences, King Saud University, Riyadh, Saudi Arabia
| | - Mohamed S. Elshikh
- Department of Botany and Microbiology, Faculty of Sciences, King Saud University, Riyadh, Saudi Arabia
| | - Munir H. Shah
- Department of Chemistry, Quaid-i-Azam University, Islamabad 45320, Pakistan
| | - Monerah A. Al-Dosary
- Department of Botany and Microbiology, Faculty of Sciences, King Saud University, Riyadh, Saudi Arabia
| | - Arshad Mehmood Abbasi
- Department of Environmental Sciences, COMSATS University Islamabad, Abbottabad Campus 22060, Pakistan
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20
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From tea to treatment; epigallocatechin gallate and its potential involvement in minimizing the metabolic changes in cancer. Nutr Res 2019; 74:23-36. [PMID: 31918176 DOI: 10.1016/j.nutres.2019.12.004] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2019] [Revised: 12/02/2019] [Accepted: 12/06/2019] [Indexed: 01/09/2023]
Abstract
As the most abundant bioactive polyphenol in green tea, epigallocatechin gallate (EGCG) is a promising natural product that should be used in the discovery and development of potential drug leads. Due to its association with chemoprevention, EGCG may find a role in the development of therapeutics for prostate cancer. Natural products have long been used as a scaffold for drug design, as their already noted bioactivity can help accelerate the development of novel treatments. Green tea and the EGCG contained within have become associated with chemoprevention, and both in vitro and in vivo studies have correlated EGCG to inhibiting cell growth and increasing the metabolic stress of cancer cells, possibly giving merit to its long utilized therapeutic use in traditional therapies. There is accumulating evidence to suggest EGCG's role as an inhibitor of the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin signaling cascade, acting upon major axis points within cancer survival pathways. The purpose of this review is to examine the research conducted on tea along with EGCG in the areas of the treatment of and/or prevention of cancer. This review discusses Camellia sinensis as well as the bioactive phytochemical compounds contained within. Clinical uses of tea are explored, and possible pathways for activity are discussed before examining the evidence for EGCG's potential for acting on these processes. EGCG is identified as being a possible lead phytochemical for future drug design investigations.
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21
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Transcriptome profiling of poly(I:C)-induced RAW 264.7 mouse macrophages in response to panaxadiol. Biologia (Bratisl) 2019. [DOI: 10.2478/s11756-019-00288-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
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22
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Roslan NH, Makpol S, Mohd Yusof YA. A Review on Dietary Intervention in Obesity Associated Colon Cancer. Asian Pac J Cancer Prev 2019; 20:1309-1319. [PMID: 31127882 PMCID: PMC6857900 DOI: 10.31557/apjcp.2019.20.5.1309] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2018] [Accepted: 04/22/2019] [Indexed: 12/13/2022] Open
Abstract
Background: Colorectal cancer (CRC) is one of the major causes of morbidity and mortality. According to National Cancer Registry, the incidence of colorectal cancer in Peninsular Malaysia increases with age. The incidence is highest among Chinese population but lower among Indians and Malays. Many reviews have suggested that obesity may be associated with a higher risk (>50%) of colorectal cancer. Methods: This study collects a comprehensive data from the literature review available from respective journals on dietary intervention and the chemo-protective mechanisms of a few natural resources in obesity -associated colon cancer based on previous and current studies. Results: In obesity-associated colon cancer, the genes of interest and pathways that are mainly involved include NFκB, P13K/Akt, and MAPK pathways, and FTO, leptin, Cyclin D, MMPs, and STAT3 genes. Dietary modification is one of the alternative steps in early prevention of colon cancer. It has been proposed that the components present in certain foods may have the ability to protect against many diseases including the prevention of cancer. Conclusion: There are many factors that lead to obesity-associated colon cancer and the mechanisms behind it is still undergoing intensive research. This review aims to scrutinize research as well as reviews that have been previously reported on obesity associated colorectal cancer and the beneficial effects of including antioxidants-rich foods such as vegetables and fruits in the diet to reduce the risk of obesity associated colorectal cancer.
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Affiliation(s)
- N H Roslan
- Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latiff, Bandar Tun Razak, Cheras, Kuala Lumpur, Malaysia.
| | - S Makpol
- Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latiff, Bandar Tun Razak, Cheras, Kuala Lumpur, Malaysia.
| | - Y A Mohd Yusof
- Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latiff, Bandar Tun Razak, Cheras, Kuala Lumpur, Malaysia.
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23
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Afshari K, Haddadi NS, Haj-Mirzaian A, Farzaei MH, Rohani MM, Akramian F, Naseri R, Sureda A, Ghanaatian N, Abdolghaffari AH. Natural flavonoids for the prevention of colon cancer: A comprehensive review of preclinical and clinical studies. J Cell Physiol 2019; 234:21519-21546. [PMID: 31087338 DOI: 10.1002/jcp.28777] [Citation(s) in RCA: 48] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2018] [Revised: 04/07/2019] [Accepted: 04/11/2019] [Indexed: 12/18/2022]
Abstract
Flavonoids comprise a group of natural polyphenols consisting of more than 5,000 subtypes mostly existing in fruits and vegetables. Flavonoids consumption could potentially attenuate the incidence and recurrence risk of colorectal cancers through their antiperoxidative, antioxidant, and anti-inflammatory effects. In addition, these compounds regulate the mitochondrial function, balance the bacterial flora and promote the apoptosis process in cancerous cells. However, some previous data failed to show the effectiveness of flavonoids in reducing the risk of colorectal cancer. In this study, we have reviewed the efficacy of different flavonoids subtypes on the risk of colon cancer and molecular mechanisms involved in this process in both clinical and animal studies. In addition, we tried to elucidate the potential synergy between these compounds and current colorectal cancer treatments.
