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Bazavar MR, Helali H, Boukani LM, Yousefi B, Valizadeh A. Enhancing Doxorubicin Sensitivity in Osteosarcoma Cancer Cells: Unveiling the Role of Resveratrol-Induced Oxidative DNA Damage. Drug Res (Stuttg) 2025. [PMID: 40273920 DOI: 10.1055/a-2567-9916] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/26/2025]
Abstract
Our current research aims to investigate how Resveratrol influences DOX-induced apoptosis in Saos-2 cells resulting from DNA damage.Saos-2 cells were cultured with DOX, and an MTT assay was conducted to evaluate cell viability. The expression levels of DNA damage markers were evaluated using qRT-PCR and western blotting methods. Apoptosis was also investigated by flow cytometry.In a dose-dependent way, DOX produced a profuse suppression of cell proliferation. This study investigates the effect of Resveratrol on DOX-induced apoptosis due to DNA damage in Saos-2 cells (P<0.05). There was an increase in H2AX, ATR, ATM, Rad51, and p53 expression, possibly contributing to subsequent apoptosis. Furthermore, Resv enhanced the apoptosis caused by DOX in Saos-2 cells.The findings from the current research provide an understanding of how Resv plays a role in potentially treating osteosarcoma by enhancing DOX-induced apoptosis.
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Affiliation(s)
- Mohammad Reza Bazavar
- Department of Orthopedic Surgery, School of Medicine and Shohada Educational Hospital, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Hamed Helali
- Department of Orthopedic Surgery, School of Medicine and Shohada Educational Hospital, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Bahman Yousefi
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Clinical Biochemistry and Laboratory Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Amir Valizadeh
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Clinical Biochemistry and Laboratory Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
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Raunak Salian T, Noushida N, Mohanto S, Gowda BHJ, Chakraborty M, Nasrine A, Narayana S, Ahmed MG. Development of optimized resveratrol/piperine-loaded phytosomal nanocomplex for isoproterenol-induced myocardial infarction treatment. J Liposome Res 2024; 34:640-657. [PMID: 39001631 DOI: 10.1080/08982104.2024.2378130] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2024] [Revised: 06/13/2024] [Accepted: 06/25/2024] [Indexed: 11/28/2024]
Abstract
Cardiovascular disease is a significant and ever-growing concern, causing high morbidity and mortality worldwide. Conventional therapy is often very precarious and requires long-term usage. Several phytochemicals, including Resveratrol (RSV) and Piperine (PIP), possess significant cardioprotection and may be restrained in clinical settings due to inadequate pharmacokinetic properties. Therefore, this study strives to develop an optimized RSV phytosomes (RSVP) and RSV phytosomes co-loaded with PIP (RPP) via solvent evaporation method using Box-Behnken design to enhance the pharmacokinetic properties in isoproterenol-induced myocardial infarction (MI). The optimized particle size (20.976 ± 0.39 and 176.53 ± 0.88 nm), zeta potential (-33.33 ± 1.5 and -48.7 ± 1.6 mV), drug content (84.57 ± 0.9 and 87.16 ± 0.6%), and %EE (70.56 ± 0.7 and 67.60 ± 0.57%) of the prepared RSVP and RPP, respectively demonstrated enhanced solubility and control release in diffusion media. The oral administration of optimized RSVP and RPP in myocardial infarction-induced rats exhibited significant (p < 0.001) improvement in heart rate, ECG, biomarker, anti-oxidant levels, and no inflammation than pure RSV. The pharmacokinetic assessment on healthy Wistar rats exhibited prolonged circulation (>24 h) of RSVP and RPP compared to free drug/s. The enhanced ability of RSVP and RPP to penetrate bio-membranes and enter the systemic circulation renders them a more promising strategy for mitigating MI.
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Affiliation(s)
- Thriveni Raunak Salian
- Department of Pharmaceutics, Yenepoya Pharmacy College & Research Centre, Yenepoya (Deemed to be University), Mangalore, Karnataka, India
| | - Nadira Noushida
- Department of Pharmacology, Yenepoya Medical College and Hospital, Yenepoya (Deemed to be University), Mangalore, Karnataka, India
| | - Sourav Mohanto
- Department of Pharmaceutics, Yenepoya Pharmacy College & Research Centre, Yenepoya (Deemed to be University), Mangalore, Karnataka, India
| | - B H Jaswanth Gowda
- Department of Pharmaceutics, Yenepoya Pharmacy College & Research Centre, Yenepoya (Deemed to be University), Mangalore, Karnataka, India
- School of Pharmacy, Queen's University Belfast, Medical Biology Centre, Belfast, UK
| | - Manodeep Chakraborty
- Department of Pharmacology, Himalayan Pharmacy Institute, Majhitar, East Sikkim, India
| | - Arfa Nasrine
- Department of Pharmaceutics, Yenepoya Pharmacy College & Research Centre, Yenepoya (Deemed to be University), Mangalore, Karnataka, India
- College of Pharmaceutical Sciences, Dayananda Sagar University, Bengaluru, Karnataka, India
| | - Soumya Narayana
- Department of Pharmaceutics, Yenepoya Pharmacy College & Research Centre, Yenepoya (Deemed to be University), Mangalore, Karnataka, India
| | - Mohammed Gulzar Ahmed
- Department of Pharmaceutics, Yenepoya Pharmacy College & Research Centre, Yenepoya (Deemed to be University), Mangalore, Karnataka, India
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Mendonça BS, Nascimento LMM, Ferro JNDS, Dos Santos Reis MD. The effect of plant-derived polyphenols on the immune system during aging: a systematic review. Immunopharmacol Immunotoxicol 2024; 46:604-617. [PMID: 39069754 DOI: 10.1080/08923973.2024.2384911] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2023] [Accepted: 07/22/2024] [Indexed: 07/30/2024]
Abstract
OBJECTIVE Polyphenols are organic compounds with diverse biological activities such as anti-inflammatory and antioxidant effects, making them important candidates for the development of anti-aging drugs. In this systematic review, we aimed to answer the question: can plant-derived polyphenols have an immunomodulatory effect in experimental models of aging? METHODS We systematically searched Web of Science, MEDLINE/Pubmed, and Embase to select articles using the following combinations of terms and synonyms: polyphenols, phenols, senescence, aging, and immune. The selected articles were evaluated for reporting quality and risk-of-bias according to standard guidelines. RESULTS The most used polyphenol was resveratrol, followed by curcumin, salidroside, and gallic acid. These molecules demonstrated an ability to restore immune function both in vitro and in vivo. The mechanism of action was not completely elucidated in these studies, but inhibition of NF-kB signaling, and antioxidant properties seemed to account for the anti-aging effects. All articles included in the review had good quality of reporting but failed to describe an adequate sample size, criteria for inclusion/exclusion, randomization, and blinding. CONCLUSION We conclude that polyphenols are promising immunomodulatory substances for use in anti-aging therapies. However, more research with standardized analysis is needed to understand the role of these molecules in the prevention or reduction of damage associated with the aging process, as well as to determine the safety profile and consequences of systemic action.
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Affiliation(s)
- Beatriz Santana Mendonça
- Laboratory of Cell Biology, Institute of Health and Biological Sciences, Federal University of Alagoas, Maceió
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Shin J, Lee Y, Ju SH, Jung YJ, Sim D, Lee SJ. Unveiling the Potential of Natural Compounds: A Comprehensive Review on Adipose Thermogenesis Modulation. Int J Mol Sci 2024; 25:4915. [PMID: 38732127 PMCID: PMC11084502 DOI: 10.3390/ijms25094915] [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: 04/04/2024] [Revised: 04/19/2024] [Accepted: 04/23/2024] [Indexed: 05/13/2024] Open
Abstract
The process of adipocyte browning has recently emerged as a novel therapeutic target for combating obesity and obesity-related diseases. Non-shivering thermogenesis is the process of biological heat production in mammals and is primarily mediated via brown adipose tissue (BAT). The recruitment and activation of BAT can be induced through chemical drugs and nutrients, with subsequent beneficial health effects through the utilization of carbohydrates and fats to generate heat to maintain body temperature. However, since potent drugs may show adverse side effects, nutritional or natural substances could be safe and effective as potential adipocyte browning agents. This review aims to provide an extensive overview of the natural food compounds that have been shown to activate brown adipocytes in humans, animals, and in cultured cells. In addition, some key genetic and molecular targets and the mechanisms of action of these natural compounds reported to have therapeutic potential to combat obesity are discussed.
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Affiliation(s)
- Jaeeun Shin
- Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02855, Republic of Korea; (J.S.); (Y.L.); (S.H.J.); (Y.J.J.); (D.S.)
| | - Yeonho Lee
- Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02855, Republic of Korea; (J.S.); (Y.L.); (S.H.J.); (Y.J.J.); (D.S.)
| | - Seong Hun Ju
- Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02855, Republic of Korea; (J.S.); (Y.L.); (S.H.J.); (Y.J.J.); (D.S.)
| | - Young Jae Jung
- Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02855, Republic of Korea; (J.S.); (Y.L.); (S.H.J.); (Y.J.J.); (D.S.)
| | - Daehyeon Sim
- Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02855, Republic of Korea; (J.S.); (Y.L.); (S.H.J.); (Y.J.J.); (D.S.)
| | - Sung-Joon Lee
- Department of Food Bioscience and Technology, College of Life Sciences and Biotechnology, Korea University, Seoul 02855, Republic of Korea
- Interdisciplinary Program in Precision Public Health, BK21 Four Institute of Precision Public Health, Korea University, Seoul 02846, Republic of Korea
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Salla M, Karaki N, El Kaderi B, Ayoub AJ, Younes S, Abou Chahla MN, Baksh S, El Khatib S. Enhancing the Bioavailability of Resveratrol: Combine It, Derivatize It, or Encapsulate It? Pharmaceutics 2024; 16:569. [PMID: 38675230 PMCID: PMC11053528 DOI: 10.3390/pharmaceutics16040569] [Citation(s) in RCA: 18] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2024] [Revised: 04/13/2024] [Accepted: 04/16/2024] [Indexed: 04/28/2024] Open
Abstract
Overcoming the limited bioavailability and extensive metabolism of effective in vitro drugs remains a challenge that limits the translation of promising drugs into clinical trials. Resveratrol, despite its well-reported therapeutic benefits, is not metabolically stable and thus has not been utilized as an effective clinical drug. This is because it needs to be consumed in large amounts to overcome the burdens of bioavailability and conversion into less effective metabolites. Herein, we summarize the more relevant approaches to modify resveratrol, aiming to increase its biological and therapeutic efficacy. We discuss combination therapies, derivatization, and the use of resveratrol nanoparticles. Interestingly, the combination of resveratrol with established chemotherapeutic drugs has shown promising therapeutic effects on colon cancer (with oxaliplatin), liver cancer (with cisplatin, 5-FU), and gastric cancer (with doxorubicin). On the other hand, derivatizing resveratrol, including hydroxylation, amination, amidation, imidation, methoxylation, prenylation, halogenation, glycosylation, and oligomerization, differentially modifies its bioavailability and could be used for preferential therapeutic outcomes. Moreover, the encapsulation of resveratrol allows its trapping within different forms of shells for targeted therapy. Depending on the nanoparticle used, it can enhance its solubility and absorption, increasing its bioavailability and efficacy. These include polymers, metals, solid lipids, and other nanoparticles that have shown promising preclinical results, adding more "hype" to the research on resveratrol. This review provides a platform to compare the different approaches to allow directed research into better treatment options with resveratrol.
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Affiliation(s)
- Mohamed Salla
- Department of Biological and Chemical Sciences, School of Arts and Sciences, Lebanese International University, Khiyara—West Bekaa, Bayrut P.O. Box 146404, Lebanon; (N.K.); (B.E.K.); (A.J.A.); (M.N.A.C.); (S.E.K.)
- Department of Biochemistry, Faculty of Medicine & Dentistry, University of Alberta, 113 Street 87 Avenue, Edmonton, AB T6G 2E1, Canada
| | - Nadine Karaki
- Department of Biological and Chemical Sciences, School of Arts and Sciences, Lebanese International University, Khiyara—West Bekaa, Bayrut P.O. Box 146404, Lebanon; (N.K.); (B.E.K.); (A.J.A.); (M.N.A.C.); (S.E.K.)
- Department of Chemistry and Biochemistry, Faculty of Arts and Sciences, Lebanese University, Zahlé 1801, Lebanon
| | - Belal El Kaderi
- Department of Biological and Chemical Sciences, School of Arts and Sciences, Lebanese International University, Khiyara—West Bekaa, Bayrut P.O. Box 146404, Lebanon; (N.K.); (B.E.K.); (A.J.A.); (M.N.A.C.); (S.E.K.)
| | - Abeer J. Ayoub
- Department of Biological and Chemical Sciences, School of Arts and Sciences, Lebanese International University, Khiyara—West Bekaa, Bayrut P.O. Box 146404, Lebanon; (N.K.); (B.E.K.); (A.J.A.); (M.N.A.C.); (S.E.K.)
| | - Samar Younes
- Department of Biomedical Sciences, School of Pharmacy, Lebanese International University, Khiyara—West Bekaa, Bayrut P.O. Box 146404, Lebanon;
- INSPECT-LB (National Institute of Public Health, Clinical Epidemiology and Toxicology-Lebanon (INSPECT-LB)), Beirut 1103, Lebanon
| | - Maya N. Abou Chahla
- Department of Biological and Chemical Sciences, School of Arts and Sciences, Lebanese International University, Khiyara—West Bekaa, Bayrut P.O. Box 146404, Lebanon; (N.K.); (B.E.K.); (A.J.A.); (M.N.A.C.); (S.E.K.)
| | - Shairaz Baksh
- BioImmuno Designs, 4747 154 Avenue, Edmonton, AB T5Y 0C2, Canada;
- Bio-Stream Diagnostics, 2011 94 Street, Edmonton, AB T6H 1N1, Canada
| | - Sami El Khatib
- Department of Biological and Chemical Sciences, School of Arts and Sciences, Lebanese International University, Khiyara—West Bekaa, Bayrut P.O. Box 146404, Lebanon; (N.K.); (B.E.K.); (A.J.A.); (M.N.A.C.); (S.E.K.)
