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Wang P, Li Z, Song Y, Zhang B, Fan C. Resveratrol-driven macrophage polarization: unveiling mechanisms and therapeutic potential. Front Pharmacol 2025; 15:1516609. [PMID: 39872049 PMCID: PMC11770351 DOI: 10.3389/fphar.2024.1516609] [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: 10/24/2024] [Accepted: 12/23/2024] [Indexed: 01/29/2025] Open
Abstract
Resveratrol, a polyphenolic compound known for its diverse biological activities, has demonstrated multiple pharmacological effects, including anti-inflammatory, anti-aging, anti-diabetic, anti-cancer, and cardiovascular protective properties. Recent studies suggest that these effects are partly mediated through the regulation of macrophage polarization, wherein macrophages differentiate into pro-inflammatory M1 or anti-inflammatory M2 phenotypes. Our review highlights how resveratrol modulates macrophage polarization through various signaling pathways to achieve therapeutic effects. For example, resveratrol can activate the senescence-associated secretory phenotype (SASP) pathway and inhibit the signal transducer and activator of transcription (STAT3) and sphingosine-1-phosphate (S1P)-YAP signaling axes, promoting M1 polarization or suppressing M2 polarization, thereby inhibiting tumor growth. Conversely, it can promote M2 polarization or suppress M1 polarization by inhibiting the NF-κB signaling pathway or activating the PI3K/Akt and AMP-activated protein kinase (AMPK) pathways, thus alleviating inflammatory responses. Notably, the effect of resveratrol on macrophage polarization is concentration-dependent; moderate concentrations tend to promote M1 polarization, while higher concentrations may favor M2 polarization. This concentration dependence offers new perspectives for clinical treatment but also underscores the necessity for precise dosage control when using resveratrol. In summary, resveratrol exhibits significant potential in regulating macrophage polarization and treating related diseases.
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Affiliation(s)
- Panting Wang
- Department of Neurosurgery West China Hospital, Sichuan University, Chengdu, China
- West China School of Nursing Sichuan University, Chengdu, China
| | - Zixi Li
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yixuan Song
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Bowei Zhang
- Southwest Institute of Technical Physics, Chengdu, China
| | - Chaofeng Fan
- Department of Neurosurgery West China Hospital, Sichuan University, Chengdu, China
- West China School of Nursing Sichuan University, Chengdu, China
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Novelle MG, Naranjo-Martínez B, López-Cánovas JL, Díaz-Ruiz A. Fecal microbiota transplantation, a tool to transfer healthy longevity. Ageing Res Rev 2025; 103:102585. [PMID: 39586550 DOI: 10.1016/j.arr.2024.102585] [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: 06/14/2024] [Revised: 10/13/2024] [Accepted: 11/12/2024] [Indexed: 11/27/2024]
Abstract
The complex gut microbiome influences host aging and plays an important role in the manifestation of age-related diseases. Restoring a healthy gut microbiome via Fecal Microbiota Transplantation (FMT) is receiving extensive consideration to therapeutically transfer healthy longevity. Herein, we comprehensively review the benefits of gut microbial rejuvenation - via FMT - to promote healthy aging, with few studies documenting life length properties. This review explores how preconditioning donors via standard - lifestyle and pharmacological - antiaging interventions reshape gut microbiome, with the resulting benefits being also FMT-transferable. Finally, we expose the current clinical uses of FMT in the context of aging therapy and address FMT challenges - regulatory landscape, protocol standardization, and health risks - that require refinement to effectively utilize microbiome interventions in the elderly.
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Affiliation(s)
- Marta G Novelle
- Department of Genetics, Physiology and Microbiology (Unity of Animal Physiology), Faculty of Biology, Complutense University of Madrid (UCM), Madrid, Spain; CIBER Physiopathology of Obesity and Nutrition (CIBERobn), Spain
| | - Beatriz Naranjo-Martínez
- Laboratory of Cellular and Molecular Gerontology, Precision Nutrition and Aging, Madrid Institute for Advanced Studies - IMDEA Food, CEI UAM+CSIC, Madrid, Spain
| | - Juan L López-Cánovas
- Laboratory of Cellular and Molecular Gerontology, Precision Nutrition and Aging, Madrid Institute for Advanced Studies - IMDEA Food, CEI UAM+CSIC, Madrid, Spain
| | - Alberto Díaz-Ruiz
- Laboratory of Cellular and Molecular Gerontology, Precision Nutrition and Aging, Madrid Institute for Advanced Studies - IMDEA Food, CEI UAM+CSIC, Madrid, Spain; CIBER Physiopathology of Obesity and Nutrition (CIBERobn), Spain.
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Baghishani M, Mehri S, Aminifard T, Jafarian A, Hosseinzadeh H. The protective properties of resveratrol against glycerol-induced acute kidney injury in rats. AVICENNA JOURNAL OF PHYTOMEDICINE 2025; 15:860-873. [PMID: 40271506 PMCID: PMC12013969 DOI: 10.22038/ajp.2024.24649] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Figures] [Subscribe] [Scholar Register] [Received: 12/21/2023] [Accepted: 04/27/2024] [Indexed: 04/25/2025]
Abstract
Objective After rhabdomyolysis, muscle tissue releases substances such as myoglobin, creatine kinase, and electrolytes into the bloodstream, potentially leading to acute kidney injury (AKI). Resveratrol (RSV) is a polyphenol compound with anti-inflammatory and antioxidant effects and it is found in various plants. This research evaluated the protective effects of RSV in rhabdomyolysis-induced AKI in rat kidneys. Materials and Methods Thirty-six male Wistar rats were randomly assigned to six groups (n=6): 1) control (normal saline), 2) glycerol only (10 ml/kg, intramuscular), 3, 4, and 5) glycerol +RSV (5, 10, and 25 mg/kg, intraperitoneal injection) and 6) RSV (25 mg/kg). After 4 days, pathological alterations and the level of blood urea nitrogen (BUN) and serum creatinine were determined. Malondialdehyde (MDA), glutathione (GSH), neutrophil gelatinase-associated lipocalin (NGAL), and tumor necrosis factor-α (TNF-α) proteins were investigated in rat kidneys. Results Injection of 50% glycerol (10 ml/kg, IM) resulted in pathological lesions, elevated levels of MDA (p<0.001), BUN (p<0.01), serum creatinine (p<0.001), TNF-α (p<0.01), and NGAL protein (p<0.001), and decreased GSH content (p<0.001) compared to the control animals. These findings indicated AKI induced by rhabdomyolysis. RSV (25 mg/kg) administration significantly decreased serum creatinine, BUN, MDA, NGAL, and TNF-α levels compared to the glycerol group. Histopathologically, tubule necrosis, myoglobin cast formation and glomerular atrophy increased in the glycerol group and reduced in animals that received RSV. Conclusion In the glycerol-induced AKI rat model, RSV administration alleviated renal dysfunction by reducing oxidative stress and inflammatory responses.
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Affiliation(s)
- Mohammadreza Baghishani
- Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Soghra Mehri
- Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
- Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Tahereh Aminifard
- Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amirhossein Jafarian
- Department of Pathology, Ghaem Hospital, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Hossein Hosseinzadeh
- Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
- Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
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de Souza Goncalves B, Sangani D, Nayyar A, Puri R, Irtiza M, Nayyar A, Khalyfa A, Sodhi K, Pillai SS. COVID-19-Associated Sepsis: Potential Role of Phytochemicals as Functional Foods and Nutraceuticals. Int J Mol Sci 2024; 25:8481. [PMID: 39126050 PMCID: PMC11312872 DOI: 10.3390/ijms25158481] [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: 07/08/2024] [Revised: 07/30/2024] [Accepted: 08/01/2024] [Indexed: 08/12/2024] Open
Abstract
The acute manifestations of coronavirus disease 2019 (COVID-19) exhibit the hallmarks of sepsis-associated complications that reflect multiple organ failure. The inflammatory cytokine storm accompanied by an imbalance in the pro-inflammatory and anti-inflammatory host response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leads to severe and critical septic shock. The sepsis signature in severely afflicted COVID-19 patients includes cellular reprogramming and organ dysfunction that leads to high mortality rates, emphasizing the importance of improved clinical care and advanced therapeutic interventions for sepsis associated with COVID-19. Phytochemicals of functional foods and nutraceutical importance have an incredible impact on the healthcare system, which includes the prevention and/or treatment of chronic diseases. Hence, in the present review, we aim to explore the pathogenesis of sepsis associated with COVID-19 that disrupts the physiological homeostasis of the body, resulting in severe organ damage. Furthermore, we have summarized the diverse pharmacological properties of some potent phytochemicals, which can be used as functional foods as well as nutraceuticals against sepsis-associated complications of SARS-CoV-2 infection. The phytochemicals explored in this article include quercetin, curcumin, luteolin, apigenin, resveratrol, and naringenin, which are the major phytoconstituents of our daily food intake. We have compiled the findings from various studies, including clinical trials in humans, to explore more into the therapeutic potential of each phytochemical against sepsis and COVID-19, which highlights their possible importance in sepsis-associated COVID-19 pathogenesis. We conclude that our review will open a new research avenue for exploring phytochemical-derived therapeutic agents for preventing or treating the life-threatening complications of sepsis associated with COVID-19.