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Affiliation(s)
- Khashayar Afshari
- Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Nazgol-Sadat Haddadi
- Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Arvin Haj-Mirzaian
- Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Hosein Farzaei
- Pharmaceutical Sciences Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.,Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Mohammad Mojtaba Rohani
- Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Freshteh Akramian
- Department of Pharmacology, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran
| | - Rozita Naseri
- Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Antoni Sureda
- Research Group on Community Nutrition and Oxidative Stress, University of the Balearic Islands, Palma de Mallorca, Spain.,CIBEROBN (Physiopathology of Obesity and Nutrition, CB12/03/30038), Instituto de Salud Carlos III, Madrid, Spain
| | - Negar Ghanaatian
- Department of Pharmacology, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran
| | - Amir Hossein Abdolghaffari
- Pharmaceutical Sciences Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.,Medicinal Plants Research Center, Institute of Medicinal Plants, ACECR, Tehran, Iran.,Department of Toxicology and Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.,Gastrointestinal Pharmacology Interest Group (GPIG), Universal Scientific Education and Research Network (USERN), Tehran, Iran
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24
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Liu C, Li P, Qu Z, Xiong W, Liu A, Zhang S. Advances in the Antagonism of Epigallocatechin-3-gallate in the Treatment of Digestive Tract Tumors. Molecules 2019; 24:molecules24091726. [PMID: 31058847 PMCID: PMC6539113 DOI: 10.3390/molecules24091726] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2019] [Revised: 04/24/2019] [Accepted: 04/30/2019] [Indexed: 12/12/2022] Open
Abstract
Due to changes in the dietary structure of individuals, the incidence of digestive tract tumors has increased significantly in recent years, causing a serious threat to the life and health of patients. This has in turn led to an increase in cancer prevention research. Many studies have shown that epigallocatechin-3-gallate (EGCG), an active ingredient in green tea, is in direct contact with the digestive tract upon ingestion, which allows it to elicit a significant antagonizing effect on digestive tract tumors. The main results of EGCG treatment include the prevention of tumor development in the digestive tract and the induction of cell cycle arrest and apoptosis. EGCG can be orally administered, is safe, and combats other resistances. The synergistic use of cancer drugs can promote the efficacy and reduce the anti-allergic properties of drugs, and is thus, favored in medical research. EGCG, however, currently possesses several shortcomings such as poor stability and low bioavailability, and its clinical application prospects need further development. In this paper, we have systematically summarized the research progress on the ability of EGCG to antagonize the activity and mechanism of action of digestive tract tumors, to achieve prevention, alleviation, delay, and even treat human gastrointestinal tract tumors via exogenous dietary EGCG supplementation or the development of new drugs containing EGCG.
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Affiliation(s)
- Changwei Liu
- Key Laboratory of Tea Science of Ministry of Education, Hunan Agricultural University, Changsha 410128, China.
- National Research Center of Engineering Technology for Utilization of Functional Ingredients from Botanicals, Collaborative Innovation Centre of Utilisation of Functional Ingredients from Botanicals, Hunan Agricultural University, Changsha 410128, China.
| | - Penghui Li
- Key Laboratory of Tea Science of Ministry of Education, Hunan Agricultural University, Changsha 410128, China.
- National Research Center of Engineering Technology for Utilization of Functional Ingredients from Botanicals, Collaborative Innovation Centre of Utilisation of Functional Ingredients from Botanicals, Hunan Agricultural University, Changsha 410128, China.
| | - Zhihao Qu
- Key Laboratory of Tea Science of Ministry of Education, Hunan Agricultural University, Changsha 410128, China.
- National Research Center of Engineering Technology for Utilization of Functional Ingredients from Botanicals, Collaborative Innovation Centre of Utilisation of Functional Ingredients from Botanicals, Hunan Agricultural University, Changsha 410128, China.
| | - Wei Xiong
- The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha 410078, China.
| | - Ailing Liu
- College of Bioscience and Biotechnology, Hunan Agricultural University, Changsha 410128, China.
| | - Sheng Zhang
- Key Laboratory of Tea Science of Ministry of Education, Hunan Agricultural University, Changsha 410128, China.
- National Research Center of Engineering Technology for Utilization of Functional Ingredients from Botanicals, Collaborative Innovation Centre of Utilisation of Functional Ingredients from Botanicals, Hunan Agricultural University, Changsha 410128, China.
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25
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Rady I, Mohamed H, Rady M, Siddiqui IA, Mukhtar H. Cancer preventive and therapeutic effects of EGCG, the major polyphenol in green tea. ACTA ACUST UNITED AC 2019. [DOI: 10.1016/j.ejbas.2017.12.001] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Affiliation(s)
- Islam Rady
- School of Medicine and Public Health, Department of Dermatology, University of Wisconsin-Madison, WI 53706, USA
- Department of Zoology, Faculty of Science, Al-Azhar University, Cairo, Egypt
| | - Hadir Mohamed
- School of Medicine and Public Health, Department of Dermatology, University of Wisconsin-Madison, WI 53706, USA
| | - Mohamad Rady
- Department of Zoology, Faculty of Science, Al-Azhar University, Cairo, Egypt
| | - Imtiaz A. Siddiqui
- School of Medicine and Public Health, Department of Dermatology, University of Wisconsin-Madison, WI 53706, USA
| | - Hasan Mukhtar
- School of Medicine and Public Health, Department of Dermatology, University of Wisconsin-Madison, WI 53706, USA
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26
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Ying L, Kong DD, Gao YY, Yan F, Wang YF, Xu P. In vitro antioxidant activity of phenolic-enriched extracts from Zhangping Narcissus tea cake and their inhibition on growth and metastatic capacity of 4T1 murine breast cancer cells. J Zhejiang Univ Sci B 2018; 19:199-210. [PMID: 29504313 DOI: 10.1631/jzus.b1700162] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Phenolics, as the main bioactive compounds in tea, have been suggested to have potential in the prevention of various human diseases. However, little is known about phenolics and their bioactivity in Zhangping Narcissue tea cake which is considered the most special kind of oolong tea. To unveil its bioactivity, three phenolic-enriched extracts were obtained from Zhangping Narcissue tea cake using ethyl acetate, n-butanol, and water. Their main chemical compositions and in vitro bioactivity were analyzed by high-performance liquid chromatography (HPLC) and ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). The ethyl acetate fraction (ZEF) consisted of higher content of phenolics, flavonoids, procyanidins, and catechin monomers (including epigallocatechin gallate (EGCG), epicatechin gallate (ECG), and gallocatechin gallate (GCG)) than n-butanol fraction (ZBF) and water fraction (ZWF). ZEF exhibited the strongest antioxidant capacity in vitro due to its abundant bioactive compounds. This was validated by Pearson correlation and hierarchical clustering analyses. ZEF also showed a remarkable inhibition on the growth, migration, and invasion of 4T1 murine breast cancer cells.