- Department of Biomedical Sciences, School of Arts and Sciences, Lebanese International University, Khiyara—West Bekaa, Bayrut P.O. Box 146404, Lebanon
- Center for Applied Mathematics and Bioinformatics (CAMB), Gulf University for Science and Technology, Mubarak Al-Abdullah 32093, Kuwait
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Tan Y, Zhou C, Miao L, Zhang X, Khan H, Xu B, Cheang WS. 3,4',5-Trimethoxy- trans-stilbene ameliorates hepatic insulin resistance and oxidative stress in diabetic obese mice through insulin and Nrf2 signaling pathways. Food Funct 2024; 15:2996-3007. [PMID: 38411214 DOI: 10.1039/d3fo04158a] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/28/2024]
Abstract
Resveratrol has profound benefits against diabetes. However, whether its methylated derivative 3,4',5-trimethoxy-trans-stilbene (3,4',5-TMS) also plays a protective role in glucose metabolism is not characterized. We aimed to study the anti-diabetic effects of 3,4',5-TMS in vitro and in vivo. Insulin-resistant HepG2 cells (IR-HepG2) were induced by high glucose plus dexamethasone whilst six-week-old male C57BL/6J mice received a 60 kcal% fat diet for 14 weeks to establish an obese diabetic model. 3,4',5-TMS did not reduce the cell viability of IR-HepG2 cells at concentrations of 0.5 and 1 μM, which enhanced the capability of glycogen synthesis and glucose consumption in IR-HepG2 cells. Four-week oral administration of 3,4',5-TMS at 10 mg kg-1 day-1 ameliorated insulin sensitivity and glucose tolerance of diet-induced obese (DIO) mice. 3,4',5-TMS activated the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway by inhibiting phosphorylation of insulin receptor substrate (IRS)-1 at Ser307 and increasing the protein levels of IRS-1 and IRS-2 to restore the insulin signaling pathway in diabetes. 3,4',5-TMS also upregulated the phosphorylation of glycogen synthase kinase 3 beta (GSK3β) at Ser9. 3,4',5-TMS suppressed oxidative stress by increasing the protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1) and NAD(P)H : quinone oxidoreductase 1 (NQO1) and antioxidant enzyme activity. In summary, 3,4',5-TMS alleviated hepatic insulin resistance in vitro and in vivo, by the activation of the insulin signaling pathway, accomplished by the suppression of oxidative stress.
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Affiliation(s)
- Yi Tan
- Institute of Chinese Medical Sciences, State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Macau SAR, China.
| | - Chunxiu Zhou
- Institute of Chinese Medical Sciences, State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Macau SAR, China.
| | - Lingchao Miao
- Institute of Chinese Medical Sciences, State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Macau SAR, China.
| | - Xutao Zhang
- Institute of Chinese Medical Sciences, State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Macau SAR, China.
| | - Haroon Khan
- Department of Pharmacy, Abdul Wali Khan University Mardan, Mardan 23200, Pakistan
| | - Baojun Xu
- Food Science and Technology Program, BNU-HKBU United International College, Zhuhai, Guangdong, China.
| | - Wai San Cheang
- Institute of Chinese Medical Sciences, State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Macau SAR, China.
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Ali M, Benfante V, Di Raimondo D, Salvaggio G, Tuttolomondo A, Comelli A. Recent Developments in Nanoparticle Formulations for Resveratrol Encapsulation as an Anticancer Agent. Pharmaceuticals (Basel) 2024; 17:126. [PMID: 38256959 PMCID: PMC10818631 DOI: 10.3390/ph17010126] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2023] [Revised: 01/13/2024] [Accepted: 01/15/2024] [Indexed: 01/24/2024] Open
Abstract
Resveratrol is a polyphenolic compound that has gained considerable attention in the past decade due to its multifaceted therapeutic potential, including anti-inflammatory and anticancer properties. However, its anticancer efficacy is impeded by low water solubility, dose-limiting toxicity, low bioavailability, and rapid hepatic metabolism. To overcome these hurdles, various nanoparticles such as organic and inorganic nanoparticles, liposomes, polymeric nanoparticles, dendrimers, solid lipid nanoparticles, gold nanoparticles, zinc oxide nanoparticles, zeolitic imidazolate frameworks, carbon nanotubes, bioactive glass nanoparticles, and mesoporous nanoparticles were employed to deliver resveratrol, enhancing its water solubility, bioavailability, and efficacy against various types of cancer. Resveratrol-loaded nanoparticle or resveratrol-conjugated nanoparticle administration exhibits excellent anticancer potency compared to free resveratrol. This review highlights the latest developments in nanoparticle-based delivery systems for resveratrol, focusing on the potential to overcome limitations associated with the compound's bioavailability and therapeutic effectiveness.
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Affiliation(s)
- Muhammad Ali
- Ri.MED Foundation, Via Bandiera 11, 90133 Palermo, Italy;
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, Molecular and Clinical Medicine, University of Palermo, 90127 Palermo, Italy; (D.D.R.); (A.T.)
| | - Viviana Benfante
- Ri.MED Foundation, Via Bandiera 11, 90133 Palermo, Italy;
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, Molecular and Clinical Medicine, University of Palermo, 90127 Palermo, Italy; (D.D.R.); (A.T.)
| | - Domenico Di Raimondo
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, Molecular and Clinical Medicine, University of Palermo, 90127 Palermo, Italy; (D.D.R.); (A.T.)
| | - Giuseppe Salvaggio
- Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, 90127 Palermo, Italy;
| | - Antonino Tuttolomondo
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, Molecular and Clinical Medicine, University of Palermo, 90127 Palermo, Italy; (D.D.R.); (A.T.)
| | - Albert Comelli
- Ri.MED Foundation, Via Bandiera 11, 90133 Palermo, Italy;
- National Biodiversity Future Center (NBFC), 90133 Palermo, Italy
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Ghavidel F, Amiri H, Tabrizi MH, Alidadi S, Hosseini H, Sahebkar A. The Combinational Effect of Inulin and Resveratrol on the Oxidative Stress and Inflammation Level in a Rat Model of Diabetic Nephropathy. Curr Dev Nutr 2024; 8:102059. [PMID: 38292928 PMCID: PMC10826146 DOI: 10.1016/j.cdnut.2023.102059] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2023] [Revised: 11/09/2023] [Accepted: 12/04/2023] [Indexed: 02/01/2024] Open
Abstract
Background Using inulin can enhance resveratrol's effects by improving the intestinal microbiome and the stability of resveratrol. Objectives We aimed to investigate the effect of therapeutic intervention with combined inulin and resveratrol on kidney function in diabetic rats. Methods Diabetic model was induced by intraperitoneal injection of streptozotocin. Afterward, rats were divided into 6 groups: control, diabetic without treatment, diabetic treated with insulin, diabetic treated with resveratrol, diabetic treated with inulin, and diabetic treated with a combination of inulin and resveratrol. After 10 wk, the creatinine, urea, insulin, urinary proteins, and inflammatory and oxidative stress markers were evaluated. Pathologic changes were examined in kidney tissues. Results Renal dysfunction, accompanied by increased inflammation and oxidative stress, was observed. Our results showed that treatment with resveratrol and inulin had antidiabetic effects and was associated with reduced renal dysfunction, oxidative stress, and kidney inflammation. In addition, it was observed that combined treatment with inulin and resveratrol outperformed monotherapies in improving kidney function and reducing oxidative stress and inflammation. Conclusions Treatment with resveratrol and inulin can have renoprotective effects by improving oxidative stress and inflammation in kidney tissues. Therefore, employing these 2 compounds is suggested as an inexpensive and available method for diabetic nephropathy.
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Affiliation(s)
- Farideh Ghavidel
- Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Hamed Amiri
- Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | | | - Soodeh Alidadi
- Department of Pathobiology, Faculty of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Iran
| | - Hossein Hosseini
- Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amirhossein Sahebkar
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
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Mohammadi S, Moghadam MD, Nasiriasl M, Akhzari M, Barazesh M. Insights into the Therapeutic and Pharmacological Properties of Resveratrol as a Nutraceutical Antioxidant Polyphenol in Health Promotion and Disease Prevention. Curr Rev Clin Exp Pharmacol 2024; 19:327-354. [PMID: 38192151 DOI: 10.2174/0127724328268507231218051058] [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: 06/22/2023] [Revised: 11/20/2023] [Accepted: 11/22/2023] [Indexed: 01/10/2024]
Abstract
Resveratrol (3, 5, 4'-trihydroxystilbene) is a polyphenolic derivative with herbal origin. It has attracted considerable attention in recent decades. Many studies have revealed the benefits of Resveratrol over several human disease models, including heart and neurological diseases, nephroprotective, immune regulation, antidiabetic, anti-obesity, age-related diseases, antiviral, and anticancer in experimental and clinical conditions. Recently, the antioxidant and anti-inflammatory activities of Resveratrol have been observed, and it has been shown that Resveratrol reduces inflammatory biomarkers, such as tissue degradation factor, cyclooxygenase 2, nitric oxide synthase, and interleukins. All of these activities appear to be dependent on its structural properties, such as the number and position of the hydroxyl group, which regulates oxidative stress, cell death, and inflammation. Resveratrol is well tolerated and safe even at higher pharmacological doses and desirably affects cardiovascular, neurological, and diabetic diseases. Consequently, it is plausible that Resveratrol can be regarded as a beneficial nutritional additive and a complementary drug, particularly for therapeutic applications. The present review provides an overview of currently available investigations on preventive and therapeutic characteristics and the main molecular mechanisms of Resveratrol and its potent derivatives in various diseases. Thus, this review would enhance knowledge and information about Resveratrol and encourage researchers worldwide to consider it as a pharmaceutical drug to struggle with future health crises against different human disorders.
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Affiliation(s)
- Shiva Mohammadi
- Department of Medical Biotechnology, School of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran
| | - Maryam Dalaei Moghadam
- Razi Herbal Medicines Research Center, Department of Endodontic, Faculty of Dentistry, Lorestan University of Medical Sciences, Khorramabad, Iran
| | - Maryam Nasiriasl
- Radiology Department, Fasa University of Medical Sciences, Fasa, Iran
| | - Morteza Akhzari
- School of Nursing, Larestan University of Medical Sciences, Larestan, Iran
| | - Mahdi Barazesh
- School of Paramedical Sciences, Gerash University of Medical Sciences, Gerash, Iran
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10
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Kaag S, Lorentz A. Effects of Dietary Components on Mast Cells: Possible Use as Nutraceuticals for Allergies? Cells 2023; 12:2602. [PMID: 37998337 PMCID: PMC10670325 DOI: 10.3390/cells12222602] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2023] [Revised: 11/03/2023] [Accepted: 11/06/2023] [Indexed: 11/25/2023] Open
Abstract
Allergic diseases affect an estimated 30 percent of the world's population. Mast cells (MC) are the key effector cells of allergic reactions by releasing pro-inflammatory mediators such as histamine, lipid mediators, and cytokines/chemokines. Components of the daily diet, including certain fatty acids, amino acids, and vitamins, as well as secondary plant components, may have effects on MC and thus may be of interest as nutraceuticals for the prevention and treatment of allergies. This review summarizes the anti-inflammatory effects of dietary components on MC, including the signaling pathways involved, in in vitro and in vivo models. Butyrate, calcitriol, kaempferol, quercetin, luteolin, resveratrol, curcumin, and cinnamon extract were the most effective in suppressing the release of preformed and de novo synthesized mediators from MC or in animal models. In randomized controlled trials (RCT), vitamin D, quercetin, O-methylated epigallocatechin gallate (EGCG), resveratrol, curcumin, and cinnamon extract improved symptoms of allergic rhinitis (AR) and reduced the number of inflammatory cells in patients. However, strategies to overcome the poor bioavailability of these nutrients are an important part of current research.
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Affiliation(s)
| | - Axel Lorentz
- Institute of Nutritional Medicine, University of Hohenheim, D-70593 Stuttgart, Germany
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DA Silva Prade J, DE Souza RS, DA Silva D'Αvila CM, DA Silva TC, Livinalli IC, Bertoncelli ACZ, Saccol FK, DE Oliveira Mendes T, Wenning LG, DA Rosa Salles T, Rhoden CRB, Cadona FC. An Overview of Renal Cell Carcinoma Hallmarks, Drug Resistance, and Adjuvant Therapies. CANCER DIAGNOSIS & PROGNOSIS 2023; 3:616-634. [PMID: 37927802 PMCID: PMC10619564 DOI: 10.21873/cdp.10264] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/11/2023] [Accepted: 09/15/2023] [Indexed: 11/07/2023]
Abstract
Renal neoplasms are highlighted as one of the 10 most common types of cancer. Renal cell carcinoma (RCC) is the most common type of renal cancer, considered the seventh most common type of cancer in the Western world. The most frequently altered genes described as altered are VHL, PBRM1, SETD2, KDM5C, PTEN, BAP1, mTOR, TP53, TCEB1 (ELOC), SMARCA4, ARID1A, and PIK3CA. RCC therapies can be classified in three groups: monoclonal antibodies, tyrosine kinase inhibitors, and mTOR inhibitors. Besides, there are targeted agents to treat RCC. However, frequently patients present side effects and resistance. Even though many multidrug resistance mechanisms already have been reported to RCC, studies focused on revealing new biomarkers as well as more effective antitumor therapies with no or low side effects are very important. Some studies reported that natural products, such as honey, epigallocatechin-3-gallate (EGCG), curcumin, resveratrol, and englerin A showed antitumor activity against RCC. Moreover, nanoscience is another strategy to improve RCC treatment and reduce the side effects due to the improvement in pharmacokinetics and reduction of toxicities of chemotherapies. Taking this into account, we conducted a systemic review of recent research findings on RCC hallmarks, drug resistance, and adjuvant therapies. In conclusion, a range of studies reported that RCC is characterized by high incidence and increased mortality rates because of the development of resistance to standard therapies. Given the importance of improving RCC treatment and reducing adverse effects, nanoscience and natural products can be included in therapeutic strategies.