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Affiliation(s)
- Bruno de Souza Goncalves
- Department of Surgery, Internal Medicine and Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25701, USA; (B.d.S.G.); (D.S.); (R.P.); (M.I.); (A.N.); (A.K.); (K.S.)
| | - Darshan Sangani
- Department of Surgery, Internal Medicine and Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25701, USA; (B.d.S.G.); (D.S.); (R.P.); (M.I.); (A.N.); (A.K.); (K.S.)
| | - Aleen Nayyar
- Department of Medicine, Sharif Medical and Dental College, Lahore 55150, Pakistan;
| | - Raghav Puri
- Department of Surgery, Internal Medicine and Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25701, USA; (B.d.S.G.); (D.S.); (R.P.); (M.I.); (A.N.); (A.K.); (K.S.)
| | - Mahir Irtiza
- Department of Surgery, Internal Medicine and Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25701, USA; (B.d.S.G.); (D.S.); (R.P.); (M.I.); (A.N.); (A.K.); (K.S.)
| | - Asma Nayyar
- Department of Surgery, Internal Medicine and Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25701, USA; (B.d.S.G.); (D.S.); (R.P.); (M.I.); (A.N.); (A.K.); (K.S.)
| | - Abdelnaby Khalyfa
- Department of Surgery, Internal Medicine and Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25701, USA; (B.d.S.G.); (D.S.); (R.P.); (M.I.); (A.N.); (A.K.); (K.S.)
| | - Komal Sodhi
- Department of Surgery, Internal Medicine and Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25701, USA; (B.d.S.G.); (D.S.); (R.P.); (M.I.); (A.N.); (A.K.); (K.S.)
| | - Sneha S. Pillai
- Department of Surgery, Internal Medicine and Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25701, USA; (B.d.S.G.); (D.S.); (R.P.); (M.I.); (A.N.); (A.K.); (K.S.)
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Wahab M, Janaswamy S. Porous corn starch granules as effective host matrices for encapsulation and sustained release of curcumin and resveratrol. Carbohydr Polym 2024; 333:121967. [PMID: 38494222 DOI: 10.1016/j.carbpol.2024.121967] [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: 11/13/2023] [Revised: 02/07/2024] [Accepted: 02/16/2024] [Indexed: 03/19/2024]
Abstract
Type 2 Diabetes Mellitus (T2DM) is a carbohydrate-rich diet-regulated ailment with carbohydrates digested and absorbed rapidly. Hence, modulating carbohydrate digestion is warranted; to this end, polyphenols from plant sources are handy. However, polyphenols' instability and low bioavailability limit their wholesome use, and thus, encapsulating them into an inexpensive and suitable wall material would be the best strategy. Herein, the potential of porous starch granules is demonstrated. Curcumin and resveratrol were chosen as the test polyphenols due to their proven health benefits, and porous corn starch granules were chosen as the wall material. Porous corn starch granules were prepared through enzymatic modification with 11, 22, and 33 units of amyloglucosidase at three reaction times of 2, 4, and 6 h. The polyphenols were loaded at 100, 200, and 500 mg concentrations in 1 g of starch for 21 days and were characterized through Scanning Electron Microscope (SEM) and Fourier Transform Infrared spectroscopy (FTIR) analyses. The encapsulation efficiency was determined, the rate of starch digestion was calculated through the Englyst test, and polyphenols' in vitro release behavior in gastric and intestinal fluids was measured. Results suggest that 33 enzyme units for a 2 h reaction time were optimal for forming spherical-oval pores on corn starch granules with the maximum encapsulation efficiency of 80.16 % and 88.33 % for curcumin and resveratrol, respectively. The FTIR results suggest the entrapment of polyphenols inside the starch matrix. The inclusion significantly reduced starch digestion and increased the percentage of resistant starch up to 41.11 % and 66.36 % with curcumin and resveratrol, respectively. The in vitro release behavior demonstrated good stability in the simulated gastric fluids and sustained release in simulated intestinal fluids. The encapsulated polyphenols showed a complex Fickian type of diffusion mechanism. Overall, the results suggest that porous corn starch granules could be a potential delivery system for curcumin and resveratrol and will aid in developing novel functional foods to address the T2DM concerns.
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Affiliation(s)
- Maryam Wahab
- Department of Dairy and Food Science, South Dakota State University, Brookings, SD 57007, USA
| | - Srinivas Janaswamy
- Department of Dairy and Food Science, South Dakota State University, Brookings, SD 57007, USA.
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Chen M, Tan J, Jin Z, Jiang T, Wu J, Yu X. Research progress on Sirtuins (SIRTs) family modulators. Biomed Pharmacother 2024; 174:116481. [PMID: 38522239 DOI: 10.1016/j.biopha.2024.116481] [Citation(s) in RCA: 14] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2024] [Revised: 03/15/2024] [Accepted: 03/19/2024] [Indexed: 03/26/2024] Open
Abstract
Sirtuins (SIRTs) represent a class of nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylases that exert a crucial role in cellular signal transduction and various biological processes. The mammalian sirtuins family encompasses SIRT1 to SIRT7, exhibiting therapeutic potential in counteracting cellular aging, modulating metabolism, responding to oxidative stress, inhibiting tumors, and improving cellular microenvironment. These enzymes are intricately linked to the occurrence and treatment of diverse pathological conditions, including cancer, autoimmune diseases, and cardiovascular disorders. Given the significance of histone modification in gene expression and chromatin structure, maintaining the equilibrium of the sirtuins family is imperative for disease prevention and health restoration. Mounting evidence suggests that modulators of SIRTs play a crucial role in treating various diseases and maintaining physiological balance. This review delves into the molecular structure and regulatory functions of the sirtuins family, reviews the classification and historical evolution of SIRTs modulators, offers a systematic overview of existing SIRTs modulation strategies, and elucidates the regulatory mechanisms of SIRTs modulators (agonists and inhibitors) and their clinical applications. The article concludes by summarizing the challenges encountered in SIRTs modulator research and offering insights into future research directions.
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Affiliation(s)
- Mingkai Chen
- Wujin Hospital Affiliated with Jiangsu University, Changzhou, Jiangsu, China; School of Medicine Jiangsu University, Zhenjiang, Jiangsu, China
| | - Junfei Tan
- School of Medicine Jiangsu University, Zhenjiang, Jiangsu, China
| | - Zihan Jin
- Changzhou Second People's Hospital Affiliated to Nanjing Medical University, Changzhou City, China
| | - Tingting Jiang
- Wujin Hospital Affiliated with Jiangsu University, Changzhou, Jiangsu, China
| | - Jiabiao Wu
- Wujin Hospital Affiliated with Jiangsu University, Changzhou, Jiangsu, China
| | - Xiaolong Yu
- Wujin Hospital Affiliated with Jiangsu University, Changzhou, Jiangsu, China; The Wujin Clinical College of Xuzhou Medical University, Changzhou, Jiangsu, China.