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Affiliation(s)
- Le Ying
- Department of Tea Science, Zhejiang University, Hangzhou 310058, China.,Department of Molecular and Translational Science, Monash University, Clayton, Victoria 3168, Australia
| | - De-Dong Kong
- Department of Tea Science, Zhejiang University, Hangzhou 310058, China
| | - Yuan-Yuan Gao
- Department of Tea Science, Zhejiang University, Hangzhou 310058, China
| | - Feng Yan
- Department of Molecular and Translational Science, Monash University, Clayton, Victoria 3168, Australia
| | - Yue-Fei Wang
- Department of Tea Science, Zhejiang University, Hangzhou 310058, China
| | - Ping Xu
- Department of Tea Science, Zhejiang University, Hangzhou 310058, China
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27
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Save SN, Choudhary S. Elucidation of energetics and mode of recognition of green tea polyphenols by human serum albumin. J Mol Liq 2018. [DOI: 10.1016/j.molliq.2018.07.017] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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28
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Pal D, Sur S, Roy R, Mandal S, Kumar Panda C. Epigallocatechin gallate in combination with eugenol or amarogentin shows synergistic chemotherapeutic potential in cervical cancer cell line. J Cell Physiol 2018; 234:825-836. [PMID: 30078217 DOI: 10.1002/jcp.26900] [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: 02/28/2018] [Accepted: 06/13/2018] [Indexed: 01/07/2023]
Abstract
In this study, antitumor activity of epigallocatechin gallate (EGCG; major component of green tea polyphenol), eugenol (active component of clove), and amarogentin (active component of chirata plant) either alone or in combination were evaluated in Hela cell line. It was evident that EGCG with eugenol-amrogentin could highly inhibit the cellular proliferation and colony formation than individual treatments. Induction of apoptosis was also higher after treatment with EGCG in combination with eugenol-amrogentin than individual compound treatments. The antiproliferative effect of these compounds was due to downregulation of cyclinD1 and upregulation of cell cycle inhibitors LIMD1, RBSP3, and p16 at G1/S phase of cell cycle. Treatment of these compounds could induce promoter hypomethylation of LimD1 and P16 genes as a result of reduced expression of DNA methyltransferase 1 (DNMT1). Thus, our study indicated the better chemotherapeutic effect of EGCG in combination with eugenol-amarogentin in Hela cell line. The chemotherapeutic effect might be due to the epigenetic modification particularly DNA hypomethylation through downregulation of DNMT1.
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Affiliation(s)
- Debolina Pal
- Department of Oncogene Regulation, Chittarangan National Cancer Institute, Kolkata, India
| | - Subhayan Sur
- Department of Oncogene Regulation, Chittarangan National Cancer Institute, Kolkata, India
| | - Rituparna Roy
- Department of Oncogene Regulation, Chittarangan National Cancer Institute, Kolkata, India
| | - Suvra Mandal
- Department of Chemistry, National Research Institute for Ayurvedic Drug Development, Kolkata, India
| | - Chinmay Kumar Panda
- Department of Oncogene Regulation, Chittarangan National Cancer Institute, Kolkata, India
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Shavandi A, Bekhit AEDA, Saeedi P, Izadifar Z, Bekhit AA, Khademhosseini A. Polyphenol uses in biomaterials engineering. Biomaterials 2018; 167:91-106. [PMID: 29567389 PMCID: PMC5973878 DOI: 10.1016/j.biomaterials.2018.03.018] [Citation(s) in RCA: 128] [Impact Index Per Article: 18.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2017] [Revised: 02/21/2018] [Accepted: 03/12/2018] [Indexed: 12/26/2022]
Abstract
Polyphenols are micronutrients obtained from diet that have been suggested to play an important role in health. The health benefits of polyphenols and their protective effects in food systems as antioxidant compounds are well known and have been extensively investigated. However, their functional roles as a "processing cofactor" in tissue engineering applications are less widely known. This review focuses on the functionality of polyphenols and their application in biomaterials. Polyphenols have been used to stabilize collagen and to improve its resistance to degradation in biological systems. Therefore, they have been proposed to improve the performance of biomedical devices used in cardiovascular systems by improving the mechanical properties of grafted heart valves, enhancing microcirculation through the relaxation of the arterial walls and improving the capillary blood flow and pressure resistance. Polyphenols have been found to stimulate bone formation, mineralization, as well as the proliferation, differentiation, and the survival of osteoblasts. These effects are brought about by the stimulatory effect of polyphenols on osteoblast cells and their protective effect against oxidative stress and inflammatory cytokines. In addition, polyphenols inhibit the differentiation of the osteoclast cells. Collectively, these actions lead to promote bone formation and to reduce bone resorption, respectively. Moreover, polyphenols can increase the cross-linking of dentine and hence its mechanical stability. Overall, polyphenols provide interesting properties that will stimulate further research in the bioengineering field.