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Affiliation(s)
- Josiele DA Silva Prade
- Post-graduate Program in Health and Life Sciences, Franciscan University, Santa Maria, RS, Brazil
| | | | | | | | | | | | | | | | | | - Theodoro DA Rosa Salles
- Laboratory of Nanostructured Magnetic Materials - LaMMaN, Franciscan University, Santa Maria, RS, Brazil
- Graduate Program in Nanosciences, Franciscan University, Santa Maria, RS, Brazil
| | - Cristiano Rodrigo Bohn Rhoden
- Laboratory of Nanostructured Magnetic Materials - LaMMaN, Franciscan University, Santa Maria, RS, Brazil
- Graduate Program in Nanosciences, Franciscan University, Santa Maria, RS, Brazil
| | - Francine Carla Cadona
- Post-graduate Program in Health and Life Sciences, Franciscan University, Santa Maria, RS, Brazil
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Shoaib SM, Afzal S, Feezan A, Akash MSH, Nadeem A, Mir TM. Metabolomics Analysis and Biochemical Profiling of Arsenic-Induced Metabolic Impairment and Disease Susceptibility. Biomolecules 2023; 13:1424. [PMID: 37759824 PMCID: PMC10526798 DOI: 10.3390/biom13091424] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2023] [Revised: 09/17/2023] [Accepted: 09/17/2023] [Indexed: 09/29/2023] Open
Abstract
Our study aimed to conduct a comprehensive biochemical profiling and metabolomics analysis to investigate the effects of arsenic-induced metabolic disorders, with a specific focus on disruptions in lipid metabolism, amino acid metabolism, and carbohydrate metabolism. Additionally, we sought to assess the therapeutic potential of resveratrol (RSV) as a remedy for arsenic-induced diabetes, using metformin (MF) as a standard drug for comparison. We measured the total arsenic content in mouse serum by employing inductively coupled plasma mass spectrometry (ICP-MS) after administering a 50-ppm solution of sodium arsenate (50 mg/L) in purified water. Our findings revealed a substantial increase in total arsenic content in the exposed group, with a mean value of 166.80 ± 8.52 ppb (p < 0.05). Furthermore, we investigated the impact of arsenic exposure on various biomarkers using enzyme-linked immunosorbent assay (ELISA) methods. Arsenic exposed mice exhibited significant hyperglycemia (p < 0.001) and elevated levels of homeostatic model assessment of insulin resistance (HOMA-IR), hemoglobin A1c (Hb1Ac), Inflammatory biomarkers as well as liver and kidney function biomarkers (p < 0.05). Additionally, the levels of crucial enzymes linked to carbohydrate metabolism, including α-glucosidase, hexokinase, and glucose-6-phosphatase (G6PS), and oxidative stress biomarkers, such as levels of glutathione (GSH), glutathione reductase (GR), glutathione peroxidase (GPx), catalase, and superoxide dismutase (SOD), were significantly reduced in the arsenic-exposed group compared to the control group (p < 0.05). However, the level of MDA was significantly increased. Molecular analysis of gene expression indicated significant upregulation of key enzymes involved in lipid metabolism, such as carnitine palmitoyl-transferase-I (CPT-I), carnitine palmitoyl-transferase-II (CPT-II), lecithin-cholesterol acyltransferase (LCAT), and others. Additionally, alterations in gene expression related to glucose transporter-2 (GLUT-2), glucose-6-phosphatase (G6PC), and glucokinase (GK), associated with carbohydrate metabolism, were observed. Amino acid analysis revealed significant decreases in nine amino acids in arsenic-exposed mice. Metabolomics analysis identified disruptions in lipid metabolomes, amino acids, and arsenic metabolites, highlighting their involvement in essential metabolic pathways. Histopathological observations revealed significant changes in liver architecture, hepatocyte degeneration, and increased Kupffer cells in the livers of arsenic-exposed mice. In conclusion, these findings enhance our comprehension of the impact of environmental toxins on metabolic health and offer potential avenues for remedies against such disruptions.
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Affiliation(s)
- Syed Muhammad Shoaib
- Department of Pharmaceutical Chemistry, Bahauddin Zakariya University, Multan 60800, Pakistan
| | - Samina Afzal
- Department of Pharmaceutical Chemistry, Bahauddin Zakariya University, Multan 60800, Pakistan
| | - Ali Feezan
- Department of Pharmaceutical Chemistry, Bahauddin Zakariya University, Multan 60800, Pakistan
| | | | - Ahmed Nadeem
- Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
| | - Tahir Maqbool Mir
- National Center for Natural Products Research, School of Pharmacy, University of Mississippi, Oxford, MS 38677, USA
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Gao L, Liu X, Luo X, Lou X, Li P, Li X, Liu X. Antiaging effects of dietary supplements and natural products. Front Pharmacol 2023; 14:1192714. [PMID: 37441528 PMCID: PMC10333707 DOI: 10.3389/fphar.2023.1192714] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2023] [Accepted: 06/12/2023] [Indexed: 07/15/2023] Open
Abstract
Aging is an inevitable process influenced by genetics, lifestyles, and environments. With the rapid social and economic development in recent decades, the proportion of the elderly has increased rapidly worldwide, and many aging-related diseases have shown an upward trend, including nervous system diseases, cardiovascular diseases, metabolic diseases, and cancer. The rising burden of aging-related diseases has become an urgent global health challenge and requires immediate attention and solutions. Natural products have been used for a long time to treat various human diseases. The primary cellular pathways that mediate the longevity-extending effects of natural products involve nutrient-sensing pathways. Among them, the sirtuin, AMP-activated protein kinase, mammalian target of rapamycin, p53, and insulin/insulin-like growth factor-1 signaling pathways are most widely studied. Several studies have reviewed the effects of individual natural compounds on aging and aging-related diseases along with the underlying mechanisms. Natural products from food sources, such as polyphenols, saponins, alkaloids, and polysaccharides, are classified as antiaging compounds that promote health and prolong life via various mechanisms. In this article, we have reviewed several recently identified natural products with potential antiaging properties and have highlighted their cellular and molecular mechanisms. The discovery and use of dietary supplements and natural products that can prevent and treat multiple aging-related diseases in humans will be beneficial. Thus, this review provides theoretical background for existing dietary supplements and natural products as potential antiaging agents.
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Suriyaprom S, Srisai P, Intachaisri V, Kaewkod T, Pekkoh J, Desvaux M, Tragoolpua Y. Antioxidant and Anti-Inflammatory Activity on LPS-Stimulated RAW 264.7 Macrophage Cells of White Mulberry ( Morus alba L.) Leaf Extracts. Molecules 2023; 28:molecules28114395. [PMID: 37298871 DOI: 10.3390/molecules28114395] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2023] [Revised: 05/22/2023] [Accepted: 05/25/2023] [Indexed: 06/12/2023] Open
Abstract
The white mulberry (Morus alba L.) is widely used as a medicinal plant in Asia. In this study, the bioactive compounds of ethanolic extracts of white mulberry leaves from the Sakon Nakhon and Buriram cultivars were evaluated. The ethanolic extracts of mulberry leaves from the Sakon Nakhon cultivar showed the highest total phenolic content of 49.68 mg GAE/g extract and antioxidant activities of 4.38 mg GAE/g extract, 4.53 mg TEAC/g extract, and 92.78 mg FeSO4/g extract using 2,2 diphenyl-1-picrylhydrazyl (DPPH), 2,20-azinobis-(3-ethylbenzothiazolin-6-sulfonic acid) (ABTS), and ferric reducing antioxidant power (FRAP) assays, respectively. The resveratrol and oxyresveratrol compounds in mulberry leaves were also investigated by high-performance liquid chromatography (HPLC). The mulberry leaf extracts from the Sakon Nakhon and Buriram cultivars showed oxyresveratrol contents of 1.20 ± 0.04 mg/g extract and 0.39 ± 0.02 mg/g extract, respectively, whereas resveratrol was not detected. It was also found that the potent anti-inflammatory properties of mulberry leaf extracts and its compounds, resveratrol and oxyresveratrol, suppressed the LPS-stimulated inflammatory responses in RAW 264.7 macrophage cells by significantly reducing nitric oxide production in a concentration-dependent manner. These compounds further inhibited interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) production and suppressed the mRNA and protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in LPS-stimulated RAW 264.7 macrophage cells. Therefore, it is established that mulberry leaf extract and its bioactive compounds contribute to its anti-inflammatory activity.
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Affiliation(s)
- Sureeporn Suriyaprom
- Department of Biology, Faculty of Science, Chiang Mai University, Chiang Mai 50200, Thailand
- Graduate School, Chiang Mai University, Chiang Mai 50200, Thailand
- INRAE, UCA, UMR0454 MEDIS, 63000 Clermont-Ferrand, France
| | | | - Varachaya Intachaisri
- Department of Biology, Faculty of Science, Chiang Mai University, Chiang Mai 50200, Thailand
- Graduate School, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Thida Kaewkod
- Department of Biology, Faculty of Science, Chiang Mai University, Chiang Mai 50200, Thailand
- Natural Extracts and Innovative Products for Alternative Healthcare Research Group, Faculty of Science, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Jeeraporn Pekkoh
- Department of Biology, Faculty of Science, Chiang Mai University, Chiang Mai 50200, Thailand
| | | | - Yingmanee Tragoolpua
- Department of Biology, Faculty of Science, Chiang Mai University, Chiang Mai 50200, Thailand
- Natural Extracts and Innovative Products for Alternative Healthcare Research Group, Faculty of Science, Chiang Mai University, Chiang Mai 50200, Thailand
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15
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Vašková J, Klepcová Z, Špaková I, Urdzík P, Štofilová J, Bertková I, Kľoc M, Rabajdová M. The Importance of Natural Antioxidants in Female Reproduction. Antioxidants (Basel) 2023; 12:antiox12040907. [PMID: 37107282 PMCID: PMC10135990 DOI: 10.3390/antiox12040907] [Citation(s) in RCA: 23] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2023] [Revised: 04/03/2023] [Accepted: 04/08/2023] [Indexed: 04/29/2023] Open
Abstract
Oxidative stress (OS) has an important role in female reproduction, whether it is ovulation, endometrium decidualization, menstruation, oocyte fertilization, or development andimplantation of an embryo in the uterus. The menstrual cycle is regulated by the physiological concentration of reactive forms of oxygen and nitrogen as redox signal molecules, which trigger and regulate the length of individual phases of the menstrual cycle. It has been suggested that the decline in female fertility is modulated by pathological OS. The pathological excess of OS compared to antioxidants triggers many disorders of female reproduction which could lead to gynecological diseases and to infertility. Therefore, antioxidants are crucial for proper female reproductive function. They play a part in the metabolism of oocytes; in endometrium maturation via the activation of antioxidant signaling pathways Nrf2 and NF-κB; and in the hormonal regulation of vascular action. Antioxidants can directly scavenge radicals and act as a cofactor of highly valuable enzymes of cell differentiation and development, or enhance the activity of antioxidant enzymes. Compensation for low levels of antioxidants through their supplementation can improve fertility. This review considers the role of selected vitamins, flavonoids, peptides, and trace elements with antioxidant effects in female reproduction mechanisms.
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Affiliation(s)
- Janka Vašková
- Department of Medical and Clinical Biochemistry, Faculty of Medicine, Pavol Jozef Šafárik University in Košice, Trieda SNP 1, 040 11 Košice, Slovakia
| | - Zuzana Klepcová
- Department of Medical and Clinical Biochemistry, Faculty of Medicine, Pavol Jozef Šafárik University in Košice, Trieda SNP 1, 040 11 Košice, Slovakia
- Medirex, a.s., Holubyho 35, 902 01 Pezinok, Slovakia
| | - Ivana Špaková
- Department of Medical and Clinical Biochemistry, Faculty of Medicine, Pavol Jozef Šafárik University in Košice, Trieda SNP 1, 040 11 Košice, Slovakia
| | - Peter Urdzík
- Department of Gynaecology and Obstetrics, Faculty of Medicine, Pavol Jozef Šafárik University in Košice, Trieda SNP 1, 040 11 Košice, Slovakia
| | - Jana Štofilová
- Center for Clinical and Preclinical Research MEDIPARK, Department of Experimental Medicine, Faculty of Medicine, Pavol Jozef Šafárik University in Košice, Trieda SNP 1, 040 11 Košice, Slovakia
| | - Izabela Bertková
- Center for Clinical and Preclinical Research MEDIPARK, Department of Experimental Medicine, Faculty of Medicine, Pavol Jozef Šafárik University in Košice, Trieda SNP 1, 040 11 Košice, Slovakia
| | - Marek Kľoc
- Medirex, a.s., Holubyho 35, 902 01 Pezinok, Slovakia
| | - Miroslava Rabajdová
- Department of Medical and Clinical Biochemistry, Faculty of Medicine, Pavol Jozef Šafárik University in Košice, Trieda SNP 1, 040 11 Košice, Slovakia
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Synthesis and Characterization of a Novel Resveratrol Xylobioside Obtained Using a Mutagenic Variant of a GH10 Endoxylanase. Antioxidants (Basel) 2022; 12:antiox12010085. [PMID: 36670947 PMCID: PMC9855058 DOI: 10.3390/antiox12010085] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Revised: 12/20/2022] [Accepted: 12/27/2022] [Indexed: 12/31/2022] Open
Abstract
Resveratrol is a natural polyphenol with antioxidant activity and numerous health benefits. However, in vivo application of this compound is still a challenge due to its poor aqueous solubility and rapid metabolism, which leads to an extremely low bioavailability in the target tissues. In this work, rXynSOS-E236G glycosynthase, designed from a GH10 endoxylanase of the fungus Talaromyces amestolkiae, was used to glycosylate resveratrol by using xylobiosyl-fluoride as a sugar donor. The major product from this reaction was identified by NMR as 3-O-ꞵ-d-xylobiosyl resveratrol, together with other glycosides produced in a lower amount as 4'-O-ꞵ-d-xylobiosyl resveratrol and 3-O-ꞵ-d-xylotetraosyl resveratrol. The application of response surface methodology made it possible to optimize the reaction, producing 35% of 3-O-ꞵ-d-xylobiosyl resveratrol. Since other minor glycosides are obtained in addition to this compound, the transformation of the phenolic substrate amounted to 70%. Xylobiosylation decreased the antioxidant capacity of resveratrol by 2.21-fold, but, in return, produced a staggering 4,866-fold improvement in solubility, facilitating the delivery of large amounts of the molecule and its transit to the colon. A preliminary study has also shown that the colonic microbiota is capable of releasing resveratrol from 3-O-ꞵ-d-xylobiosyl resveratrol. These results support the potential of mutagenic variants of glycosyl hydrolases to synthesize highly soluble resveratrol glycosides, which could, in turn, improve the bioavailability and bioactive properties of this polyphenol.