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Najafiyan B, Bokaii Hosseini Z, Esmaelian S, Firuzpour F, Rahimipour Anaraki S, Kalantari L, Hheidari A, Mesgari H, Nabi-Afjadi M. Unveiling the potential effects of resveratrol in lung cancer treatment: Mechanisms and nanoparticle-based drug delivery strategies. Biomed Pharmacother 2024; 172:116207. [PMID: 38295754 DOI: 10.1016/j.biopha.2024.116207] [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: 12/09/2023] [Revised: 01/17/2024] [Accepted: 01/22/2024] [Indexed: 03/03/2024] Open
Abstract
Lung cancer ranks among the most prevalent forms of cancer and remains a significant factor in cancer-related mortality across the world. It poses significant challenges to healthcare systems and society as a whole due to its high incidence, mortality rates, and late-stage diagnosis. Resveratrol (RV), a natural compound found in various plants, has shown potential as a nanomedicine for lung cancer treatment. RV has varied effects on cancer cells, including promoting apoptosis by increasing pro-apoptotic proteins (Bax and Bak) and decreasing anti-apoptotic proteins (Bcl-2). It also hinders cell proliferation by influencing important signaling pathways (MAPK, mTOR, PI3K/Akt, and Wnt/β-catenin) that govern cancer progression. In addition, RV acts as a potent antioxidant, diminishing oxidative stress and safeguarding cells against DNA damage. However, using RV alone in cancer treatment has drawbacks, such as low bioavailability, lack of targeting ability, and susceptibility to degradation. In contrast, nanoparticle-based delivery systems address these limitations and hold promise for improving treatment outcomes in lung cancer; nanoparticle formulations of RV offer advantages such as improved drug delivery, increased stability, controlled release, and targeted delivery to lung cancer cells. This article will provide an overview of lung cancer, explore the potential of RV as a therapeutic agent, discuss the benefits and challenges of nanoparticle-based drug delivery, and highlight the promise of RV nanoparticles for cancer treatment, including lung cancer. By optimizing these systems for clinical application, future studies aim to enhance overall treatment outcomes and improve the prognosis for lung cancer patients.
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Affiliation(s)
- Behnam Najafiyan
- Faculty of Pharmacy, Shiraz University of Medical Science, Shiraz, Iran
| | | | - Samar Esmaelian
- Faculty of Dentistry, Islamic Azad University, Tehran Branch, Tehran, Iran
| | - Faezeh Firuzpour
- Student of Research Committee, Babol University of Medical Sciences, Babol, Iran
| | | | - Leila Kalantari
- School of Medicine, Kashan University of Medical Sciences, Kashan, Iran
| | - Ali Hheidari
- Department of Mechanical Engineering, Islamic Azad University, Science and Research Branch, Tehran, Iran
| | - Hassan Mesgari
- Oral and Maxillofacial Surgery Department, Faculty of Dentistry, Islamic Azad University, Tehran Branch, Tehran, Iran.
| | - Mohsen Nabi-Afjadi
- Department of Biochemistry, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.
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Brown K, Theofanous D, Britton RG, Aburido G, Pepper C, Sri Undru S, Howells L. Resveratrol for the Management of Human Health: How Far Have We Come? A Systematic Review of Resveratrol Clinical Trials to Highlight Gaps and Opportunities. Int J Mol Sci 2024; 25:747. [PMID: 38255828 PMCID: PMC10815776 DOI: 10.3390/ijms25020747] [Citation(s) in RCA: 16] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2023] [Revised: 01/01/2024] [Accepted: 01/03/2024] [Indexed: 01/24/2024] Open
Abstract
Resveratrol has long been proposed as being beneficial to human health across multiple morbidities, yet there is currently no conclusive clinical evidence to advocate its recommendation in any healthcare setting. A large cohort with high-quality clinical data and clearly defined biomarkers or endpoints are required to draw meaningful conclusions. This systematic review compiles every clinical trial conducted using a defined dose of resveratrol in a purified form across multiple morbidities to highlight the current 'state-of-play' and knowledge gaps, informing future trial designs to facilitate the realisation of resveratrol's potential benefits to human health. Over the last 20 years, there have been almost 200 studies evaluating resveratrol across at least 24 indications, including cancer, menopause symptoms, diabetes, metabolic syndrome, and cardiovascular disease. There are currently no consensus treatment regimens for any given condition or endpoint, beyond the fact that resveratrol is generally well-tolerated at a dose of up to 1 g/day. Additionally, resveratrol consistently reduces inflammatory markers and improves aspects of a dysregulated metabolism. In conclusion, over the last 20 years, the increasing weight of clinical evidence suggests resveratrol can benefit human health, but more large, high-quality clinical trials are required to transition this intriguing compound from health food shops to the clinic.
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Affiliation(s)
- Karen Brown
- Leicester Cancer Research Centre, University of Leicester, Robert Kilpatrick Clinical Sciences Building, Leicester Royal Infirmary, Leicester LE2 7LX, UK; (D.T.); (R.G.B.); (G.A.); (S.S.U.); (L.H.)
| | - Despoina Theofanous
- Leicester Cancer Research Centre, University of Leicester, Robert Kilpatrick Clinical Sciences Building, Leicester Royal Infirmary, Leicester LE2 7LX, UK; (D.T.); (R.G.B.); (G.A.); (S.S.U.); (L.H.)
| | - Robert G. Britton
- Leicester Cancer Research Centre, University of Leicester, Robert Kilpatrick Clinical Sciences Building, Leicester Royal Infirmary, Leicester LE2 7LX, UK; (D.T.); (R.G.B.); (G.A.); (S.S.U.); (L.H.)
| | - Grandezza Aburido
- Leicester Cancer Research Centre, University of Leicester, Robert Kilpatrick Clinical Sciences Building, Leicester Royal Infirmary, Leicester LE2 7LX, UK; (D.T.); (R.G.B.); (G.A.); (S.S.U.); (L.H.)
| | - Coral Pepper
- Odames Library, Victoria Building, Leicester Royal Infirmary, Leicester LE1 5WW, UK
| | - Shanthi Sri Undru
- Leicester Cancer Research Centre, University of Leicester, Robert Kilpatrick Clinical Sciences Building, Leicester Royal Infirmary, Leicester LE2 7LX, UK; (D.T.); (R.G.B.); (G.A.); (S.S.U.); (L.H.)
| | - Lynne Howells
- Leicester Cancer Research Centre, University of Leicester, Robert Kilpatrick Clinical Sciences Building, Leicester Royal Infirmary, Leicester LE2 7LX, UK; (D.T.); (R.G.B.); (G.A.); (S.S.U.); (L.H.)
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Alhusaini AM, Alshehri SM, Sarawi WS, Alghibiwi HK, Alturaif SA, Al khbiah RA, Alali SM, Alsaif SM, Alsultan EN, Hasan IH. Implication of MAPK, Lipocalin-2, and Fas in the protective action of liposomal resveratrol against isoproterenol-induced kidney injury. Saudi Pharm J 2024; 32:101907. [PMID: 38178854 PMCID: PMC10764257 DOI: 10.1016/j.jsps.2023.101907] [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: 11/12/2023] [Accepted: 12/05/2023] [Indexed: 01/06/2024] Open
Abstract
Background and Objective Isoproterenol (ISO) is a non-selective β-adrenergic receptor agonist. It can be used to treat bradycardia and cardiogenic shock. Despite its usefulness, the overstimulation of β-receptors by ISO can cause "cardiorenal syndrome," a term used to describe heart and kidney damage. Resveratrol (RES), a natural polyphenol, has marked anti-inflammatory and antioxidant activities. The present work was designed to study the protective efficacy of liposomal resveratrol (L-RES) against ISO-induced kidney injury. Materials and Methods The kidney injury was induced in rats by administering ISO (50 mg/kg, s.c.) twice a week for 2 weeks. RES and L-RES were administered at a dose (20 mg/kg/ day, p.o.) along with ISO for 2 weeks. Inflammatory and apoptotic biomarkers were analyzed, which were validated using histochemical analysis. Results ISO caused renal dysfunction, which manifested as elevated urea, creatinine and uric acid, besides cystatin c and MAPK protein overexpression. In addition, ISO induced gene expression of Fas and lipocalin-2 and provoked genomic DNA fragmentation in renal tissues as compared with the control group. Histological examination confirmed morphological alterations of the kidney tissues obtained from the ISO group. Concurrent treatment of either RES or L-RES with ISO significantly ameliorated kidney damage as demonstrated by the improvement of all measured parameters with the best results for L-RES. The histopathological findings were correlated with the above biochemical parameters. Conclusion L-RES could be a promising approach for the prevention of kidney injury induced by ISO, most likely via the downregulation of MAPK, cystatin c, Fas, and lipocalin-2.