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Affiliation(s)
- Amin Shavandi
- Department of Food Science, University of Otago, Dunedin, New Zealand.
| | | | - Pouya Saeedi
- Department of Human Nutrition, University of Otago, Dunedin, New Zealand
| | - Zohreh Izadifar
- The Lunenfeld-Tanenbaum Research Institute, University of Toronto, Toronto, Canada
| | - Adnan A Bekhit
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Alexandria, Alexandria, Egypt; Pharmacy Program, Allied Health Department, College of Health Sciences, University of Bahrain, P.O. Box 32038, Kingdom of Bahrain
| | - Ali Khademhosseini
- Department of Bioengineering, Department of Chemical and Biomolecular Engineering, Henry Samueli School of Engineering and Applied Sciences, University of California-Los Angeles, Los Angeles, CA, USA; Department of Radiology, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA; Center for Minimally Invasive Therapeutics (C-MIT), University of California-Los Angeles, Los Angeles, CA, USA; California NanoSystems Institute (CNSI), University of California-Los Angeles, Los Angeles, CA, USA.
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Iqbal J, Abbasi BA, Mahmood T, Kanwal S, Ali B, Shah SA, Khalil AT. Plant-derived anticancer agents: A green anticancer approach. Asian Pac J Trop Biomed 2017. [DOI: 10.1016/j.apjtb.2017.10.016] [Citation(s) in RCA: 294] [Impact Index Per Article: 36.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
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Gan RY, Li HB, Sui ZQ, Corke H. Absorption, metabolism, anti-cancer effect and molecular targets of epigallocatechin gallate (EGCG): An updated review. Crit Rev Food Sci Nutr 2017. [DOI: 10.1080/10408398.2016.1231168 pmid: 27645804] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/30/2022]
Affiliation(s)
- Ren-You Gan
- Department of Food Science and Engineering, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, China
- School of Biological Sciences, The University of Hong Kong, Hong Kong
| | - Hua-Bin Li
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou, China
| | - Zhong-Quan Sui
- Department of Food Science and Engineering, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, China
| | - Harold Corke
- Department of Food Science and Engineering, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, China
- School of Biological Sciences, The University of Hong Kong, Hong Kong
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Gan RY, Li HB, Sui ZQ, Corke H. Absorption, metabolism, anti-cancer effect and molecular targets of epigallocatechin gallate (EGCG): An updated review. Crit Rev Food Sci Nutr 2017; 58:924-941. [PMID: 27645804 DOI: 10.1080/10408398.2016.1231168] [Citation(s) in RCA: 287] [Impact Index Per Article: 35.9] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Green tea is one of the most popular beverages in the world, especially in Asian countries. Consumption of green tea has been demonstrated to possess many health benefits, which mainly attributed to the main bioactive compound epigallocatechin gallate (EGCG), a flavone-3-ol polyphenol, in green tea. EGCG is mainly absorbed in the intestine, and gut microbiota play a critical role in its metabolism prior to absorption. EGCG exhibits versatile bioactivities, with its anti-cancer effect most attracting due to the cancer preventive effect of green tea consumption, and a great number of studies intensively investigated its anti-cancer effect. In this review, we therefore, first stated the absorption and metabolism process of EGCG, and then summarized its anti-cancer effect in vitro and in vivo, including its manifold anti-cancer actions and mechanisms, especially its anti-cancer stem cell effect, and next highlighted its various molecular targets involved in cancer inhibition. Finally, the anti-cancer effect of EGCG analogs and nanoparticles, as well as the potential cancer promoting effect of EGCG were also discussed. Understanding of the absorption, metabolism, anti-cancer effect and molecular targets of EGCG can be of importance to better utilize it as a chemopreventive and chemotherapeutic agent.
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Affiliation(s)
- Ren-You Gan
- a Department of Food Science and Engineering, School of Agriculture and Biology , Shanghai Jiao Tong University , Shanghai , China.,b School of Biological Sciences , The University of Hong Kong , Hong Kong
| | - Hua-Bin Li
- c Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition , School of Public Health, Sun Yat-Sen University , Guangzhou , China
| | - Zhong-Quan Sui
- a Department of Food Science and Engineering, School of Agriculture and Biology , Shanghai Jiao Tong University , Shanghai , China
| | - Harold Corke
- a Department of Food Science and Engineering, School of Agriculture and Biology , Shanghai Jiao Tong University , Shanghai , China.,b School of Biological Sciences , The University of Hong Kong , Hong Kong
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DFT study of structural and electronic properties of gallic acid and its anions in gas phase and in aqueous solution. Struct Chem 2017. [DOI: 10.1007/s11224-017-0958-3] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
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Hu XQ, Sun Y, Lau E, Zhao M, Su SB. Advances in Synergistic Combinations of Chinese Herbal Medicine for the Treatment of Cancer. Curr Cancer Drug Targets 2016; 16:346-56. [PMID: 26638885 PMCID: PMC5425653 DOI: 10.2174/1568009616666151207105851] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2015] [Revised: 09/15/2015] [Accepted: 12/04/2015] [Indexed: 12/13/2022]
Abstract
The complex pathology of cancer development requires correspondingly complex treatments. The traditional application of individual single-target drugs fails to sufficiently treat cancer with durable therapeutic effects and tolerable adverse events. Therefore, synergistic combinations of drugs represent a promising way to enhance efficacy, overcome toxicity and optimize safety. Chinese Herbal Medicines (CHMs) have long been used as such synergistic combinations. Therefore, we summarized the synergistic combinations of CHMs used in the treatment of cancer and their roles in chemotherapy in terms of enhancing efficacy, reducing side effects, immune modulation, as well as abrogating drug resistance. Our conclusions support the development of further science-based holistic modalities for cancer care.