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Resveratrol: Its Path from Isolation to Therapeutic Action in Eye Diseases. Antioxidants (Basel) 2022; 11:antiox11122447. [PMID: 36552655 PMCID: PMC9774148 DOI: 10.3390/antiox11122447] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2022] [Revised: 12/05/2022] [Accepted: 12/07/2022] [Indexed: 12/14/2022] Open
Abstract
Due to the confirmed therapeutic potential of resveratrol (Rv) for eye diseases, namely its powerful anti-angiogenic and antioxidant effects, this molecule must be studied more deeply. Nowadays, the pharmaceutic and pharmacokinetic available studies offer a troubling picture because of its low stability and bioavailability. To overcome this problem, researchers started to design and create different delivery systems that could improve the delivery amount of Rv. Therefore, this review aims to shed light on the proper and efficient techniques to isolate, purify and quantify the Rv molecule, and how this therapeutic molecule can be a part of a delivery system. The Rv great impact on aspects regarding its stability, bioavailability and absorption are also debated here, based on the existent literature on in vitro and in vivo human and animal studies. Moreover, after its absorption the Rv influence at the molecular level in ocular pathologies is described. In addition, the present review summarizes the available literature about Rv, hoping that Rv will gain more attention to investigate its unexplored side.
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Molaaghaee‐Rouzbahani S, Asri N, Jahani‐Sherafat S, Amani D, Masotti A, Baghaei K, Yadegar A, Mirjalali H, Rostami‐Nejad M. The modulation of macrophage subsets in celiac disease pathogenesis. Immun Inflamm Dis 2022; 10:e741. [PMID: 36444633 PMCID: PMC9667199 DOI: 10.1002/iid3.741] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2022] [Revised: 10/12/2022] [Accepted: 11/06/2022] [Indexed: 11/18/2022] Open
Abstract
BACKGROUND So far, limited studies have focused on the role of Macrophages (MQs) in the development or progression of celiac disease (CD). Researchers believe that increasing knowledge about the function of MQs in inflammatory disorders plays a critical role in finding a new treatment for these kinds of diseases. MAIN BODY CD is a permanent autoimmune intestinal disorder triggered by gluten exposure in predisposed individuals. This disorder happens due to the loss of intestinal epithelial barrier integrity characterized by dysregulated innate and adaptive immune responses. MQs are known as key players of the innate immune system that link innate and adaptive immunity. MQs of human intestinal lamina propria participate in maintaining tissue homeostasis, and also intestinal inflammation development. Previous studies suggested that gliadin triggers a proinflammatory phenotype (M1 MQ) in human primary MQs. Moreover, M2-related immunosuppressive mediators are also present in CD. In fact, CD patients present an impaired transition from pro-inflammatory to anti-inflammatory responses due to inappropriate responses to gliadin peptides. CONCLUSION The M1/M2 MQs polarization balancing regulators can be considered novel therapeutic targets for celiac disease.
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Affiliation(s)
| | - Nastaran Asri
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver DiseasesShahid Beheshti University of Medical SciencesTehranIran
| | - Somayeh Jahani‐Sherafat
- Laser Application in Medical Sciences Research CenterShahid Beheshti University of Medical SciencesTehranIran
| | - Davar Amani
- Department of Immunology, School of MedicineShahid Beheshti University of Medical SciencesTehranIran
| | - Andrea Masotti
- Bambino Gesù Children's Hospital‐IRCCSResearch LaboratoriesRomeItaly
| | - Kaveh Baghaei
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver DiseasesShahid Beheshti University of Medical SciencesTehranIran
| | - Abbas Yadegar
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver DiseasesShahid Beheshti University of Medical SciencesTehranIran
| | - Hamed Mirjalali
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver DiseasesShahid Beheshti University of Medical SciencesTehranIran
| | - Mohammad Rostami‐Nejad
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver DiseasesShahid Beheshti University of Medical SciencesTehranIran
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Puri V, Kanojia N, Sharma A, Huanbutta K, Dheer D, Sangnim T. Natural product-based pharmacological studies for neurological disorders. Front Pharmacol 2022; 13:1011740. [PMID: 36419628 PMCID: PMC9676372 DOI: 10.3389/fphar.2022.1011740] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Accepted: 10/18/2022] [Indexed: 11/07/2023] Open
Abstract
Central nervous system (CNS) disorders and diseases are expected to rise sharply in the coming years, partly because of the world's aging population. Medicines for the treatment of the CNS have not been successfully made. Inadequate knowledge about the brain, pharmacokinetic and dynamic errors in preclinical studies, challenges with clinical trial design, complexity and variety of human brain illnesses, and variations in species are some potential scenarios. Neurodegenerative diseases (NDDs) are multifaceted and lack identifiable etiological components, and the drugs developed to treat them did not meet the requirements of those who anticipated treatments. Therefore, there is a great demand for safe and effective natural therapeutic adjuvants. For the treatment of NDDs and other memory-related problems, many herbal and natural items have been used in the Ayurvedic medical system. Anxiety, depression, Parkinson's, and Alzheimer's diseases (AD), as well as a plethora of other neuropsychiatric disorders, may benefit from the use of plant and food-derived chemicals that have antidepressant or antiepileptic properties. We have summarized the present level of knowledge about natural products based on topological evidence, bioinformatics analysis, and translational research in this review. We have also highlighted some clinical research or investigation that will help us select natural products for the treatment of neurological conditions. In the present review, we have explored the potential efficacy of phytoconstituents against neurological diseases. Various evidence-based studies and extensive recent investigations have been included, which will help pharmacologists reduce the progression of neuronal disease.
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Affiliation(s)
- Vivek Puri
- Chitkara School of Pharmacy, Chitkara University, Baddi, Himachal Pradesh, India
| | - Neha Kanojia
- Chitkara School of Pharmacy, Chitkara University, Baddi, Himachal Pradesh, India
| | - Ameya Sharma
- Chitkara School of Pharmacy, Chitkara University, Baddi, Himachal Pradesh, India
| | - Kampanart Huanbutta
- School of Pharmacy, Eastern Asia University, Rangsit, Pathum Thani, Thailand
| | - Divya Dheer
- Chitkara School of Pharmacy, Chitkara University, Baddi, Himachal Pradesh, India
| | - Tanikan Sangnim
- Faculty of Pharmaceutical Sciences, Burapha University, Muang, Chon Buri, Thailand
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NAUREEN ZAKIRA, MEDORI MARIACHIARA, DHULI KRISTJANA, DONATO KEVIN, CONNELLY STEPHENTHADDEUS, BELLINATO FRANCESCO, GISONDI PAOLO, BERTELLI MATTEO. Polyphenols and Lactobacillus reuteri in oral health. JOURNAL OF PREVENTIVE MEDICINE AND HYGIENE 2022; 63:E246-E254. [PMID: 36479495 PMCID: PMC9710395 DOI: 10.15167/2421-4248/jpmh2022.63.2s3.2767] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Oral health is one of the necessary preludes to the overall quality of life. Several medical procedures and therapies are available to treat oral diseases in general and periodontal diseases in particular, yet caries, periodontitis, oral cancer, and oral infections remain a global concern. Natural molecules, with their anti-oxidant, anti-inflammatory, and anti-microbic properties, are one of the main sources of oral health and dental health care, and should be supplemented to exploit their beneficial effects. A possible way to improve the intake of these molecules is adhering to a diet that is rich in fruits, vegetables, and probiotics, which has many beneficial properties and can improve overall health and wellbeing. The Mediterranean diet, in particular, provides several beneficial natural molecules, mainly because of the precious nutrients contained in its typical ingredients, mainly plant-based (olives, wine, citrus fruits, and many more). Its beneficial effects on several diseases and in increasing the overall wellbeing of the population are currently being studied by physicians. Among its nutrients, polyphenols (including, among other molecules, lignans, tannins, and flavonoids) seem to be of outmost importance: several studies showed their anticariogenic properties, as well as their effects in decreasing the incidence of non-communicable diseases. Therefore, plant-derived molecules - such as polyphenols - and probiotics - such as Lactobacillus reuteri - have shown a significant potential in treating and curing oral diseases, either alone or in combination, owing to their antioxidant and antimicrobial properties, respectively.
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Affiliation(s)
| | | | - KRISTJANA DHULI
- MAGI’S LAB, Rovereto (TN), Italy
- Correspondence: Kristjana Dhuli, MAGI’S LAB, Rovereto (TN), 38068, Italy; E-mail:
| | | | | | - FRANCESCO BELLINATO
- Section of Dermatology and Venereology, Department of Medicine, University of Verona, Verona, Italy
| | - PAOLO GISONDI
- Section of Dermatology and Venereology, Department of Medicine, University of Verona, Verona, Italy
| | - MATTEO BERTELLI
- MAGI Euregio, Bolzano, Italy
- MAGI’S LAB, Rovereto (TN), Italy
- MAGISNAT, Peachtree Corners (GA), USA
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Hafezi H, Vahdati A, Forouzanfar M, Shariatic M. Ameliorate effects of resveratrol and l-carnitine on the testicular tissue and sex hormones level in busulfan induced azoospermia rats. Theriogenology 2022; 191:47-53. [PMID: 35964476 DOI: 10.1016/j.theriogenology.2022.06.006] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2021] [Revised: 04/04/2022] [Accepted: 06/06/2022] [Indexed: 12/01/2022]
Abstract
Busulfan (Bus), is an alkylating agent widely used in chemotherapy which has been proven to possess toxic side effects on testicles. This study was carried out to compare the probable treatment effects of resveratrol (Res) or/and l-carnitine (Lca), as strong antioxidants, on the testicular tissue as well as on the level of sex hormones in busulfan-induced azoospermic rat models. A total of 78 adult male rats, were divided into six different experimental groups including: 1) Control; 2) Lca + Res; 3) BUS; 4) Bus + Lca; 5) BUS + Res and 6) Bus + Lca + Res. Busulfan was intraperitoneally administered in a single dose (10 mg/kg b.w), while resveratrol (20 mg/kg b.w/day) and l-carnitine (200 mg/kg b.w/day) were orally administered by gavage during 48 consecutive days to the rats. At the end of the experiment in all groups the level of LH, FSH, and testosterone were biochemically analyzed by ELISA and the testicular tissue evaluated histologically using stereological technique. Results showed that Lca or/and Res, increased the body and testis weight, the volume of the testis, interstitial tissue, germinal epithelium, and seminiferous tubule, the number of the different cells of germinal epithelium and the level of testosterone. On the other hand, Lca, Res and their combination decreased the concentration of LH and FSH compared to the group treated with Bus. In conclusion, these results suggested that l-carnitine or/and resveratrol treatment significantly attenuated busulfan -induced changes of the rat reproductive system led to the recovery of both testis and sperm parameters. However, co-administration of L-ca and Res was more effective than their individual treatment. This combination may alleviate the side effects of alkylating drugs, such as busulfan and may be beneficial for spermatogenesis.
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Affiliation(s)
- Hananeh Hafezi
- Department of Biology, Fars Science and Research Branch, Islamic Azad University, Fars, Iran; Department of Biology, Shiraz Branch, Islamic Azad University, Shiraz, Iran
| | - Akbar Vahdati
- Department of Biology, Shiraz Branch, Islamic Azad University, Shiraz, Iran
| | - Mohsen Forouzanfar
- Department of Biology, Marvdasht Branch, Islamic Azad University, Marvdasht, Iran.
| | - Mehrdad Shariatic
- Department of Biology, Kazerun Branch, Islamic Azad University, Kazerun, Iran
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22
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Santhiravel S, Bekhit AEDA, Mendis E, Jacobs JL, Dunshea FR, Rajapakse N, Ponnampalam EN. The Impact of Plant Phytochemicals on the Gut Microbiota of Humans for a Balanced Life. Int J Mol Sci 2022; 23:ijms23158124. [PMID: 35897699 PMCID: PMC9332059 DOI: 10.3390/ijms23158124] [Citation(s) in RCA: 55] [Impact Index Per Article: 18.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2022] [Revised: 07/19/2022] [Accepted: 07/21/2022] [Indexed: 02/01/2023] Open
Abstract
The gastrointestinal tract of humans is a complex microbial ecosystem known as gut microbiota. The microbiota is involved in several critical physiological processes such as digestion, absorption, and related physiological functions and plays a crucial role in determining the host’s health. The habitual consumption of specific dietary components can impact beyond their nutritional benefits, altering gut microbiota diversity and function and could manipulate health. Phytochemicals are non-nutrient biologically active plant components that can modify the composition of gut microflora through selective stimulation of proliferation or inhibition of certain microbial communities in the intestine. Plants secrete these components, and they accumulate in the cell wall and cell sap compartments (body) for their development and survival. These compounds have low bioavailability and long time-retention in the intestine due to their poor absorption, resulting in beneficial impacts on gut microbiota population. Feeding diets containing phytochemicals to humans and animals may offer a path to improve the gut microbiome resulting in improved performance and/or health and wellbeing. This review discusses the effects of phytochemicals on the modulation of the gut microbiota environment and the resultant benefits to humans; however, the effect of phytochemicals on the gut microbiota of animals is also covered, in brief.
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Affiliation(s)
- Sarusha Santhiravel
- Postgraduate Institute of Agriculture, University of Peradeniya, Peradeniya 20400, Sri Lanka
- Department of Biochemistry, Memorial University of Newfoundland, St. John's, NL A1C 5S7, Canada
| | - Alaa El-Din A Bekhit
- Department of Food Sciences, University of Otago, P.O. Box 56, Dunedin 9054, New Zealand
| | - Eresha Mendis
- Department of Food Science and Technology, Faculty of Agriculture, University of Peradeniya, Peradeniya 20400, Sri Lanka
| | - Joe L Jacobs
- Animal Production Sciences, Agriculture Victoria Research, Department of Jobs, Precincts and Regions, Ellinbank, VIC 3821, Australia
- Centre for Agricultural Innovation, School of Agriculture and Food, Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, Parkville, VIC 3010, Australia
| | - Frank R Dunshea
- School of Agriculture and Food, Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, Parkville, VIC 3010, Australia
- Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK
| | - Niranjan Rajapakse
- Department of Food Science and Technology, Faculty of Agriculture, University of Peradeniya, Peradeniya 20400, Sri Lanka
| | - Eric N Ponnampalam
- Animal Production Sciences, Agriculture Victoria Research, Department of Jobs, Precincts and Regions, Bundoora, VIC 3083, Australia
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23
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Civelek M, Bilotta S, Lorentz A. Resveratrol Attenuates Mast Cell Mediated Allergic Reactions: Potential for Use as a Nutraceutical in Allergic Diseases? Mol Nutr Food Res 2022; 66:e2200170. [PMID: 35598149 DOI: 10.1002/mnfr.202200170] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2022] [Revised: 04/29/2022] [Indexed: 01/06/2023]
Abstract
Allergic diseases are one of the most common health disorders affecting about 30% of the world population. Mast cells (MCs) are key effector cells of allergic reactions by releasing proinflammatory mediators including histamine, lipid mediators, and cytokines/chemokines. Natural substances like secondary plant substances such as resveratrol (RESV), which can contribute to prevention and treatment of diseases, are becoming increasingly interesting for use as nutraceuticals. In this review, the anti-inflammatory effects of RESV on MC-mediated allergic reactions in vitro and in vivo models are summarized. The studies indicate that RESV inhibits MC degranulation, synthesis of arachidonic acid metabolites, expression of cytokines and chemokines as well as activation of signal molecules involved in proinflammatory mechanisms. Also, beneficial impacts by this polyphenol are reported in randomized controlled trials with allergic rhinitis patients. Although it cannot yet be concluded that RESV can be used successfully in allergy patients in general, there are many results that indicate a possible role for RESV for use as an anti-inflammatory nutraceutical. However, strategies to favorably influence the poor bioavailability of RESV would be helpful.