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Affiliation(s)
- Ahlam M. Alhusaini
- Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O Box 22452, Riyadh 11495, Saudi Arabia
| | - Samiyah M. Alshehri
- Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O Box 22452, Riyadh 11495, Saudi Arabia
| | - Wedad S. Sarawi
- Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O Box 22452, Riyadh 11495, Saudi Arabia
| | - Hanan K. Alghibiwi
- Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O Box 22452, Riyadh 11495, Saudi Arabia
| | - Sumayya A. Alturaif
- Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O Box 22452, Riyadh 11495, Saudi Arabia
| | - Reema A. Al khbiah
- Pharm D Program, College of Pharmacy, King Saud University, P.O Box 22452, Riyadh 11495, Saudi Arabia
| | - Shog M. Alali
- Pharm D Program, College of Pharmacy, King Saud University, P.O Box 22452, Riyadh 11495, Saudi Arabia
| | - Shaikha M. Alsaif
- Department of Pharmaceutics, College of Pharmacy, King Saud University, P.O Box 22452, Riyadh 11495, Saudi Arabia
| | - Ebtesam N. Alsultan
- Department of Pharmacognosy, College of Pharmacy, King Saud University, P.O Box 22452, Riyadh 11495, Saudi Arabia
| | - Iman H. Hasan
- Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O Box 22452, Riyadh 11495, Saudi Arabia
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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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Silva AFR, Silva-Reis R, Ferreira R, Oliveira PA, Faustino-Rocha AI, Pinto MDL, Coimbra MA, Silva AMS, Cardoso SM. The Impact of Resveratrol-Enriched Bread on Cardiac Remodeling in a Preclinical Model of Diabetes. Antioxidants (Basel) 2023; 12:antiox12051066. [PMID: 37237932 DOI: 10.3390/antiox12051066] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2023] [Revised: 04/27/2023] [Accepted: 05/04/2023] [Indexed: 05/28/2023] Open
Abstract
The World Health Organization aims to stop the rise of diabetes by 2025, and diet is one of the most efficient non-pharmacological strategies used to prevent it. Resveratrol (RSV) is a natural compound with anti-diabetic properties, and incorporating it into bread is a suitable way to make it more accessible to consumers as it can be included as part of their daily diet. This study aimed to evaluate the effect of RSV-enriched bread in preventing early type 2 diabetes cardiomyopathy in vivo. Male Sprague Dawley rats (3 weeks old) were divided into four groups: controls with plain bread (CB) and RSV bread (CBR), and diabetics with plain bread (DB) and RSV bread (DBR). Type 2 diabetes was induced by adding fructose to the drinking water for two weeks followed by an injection of streptozotocin (STZ) (40 mg/kg). Then, plain bread and RSV bread (10 mg RSV/kg body weight) were included in the rats' diet for four weeks. Cardiac function, anthropometric, and systemic biochemical parameters were monitored, as well as the histology of the heart and molecular markers of regeneration, metabolism, and oxidative stress. Data showed that an RSV bread diet decreased the polydipsia and body weight loss observed in the early stages of the disease. At the cardiac level, an RSV bread diet diminished fibrosis but did not counteract the dysfunction and metabolic changes seen in fructose-fed STZ-injected rats.
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Affiliation(s)
- Andreia F R Silva
- LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal
| | - Rita Silva-Reis
- LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal
| | - Rita Ferreira
- LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal
| | - Paula A Oliveira
- Center for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), Inov4Agro, University of Trás-os-Montes and Alto Douro (UTAD), 5000-801 Vila Real, Portugal
- Department of Veterinary Sciences, University of Trás-os-Montes and Alto Douro UTAD, 5000-801 Vila Real, Portugal
| | - Ana I Faustino-Rocha
- Center for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), Inov4Agro, University of Trás-os-Montes and Alto Douro (UTAD), 5000-801 Vila Real, Portugal
- Department of Zootechnics, Comprehensive Health Research Center, School of Sciences and Technology, University of Évora, 7004-516 Évora, Portugal
| | - Maria de Lurdes Pinto
- Center for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), Inov4Agro, University of Trás-os-Montes and Alto Douro (UTAD), 5000-801 Vila Real, Portugal
- Department of Veterinary Sciences, University of Trás-os-Montes and Alto Douro UTAD, 5000-801 Vila Real, Portugal
| | - Manuel A Coimbra
- LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal
| | - Artur M S Silva
- LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal
| | - Susana M Cardoso
- LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal
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Venkat R, Verma E, Daimary UD, Kumar A, Girisa S, Dutta U, Ahn KS, Kunnumakkara AB. The Journey of Resveratrol from Vineyards to Clinics. Cancer Invest 2023; 41:183-220. [PMID: 35993769 DOI: 10.1080/07357907.2022.2115057] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
With rising technological advancements, several factors influence the lifestyle of people and stimulate chronic inflammation that severely affects the human body. Chronic inflammation leads to a broad range of physical and pathophysiological distress. For many years, non-steroidal drugs and corticosteroids were most frequently used in treating inflammation and related ailments. However, long-term usage of these drugs aggravates the conditions of chronic diseases and is presented with morbid side effects, especially in old age. Hence, the quest for safe and less toxic anti-inflammatory compounds of high therapeutic potential with least adverse side effects has shifted researchers' attention to ancient medicinal system. Resveratrol (RSV) - 3,4,5' trihydroxystilbene is one such naturally available polyphenolic stilbene derivative obtained from various plant sources. For over 2000 years, these plants have been used in Asian medicinal system for curing inflammation-associated disorders. There is a wealth of in vitro, in vivo and clinical evidence that shows RSV could induce anti-aging health benefits including, anti-cancer, anti-inflammatory, anti-oxidant, phytoesterogenic, and cardio protective properties. However, the issue of rapid elimination of RSV through the metabolic system and its low bio-availability is of paramount importance which is being studied extensively. Therefore, in this article, we scientifically reviewed the molecular targets, biological activities, beneficial and contradicting effects of RSV as evinced by clinical studies for the prevention and treatment of inflammation-mediated chronic disorders.
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Affiliation(s)
- Ramya Venkat
- Department of Biosciences and Bioengineering, Cancer Biology Laboratory, Indian Institute of Technology (IIT) Guwahati, Guwahati, India
| | - Elika Verma
- Department of Biosciences and Bioengineering, Cancer Biology Laboratory, Indian Institute of Technology (IIT) Guwahati, Guwahati, India
| | - Uzini Devi Daimary
- Department of Biosciences and Bioengineering, Cancer Biology Laboratory, Indian Institute of Technology (IIT) Guwahati, Guwahati, India
| | - Aviral Kumar
- Department of Biosciences and Bioengineering, Cancer Biology Laboratory, Indian Institute of Technology (IIT) Guwahati, Guwahati, India
| | - Sosmitha Girisa
- Department of Biosciences and Bioengineering, Cancer Biology Laboratory, Indian Institute of Technology (IIT) Guwahati, Guwahati, India
| | - Uma Dutta
- Department of Zoology, Cell and Molecular Biology Laboratory, Cotton University, Guwahati, India
| | - Kwang Seok Ahn
- Department of Science in Korean Medicine, Kyung Hee University, Seoul, Republic of Korea
| | - Ajaikumar B Kunnumakkara
- Department of Biosciences and Bioengineering, Cancer Biology Laboratory, Indian Institute of Technology (IIT) Guwahati, Guwahati, India
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García-Martínez BI, Ruiz-Ramos M, Pedraza-Chaverri J, Santiago-Osorio E, Mendoza-Núñez VM. Influence of Age and Dose on the Effect of Resveratrol for Glycemic Control in Type 2 Diabetes Mellitus: Systematic Review and Meta-Analysis. Molecules 2022; 27:molecules27165232. [PMID: 36014469 PMCID: PMC9416262 DOI: 10.3390/molecules27165232] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Revised: 08/10/2022] [Accepted: 08/13/2022] [Indexed: 11/16/2022] Open
Abstract
Background: Several clinical trials have suggested that resveratrol has hypoglycemic properties; however, there are other studies in which such an effect has not been observed. Methods: We carried out a systematic search in several databases; seventeen studies were selected for the systematic review and fifteen were included in the meta-analysis. Results: Resveratrol decreases glucose levels in subjects aged 45−59 years at doses <250 mg/day (−8.64 mg/dL, p < 0.00001), 250−500 mg/day (−22.24 mg/dL, p = 0.0003), and 500−1000 mg/day (−28.40 mg/dL, p = 0.0008), while in subjects older than 60 years, it only decreases with doses of 250−500 mg/day. Likewise, HbA1c improved in subjects aged 45−59 years with doses of 250−500 mg (−0.60%, p < 0.00001), but not in subjects older than 60 years. Insulin levels improved in subjects aged 45−59 years with doses < 250 mg/day (−0.80 mIU/L, p = 0.0003) and doses of 250−500 mg/day (−5.0 mIU/L, p = 0.0003), although in subjects older than 60 years, they only improved with doses of 250−500 mg/day (−1.79 mIU/L, p = 0.01). On the other hand, HOMA-IR only improved in subjects older than 60 years with doses of 250−500 mg/day (−0.40, p = 0.01). Conclusions: Resveratrol has a statistically significant dose−response effect on glucose concentrations, HbA1c, and insulin levels; however, there is not enough scientific evidence to propose a therapeutic dose.