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Affiliation(s)
| | | | | | | | - Shi-Bing Su
- Department of Research Center for Traditional Chinese Medicine Complexity System, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
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Lu J, Xu J, Shi Q. Effect of ethanol extract of HPRS, a Traditional Chinese Medicine formula, on HCT116 cell Line. J TRADIT CHIN MED 2016; 36:760-7. [PMID: 29949709 DOI: 10.1016/s0254-6272(17)30012-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
OBJECTIVE In this study, we investigated the effects of ethanol extract of Hupiruisu Fang (HPRS), a
formula of Traditional Chinese Medicine, on HCT116 cell line. METHODS MKN45, A549, Hela and HCT116 cells were treated with ethanol extract of HPRS alone or
the extract plus 5-Fluorouracil (5-FU) for 48 h, and then the cell viabilities were measured using CCK-8
Kit. The early apoptosis rate and total apoptosis rate in both HCT116 cells were evaluated by flow
cytometry. The mRNA levels of apoptosis-related genes including caspase-3, caspase-8, Bcl2 and Bax were detected by real-time quantitative polymerase chain reaction. Lastly, the protein activities
and expressions of those apoptosis related genes were observed for further verifying the pro-apoptosis
of the extract of HPRS. RESULTS Ethanol extract of HPRS could significantly induce apoptosis in HCT116 cell line. Synergistic
analysis revealed that the extract exhibited a significant effect upon 5-FU-associated cytotoxicity in the
cell line. CONCLUSION The ethanol extract of HPRS plus 5-FU might have the potential to improve the treatment of colorectal cancer.
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Jaramillo S, Muriana FJ, Guillen R, Jimenez-Araujo A, Rodriguez-Arcos R, Lopez S. Saponins from edible spears of wild asparagus inhibit AKT, p70S6K, and ERK signalling, and induce apoptosis through G0/G1 cell cycle arrest in human colon cancer HCT-116 cells. J Funct Foods 2016. [DOI: 10.1016/j.jff.2016.07.007] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
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Singh S, Sharma B, Kanwar SS, Kumar A. Lead Phytochemicals for Anticancer Drug Development. FRONTIERS IN PLANT SCIENCE 2016; 7:1667. [PMID: 27877185 PMCID: PMC5099879 DOI: 10.3389/fpls.2016.01667] [Citation(s) in RCA: 209] [Impact Index Per Article: 23.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/07/2016] [Accepted: 10/24/2016] [Indexed: 05/07/2023]
Abstract
Cancer is a serious concern at present. A large number of patients die each year due to cancer illnesses in spite of several interventions available. Development of an effective and side effects lacking anticancer therapy is the trending research direction in healthcare pharmacy. Chemical entities present in plants proved to be very potential in this regard. Bioactive phytochemicals are preferential as they pretend differentially on cancer cells only, without altering normal cells. Carcinogenesis is a complex process and includes multiple signaling events. Phytochemicals are pleiotropic in their function and target these events in multiple manners; hence they are most suitable candidate for anticancer drug development. Efforts are in progress to develop lead candidates from phytochemicals those can block or retard the growth of cancer without any side effect. Several phytochemicals manifest anticancer function in vitro and in vivo. This article deals with these lead phytomolecules with their action mechanisms on nuclear and cellular factors involved in carcinogenesis. Additionally, druggability parameters and clinical development of anticancer phytomolecules have also been discussed.
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Wong AST, Che CM, Leung KW. Recent advances in ginseng as cancer therapeutics: a functional and mechanistic overview. Nat Prod Rep 2015; 32:256-72. [PMID: 25347695 DOI: 10.1039/c4np00080c] [Citation(s) in RCA: 197] [Impact Index Per Article: 19.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
Cancer is one of the leading causes of death worldwide. Ginseng, a key ingredient in traditional Chinese medicine, shows great promise as a new treatment option. As listed by the U.S. National Institutes of Health as a complementary and alternative medicine, its anti-cancer functions are being increasingly recognized. This review covers the mechanisms of action of ginsenosides and their metabolites, which can modulate signaling pathways associated with inflammation, oxidative stress, angiogenesis, metastasis, and stem/progenitor-like properties of cancer cells. The emerging use of structurally modified ginsenosides and recent clinical studies on the use of ginseng either alone or in combination with other herbs or Western medicines which are exploited as novel therapeutic strategies will also be explored.
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Affiliation(s)
- Alice S T Wong
- State Key Laboratory of Oncogenes and Related Genes, and School of Biological Sciences, The University of Hong Kong, Hong Kong.
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Badhani B, Sharma N, Kakkar R. Gallic acid: a versatile antioxidant with promising therapeutic and industrial applications. RSC Adv 2015. [DOI: 10.1039/c5ra01911g] [Citation(s) in RCA: 486] [Impact Index Per Article: 48.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
Oxidative stress, a result of an overproduction and accumulation of free radicals, is the leading cause of several degenerative diseases such as cancer, atherosclerosis, cardiovascular diseases, ageing and inflammatory diseases.