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Affiliation(s)
- Mehtap Civelek
- Institute of Nutritional Medicine, University of Hohenheim, 70599, Stuttgart, Germany
| | - Sabrina Bilotta
- Institute of Nutritional Medicine, University of Hohenheim, 70599, Stuttgart, Germany
| | - Axel Lorentz
- Institute of Nutritional Medicine, University of Hohenheim, 70599, Stuttgart, Germany
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24
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Yadav A, Yadav SS, Singh S, Dabur R. Natural products: Potential therapeutic agents to prevent skeletal muscle atrophy. Eur J Pharmacol 2022; 925:174995. [PMID: 35523319 DOI: 10.1016/j.ejphar.2022.174995] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2021] [Revised: 04/19/2022] [Accepted: 04/28/2022] [Indexed: 12/16/2022]
Abstract
The skeletal muscle (SkM) is the largest organ, which plays a vital role in controlling musculature, locomotion, body heat regulation, physical strength, and metabolism of the body. A sedentary lifestyle, aging, cachexia, denervation, immobilization, etc. Can lead to an imbalance between protein synthesis and degradation, which is further responsible for SkM atrophy (SmA). To date, the understanding of the mechanism of SkM mass loss is limited which also restricted the number of drugs to treat SmA. Thus, there is an urgent need to develop novel approaches to regulate muscle homeostasis. Presently, some natural products attained immense attraction to regulate SkM homeostasis. The natural products, i.e., polyphenols (resveratrol, curcumin), terpenoids (ursolic acid, tanshinone IIA, celastrol), flavonoids, alkaloids (tomatidine, magnoflorine), vitamin D, etc. exhibit strong potential against SmA. Some of these natural products have been reported to have equivalent potential to standard treatments to prevent body lean mass loss. Indeed, owing to the large complexity, diversity, and slow absorption rate of bioactive compounds made their usage quite challenging. Moreover, the use of natural products is controversial due to their partially known or elusive mechanism of action. Therefore, the present review summarizes various experimental and clinical evidence of some important bioactive compounds that shall help in the development of novel strategies to counteract SmA elicited by various causes.
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Affiliation(s)
- Aarti Yadav
- Clinical Biochemistry Laboratory, Department of Biochemistry, Maharshi Dayanand University, Rohtak, 124001, Haryana, India
| | - Surender Singh Yadav
- Department of Botany, Maharshi Dayanand University, Rohtak, 124001, Haryana, India
| | - Sandeep Singh
- Department of Biochemistry, Maharshi Dayanand University, Rohtak, 124001, Haryana, India
| | - Rajesh Dabur
- Clinical Biochemistry Laboratory, Department of Biochemistry, Maharshi Dayanand University, Rohtak, 124001, Haryana, India.
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25
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Persano F, Gigli G, Leporatti S. Natural Compounds as Promising Adjuvant Agents in The Treatment of Gliomas. Int J Mol Sci 2022; 23:3360. [PMID: 35328780 PMCID: PMC8955269 DOI: 10.3390/ijms23063360] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Revised: 03/17/2022] [Accepted: 03/18/2022] [Indexed: 02/07/2023] Open
Abstract
In humans, glioblastoma is the most prevalent primary malignant brain tumor. Usually, glioblastoma has specific characteristics, such as aggressive cell proliferation and rapid invasion of surrounding brain tissue, leading to a poor patient prognosis. The current therapy-which provides a multidisciplinary approach with surgery followed by radiotherapy and chemotherapy with temozolomide-is not very efficient since it faces clinical challenges such as tumor heterogeneity, invasiveness, and chemoresistance. In this respect, natural substances in the diet, integral components in the lifestyle medicine approach, can be seen as potential chemotherapeutics. There are several epidemiological studies that have shown the chemopreventive role of natural dietary compounds in cancer progression and development. These heterogeneous compounds can produce anti-glioblastoma effects through upregulation of apoptosis and autophagy; allowing the promotion of cell cycle arrest; interfering with tumor metabolism; and permitting proliferation, neuroinflammation, chemoresistance, angiogenesis, and metastasis inhibition. Although these beneficial effects are promising, the efficacy of natural compounds in glioblastoma is limited due to their bioavailability and blood-brain barrier permeability. Thereby, further clinical trials are necessary to confirm the in vitro and in vivo anticancer properties of natural compounds. In this article, we overview the role of several natural substances in the treatment of glioblastoma by considering the challenges to be overcome and future prospects.
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Affiliation(s)
- Francesca Persano
- Department of Mathematics and Physics, University of Salento, Via Per Arnesano, 73100 Lecce, Italy;
- CNR Nanotec-Istituto di Nanotecnologia, Via Monteroni, 73100 Lecce, Italy
| | - Giuseppe Gigli
- Department of Mathematics and Physics, University of Salento, Via Per Arnesano, 73100 Lecce, Italy;
- CNR Nanotec-Istituto di Nanotecnologia, Via Monteroni, 73100 Lecce, Italy
| | - Stefano Leporatti
- CNR Nanotec-Istituto di Nanotecnologia, Via Monteroni, 73100 Lecce, Italy
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26
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De Luca A, Bellavia D, Raimondi L, Carina V, Costa V, Fini M, Giavaresi G. Multiple Effects of Resveratrol on Osteosarcoma Cell Lines. Pharmaceuticals (Basel) 2022; 15:342. [PMID: 35337142 PMCID: PMC8956103 DOI: 10.3390/ph15030342] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Revised: 03/08/2022] [Accepted: 03/09/2022] [Indexed: 02/04/2023] Open
Abstract
Osteosarcoma (OS) is the most common primary bone sarcoma affecting the life of pediatric patients. The clinical treatment faces numerous difficulties, including the adverse effects of chemotherapies, chemoresistance, and recurrences. In this study, the effects of resveratrol (RSV), a natural polyphenol, on OS cell lines were investigated to evaluate its action as an adjuvant therapy to the current chemotherapy regimens. RSV exhibited multiple tumor-suppressing activities on OS cell lines, inducing a series of critical events. We found (1) a cell growth inhibition due to an increase in cell distress, which was, in part, due to the involvement of the AKT and caspase-3 pathways, (2) an increase in cellular differentiation due to major gene expression levels of the osteoblastic differentiation genes, (3) an inhibition of IL-6 secretion due to an epigenetic effect on the IL-6 promoter, and (4) an inhibition of OS cells migration related to the decrease in IL-8 secretion levels due to an epigenetic effect on its promoter. Finally, the cotreatment of RSV with doxorubicin and cisplatin increased their cytotoxic effect on OS cells. Although further investigations are mandatory, it seems RSV might be a promising therapeutic adjuvant agent for OS cell treatment, exerting an antitumor effect when combined with chemotherapy.
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Affiliation(s)
- Angela De Luca
- IRCCS Istituto Ortopedico Rizzoli, CS Surgical Sciences and Technologies—SS Omics Science Platform for Personalized Orthopedics, 40136 Bologna, Italy; (D.B.); (L.R.); (V.C.); (V.C.); (M.F.); (G.G.)
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27
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Ibrahim KA, Abdelgaid HA, Eleyan M, Mohamed RA, Gamil NM. Resveratrol alleviates cardiac apoptosis following exposure to fenitrothion by modulating the sirtuin1/c-Jun N-terminal kinases/p53 pathway through pro-oxidant and inflammatory response improvements: In vivo and in silico studies. Life Sci 2022; 290:120265. [PMID: 34968465 DOI: 10.1016/j.lfs.2021.120265] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2021] [Revised: 12/18/2021] [Accepted: 12/19/2021] [Indexed: 02/07/2023]
Abstract
Fenitrothion (FNT), a commonly used organophosphate, can cause oxidative damage and apoptosis on various organs. However, the underlying mechanisms for FNT-induced cardiotoxicity did not formally report. Here, we have evaluated the possible ameliorative roles of resveratrol (RSV) against FNT-induced cardiac apoptosis in male rats through the sirtuin1 (SIRT1)/c-Jun N-terminal kinase (c-JNK)/p53 pathway concerning pro-oxidant and inflammatory cytokines. Forty-eight male rats were equally grouped into control, RSV (20 mg/kg), 5-FNT (5 mg/kg), 10-FNT (10 mg/kg), 20-FNT (20 mg/kg), 5-FNT-RSV, 10-FNT-RSV, and 20-FNT-RSV where all doses administrated by gavage for four weeks. The present findings demonstrated that RSV markedly diminished the level of hyperlipidemia and elevation in lactate dehydrogenase (LDH), total creatine kinase (CK-T), and troponin T (TnT) levels following FNT intoxication. Furthermore, RSV significantly reduced FNT-induced cardiac oxidative injury by reducing malondialdehyde (MDA) level and improving the levels of glutathione (GSH), glutathione reductase (GR), superoxide dismutase (SOD), catalase (CAT), and acetylcholinesterase (AchE). Also, the levels of interleukin-1β (IL1β,), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were significantly attenuated in the co-treated groups. Moreover, RSV alleviated the histopathological changes promoted by FNT and repaired the transcript levels of SIRT1, c-JNK, and caspase-9/3 along with p53 immunoreactivity. In silico study revealed that the free binding energies of RSV complexes with protein and DNA sequences of SIRT1 were lower than docked complexes of FNT. Therefore, RSV reserved myocardial injury-induced apoptosis following exposure to FNT by modulating the SIRT1/c-JNK/p53 pathway through cellular redox status and inflammatory response improvements.
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Affiliation(s)
- Khairy A Ibrahim
- Mammalian Toxicology Department, Central Agricultural Pesticides Laboratory, Agricultural Research Center, Dokki, Giza 12618, Egypt.
| | - Hala A Abdelgaid
- Biochemistry Department, National Hepatology and Tropical Medicine Research Institute, Cairo 11796, Egypt
| | - Mohammed Eleyan
- Department of Laboratory Medical Sciences, Alaqsa University, Gaza, 4051, Palestine
| | - Rania A Mohamed
- Mammalian Toxicology Department, Central Agricultural Pesticides Laboratory, Agricultural Research Center, Dokki, Giza 12618, Egypt
| | - Noha M Gamil
- Department of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences and Drug Manufacturing, Misr University for Science and Technology, 6(th) of October City, Egypt
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28
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Bilotta S, Arbogast J, Schart N, Frei M, Lorentz A. Resveratrol Treatment Prevents Increase of Mast Cells in Both Murine OVA Enteritis and IL-10 -/- Colitis. Int J Mol Sci 2022; 23:ijms23031213. [PMID: 35163137 PMCID: PMC8836010 DOI: 10.3390/ijms23031213] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2021] [Revised: 01/11/2022] [Accepted: 01/19/2022] [Indexed: 02/07/2023] Open
Abstract
Mast cells are involved in allergic and other inflammatory diseases. The polyphenol resveratrol is known for its anti-inflammatory properties and may be used as nutraceutical in mast cell associated diseases. We analyzed the effect of resveratrol on mast cells in vivo in ovalbumin-induced allergic enteritis as well as experimental colitis in IL-10−/− mice which received resveratrol via drinking water. Treatment with resveratrol prevented the increase in mast cells in both allergic enteritis and chronic colitis in duodenum as well as in colon. Further, it delayed the onset of diseases symptoms and ameliorated diseases associated parameters such as tissue damage as well as inflammatory cell infiltration in affected colon sections. In addition to the findings in vivo, resveratrol inhibited IgE-dependent degranulation and expression of pro-inflammatory cytokines such as TNF-α in IgE/DNP-activated as well as in LPS-activated bone marrow-derived mast cells. These results indicate that resveratrol may be considered as an anti-allergic and anti-inflammatory plant-derived component for the prevention or treatment of mast cell-associated disorders of the gastrointestinal tract.
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29
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Rai SN, Tiwari N, Singh P, Mishra D, Singh AK, Hooshmandi E, Vamanu E, Singh MP. Therapeutic Potential of Vital Transcription Factors in Alzheimer's and Parkinson's Disease With Particular Emphasis on Transcription Factor EB Mediated Autophagy. Front Neurosci 2022; 15:777347. [PMID: 34970114 PMCID: PMC8712758 DOI: 10.3389/fnins.2021.777347] [Citation(s) in RCA: 64] [Impact Index Per Article: 21.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2021] [Accepted: 11/22/2021] [Indexed: 12/12/2022] Open
Abstract
Autophagy is an important cellular self-digestion and recycling pathway that helps in maintaining cellular homeostasis. Dysregulation at various steps of the autophagic and endolysosomal pathway has been reported in several neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington disease (HD) and is cited as a critically important feature for central nervous system (CNS) proteostasis. Recently, another molecular target, namely transcription factor EB (TFEB) has been explored globally to treat neurodegenerative disorders. This TFEB, is a key regulator of autophagy and lysosomal biogenesis pathway. Multiple research studies suggested therapeutic potential by targeting TFEB to treat human diseases involving autophagy-lysosomal dysfunction, especially neurodegenerative disorders. A common observation involving all neurodegenerative disorders is their poor efficacy in clearing and recycle toxic aggregated proteins and damaged cellular organelles due to impairment in the autophagy pathway. This dysfunction in autophagy characterized by the accumulation of toxic protein aggregates leads to a progressive loss in structural integrity/functionality of neurons and may even result in neuronal death. In recent years TFEB, a key regulator of autophagy and lysosomal biogenesis, has received considerable attention. It has emerged as a potential therapeutic target in numerous neurodegenerative disorders like AD and PD. In various neurobiology studies involving animal models, TFEB has been found to ameliorate neurotoxicity and rescue neurodegeneration. Since TFEB is a master transcriptional regulator of autophagy and lysosomal biogenesis pathway and plays a crucial role in defining autophagy activation. Studies have been done to understand the mechanisms for TFEB dysfunction, which may yield insights into how TFEB might be targeted and used for the therapeutic strategy to develop a treatment process with extensive application to neurodegenerative disorders. In this review, we explore the role of different transcription factor-based targeted therapy by some natural compounds for AD and PD with special emphasis on TFEB.