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Affiliation(s)
| | - Mirna Ruiz-Ramos
- Research Unit on Gerontology, FES Zaragoza, National Autonomous University of Mexico, Mexico City 09230, Mexico
| | - José Pedraza-Chaverri
- Department of Biology, Faculty of Chemistry, National Autonomous University of Mexico (UNAM), Mexico City 04510, Mexico
| | - Edelmiro Santiago-Osorio
- Hematopoiesis and Leukemia Laboratory, Research Unit on Cell Differentiation and Cancer, FES Zaragoza, National Autonomous University of Mexico, Mexico City 09230, Mexico
| | - Víctor Manuel Mendoza-Núñez
- Research Unit on Gerontology, FES Zaragoza, National Autonomous University of Mexico, Mexico City 09230, Mexico
- Correspondence:
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Neuroprotective Effects of Resveratrol by Modifying Cholesterol Metabolism and Aβ Processing in SAMP8 Mice. Int J Mol Sci 2022; 23:ijms23147580. [PMID: 35886936 PMCID: PMC9324102 DOI: 10.3390/ijms23147580] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2022] [Revised: 07/04/2022] [Accepted: 07/07/2022] [Indexed: 11/17/2022] Open
Abstract
Cholesterol metabolism seems dysregulated and linked to amyloid-β (Aβ) formation in neurodegeneration, but the underlying mechanisms are poorly known. Resveratrol (RSV) is a polyphenol with antioxidant activity and neuroprotective properties. Here, we analyzed the effect of age and RSV supplementation on cholesterol metabolism in the brain and blood serum, and its potential link to Aβ processing, in SAMP8 mice—an animal model of aging and Alzheimer’s disease. In the brain, our results revealed an age-related increase in ApoE and unesterified cholesterol in the plasma membrane whereas LDL receptor, HMG-CoA reductase, HMG-CoA-C1 synthase, and ABCA1 transporter remained unaltered. Furthermore, BACE-1 and APP gene expression was decreased. This dysregulation could be involved in the amyloidogenic processing pathway of APP towards Aβ formation. In turn, RSV exhibited an age-dependent effect. While levels of unesterified cholesterol in the plasma membrane were not affected by RSV, several participants in cholesterol uptake, release, and de novo synthesis differed, depending on age. Thus, RSV supplementation exhibited a different neuroprotective effect acting on Aβ processing or cholesterol metabolism in the brain at earlier or later ages, respectively. In blood serum, HDL lipoprotein and free cholesterol were increased by age, whereas VLDL and LDL lipoproteins remained unaltered. Again, the protective effect of RSV by decreasing the LDL or increasing the HDL levels also seems to depend on the intervention’s moment. In conclusion, age is a prominent factor for cholesterol metabolism dysregulation in the brain of SAMP8 mice and influences the protective effects of RSV through cholesterol metabolism and Aβ processing.
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Pang L, Jiang X, Lian X, Chen J, Song EF, Jin LG, Xia ZY, Ma HC, Cai Y. Caloric restriction-mimetics for the reduction of heart failure risk in aging heart: with consideration of gender-related differences. Mil Med Res 2022; 9:33. [PMID: 35786219 PMCID: PMC9252041 DOI: 10.1186/s40779-022-00389-w] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2021] [Accepted: 05/30/2022] [Indexed: 11/10/2022] Open
Abstract
The literature is full of claims regarding the consumption of polyphenol or polyamine-rich foods that offer some protection from developing cardiovascular disease (CVD). This is achieved by preventing cardiac hypertrophy and protecting blood vessels through improving the function of endothelium. However, do these interventions work in the aged human hearts? Cardiac aging is accompanied by an increase in left ventricular hypertrophy, along with diastolic and systolic dysfunction. It also confers significant cardiovascular risks for both sexes. The incidence and prevalence of CVD increase sharply at an earlier age in men than women. Furthermore, the patterns of heart failure differ between sexes, as do the lifetime risk factors. Do caloric restriction (CR)-mimetics, rich in polyphenol or polyamine, delay or reverse cardiac aging equally in both men and women? This review will discuss three areas: (1) mechanisms underlying age-related cardiac remodeling; (2) gender-related differences and potential mechanisms underlying diminished cardiac response in older men and women; (3) we select a few polyphenol or polyamine rich compounds as the CR-mimetics, such as resveratrol, quercetin, curcumin, epigallocatechin gallate and spermidine, due to their capability to extend health-span and induce autophagy. We outline their abilities and issues on retarding aging in animal hearts and preventing CVD in humans. We discuss the confounding factors that should be considered for developing therapeutic strategies against cardiac aging in humans.
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Affiliation(s)
- Lei Pang
- Department of Anesthesiology, the First Hospital of Jilin University, Changchun, 130021, China
| | - Xi Jiang
- Health Promotion Center, the First Hospital of Jilin University, Changchun, 130021, China
| | - Xin Lian
- Department of Urology, the First Hospital of Jilin University, Changchun, 130021, China
| | - Jie Chen
- Henry Fok School of Biology and Agriculture, Shaoguan University, Shaoguan, 512000, Guangdong, China
| | - Er-Fei Song
- Department of Metabolic and Bariatric Surgery, Jinan University First Affiliated Hospital, Guangzhou, 510630, China.,Department of Medicine, LKS Faculty of Medicine, the University of Hong Kong, Hong Kong, China
| | - Lei-Gang Jin
- Department of Medicine, LKS Faculty of Medicine, the University of Hong Kong, Hong Kong, China.,State Key Laboratory of Pharmaceutical Biotechnology, LKS Faculty of Medicine, the University of Hong Kong, Hong Kong, China
| | - Zheng-Yuan Xia
- State Key Laboratory of Pharmaceutical Biotechnology, LKS Faculty of Medicine, the University of Hong Kong, Hong Kong, China.,Department of Anesthesiology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524000, Guangdong, China
| | - Hai-Chun Ma
- Department of Anesthesiology, the First Hospital of Jilin University, Changchun, 130021, China.
| | - Yin Cai
- Department of Health Technology and Informatics, the Hong Kong Polytechnic University, Hong Kong, China.