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Affiliation(s)
- Bharti Badhani
- Computational Chemistry Laboratory
- Department of Chemistry
- University of Delhi
- Delhi-110007
- India
| | - Neha Sharma
- Computational Chemistry Laboratory
- Department of Chemistry
- University of Delhi
- Delhi-110007
- India
| | - Rita Kakkar
- Computational Chemistry Laboratory
- Department of Chemistry
- University of Delhi
- Delhi-110007
- India
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Fangueiro JF, Parra A, Silva AM, Egea MA, Souto EB, Garcia ML, Calpena AC. Validation of a high performance liquid chromatography method for the stabilization of epigallocatechin gallate. Int J Pharm 2014; 475:181-90. [DOI: 10.1016/j.ijpharm.2014.08.053] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2014] [Revised: 08/23/2014] [Accepted: 08/27/2014] [Indexed: 11/16/2022]
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Fangueiro JF, Andreani T, Fernandes L, Garcia ML, Egea MA, Silva AM, Souto EB. Physicochemical characterization of epigallocatechin gallate lipid nanoparticles (EGCG-LNs) for ocular instillation. Colloids Surf B Biointerfaces 2014; 123:452-60. [PMID: 25303852 DOI: 10.1016/j.colsurfb.2014.09.042] [Citation(s) in RCA: 75] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2014] [Revised: 08/04/2014] [Accepted: 09/19/2014] [Indexed: 11/15/2022]
Abstract
The encapsulation of epigallocatechin gallate (EGCG) in lipid nanoparticles (LNs) could be a suitable approach to avoid drug oxidation and epimerization, which are common processes that lead to low bioavailability of the drug limiting its therapeutic efficacy. The human health benefits of EGCG gained much interest in the pharmaceutical field, and so far there are no studies reporting its encapsulation in LNs. The purpose of this study has been the development of an innovative system for the ocular delivery of EGCG using LNs as carrier for the future treatment of several diseases, such as dry eye, age-related macular degeneration (AMD), glaucoma, diabetic retinopathy and macular oedema. LNs dispersions have been produced by multiple emulsion technique and previously optimized by a factorial design. In order to increase ocular retention time and mucoadhesion by electrostatic attraction, two distinct cationic lipids were used, namely, cetyltrimethylammonium bromide (CTAB) and dimethyldioctadecylammonium bromide (DDAB). EGCG has been successfully loaded in the LNs dispersions and the nanoparticles analysis over 30 days of storage time predicted a good physicochemical stability. The particles were found to be in the nanometer range (<300 nm) and all the evaluated parameters, namely pH, osmolarity and viscosity, were compatible to the ocular administration. The evaluation of the cationic lipid used was compared regarding physical and chemical parameters, lipid crystallization and polymorphism, and stability of dispersion during storage. The results show that different lipids lead to different characteristics mainly associated with the acyl chain composition, i.e. double lipid shows to have influence in the crystallization and stability. Despite the recorded differences between DTAB and DDAB, both cationic LNs seem to fit the parameters for ocular drug delivery.
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Affiliation(s)
- Joana F Fangueiro
- CEBIMED, Research Centre for Biomedicine, Fernando Pessoa University, UFP-FCS, Praça 9 de Abril, 349, P-4249-004 Porto, Portugal; Faculty of Health Sciences, Fernando Pessoa University, UFP-FCS, Rua Carlos da Maia, 296, 4200-150 Porto, Portugal
| | - Tatiana Andreani
- Faculty of Health Sciences, Fernando Pessoa University, UFP-FCS, Rua Carlos da Maia, 296, 4200-150 Porto, Portugal; Centre for Research and Technology of Agro-Environmental and Biological Sciences, CITAB, University of Trás-os-Montes e Alto Douro, UTAD, Quinta de Prados, 5000-801 Vila Real, Portugal; Department of Biology and Environment, University of Trás-os-Montes e Alto Douro, UTAD, Quinta de Prados, 5000-801 Vila Real, Portugal
| | - Lisete Fernandes
- Electron Microscopy Unit, University of Trás-os-Montes e Alto Douro, UTAD, Quinta de Prados, 5000-801 Vila Real, Portugal
| | - Maria L Garcia
- Department of Physical Chemistry, Faculty of Pharmacy, University of Barcelona, Av. Joan XXIII s/n, 08028 Barcelona, Spain; Institute of Nanoscience and Nanotechnology, University of Barcelona, Av. Joan XXIII s/n, 08028 Barcelona, Spain
| | - Maria A Egea
- Department of Physical Chemistry, Faculty of Pharmacy, University of Barcelona, Av. Joan XXIII s/n, 08028 Barcelona, Spain; Institute of Nanoscience and Nanotechnology, University of Barcelona, Av. Joan XXIII s/n, 08028 Barcelona, Spain
| | - Amélia M Silva
- Centre for Research and Technology of Agro-Environmental and Biological Sciences, CITAB, University of Trás-os-Montes e Alto Douro, UTAD, Quinta de Prados, 5000-801 Vila Real, Portugal; Department of Biology and Environment, University of Trás-os-Montes e Alto Douro, UTAD, Quinta de Prados, 5000-801 Vila Real, Portugal
| | - Eliana B Souto
- CEBIMED, Research Centre for Biomedicine, Fernando Pessoa University, UFP-FCS, Praça 9 de Abril, 349, P-4249-004 Porto, Portugal; Faculty of Pharmacy of University of Coimbra (FFUC), Polo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal.
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Kim MY, Yoo BC, Cho JY. Ginsenoside-Rp1-induced apolipoprotein A-1 expression in the LoVo human colon cancer cell line. J Ginseng Res 2014; 38:251-5. [PMID: 25379004 PMCID: PMC4213851 DOI: 10.1016/j.jgr.2014.06.003] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2014] [Revised: 06/07/2014] [Accepted: 06/09/2014] [Indexed: 12/22/2022] Open
Abstract
Background Ginsenoside Rp1 (G-Rp1) is a novel ginsenoside derived from ginsenoside Rk1. This compound was reported to have anticancer, anti-platelet, and anti-inflammatory activities. In this study, we examined the molecular target of the antiproliferative and proapoptotic activities of G-Rp1. Methods To examine the effects of G-Rp1, cell proliferation assays, propidium iodine staining, proteomic analysis by two-dimensional gel electrophoresis, immunoblotting analysis, and a knockdown strategy were used. Results G-Rp1 dose-dependently suppressed the proliferation of colorectal cancer LoVo cells and increased their apoptosis. G-Rp1 markedly upregulated the protein level of apolipoprotein (Apo)-A1 in LoVo, SNU-407, DLD-1, SNU-638, AGS, KPL-4, and SK-BR-3 cells. The knockdown of Apo-A1 by its small-interfering RNA increased the levels of cleaved poly(ADP-ribose) polymerase and p53 and diminished the proliferation of LoVo cells. Conclusion These results suggest that G-Rp1 may act as an anticancer agent by strongly inhibiting cell proliferation and enhancing apoptosis through upregulation of Apo-A1.