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Affiliation(s)
| | - Neeraj Tiwari
- Faculty of Biosciences, Institute of Biosciences and Technology, Shri Ramswaroop Memorial University, Barabanki, India
| | - Payal Singh
- Department of Zoology, Mahila Mahavidyalaya, Banaras Hindu University, Varanasi, India
| | - Divya Mishra
- Centre of Bioinformatics, University of Allahabad, Prayagraj, India
| | - Anurag Kumar Singh
- Centre of Experimental Medicine and Surgery, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India
| | - Etrat Hooshmandi
- Clinical Neurology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Emanuel Vamanu
- Faculty of Biotechnology, University of Agronomic Science and Veterinary Medicine, Bucharest, Romania
| | - Mohan P Singh
- Centre of Biotechnology, University of Allahabad, Prayagraj, India
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30
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de Keijzer MJ, de Klerk DJ, de Haan LR, van Kooten RT, Franchi LP, Dias LM, Kleijn TG, van Doorn DJ, Heger M. Inhibition of the HIF-1 Survival Pathway as a Strategy to Augment Photodynamic Therapy Efficacy. Methods Mol Biol 2022; 2451:285-403. [PMID: 35505024 DOI: 10.1007/978-1-0716-2099-1_19] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/14/2023]
Abstract
Photodynamic therapy (PDT) is a non-to-minimally invasive treatment modality that utilizes photoactivatable drugs called photosensitizers to disrupt tumors with locally photoproduced reactive oxygen species (ROS). Photosensitizer activation by light results in hyperoxidative stress and subsequent tumor cell death, vascular shutdown and hypoxia, and an antitumor immune response. However, sublethally afflicted tumor cells initiate several survival mechanisms that account for decreased PDT efficacy. The hypoxia inducible factor 1 (HIF-1) pathway is one of the most effective cell survival pathways that contributes to cell recovery from PDT-induced damage. Several hundred target genes of the HIF-1 heterodimeric complex collectively mediate processes that are involved in tumor cell survival directly and indirectly (e.g., vascularization, glucose metabolism, proliferation, and metastasis). The broad spectrum of biological ramifications culminating from the activation of HIF-1 target genes reflects the importance of HIF-1 in the context of therapeutic recalcitrance. This chapter elaborates on the involvement of HIF-1 in cancer biology, the hypoxic response mechanisms, and the role of HIF-1 in PDT. An overview of inhibitors that either directly or indirectly impede HIF-1-mediated survival signaling is provided. The inhibitors may be used as pharmacological adjuvants in combination with PDT to augment therapeutic efficacy.
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Affiliation(s)
- Mark J de Keijzer
- Jiaxing Key Laboratory for Photonanomedicine and Experimental Therapeutics, Department of Pharmaceutics, College of Medicine, Jiaxing University, Jiaxing, Zhejiang, People's Republic of China
- Department of Pharmaceutics, Utrecht Institute of Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands
| | - Daniel J de Klerk
- Jiaxing Key Laboratory for Photonanomedicine and Experimental Therapeutics, Department of Pharmaceutics, College of Medicine, Jiaxing University, Jiaxing, Zhejiang, People's Republic of China
- Laboratory of Experimental Oncology, Department of Pathology, Erasmus MC, Rotterdam, The Netherlands
| | - Lianne R de Haan
- Laboratory of Experimental Oncology, Department of Pathology, Erasmus MC, Rotterdam, The Netherlands
| | - Robert T van Kooten
- Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
| | - Leonardo P Franchi
- Departamento de Bioquímica e Biologia Molecular, Instituto de Ciências Biológicas (ICB) 2, Universidade Federal de Goiás (UFG), Goiânia, GO, Brazil
- Faculty of Philosophy, Sciences, and Letters of Ribeirão Preto, epartment of Chemistry, Center of Nanotechnology and Tissue Engineering-Photobiology and Photomedicine Research Group,University of São Paulo, São Paulo, Brazil
| | - Lionel M Dias
- Jiaxing Key Laboratory for Photonanomedicine and Experimental Therapeutics, Department of Pharmaceutics, College of Medicine, Jiaxing University, Jiaxing, Zhejiang, People's Republic of China
- Laboratory of Experimental Oncology, Department of Pathology, Erasmus MC, Rotterdam, The Netherlands
| | - Tony G Kleijn
- Jiaxing Key Laboratory for Photonanomedicine and Experimental Therapeutics, Department of Pharmaceutics, College of Medicine, Jiaxing University, Jiaxing, Zhejiang, People's Republic of China
- Laboratory of Experimental Oncology, Department of Pathology, Erasmus MC, Rotterdam, The Netherlands
| | - Diederick J van Doorn
- Department of Gastroenterology and Hepatology, Amsterdam UMC, Location AMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Michal Heger
- Jiaxing Key Laboratory for Photonanomedicine and Experimental Therapeutics, Department of Pharmaceutics, College of Medicine, Jiaxing University, Jiaxing, Zhejiang, People's Republic of China.
- Department of Pharmaceutics, Utrecht Institute of Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
- Laboratory of Experimental Oncology, Department of Pathology, Erasmus MC, Rotterdam, The Netherlands.
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31
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Zbinden-Foncea H, Castro-Sepulveda M, Fuentes J, Speisky H. Effect of epicatechin on skeletal muscle. Curr Med Chem 2021; 29:1110-1123. [DOI: 10.2174/0929867329666211217100020] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2021] [Revised: 10/04/2021] [Accepted: 10/06/2021] [Indexed: 11/22/2022]
Abstract
:
Loss of skeletal muscle (SkM) quality is associated with different clinical conditions such as aging, diabetes, obesity, cancer and heart failure. Nutritional research has focused on identifying naturally occurring molecules that mitigate the loss of SkM quality induced by a pathology or syndrome. In this context, although few human studies have been conducted, Epicatechin (Epi) is a prime candidate that may positively affect SkM quality by its potential ability to mitigate muscle mass loss. This seems to be a consequence of its antioxidant, anti-inflammatory properties, and its stimulation of mitochondrial biogenesis to increase myogenic differentiation, as well as its modulation of key proteins involved in SkM structure, function, metabolism, and growth. In conclusion, the Epi could prevent, mitigate, delay, and even treat muscle-related disorders caused by aging and diseases, however, studies in humans are needed.
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Affiliation(s)
| | | | - Jocelyn Fuentes
- School of Kinesiology, Faculty of Medicine, Universidad Finis Terrae, Santiago, Chile
| | - Hernan Speisky
- Laboratory of Antioxidants, Nutrition and Food Technology Institute, University of Chile, Santiago, Chile
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32
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Ergin Kızılçay G, Ertürk Toker S. Effect of glycyrrhizic acid on the bioavailability of resveratrol after oral administration in rabbit plasma using HPLC with fluorescence detection. Microchem J 2021. [DOI: 10.1016/j.microc.2021.106360] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
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33
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Gu J, Li Z, Chen H, Xu X, Li Y, Gui Y. Neuroprotective Effect of Trans-Resveratrol in Mild to Moderate Alzheimer Disease: A Randomized, Double-Blind Trial. Neurol Ther 2021; 10:905-917. [PMID: 34402024 PMCID: PMC8571425 DOI: 10.1007/s40120-021-00271-2] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2021] [Accepted: 07/30/2021] [Indexed: 12/17/2022] Open
Abstract
Introduction Amyloid-beta (Aβ) protein is a major component of the extracellular plaque found in the brains of individuals with Alzheimer's disease (AD). In this study, we investigated the effect of trans-resveratrol as an antagonist treatment for moderate to mild AD, as well as its safety and tolerability. Methods This was a case–control study that enrolled 30 selected patients who had been clinically diagnosed with moderate to mild AD. These patients were randomly divided into two groups, namely, a placebo group (n = 15) and a trans-resveratrol group (n = 15) who received 500 mg trans-resveratrol orally once daily for 52 weeks. Brain magnetic resonance imaging (MRI) examinations were performed on and cerebrospinal fluid (CSF) samples were obtained from all participants before (baseline) and after the study (52 weeks). Enzyme-linked immunosorbent assays were used to determine the levels of plasma Aβ40 and Aβ42 and CSF Aβ40 and Aβ42. Results The results showed that the changes over the study period in the levels of Aβ40 in the blood and CSF of the patients treated with trans-resveratrol were not statistically significant (P > 0.05). In contrast, patients who received placebo showed a significant decrease in Aβ40 levels compared with that at the beginning of the study (CSF Aβ40: P = 0.024, plasma Aβ40: P = 0.036). Analysis of the images on the brain MRI scans revealed that the brain volume of the patients treated with trans-resveratrol was significantly reduced at 52 weeks (P = 0.011) compared with that of patients in the placebo treatment group, Further analysis indicated that the level of matrix metallopeptidase 9 in the CSF of the patients treated with trans-resveratrol at 52 weeks decreased by 46% compared with that of patients in the placebo group (P = 0.033). Conclusion These results indicate that trans-resveratrol has potential neuroprotective roles in the treatment of moderate to mild AD and that its mechanism may involve a reduction in the accumulation and toxicity of Aβ in the brain of patients, thereby reducing neuroinflammation. Trial Registration Chinese clinical trial registry: CTR20151780X. Supplementary Information The online version contains supplementary material available at 10.1007/s40120-021-00271-2.
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Affiliation(s)
- Jiachen Gu
- Department of Neurology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zongshan Li
- Department of Neurology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Huimin Chen
- Department of Neurology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Xiaomin Xu
- Department of Neurology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Yongang Li
- Department of Neurology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.,Department of Neurology, First People' Hospital of Wenling, Wenling, China
| | - Yaxing Gui
- Department of Neurology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
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Fatfat Z, Fatfat M, Gali-Muhtasib H. Therapeutic potential of thymoquinone in combination therapy against cancer and cancer stem cells. World J Clin Oncol 2021; 12:522-543. [PMID: 34367926 PMCID: PMC8317652 DOI: 10.5306/wjco.v12.i7.522] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2021] [Revised: 04/11/2021] [Accepted: 06/18/2021] [Indexed: 02/06/2023] Open
Abstract
The long-term success of standard anticancer monotherapeutic strategies has been hampered by intolerable side effects, resistance to treatment and cancer relapse. These monotherapeutic strategies shrink the tumor bulk but do not effectively eliminate the population of self-renewing cancer stem cells (CSCs) that are normally present within the tumor. These surviving CSCs develop mechanisms of resistance to treatment and refuel the tumor, thus causing cancer relapse. To ensure durable tumor control, research has moved away from adopting the monotreatment paradigm towards developing and using combination therapy. Combining different therapeutic modalities has demonstrated significant therapeutic outcomes by strengthening the anti-tumor potential of monotreatment against cancer and cancer stem cells, mitigating their toxic adverse effects, and ultimately overcoming resistance. Recently, there has been growing interest in combining natural products from different sources or with clinically used chemotherapeutics to further improve treatment efficacy and tolerability. Thymoquinone (TQ), the main bioactive constituent of Nigella sativa, has gained great attention in combination therapy research after demonstrating its low toxicity to normal cells and remarkable anticancer efficacy in extensive preclinical studies in addition to its ability to target chemoresistant CSCs. Here, we provide an overview of the therapeutic responses resulting from combining TQ with conventional therapeutic agents such as alkylating agents, antimetabolites and antimicrotubules as well as with topoisomerase inhibitors and non-coding RNA. We also review data on anticancer effects of TQ when combined with ionizing radiation and several natural products such as vitamin D3, melatonin and other compounds derived from Chinese medicinal plants. The focus of this review is on two outcomes of TQ combination therapy, namely eradicating CSCs and treating various types of cancers. In conclusion, the ability of TQ to potentiate the anticancer activity of many chemotherapeutic agents and sensitize cancer cells to radiotherapy makes it a promising molecule that could be used in combination therapy to overcome resistance to standard chemotherapeutic agents and reduce their associated toxicities.
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Affiliation(s)
- Zaynab Fatfat
- Department of Biology, American University of Beirut, Beirut 1107 2020, Lebanon
| | - Maamoun Fatfat
- Department of Biology, American University of Beirut, Beirut 1107 2020, Lebanon
| | - Hala Gali-Muhtasib
- Department of Biology, American University of Beirut, Beirut 1107 2020, Lebanon
- Center for Drug Discovery, American University of Beirut, Beirut 1107 2020, Lebanon
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Annaji M, Poudel I, Boddu SHS, Arnold RD, Tiwari AK, Babu RJ. Resveratrol-loaded nanomedicines for cancer applications. Cancer Rep (Hoboken) 2021; 4:e1353. [PMID: 33655717 PMCID: PMC8222557 DOI: 10.1002/cnr2.1353] [Citation(s) in RCA: 65] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2020] [Revised: 12/16/2020] [Accepted: 01/04/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Resveratrol (3, 5, 4' -trihydroxystilbene), a natural polyphenol and phytoalexin, has drawn considerable attention in the past decade due to its wide variety of therapeutic activities such as anticancer, anti-inflammatory, and antioxidant properties. However, its poor water solubility, low chemical stability, and short biological half-life limit its clinical utility. RECENT FINDINGS Nanoparticles overcome the limitations associated with conventional chemotherapeutic drugs, such as limited availability of drugs to the tumor tissues, high systemic exposures, and consequent toxicity to healthy tissues. This review focuses on the physicochemical properties of resveratrol, the therapeutic potential of resveratrol nano-formulations, and the anticancer activity of resveratrol encapsulated nanoparticles on various malignancies such as skin, breast, prostate, colon, liver, ovarian, and lung cancers (focusing on both in vitro and in vivo studies). CONCLUSIONS Nanotechnology approaches have been extensively utilized to achieve higher solubility, improved oral bioavailability, enhanced stability, and controlled release of resveratrol. The resveratrol nanoparticles have markedly enhanced its anticancer activity both in vitro and in vivo, thus considering it as a potential strategy to fight various cancers.