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Blocking of SGLT2 to Eliminate NADPH-Induced Oxidative Stress in Lenses of Animals with Fructose-Induced Diabetes Mellitus. Int J Mol Sci 2022; 23:ijms23137142. [PMID: 35806147 PMCID: PMC9266761 DOI: 10.3390/ijms23137142] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2022] [Revised: 06/20/2022] [Accepted: 06/24/2022] [Indexed: 12/13/2022] Open
Abstract
Chronic hyperglycemia triggers an abnormal rise in reactive oxygen species (ROS) that leads to blindness in patients with diabetes mellitus (DM) and cataracts. In this study, the effects of dapagliflozin, metformin and resveratrol on ROS production were investigated in lens epithelial cells (LECs) of animals with fructose-induced DM. LECs were isolated from patients without DM, or with DM devoid of diabetic retinopathy. Animals were treated with 10% fructose for 8 weeks to induce DM, which was verified by monitoring blood pressure and serum parameters. For drug treatments, 1.2 mg/day of dapagliflozin was given for 2 weeks, 500 mg/kg/day of metformin was given, and 10 mg/kg/day of resveratrol was given. Dihydroethidium was used to stain endogenous O2˙− production in vivo of the LECs. Superoxide production was expressed in the cataract of DM, or patients without DM. Sodium–glucose cotransporter 2 (SGLT2), glucose transporter 1 (GLUT1), GLUT5, the reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit p47/p67-phox, NOX4 and RAGE were significantly increased in LECs with DM. In addition, the dapagliflozin treatment reduced GLUT5, p47/p67-phox, NADPH oxidase 4 (NOX4) and receptor for advanced glycation end products (RAGE) expressions. On the contrary, metformin or resveratrol inhibited p47-phox, GLUT5, and SGLT2 expressions, but not nuclear factor erythroid 2–related factor 2 (NRF2). In summary, dapagliflozin, metformin or resveratrol down-regulated p47-phox expression through SGLT2 inactivation and ROS reduction. These important findings imply that SGLT2 can be blocked to ameliorate oxidative stress in the cataracts of DM patients.
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De Moudt S, Hendrickx JO, Neutel C, De Munck D, Leloup A, De Meyer GR, Martinet W, Fransen P. Aortic Stiffness in L-NAME Treated C57Bl/6 Mice Displays a Shift From Early Endothelial Dysfunction to Late-Term Vascular Smooth Muscle Cell Dysfunction. Front Physiol 2022; 13:874015. [PMID: 35800344 PMCID: PMC9254682 DOI: 10.3389/fphys.2022.874015] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2022] [Accepted: 05/26/2022] [Indexed: 12/22/2022] Open
Abstract
Introduction and Aims: Endothelial dysfunction is recognized as a cardiovascular aging hallmark. Administration of nitric oxide synthase blocker N-Ω-Nitro-L-arginine methyl ester hydrochloride (L-NAME) constitutes a well-known small animal model of cardiovascular aging. Despite extensive phenotypic characterization, the exact aortic function changes in L-NAME treated mice are largely unknown. Therefore, this study presents a longitudinal characterization of the aortic reactivity and biomechanical alterations in L-NAME treated C57Bl/6 mice. Methods and Results: Male C57Bl/6 mice were treated with L-NAME (0.5 mg/ml drinking water) for 1, 2, 4, 8, or 16 weeks. Peripheral blood pressure measurement (tail-cuff) and transthoracic echocardiograms were recorded, showing progressive hypertension after 4 weeks of treatment and progressive cardiac hypertrophy after 8–16 weeks of treatment. Aortic stiffness was measured in vivo as aortic pulse wave velocity (aPWV, ultrasound) and ex vivo as Peterson modulus (Ep). Aortic reactivity and biomechanics were investigated ex vivo in thoracic aortic rings, mounted isometrically or dynamically-stretched in organ bath set-ups. Aortic stiffening was heightened in L-NAME treated mice after all treatment durations, thereby preceding the development of hypertension and cardiac aging. L-NAME treatment doubled the rate of arterial stiffening compared to control mice, and displayed an attenuation of the elevated aortic stiffness at high distending pressure, possibly due to late-term reduction of medial collagen types I, III, and IV content. Remarkably, endothelial dysfunction, measured by acetylcholine concentration-response stimulation in precontracted aortic rings, was only observed after short-term (1–4 weeks) treatment, followed by restoration of endothelial function which coincided with increased phosphorylation of endothelial nitric oxide synthase (S1177). In the late-disease phase (8–16 weeks), vascular smooth muscle cell (VSMC) dysfunction developed, including increased contribution of voltage-dependent calcium channels (assessed by inhibition with diltiazem), basal VSMC cytoplasmic calcium loading (assessed by removal of extracellular calcium), and heightened intracellular contractile calcium handling (assessed by measurement of sarcoplasmic reticulum-mediated transient contractions). Conclusion: Arterial stiffness precedes peripheral hypertension and cardiac hypertrophy in chronic L-NAME treated male C57Bl/6 mice. The underlying aortic disease mechanisms underwent a distinct shift from early endothelial dysfunction to late-term VSMC dysfunction, with continued disease progression.
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De Moudt S, Hendrickx JO, De Meyer GRY, Martinet W, Fransen P. Basal Vascular Smooth Muscle Cell Tone in eNOS Knockout Mice Can Be Reversed by Cyclic Stretch and Is Independent of Age. Front Physiol 2022; 13:882527. [PMID: 35574444 PMCID: PMC9096105 DOI: 10.3389/fphys.2022.882527] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2022] [Accepted: 04/11/2022] [Indexed: 11/14/2022] Open
Abstract
Introduction and Aims: Endothelial nitric oxide synthase (eNOS) knockout mice develop pronounced cardiovascular disease. In the present study, we describe the alterations in aortic physiology and biomechanics of eNOS knockout and C57Bl/6 control mice at 2–12 months of age, including a thorough physiological investigation of age and cyclic stretch-dependent VSMC contractility and aortic stiffness. Methods and Results: Peripheral blood pressure and aortic pulse wave velocity were measured in vivo, and aortic biomechanical studies and isometric contractions were investigated ex vivo. Age-dependent progression of aortic stiffness, peripheral hypertension, and aortic contractility in eNOS knockout mice was absent, attenuated, or similar to C57Bl/6 control mice. Voltage-gated calcium channel (VGCC)-dependent calcium influx inversely affected isometric contraction and aortic stiffening by α1-adrenergic stimulation in eNOS knockout mice. Baseline aortic stiffness was selectively reduced in eNOS knockout mice after ex vivo cyclic stretch exposure in an amplitude-dependent manner, which prompted us to investigate cyclic stretch dependent regulation of aortic contractility and stiffness. Aortic stiffness, both in baseline conditions and after activation of vascular smooth muscle cell (VSMC) contraction, was reduced with increasing cyclic stretch amplitude. This cyclic stretch dependency was attenuated with age, although aged eNOS knockout mice displayed better preservation of cyclic stretch-dependency compared to C57Bl/6 control mice. Store operated calcium entry-medicated aortic stiffening as induced by inhibiting sarcoplasmic reticulum calcium ATPase pumps with 10 µM CPA was most pronounced in the aorta of aged mice and at low cyclic stretch amplitude, but independent of eNOS. Basal aortic tonus and VSMC depolarization were highly dependent on eNOS, and were most pronounced at low cyclic stretch, with attenuation at increasing cyclic stretch amplitude. Conclusion: eNOS knockout mice display attenuated progression of arterial disease as compared to C57Bl/6 control mice. Basal VSMC tone in eNOS knockout mice could be reduced by ex vivo exposure to cyclic stretch through stretch-dependent regulation of cytosolic calcium. Both baseline and active aortic stiffness were highly dependent on cyclic stretch regulation, which was more pronounced in young versus aged mice. Other mediators of VSMC contraction and calcium handling were dependent on cyclic stretch mechanotransduction, but independent of eNOS.
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Inchingolo AD, Malcangi G, Inchingolo AM, Piras F, Settanni V, Garofoli G, Palmieri G, Ceci S, Patano A, De Leonardis N, Di Pede C, Montenegro V, Azzollini D, Garibaldi MG, Kruti Z, Tarullo A, Coloccia G, Mancini A, Rapone B, Semjonova A, Hazballa D, D’Oria MT, Jones M, Macchia L, Bordea IR, Scarano A, Lorusso F, Tartaglia GM, Maspero C, Del Fabbro M, Nucci L, Ferati K, Ferati AB, Brienza N, Corriero A, Inchingolo F, Dipalma G. Benefits and Implications of Resveratrol Supplementation on Microbiota Modulations: A Systematic Review of the Literature. Int J Mol Sci 2022; 23:4027. [PMID: 35409389 PMCID: PMC8999966 DOI: 10.3390/ijms23074027] [Citation(s) in RCA: 45] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2022] [Revised: 03/24/2022] [Accepted: 03/31/2022] [Indexed: 01/27/2023] Open
Abstract
Resveratrol is a polyphenol that has been shown to possess many applications in different fields of medicine. This systematic review has drawn attention to the axis between resveratrol and human microbiota, which plays a key role in maintaining an adequate immune response that can lead to different diseases when compromised. Resveratrol can also be an asset in new technologies, such as gene therapy. PubMed, Cochrane Library, Scopus, Web of Science, and Google Scholar were searched to find papers that matched our topic dating from 1 January 2017 up to 18 January 2022, with English-language restriction using the following Boolean keywords: ("resveratrol" AND "microbio*"). Eighteen studies were included as relevant papers matching the purpose of our investigation. Immune response, prevention of thrombotic complications, microbiota, gene therapy, and bone regeneration were retrieved as the main topics. The analyzed studies mostly involved resveratrol supplementation and its effects on human microbiota by trials in vitro, in vivo, and ex vivo. The beneficial activity of resveratrol is evident by analyzing the changes in the host's genetic expression and the gastrointestinal microbial community with its administration. The possibility of identifying individual microbial families may allow to tailor therapeutic plans with targeted polyphenolic diets when associated with microbial dysbiosis, such as inflammatory diseases of the gastrointestinal tract, degenerative diseases, tumors, obesity, diabetes, bone tissue regeneration, and metabolic syndrome.