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Affiliation(s)
- Mi-Yeon Kim
- Department of Bioinformatics and Life Science, Soongsil University, Seoul, Korea
| | - Byong Chul Yoo
- Research Institute and Hospital, National Cancer Center, Goyang, Korea
| | - Jae Youl Cho
- Department of Genetic Engineering, Sungkyunkwan University, Suwon, Korea
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Qi H, Abe N, Zhu B, Murata Y, Nakamura Y. (−)-Epigallocatechin-3-Gallate Ameliorates Photodynamic Therapy Responses in an In Vitro
T Lymphocyte Model. Phytother Res 2014; 28:1486-91. [DOI: 10.1002/ptr.5152] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2013] [Revised: 02/22/2014] [Accepted: 03/13/2014] [Indexed: 12/22/2022]
Affiliation(s)
- Hang Qi
- School of Food Science and Technology; Dalian Polytechnic University; Dalian 116034 China
| | - Naomi Abe
- Graduate School of Environmental and Life Science; Okayama University; Okayama 700-8530 Japan
| | - Beiwei Zhu
- School of Food Science and Technology; Dalian Polytechnic University; Dalian 116034 China
| | - Yoshiyuki Murata
- Graduate School of Environmental and Life Science; Okayama University; Okayama 700-8530 Japan
| | - Yoshimasa Nakamura
- Graduate School of Environmental and Life Science; Okayama University; Okayama 700-8530 Japan
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Zhang A, Sun H, Wang X. Potentiating therapeutic effects by enhancing synergism based on active constituents from traditional medicine. Phytother Res 2013; 28:526-33. [PMID: 23913598 DOI: 10.1002/ptr.5032] [Citation(s) in RCA: 74] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2013] [Revised: 05/31/2013] [Accepted: 06/03/2013] [Indexed: 12/13/2022]
Abstract
Shifting current drug discovery tide from 'finding new drugs' to 'screening natural products' may be helpful for overcoming the 'more investment, fewer drugs' challenge. Traditional Chinese medicine (TCM), relying on natural products, has been playing a very important role in health protection and disease control for thousands of years in Asia, whose therapeutic efficacy is based on the 'synergism', that is, the combinational effects to be greater than that of the individual drug. Based on syndromes and patient characteristics and guided by the theories of TCM, formulae are designed to contain a combination of various kinds of crude drugs that, when combined, generally assume that a synergism of all ingredients will bring about the maximum of therapeutic efficacy. The increasing evidence has shown that multiple active component combinations of TCM could amplify the therapeutic efficacy of each agent, representing a new trend for modern medicine. However, the precise mechanism of synergistic action remains poorly understood. The present review highlights the concept of synergy and gives some examples of synergistic effects of TCM, and provides an overview of the recent and potential developments of advancing drug discovery towards more agile development of targeted combination therapies from TCM.
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Affiliation(s)
- Aihua Zhang
- National TCM Key Lab of Serum Pharmacochemistry, Key Lab of Chinmedomics, Key Pharmacometabolomics Platform of Chinese Medicines, Heilongjiang University of Chinese Medicine, Heping Road 24, Harbin, 150040, China
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Gao JL, Lv GY, He BC, Zhang BQ, Zhang H, Wang N, Wang CZ, Du W, Yuan CS, He TC. Ginseng saponin metabolite 20(S)-protopanaxadiol inhibits tumor growth by targeting multiple cancer signaling pathways. Oncol Rep 2013; 30:292-8. [PMID: 23633038 PMCID: PMC3729206 DOI: 10.3892/or.2013.2438] [Citation(s) in RCA: 69] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2013] [Accepted: 04/05/2013] [Indexed: 12/15/2022] Open
Abstract
Plant-derived active constituents and their semi-synthetic or synthetic analogs have served as major sources of anticancer drugs. 20(S)-protopanaxadiol (PPD) is a metabolite of ginseng saponin of both American ginseng (Panax quinquefolius L.) and Asian ginseng (Panax ginseng C.A. Meyer). We previously demonstrated that ginsenoside Rg3, a glucoside precursor of PPD, exhibits anti-proliferative effects on HCT116 cells and reduces tumor size in a xenograft model. Our subsequent study indicated that PPD has more potent antitumor activity than that of Rg3 in vitro although the mechanism underlying the anticancer activity of PPD remains to be defined. Here, we investigated the mechanism underlying the anticancer activity of PPD in human cancer cells in vitro and in vivo. PPD was shown to inhibit growth and induce cell cycle arrest in HCT116 cells. The in vivo studies indicate that PPD inhibits xenograft tumor growth in athymic nude mice bearing HCT116 cells. The xenograft tumor size was significantly reduced when the animals were treated with PPD (30 mg/kg body weight) for 3 weeks. When the expression of previously identified Rg3 targets, A kinase (PRKA) anchor protein 8 (AKAP8L) and phosphatidylinositol transfer protein α (PITPNA), was analyzed, PPD was shown to inhibit the expression of PITPNA while upregulating AKAP8L expression in HCT116 cells. Pathway-specific reporter assays indicated that PPD effectively suppressed the NF-κB, JNK and MAPK/ERK signaling pathways. Taken together, our results suggest that the anticancer activity of PPD in colon cancer cells may be mediated through targeting NF-κB, JNK and MAPK/ERK signaling pathways, although the detailed mechanisms underlying the anticancer mode of PPD action need to be fully elucidated.
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Affiliation(s)
- Jian-Li Gao
- Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, P.R. China.