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Affiliation(s)
- Manjusha Annaji
- Department of Drug Discovery and DevelopmentAuburn UniversityAuburnAlabamaUSA
| | - Ishwor Poudel
- Department of Drug Discovery and DevelopmentAuburn UniversityAuburnAlabamaUSA
| | - Sai H. S. Boddu
- Department of Pharmaceutical Sciences, College of Pharmacy and Health SciencesAjman UniversityAjmanUnited Arab Emirates
| | - Robert D. Arnold
- Department of Drug Discovery and DevelopmentAuburn UniversityAuburnAlabamaUSA
| | - Amit K. Tiwari
- Department of Pharmacology and Experimental Therapeutics, College of Pharmacy & Pharmaceutical SciencesUniversity of ToledoToledoOhioUSA
| | - R. Jayachandra Babu
- Department of Drug Discovery and DevelopmentAuburn UniversityAuburnAlabamaUSA
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Thi Oanh H, Hac Thi N, Nhan Nguyen T, Anh Dang Thi T, Van Nguyen T, Hoang MH. Co-Encapsulation of Lycopene and Resveratrol in Polymeric Nanoparticles: Morphology and Lycopene Stability. JOURNAL OF NANOSCIENCE AND NANOTECHNOLOGY 2021; 21:3156-3164. [PMID: 33653491 DOI: 10.1166/jnn.2021.19146] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/12/2023]
Abstract
Lycopene and resveratrol are well-known for their high bioactivity, anti-inflammatory effects, and strong antioxidant properties. The combination of lycopene and resveratrol was synergistic in the potentializing immunity of the mammal body. In this study, the scalable co-encapsulation of lycopene and resveratrol into polymeric nanoparticles was performed using lycopene extracted from ripe gac fruit. These nanoparticles exhibited excellent water dispersion and spherical morphology with average particle diameters of 66.102 nm. The particle size was proportional to the lycopene/resveratrol ratio. The combinative use of lecithin and Tween® as surfactants and the use of a polylactide-polyethylene glycol copolymer as an encapsulation agent generated well-defined lycopene/resveratrol nanoparticles although the total content of these active compounds reached 12%. The stability of lycopene was enhanced when combined with resveratrol and antioxidants such as vitamin E and butylated hydroxytoluene. After 3 months of storage at -16 °C, the lycopene content in the lycopene/resveratrol nanopowder remained at ∼95%.
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Affiliation(s)
- Ho Thi Oanh
- Institute of Chemistry, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Cau Giay, Hanoi, 100000, Vietnam
| | - Nhung Hac Thi
- Institute of Chemistry, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Cau Giay, Hanoi, 100000, Vietnam
| | - Thanh Nhan Nguyen
- Institute of Chemistry, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Cau Giay, Hanoi, 100000, Vietnam
| | - Tuyet Anh Dang Thi
- Institute of Chemistry, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Cau Giay, Hanoi, 100000, Vietnam
| | - Tuyen Van Nguyen
- Institute of Chemistry, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Cau Giay, Hanoi, 100000, Vietnam
| | - Mai Ha Hoang
- Institute of Chemistry, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Cau Giay, Hanoi, 100000, Vietnam
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Porto ICCDM, Rocha ABDB, Ferreira IIS, de Barros BM, Ávila EC, da Silva MC, de Oliveira MPS, Lôbo TDLGF, Oliveira JMDS, do Nascimento TG, de Freitas JMD, de Freitas JD. Polyphenols and Brazilian red propolis incorporated into a total-etching adhesive system help in maintaining bonding durability. Heliyon 2021; 7:e06237. [PMID: 33665421 PMCID: PMC7898005 DOI: 10.1016/j.heliyon.2021.e06237] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2020] [Revised: 11/21/2020] [Accepted: 02/05/2021] [Indexed: 11/28/2022] Open
Abstract
Objectives The aim of this study was to evaluate the degree of conversion and bond strength of a commercial dental adhesive modified by the incorporation of quercetin, resveratrol (RES), and Brazilian red propolis (BRP). Methods BRP markers were identified using ultra-performance liquid chromatography coupled with a diode array detector, and the antioxidant activity (AAO) of the three substances was analyzed. Single Bond 2 adhesive (3M ESPE) was modified by adding BRP, quercetin, and RES, separately, at 20 μg/mL, 250 μg/mL, and 500 μg/mL, respectively. The degree of conversion (DC) was measured using near-infrared spectroscopy 24 h after photopolymerization. Measurements of the resin-dentin microtensile bond strength (μTBS) were carried out after 1 day and 1 year. Student's t test and ANOVA with Tukey's test were used for data analysis (α = 0.05). Results The markers daidzein, liquiritigenin, pinobanksin, isoliquiritigenin, formononetin, pinocembrin, and biochanin A were found in the ethanolic extract of BRP. Quercetin, RES, and BRP showed high AAO. The DC of the tested adhesives remained adequate for this category of material, with a slight increase in the DC of adhesives with quercetin and BRP (P > 0.05). Comparisons between μTBS measurements made at 1 day and 1 year showed that, contrary to the control group, μTBS values for all modified adhesives were maintained after 1 year in distilled water (P > 0.05). Conclusions These findings suggest that quercetin, RES, or BRP might be useful in adhesive dentistry to help improve hybrid layer resistance. Clinical significance Dentin bonding agents with quercetin, RES, and BRP have potential to increase the longevity of composite restorations.
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Affiliation(s)
- Isabel Cristina Celerino de Moraes Porto
- Laboratoty of Characterization and Analysis of Biomaterials, Faculty of Dentistry, Federal University of Alagoas, Campus AC Simões, Av. Lourival Melo Mota, S/N, Tabuleiro do Martins, CEP 57072-970, Maceió, Alagoas, Brazil.,Laboratory of Pharmaceutical and Food Analysis, Postgraduate Program in Pharmaceutical Sciences, Institute of Pharmaceutical Sciences, Federal University of Alagoas, Campus A. C. Simões, CEP 57072-970, Maceió, Alagoas, Brazil
| | - Arthur Bezerra de Barros Rocha
- Laboratoty of Characterization and Analysis of Biomaterials, Faculty of Dentistry, Federal University of Alagoas, Campus AC Simões, Av. Lourival Melo Mota, S/N, Tabuleiro do Martins, CEP 57072-970, Maceió, Alagoas, Brazil
| | - Iverson Iago Soares Ferreira
- Laboratoty of Characterization and Analysis of Biomaterials, Faculty of Dentistry, Federal University of Alagoas, Campus AC Simões, Av. Lourival Melo Mota, S/N, Tabuleiro do Martins, CEP 57072-970, Maceió, Alagoas, Brazil
| | - Bruna Muritiba de Barros
- Laboratoty of Characterization and Analysis of Biomaterials, Faculty of Dentistry, Federal University of Alagoas, Campus AC Simões, Av. Lourival Melo Mota, S/N, Tabuleiro do Martins, CEP 57072-970, Maceió, Alagoas, Brazil
| | - Eryck Canabarra Ávila
- Laboratoty of Characterization and Analysis of Biomaterials, Faculty of Dentistry, Federal University of Alagoas, Campus AC Simões, Av. Lourival Melo Mota, S/N, Tabuleiro do Martins, CEP 57072-970, Maceió, Alagoas, Brazil
| | - Matheus Corrêa da Silva
- Laboratoty of Characterization and Analysis of Biomaterials, Faculty of Dentistry, Federal University of Alagoas, Campus AC Simões, Av. Lourival Melo Mota, S/N, Tabuleiro do Martins, CEP 57072-970, Maceió, Alagoas, Brazil
| | - Marcos Paulo Santana de Oliveira
- Laboratoty of Characterization and Analysis of Biomaterials, Faculty of Dentistry, Federal University of Alagoas, Campus AC Simões, Av. Lourival Melo Mota, S/N, Tabuleiro do Martins, CEP 57072-970, Maceió, Alagoas, Brazil
| | - Teresa de Lisieux Guedes Ferreira Lôbo
- Laboratory of Pharmaceutical and Food Analysis, Postgraduate Program in Pharmaceutical Sciences, Institute of Pharmaceutical Sciences, Federal University of Alagoas, Campus A. C. Simões, CEP 57072-970, Maceió, Alagoas, Brazil
| | - José Marcos Dos Santos Oliveira
- Postgraduate Program in Health Research, Cesmac University Center, Rua Prof. Ângelo Neto, 51, Farol, CEP 57051-530, Maceió, Alagoas, Brazil
| | - Ticiano Gomes do Nascimento
- Laboratory of Pharmaceutical and Food Analysis, Postgraduate Program in Pharmaceutical Sciences, Institute of Pharmaceutical Sciences, Federal University of Alagoas, Campus A. C. Simões, CEP 57072-970, Maceió, Alagoas, Brazil
| | - Jeniffer Mclaine Duarte de Freitas
- Laboratory of Pharmaceutical and Food Analysis, Postgraduate Program in Nutrition, Faculty of Nutrition, Federal University of Alagoas, Campus A. C. Simões, CEP 57072-970, Maceió, Alagoas, Brazil
| | - Johnnatan Duarte de Freitas
- Department of Chemistry, Federal Institute of Alagoas, Rua Mizael Domingues, 75, Campus Maceió, CEP 57020-600, Maceió, Alagoas, Brazil
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AbouAitah K, Lojkowski W. Delivery of Natural Agents by Means of Mesoporous Silica Nanospheres as a Promising Anticancer Strategy. Pharmaceutics 2021; 13:143. [PMID: 33499150 PMCID: PMC7912645 DOI: 10.3390/pharmaceutics13020143] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2020] [Revised: 01/12/2021] [Accepted: 01/14/2021] [Indexed: 12/11/2022] Open
Abstract
Natural prodrugs derived from different natural origins (e.g., medicinal plants, microbes, animals) have a long history in traditional medicine. They exhibit a broad range of pharmacological activities, including anticancer effects in vitro and in vivo. They have potential as safe, cost-effective treatments with few side effects, but are lacking in solubility, bioavailability, specific targeting and have short half-lives. These are barriers to clinical application. Nanomedicine has the potential to offer solutions to circumvent these limitations and allow the use of natural pro-drugs in cancer therapy. Mesoporous silica nanoparticles (MSNs) of various morphology have attracted considerable attention in the search for targeted drug delivery systems. MSNs are characterized by chemical stability, easy synthesis and functionalization, large surface area, tunable pore sizes and volumes, good biocompatibility, controlled drug release under different conditions, and high drug-loading capacity, enabling multifunctional purposes. In vivo pre-clinical evaluations, a significant majority of results indicate the safety profile of MSNs if they are synthesized in an optimized way. Here, we present an overview of synthesis methods, possible surface functionalization, cellular uptake, biodistribution, toxicity, loading strategies, delivery designs with controlled release, and cancer targeting and discuss the future of anticancer nanotechnology-based natural prodrug delivery systems.
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Affiliation(s)
- Khaled AbouAitah
- Laboratory of Nanostructures and Nanomedicine, Institute of High Pressure Physics, Polish Academy of Sciences, Sokolowska 29/37, 01-142 Warsaw, Poland
- Medicinal and Aromatic Plants Research Department, Pharmaceutical and Drug Industries Research Division, National Research Centre (NRC), 33 El-Behouth St., Dokki 12622, Giza, Egypt
| | - Witold Lojkowski
- Laboratory of Nanostructures and Nanomedicine, Institute of High Pressure Physics, Polish Academy of Sciences, Sokolowska 29/37, 01-142 Warsaw, Poland
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Li Y, Zheng Y, Wang H. Anticancer activity of Vicenin-2 against 7,12 dimethylbenz[a]anthracene-induced buccal pouch carcinoma in hamsters. J Biochem Mol Toxicol 2020; 35:e22673. [PMID: 33314472 DOI: 10.1002/jbt.22673] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2020] [Revised: 09/24/2020] [Accepted: 11/04/2020] [Indexed: 12/24/2022]
Abstract
Buccal mucosa carcinoma is a significant cause of death in developing nations. Vicenin-2 is a significant bioactive compound found in Ocimum sanctum Linn or Tulsi that possesses several pharmacologic properties. Our focus is to understand the possible impact of Vicenin-2 on 7,12-dimethylbenz[a]anthracene (DMBA)-induced oral carcinogenesis in hamsters. Buccal carcinoma was induced by treatment with carcinogenic DMBA, three times a week for 14 weeks. We determined 100% tumor incidence, abnormal tumor volume, inclined tumor burden, and deduced body weight in DMBA-induced oral squamous cell carcinoma (OSCC) hamsters. The upregulation of cytokine levels (interleukin [IL]-6, IL-1β, and tumor necrosis factor-alpha [TNF-α]) was observed in DMBA-induced OSCC hamsters. Moreover, dysplastic, hyperplastic, and squamous cell carcinoma was identified in the DMBA-induced OSCC hamsters. The diminished activities of lipid peroxidation and enzymatic/nonenzymatic antioxidants were observed in DMBA-induced hamsters. Furthermore, the high expression of proliferating cell nuclear antigen (PCNA), Cyclin-D1, and Bcl-2, and attenuated Bax expression were observed in DMBA-induced hamsters. Our study results explored that Vicenin-2 (30 mg/kg) treated with DMBA-brushed hamsters averted tumor incidence, improved the antioxidant status, and inhibited lipid peroxidation. Moreover, Vicenin-2 inhibited the immunohistochemical expression of PCNA, Cyclin-D1, and Bcl-2, and significantly restored apoptotic Bax levels. The Vicenin-2 treatment prevents the lesion formation in the oral epithelium of the DMBA-induced hamsters. The Vicenin-2 treatment potentially halts the proinflammatory cytokines (IL-6, IL-1β, and TNF-α) production in OSCC hamsters. Thus, we proved that Vicenin-2 prevents DMBA-induced buccal carcinogenesis in hamsters via improving antioxidants by modulating apoptotic and cytokines signaling pathways.