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Affiliation(s)
- Alessio Danilo Inchingolo
- Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, 70121 Bari, Italy; (A.D.I.); (G.M.); (A.M.I.); (F.P.); (V.S.); (G.G.); (G.P.); (S.C.); (A.P.); (N.D.L.); (C.D.P.); (V.M.); (D.A.); (M.G.G.); (Z.K.); (A.T.); (G.C.); (A.M.); (B.R.); (A.S.); (D.H.); (M.T.D.); (M.J.); (F.I.); (G.D.)
| | - Giuseppina Malcangi
- Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, 70121 Bari, Italy; (A.D.I.); (G.M.); (A.M.I.); (F.P.); (V.S.); (G.G.); (G.P.); (S.C.); (A.P.); (N.D.L.); (C.D.P.); (V.M.); (D.A.); (M.G.G.); (Z.K.); (A.T.); (G.C.); (A.M.); (B.R.); (A.S.); (D.H.); (M.T.D.); (M.J.); (F.I.); (G.D.)
| | - Angelo Michele Inchingolo
- Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, 70121 Bari, Italy; (A.D.I.); (G.M.); (A.M.I.); (F.P.); (V.S.); (G.G.); (G.P.); (S.C.); (A.P.); (N.D.L.); (C.D.P.); (V.M.); (D.A.); (M.G.G.); (Z.K.); (A.T.); (G.C.); (A.M.); (B.R.); (A.S.); (D.H.); (M.T.D.); (M.J.); (F.I.); (G.D.)
| | - Fabio Piras
- Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, 70121 Bari, Italy; (A.D.I.); (G.M.); (A.M.I.); (F.P.); (V.S.); (G.G.); (G.P.); (S.C.); (A.P.); (N.D.L.); (C.D.P.); (V.M.); (D.A.); (M.G.G.); (Z.K.); (A.T.); (G.C.); (A.M.); (B.R.); (A.S.); (D.H.); (M.T.D.); (M.J.); (F.I.); (G.D.)
| | - Vito Settanni
- Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, 70121 Bari, Italy; (A.D.I.); (G.M.); (A.M.I.); (F.P.); (V.S.); (G.G.); (G.P.); (S.C.); (A.P.); (N.D.L.); (C.D.P.); (V.M.); (D.A.); (M.G.G.); (Z.K.); (A.T.); (G.C.); (A.M.); (B.R.); (A.S.); (D.H.); (M.T.D.); (M.J.); (F.I.); (G.D.)
| | - Grazia Garofoli
- Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, 70121 Bari, Italy; (A.D.I.); (G.M.); (A.M.I.); (F.P.); (V.S.); (G.G.); (G.P.); (S.C.); (A.P.); (N.D.L.); (C.D.P.); (V.M.); (D.A.); (M.G.G.); (Z.K.); (A.T.); (G.C.); (A.M.); (B.R.); (A.S.); (D.H.); (M.T.D.); (M.J.); (F.I.); (G.D.)
| | - Giulia Palmieri
- Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, 70121 Bari, Italy; (A.D.I.); (G.M.); (A.M.I.); (F.P.); (V.S.); (G.G.); (G.P.); (S.C.); (A.P.); (N.D.L.); (C.D.P.); (V.M.); (D.A.); (M.G.G.); (Z.K.); (A.T.); (G.C.); (A.M.); (B.R.); (A.S.); (D.H.); (M.T.D.); (M.J.); (F.I.); (G.D.)
| | - Sabino Ceci
- Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, 70121 Bari, Italy; (A.D.I.); (G.M.); (A.M.I.); (F.P.); (V.S.); (G.G.); (G.P.); (S.C.); (A.P.); (N.D.L.); (C.D.P.); (V.M.); (D.A.); (M.G.G.); (Z.K.); (A.T.); (G.C.); (A.M.); (B.R.); (A.S.); (D.H.); (M.T.D.); (M.J.); (F.I.); (G.D.)
| | - Assunta Patano
- Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, 70121 Bari, Italy; (A.D.I.); (G.M.); (A.M.I.); (F.P.); (V.S.); (G.G.); (G.P.); (S.C.); (A.P.); (N.D.L.); (C.D.P.); (V.M.); (D.A.); (M.G.G.); (Z.K.); (A.T.); (G.C.); (A.M.); (B.R.); (A.S.); (D.H.); (M.T.D.); (M.J.); (F.I.); (G.D.)
| | - Nicole De Leonardis
- Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, 70121 Bari, Italy; (A.D.I.); (G.M.); (A.M.I.); (F.P.); (V.S.); (G.G.); (G.P.); (S.C.); (A.P.); (N.D.L.); (C.D.P.); (V.M.); (D.A.); (M.G.G.); (Z.K.); (A.T.); (G.C.); (A.M.); (B.R.); (A.S.); (D.H.); (M.T.D.); (M.J.); (F.I.); (G.D.)
| | - Chiara Di Pede
- Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, 70121 Bari, Italy; (A.D.I.); (G.M.); (A.M.I.); (F.P.); (V.S.); (G.G.); (G.P.); (S.C.); (A.P.); (N.D.L.); (C.D.P.); (V.M.); (D.A.); (M.G.G.); (Z.K.); (A.T.); (G.C.); (A.M.); (B.R.); (A.S.); (D.H.); (M.T.D.); (M.J.); (F.I.); (G.D.)
| | - Valentina Montenegro
- Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, 70121 Bari, Italy; (A.D.I.); (G.M.); (A.M.I.); (F.P.); (V.S.); (G.G.); (G.P.); (S.C.); (A.P.); (N.D.L.); (C.D.P.); (V.M.); (D.A.); (M.G.G.); (Z.K.); (A.T.); (G.C.); (A.M.); (B.R.); (A.S.); (D.H.); (M.T.D.); (M.J.); (F.I.); (G.D.)
| | - Daniela Azzollini
- Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, 70121 Bari, Italy; (A.D.I.); (G.M.); (A.M.I.); (F.P.); (V.S.); (G.G.); (G.P.); (S.C.); (A.P.); (N.D.L.); (C.D.P.); (V.M.); (D.A.); (M.G.G.); (Z.K.); (A.T.); (G.C.); (A.M.); (B.R.); (A.S.); (D.H.); (M.T.D.); (M.J.); (F.I.); (G.D.)
| | - Maria Grazia Garibaldi
- Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, 70121 Bari, Italy; (A.D.I.); (G.M.); (A.M.I.); (F.P.); (V.S.); (G.G.); (G.P.); (S.C.); (A.P.); (N.D.L.); (C.D.P.); (V.M.); (D.A.); (M.G.G.); (Z.K.); (A.T.); (G.C.); (A.M.); (B.R.); (A.S.); (D.H.); (M.T.D.); (M.J.); (F.I.); (G.D.)
| | - Zamira Kruti
- Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, 70121 Bari, Italy; (A.D.I.); (G.M.); (A.M.I.); (F.P.); (V.S.); (G.G.); (G.P.); (S.C.); (A.P.); (N.D.L.); (C.D.P.); (V.M.); (D.A.); (M.G.G.); (Z.K.); (A.T.); (G.C.); (A.M.); (B.R.); (A.S.); (D.H.); (M.T.D.); (M.J.); (F.I.); (G.D.)