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Wang CZ, Li B, Wen XD, Zhang Z, Yu C, Calway TD, He TC, Du W, Yuan CS. Paraptosis and NF-κB activation are associated with protopanaxadiol-induced cancer chemoprevention. Altern Ther Health Med 2013; 13:2. [PMID: 23281928 PMCID: PMC3575249 DOI: 10.1186/1472-6882-13-2] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2012] [Accepted: 12/19/2012] [Indexed: 12/27/2022]
Abstract
Background Protopanaxadiol (PPD) is a triterpenoid that can be prepared from steamed ginseng. PPD possesses anticancer potential via caspase-dependent apoptosis. Whether paraptosis, a type of the caspase-independent cell death, is also induced by PPD has not been evaluated. Methods Cell death, the cell cycle and intracellular reactive oxygen species (ROS) were analyzed by flow cytometry after staining with annexin V/PI, PI/RNase or H2DCFDA. We observed morphological changes by crystal violet staining assay. Mitochondrial swelling was measured by ultraviolet–visible spectrophotometry. The activation of NF-κB was measured by luciferase reporter assay. Results At comparable concentrations of 5-fluorouracil, PPD induced more cell death in human colorectal cancer cell lines HCT-116 and SW-480. We demonstrated that PPD induced paraptosis in these cancer cells. PPD treatment significantly increased the percentage of cancer cells with cytoplasmic vacuoles. After the cells were treated with PPD and cycloheximides, cytoplasmic vacuole generation was inhibited. The paraptotic induction effect of PPD was also supported by the results of the mitochondrial swelling assay. PPD induced ROS production in cancer cells, which activated the NF-κB pathway. Blockage of ROS by NAC or PS-1145 inhibited the activation of NF-κB signaling. Conclusions PPD induces colorectal cancer cell death in part by induction of paraptosis. The anticancer activity of PPD may be enhanced by antioxidants such as green tea, which also inhibit the activation of NF-κB signaling.
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Du GJ, Zhang Z, Wen XD, Yu C, Calway T, Yuan CS, Wang CZ. Epigallocatechin Gallate (EGCG) is the most effective cancer chemopreventive polyphenol in green tea. Nutrients 2012. [PMID: 23201840 PMCID: PMC3509513 DOI: 10.3390/nu4111679] [Citation(s) in RCA: 343] [Impact Index Per Article: 26.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Green tea is a popular drink consumed daily by millions of people around the world. Previous studies have shown that some polyphenol compounds from green tea possess anticancer activities. However, systemic evaluation was limited. In this study, we determined the cancer chemopreventive potentials of 10 representative polyphenols (caffeic acid, CA; gallic acid, GA; catechin, C; epicatechin, EC; gallocatechin, GC; catechin gallate, CG; gallocatechin gallate, GCG; epicatechin gallate, ECG; epigallocatechin, EGC; and epigallocatechin gallate, EGCG), and explored their structure-activity relationship. The effect of the 10 polyphenol compounds on the proliferation of HCT-116 and SW-480 human colorectal cancer cells was evaluated using an MTS assay. Cell cycle distribution and apoptotic effects were analyzed by flow cytometry after staining with propidium iodide (PI)/RNase or annexin V/PI. Among the 10 polyphenols, EGCG showed the most potent antiproliferative effects, and significantly induced cell cycle arrest in the G1 phase and cell apoptosis. When the relationship between chemical structure and anticancer activity was examined, C and EC did not show antiproliferative effects, and GA showed some antiproliferative effects. When C and EC esterified with GA to produce CG and ECG, the antiproliferative effects were increased significantly. A similar relationship was found between EGC and EGCG. The gallic acid group significantly enhanced catechin’s anticancer potential. This property could be utilized in future semi-synthesis of flavonoid derivatives to develop novel anticancer agents.
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Affiliation(s)
- Guang-Jian Du
- Tang Center for Herbal Medicine Research, University of Chicago, Chicago, IL 60637, USA; (G.-J.D.); (Z.Z.);
(X.-D.W); (C.Y.); (T.C.);
(C.-S.Y.)
- Department of Anesthesia and Critical Care, University of Chicago, Chicago, IL 60637, USA
| | - Zhiyu Zhang
- Tang Center for Herbal Medicine Research, University of Chicago, Chicago, IL 60637, USA; (G.-J.D.); (Z.Z.);
(X.-D.W); (C.Y.); (T.C.);
(C.-S.Y.)
- Department of Anesthesia and Critical Care, University of Chicago, Chicago, IL 60637, USA
| | - Xiao-Dong Wen
- Tang Center for Herbal Medicine Research, University of Chicago, Chicago, IL 60637, USA; (G.-J.D.); (Z.Z.);
(X.-D.W); (C.Y.); (T.C.);
(C.-S.Y.)
- Department of Anesthesia and Critical Care, University of Chicago, Chicago, IL 60637, USA
| | - Chunhao Yu
- Tang Center for Herbal Medicine Research, University of Chicago, Chicago, IL 60637, USA; (G.-J.D.); (Z.Z.);
(X.-D.W); (C.Y.); (T.C.);
(C.-S.Y.)
- Department of Anesthesia and Critical Care, University of Chicago, Chicago, IL 60637, USA
| | - Tyler Calway
- Tang Center for Herbal Medicine Research, University of Chicago, Chicago, IL 60637, USA; (G.-J.D.); (Z.Z.);
(X.-D.W); (C.Y.); (T.C.);
(C.-S.Y.)
- Department of Anesthesia and Critical Care, University of Chicago, Chicago, IL 60637, USA
| | - Chun-Su Yuan
- Tang Center for Herbal Medicine Research, University of Chicago, Chicago, IL 60637, USA; (G.-J.D.); (Z.Z.);
(X.-D.W); (C.Y.); (T.C.);
(C.-S.Y.)
- Department of Anesthesia and Critical Care, University of Chicago, Chicago, IL 60637, USA
- Committee on Clinical Pharmacology and Pharmacogenomics, University of Chicago, Chicago, IL 60637, USA
| | - Chong-Zhi Wang
- Tang Center for Herbal Medicine Research, University of Chicago, Chicago, IL 60637, USA; (G.-J.D.); (Z.Z.);
(X.-D.W); (C.Y.); (T.C.);
(C.-S.Y.)
- Department of Anesthesia and Critical Care, University of Chicago, Chicago, IL 60637, USA
- Author to whom correspondence should be addressed; ; Tel.: +1-773-702-0166; Fax: +1-773-834-0601
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