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Affiliation(s)
- Yijun Li
- VIP Comprehensive Department, Hospital of Stomatology, Jilin University, Jilin, Changchun, China
| | - Yi Zheng
- Department of Periodontics, Hospital of Stomatology, Jilin University, Jilin, Changchun, China
| | - Huibo Wang
- Department of Periodontics and Oral Medicine, Hangzhou Dental Hospital, Zhejiang, Hangzhou, China
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Zimányi L, Thekkan S, Eckert B, Condren AR, Dmitrenko O, Kuhn LR, Alabugin IV, Saltiel J. Determination of the p Ka Values of trans-Resveratrol, a Triphenolic Stilbene, by Singular Value Decomposition. Comparison with Theory. J Phys Chem A 2020; 124:6294-6302. [PMID: 32635729 DOI: 10.1021/acs.jpca.0c04792] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
Several independent determinations of the pKa values of trans-resveratrol in water have led to conflicting results. Singular value decomposition analysis of UV absorption spectra of trans-resveratrol (t-Resv) in N2-outgased aqueous solutions buffered to pH values in the 7.0-13.6 range yielded the UV spectra of the three anionic forms and the corresponding pKa values: pKa1 = 9.16, pKa2 = 9.77, and pKa3 = 10.55 in very good agreement with calculated theoretical values. The analysis of the absorption spectra guided the assignment of the fluorescence spectrum of each anionic form. With the resolved spectra on hand, we applied the Förster equation to estimate pKa* values of 2.5 and 0, respectively, for the p- and m-OH substituents of t-Resv in S1. Theory supports a proposed mechanism for the reaction of t-Resv anions with O2.
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Affiliation(s)
- László Zimányi
- Institute of Biophysics, Biological Research Centre, P.O. Box 521, Szeged, Hungary H-6701
| | - Shareefa Thekkan
- Department of Chemistry and Biochemistry, Florida State University, Tallahassee, Florida 32306-4390, United States
| | - Brett Eckert
- Department of Chemistry and Biochemistry, Florida State University, Tallahassee, Florida 32306-4390, United States
| | - Alanna R Condren
- Department of Chemistry and Biochemistry, Florida State University, Tallahassee, Florida 32306-4390, United States
| | - Olga Dmitrenko
- Department of Chemistry and Biochemistry, University of Delaware, Newark, Delaware 19716, United States
| | - Leah R Kuhn
- Department of Chemistry and Biochemistry, Florida State University, Tallahassee, Florida 32306-4390, United States
| | - Igor V Alabugin
- Department of Chemistry and Biochemistry, Florida State University, Tallahassee, Florida 32306-4390, United States
| | - Jack Saltiel
- Department of Chemistry and Biochemistry, Florida State University, Tallahassee, Florida 32306-4390, United States
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Wine Consumption and Oral Cavity Cancer: Friend or Foe, Two Faces of Janus. Molecules 2020; 25:molecules25112569. [PMID: 32486484 PMCID: PMC7321235 DOI: 10.3390/molecules25112569] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2020] [Revised: 05/21/2020] [Accepted: 05/28/2020] [Indexed: 12/29/2022] Open
Abstract
The health benefits of moderate wine consumption have been extensively studied during the last few decades. Some studies have demonstrated protective associations between moderate drinking and several diseases including oral cavity cancer (OCC). However, due to the various adverse effects related to ethanol content, the recommendation of moderate wine consumption has been controversial. The polyphenolic components of wine contribute to its beneficial effects with different biological pathways, including antioxidant, lipid regulating and anti-inflammatory effects. On the other hand, in the oral cavity, ethanol is oxidized to form acetaldehyde, a metabolite with genotoxic properties. This review is a critical compilation of both the beneficial and the detrimental effects of wine consumption on OCC.
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Application of nano/microencapsulated phenolic compounds against cancer. Adv Colloid Interface Sci 2020; 279:102153. [PMID: 32289738 DOI: 10.1016/j.cis.2020.102153] [Citation(s) in RCA: 55] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2019] [Revised: 03/30/2020] [Accepted: 03/30/2020] [Indexed: 12/19/2022]
Abstract
Nowadays, polyphenols as bioactive compounds are being used in producing anti-cancer drugs. Low stability against harsh environmental conditions, untargeted release, low solubility, and low absorption of pure phenolic molecules are significant barriers, which decrease the functions of polyphenols. Recently, the nanoencapsulation processes have been applied to overcome these restrictions, in which the anti-cancer activity of polyphenols has been noticeably increased. This review will focus on the anti-cancer activity of polyphenols, and the effect of loading polyphenolics into various micro/nanoencapsulation systems on their anti-cancer activity. Different encapsulation systems such as lipid and polymer based nanoparticles, and solid form of encapsulated phenolic molecules by nano-spray dryer and electrospinnig have been used for loading of polyphenols. Incorporation of phenolic molecules into various carriers inevitably increases their anti-cancer activity. Because, in this way, encapsulated cargos can provide a targeted release, which will increase the bioavailability of phenolic molecules and their functions such as absorption into cancer cell.
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Peng W, Yi L, Wang Z, Yang H, Huang C. Effects of resveratrol/ethanol pretreatment on dentin bonding durability. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2020; 114:111000. [PMID: 32994020 DOI: 10.1016/j.msec.2020.111000] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/24/2019] [Revised: 12/26/2019] [Accepted: 04/20/2020] [Indexed: 12/30/2022]
Abstract
To determine the effects of resveratrol/ethanol solution on the durability of resin-dentin bonding interfaces. Sixty-four non-caries third molars were randomly divided into four groups (n = 16) after sectioning, and then pretreated with one of the following concentrations of resveratrol/ethanol solutions: 0 (control group), 1, 10 and 20 mg/mL, followed by a universal adhesive and resin composites. All microtensile samples were divided into three subgroups: immediate group, collagenase ageing group and thermocycled group. The microtensile bond strength (MTBS), failure modes, interfacial nanoleakage and in situ zymography were measured, whereas the inhibitory effects of pretreated dentin slices on S. mutans biofilms were determined by confocal laser scanning microscopy and MTT assay. The results indicated that bonding strength was not only influenced by pretreatment factors (P < 0.05) but also ageing factors (P < 0.05). Regardless of collagenase ageing or thermocycling, the 10 mg/mL resveratrol/ethanol pretreatment group presented significantly higher (P < 0.05) MTBS and lower (P < 0.05) expression of nanoleakage than the control group, showed better inhibitory effect of matrix metalloproteinases and S. mutans activity with acceptable cytotoxicity. Meanwhile, cohesive failure in dentin decreased gradually with increasing resveratrol concentration. Therefore, the resveratrol/ethanol solution had the potential to serve as a versatile dentin primer, which can effectively improve dentin bonding durability and prevent secondary caries.
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Affiliation(s)
- Wenan Peng
- The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory for Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, China
| | - Luyao Yi
- The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory for Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, China
| | - Ziming Wang
- The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory for Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, China
| | - Hongye Yang
- The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory for Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, China; College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, China.
| | - Cui Huang
- The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory for Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, China.
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Platella C, Raucci U, Rega N, D'Atri S, Levati L, Roviello GN, Fuggetta MP, Musumeci D, Montesarchio D. Shedding light on the interaction of polydatin and resveratrol with G-quadruplex and duplex DNA: a biophysical, computational and biological approach. Int J Biol Macromol 2019; 151:1163-1172. [PMID: 31747572 DOI: 10.1016/j.ijbiomac.2019.10.160] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2019] [Revised: 10/09/2019] [Accepted: 10/18/2019] [Indexed: 12/17/2022]
Abstract
Among polyphenols, trans-resveratrol (tRES) and trans-polydatin (tPD) exert multiple biological effects, particularly antioxidant and antiproliferative. In this work, we have investigated the interaction of tPD with three cancer-related DNA sequences able to form G-quadruplex (G4) structures, as well as with a model duplex, and compared its behaviour with tRES. Interestingly, fluorescence analysis evidenced the ability of tPD to bind all the studied DNA systems, similarly to tRES, with tRES displaying a higher ability to discriminate G4 over duplex with respect to tPD. However, neither tRES nor tPD produced significant conformational changes of the analyzed DNA upon binding, as determined by CD-titration analysis. Computational analysis and biological data confirmed the biophysical results: indeed, molecular docking evidenced the stronger interaction of tRES with the promoter of c-myc oncogene, and immunoblotting assays revealed a reduction of c-myc expression, more effective for tRES than tPD. Furthermore, in vitro assays on melanoma cells proved that tPD was able to significantly reduce telomerase activity, and inhibit cell proliferation, with tRES producing higher effects than tPD.
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Affiliation(s)
- Chiara Platella
- Department of Chemical Sciences, University of Naples Federico II, Via Cintia 21, Naples I-80126, Italy
| | - Umberto Raucci
- Department of Chemical Sciences, University of Naples Federico II, Via Cintia 21, Naples I-80126, Italy
| | - Nadia Rega
- Department of Chemical Sciences, University of Naples Federico II, Via Cintia 21, Naples I-80126, Italy; Interdisciplinary Research Centre on Biomaterials (CRIB), University of Naples Federico II, Piazzale Tecchio 80, Naples I-80125, Italy
| | - Stefania D'Atri
- Laboratory of Molecular Oncology, IDI-IRCCS, Via dei Monti di Creta 104, Rome I-00167, Italy
| | - Lauretta Levati
- Laboratory of Molecular Oncology, IDI-IRCCS, Via dei Monti di Creta 104, Rome I-00167, Italy
| | - Giovanni N Roviello
- Institute of Biostructures and Bioimages, CNR, Via Mezzocannone 16, Naples I-80134, Italy
| | - Maria Pia Fuggetta
- Institute of Translational Pharmacology, CNR, Via Fosso del Cavaliere 100, Rome I-00133, Italy.
| | - Domenica Musumeci
- Department of Chemical Sciences, University of Naples Federico II, Via Cintia 21, Naples I-80126, Italy; Institute of Biostructures and Bioimages, CNR, Via Mezzocannone 16, Naples I-80134, Italy.
| | - Daniela Montesarchio
- Department of Chemical Sciences, University of Naples Federico II, Via Cintia 21, Naples I-80126, Italy
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de los Angeles Rodriguez Salazar M, Rafael Olivo Urbina G, do Nascimento Bezerra P, Maria Borges Cunha V, Paiva da Silva M, Cristina Seabra Pires F, Paula de Souza e Silva A, Henrique Brabo de Sousa S, Nunes de Carvalho Jr R. Antioxidant and Biological Activity of Cissus sicyoidesand Rosmarinus officinalisExtracts. Antioxidants (Basel) 2019. [DOI: 10.5772/intechopen.83733] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023] Open
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46
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Mortezaee K, Najafi M, Farhood B, Ahmadi A, Shabeeb D, Musa AE. NF‐κB targeting for overcoming tumor resistance and normal tissues toxicity. J Cell Physiol 2019; 234:17187-17204. [DOI: 10.1002/jcp.28504] [Citation(s) in RCA: 59] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2019] [Revised: 02/22/2019] [Accepted: 03/05/2019] [Indexed: 12/13/2022]
Affiliation(s)
- Keywan Mortezaee
- Department of Anatomy School of Medicine, Kurdistan University of Medical Sciences Sanandaj Iran
| | - Masoud Najafi
- Radiology and Nuclear Medicine Department School of Paramedical Sciences, Kermanshah University of Medical Sciences Kermanshah Iran
| | - Bagher Farhood
- Departments of Medical Physics and Radiology Faculty of Paramedical Sciences, Kashan University of Medical Sciences Kashan Iran
| | - Amirhossein Ahmadi
- Pharmaceutical Sciences Research Center Faculty of Pharmacy, Mazandaran University of Medical Sciences Sari Iran
| | - Dheyauldeen Shabeeb
- Department of Physiology College of Medicine, University of Misan Misan Iraq
| | - Ahmed E. Musa
- Department of Medical Physics Tehran University of Medical Sciences (International Campus) Tehran Iran
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Molecular cloning and functional characterization of an O-methyltransferase catalyzing 4'-O-methylation of resveratrol in Acorus calamus. J Biosci Bioeng 2018; 127:539-543. [PMID: 30471982 DOI: 10.1016/j.jbiosc.2018.10.011] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2018] [Revised: 09/27/2018] [Accepted: 10/13/2018] [Indexed: 01/19/2023]
Abstract
Resveratrol and its methyl ethers, which belong to a class of natural polyphenol stilbenes, play important roles as biologically active compounds in plant defense as well as in human health. Although the biosynthetic pathway of resveratrol has been fully elucidated, the characterization of resveratrol-specific O-methyltransferases remains elusive. In this study, we used RNA-seq analysis to identify a putative aromatic O-methyltransferase gene, AcOMT1, in Acorus calamus. Recombinant AcOMT1 expressed in Escherichia coli showed high 4'-O-methylation activity toward resveratrol and its derivative, isorhapontigenin. We purified a reaction product enzymatically formed from resveratrol by AcOMT1 and confirmed it as 4'-O-methylresveratrol (deoxyrhapontigenin). Resveratrol and isorhapontigenin were the most preferred substrates with apparent Km values of 1.8 μM and 4.2 μM, respectively. Recombinant AcOMT1 exhibited reduced activity toward other resveratrol derivatives, piceatannol, oxyresveratrol, and pinostilbene. In contrast, recombinant AcOMT1 exhibited no activity toward pterostilbene or pinosylvin. These results indicate that AcOMT1 showed high 4'-O-methylation activity toward stilbenes with non-methylated phloroglucinol rings.
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Ganesan K, Xu B. Telomerase Inhibitors from Natural Products and Their Anticancer Potential. Int J Mol Sci 2017; 19:ijms19010013. [PMID: 29267203 PMCID: PMC5795965 DOI: 10.3390/ijms19010013] [Citation(s) in RCA: 80] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2017] [Revised: 12/10/2017] [Accepted: 12/19/2017] [Indexed: 12/25/2022] Open
Abstract
Telomeres and telomerase are nowadays exploring traits on targets for anticancer therapy. Telomerase is a unique reverse transcriptase enzyme, considered as a primary factor in almost all cancer cells, which is mainly responsible to regulate the telomere length. Hence, telomerase ensures the indefinite cell proliferation during malignancy—a hallmark of cancer—and this distinctive feature has provided telomerase as the preferred target for drug development in cancer therapy. Deactivation of telomerase and telomere destabilization by natural products provides an opening to succeed new targets for cancer therapy. This review aims to provide a fundamental knowledge for research on telomere, working regulation of telomerase and its various binding proteins to inhibit the telomere/telomerase complex. In addition, the review summarizes the inhibitors of the enzyme catalytic subunit and RNA component, natural products that target telomeres, and suppression of transcriptional and post-transcriptional levels. This extensive understanding of telomerase biology will provide indispensable information for enhancing the efficiency of rational anti-cancer drug design.
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Affiliation(s)
- Kumar Ganesan
- Food Science and Technology Program, Beijing Normal University-Hong Kong Baptist University United International College, Zhuhai 519087, China.
| | - Baojun Xu
- Food Science and Technology Program, Beijing Normal University-Hong Kong Baptist University United International College, Zhuhai 519087, China.
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