| | - Antonella Tarullo
- Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, 70121 Bari, Italy; (A.D.I.); (G.M.); (A.M.I.); (F.P.); (V.S.); (G.G.); (G.P.); (S.C.); (A.P.); (N.D.L.); (C.D.P.); (V.M.); (D.A.); (M.G.G.); (Z.K.); (A.T.); (G.C.); (A.M.); (B.R.); (A.S.); (D.H.); (M.T.D.); (M.J.); (F.I.); (G.D.)
| | - Giovanni Coloccia
- Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, 70121 Bari, Italy; (A.D.I.); (G.M.); (A.M.I.); (F.P.); (V.S.); (G.G.); (G.P.); (S.C.); (A.P.); (N.D.L.); (C.D.P.); (V.M.); (D.A.); (M.G.G.); (Z.K.); (A.T.); (G.C.); (A.M.); (B.R.); (A.S.); (D.H.); (M.T.D.); (M.J.); (F.I.); (G.D.)
| | - Antonio Mancini
- Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, 70121 Bari, Italy; (A.D.I.); (G.M.); (A.M.I.); (F.P.); (V.S.); (G.G.); (G.P.); (S.C.); (A.P.); (N.D.L.); (C.D.P.); (V.M.); (D.A.); (M.G.G.); (Z.K.); (A.T.); (G.C.); (A.M.); (B.R.); (A.S.); (D.H.); (M.T.D.); (M.J.); (F.I.); (G.D.)
| | - Biagio Rapone
- Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, 70121 Bari, Italy; (A.D.I.); (G.M.); (A.M.I.); (F.P.); (V.S.); (G.G.); (G.P.); (S.C.); (A.P.); (N.D.L.); (C.D.P.); (V.M.); (D.A.); (M.G.G.); (Z.K.); (A.T.); (G.C.); (A.M.); (B.R.); (A.S.); (D.H.); (M.T.D.); (M.J.); (F.I.); (G.D.)
| | - Alexandra Semjonova
- Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, 70121 Bari, Italy; (A.D.I.); (G.M.); (A.M.I.); (F.P.); (V.S.); (G.G.); (G.P.); (S.C.); (A.P.); (N.D.L.); (C.D.P.); (V.M.); (D.A.); (M.G.G.); (Z.K.); (A.T.); (G.C.); (A.M.); (B.R.); (A.S.); (D.H.); (M.T.D.); (M.J.); (F.I.); (G.D.)
| | - Denisa Hazballa
- Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, 70121 Bari, Italy; (A.D.I.); (G.M.); (A.M.I.); (F.P.); (V.S.); (G.G.); (G.P.); (S.C.); (A.P.); (N.D.L.); (C.D.P.); (V.M.); (D.A.); (M.G.G.); (Z.K.); (A.T.); (G.C.); (A.M.); (B.R.); (A.S.); (D.H.); (M.T.D.); (M.J.); (F.I.); (G.D.)
- Kongresi Elbasanit, Aqif Pasha, Rruga, 3001 Elbasan, Albania
| | - Maria Teresa D’Oria
- Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, 70121 Bari, Italy; (A.D.I.); (G.M.); (A.M.I.); (F.P.); (V.S.); (G.G.); (G.P.); (S.C.); (A.P.); (N.D.L.); (C.D.P.); (V.M.); (D.A.); (M.G.G.); (Z.K.); (A.T.); (G.C.); (A.M.); (B.R.); (A.S.); (D.H.); (M.T.D.); (M.J.); (F.I.); (G.D.)
- Department of Medical and Biological Sciences, University of Udine, Via delle Scienze, 206, 33100 Udine, Italy
| | - Megan Jones
- Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, 70121 Bari, Italy; (A.D.I.); (G.M.); (A.M.I.); (F.P.); (V.S.); (G.G.); (G.P.); (S.C.); (A.P.); (N.D.L.); (C.D.P.); (V.M.); (D.A.); (M.G.G.); (Z.K.); (A.T.); (G.C.); (A.M.); (B.R.); (A.S.); (D.H.); (M.T.D.); (M.J.); (F.I.); (G.D.)
| | - Luigi Macchia
- Department of Emergency and Organ Transplantation (D.E.T.O.), University of Bari “Aldo Moro”, 70121 Bari, Italy;
| | - Ioana Roxana Bordea
- Department of Oral Rehabilitation, Faculty of Dentistry, Iuliu Hațieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania
| | - Antonio Scarano
- Department of Innovative Technologies in Medicine and Dentistry, University of Chieti-Pescara, 66100 Chieti, Italy;
| | - Felice Lorusso
- Department of Innovative Technologies in Medicine and Dentistry, University of Chieti-Pescara, 66100 Chieti, Italy;
| | - Gianluca Martino Tartaglia
- Department of Biomedical, Surgical and Dental Sciences, School of Dentistry, University of Milan, 20122 Milan, Italy; (G.M.T.); (C.M.); (M.D.F.)
- UOC Maxillo-Facial Surgery and Dentistry, Fondazione IRCCS Ca Granda, Ospedale Maggiore Policlinico, 20122 Milan, Italy
| | - Cinzia Maspero
- Department of Biomedical, Surgical and Dental Sciences, School of Dentistry, University of Milan, 20122 Milan, Italy; (G.M.T.); (C.M.); (M.D.F.)
- UOC Maxillo-Facial Surgery and Dentistry, Fondazione IRCCS Ca Granda, Ospedale Maggiore Policlinico, 20122 Milan, Italy
| | - Massimo Del Fabbro
- Department of Biomedical, Surgical and Dental Sciences, School of Dentistry, University of Milan, 20122 Milan, Italy; (G.M.T.); (C.M.); (M.D.F.)
- IRCCS Orthopedic Institute Galeazzi, 20161 Milan, Italy
| | - Ludovica Nucci
- Multidisciplinary Department of Medical-Surgical and Dental Specialties, University of Campania Luigi Vanvitelli, Via Luigi de Crecchio, 6, 80138 Naples, Italy;
| | - Kenan Ferati
- Faculty of Medical Sciences, University of Tetovo, 1220 Tetovo, North Macedonia; (K.F.); (A.B.F.)
| | - Arberesha Bexheti Ferati
- Faculty of Medical Sciences, University of Tetovo, 1220 Tetovo, North Macedonia; (K.F.); (A.B.F.)
| | - Nicola Brienza
- Unit of Anesthesia and Resuscitation, Department of Emergencies and Organ Transplantations, Aldo Moro University, 70124 Bari, Italy; (N.B.); (A.C.)
| | - Alberto Corriero
- Unit of Anesthesia and Resuscitation, Department of Emergencies and Organ Transplantations, Aldo Moro University, 70124 Bari, Italy; (N.B.); (A.C.)
| | - Francesco Inchingolo
- Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, 70121 Bari, Italy; (A.D.I.); (G.M.); (A.M.I.); (F.P.); (V.S.); (G.G.); (G.P.); (S.C.); (A.P.); (N.D.L.); (C.D.P.); (V.M.); (D.A.); (M.G.G.); (Z.K.); (A.T.); (G.C.); (A.M.); (B.R.); (A.S.); (D.H.); (M.T.D.); (M.J.); (F.I.); (G.D.)
| | - Gianna Dipalma
- Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, 70121 Bari, Italy; (A.D.I.); (G.M.); (A.M.I.); (F.P.); (V.S.); (G.G.); (G.P.); (S.C.); (A.P.); (N.D.L.); (C.D.P.); (V.M.); (D.A.); (M.G.G.); (Z.K.); (A.T.); (G.C.); (A.M.); (B.R.); (A.S.); (D.H.); (M.T.D.); (M.J.); (F.I.); (G.D.)
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Nautiyal H, Imam SS, Alshehri S, Ghoneim MM, Afzal M, Alzarea SI, Güven E, Al-Abbasi FA, Kazmi I. Polycystic Ovarian Syndrome: A Complex Disease with a Genetics Approach. Biomedicines 2022; 10:biomedicines10030540. [PMID: 35327342 PMCID: PMC8945152 DOI: 10.3390/biomedicines10030540] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2021] [Revised: 02/13/2022] [Accepted: 02/16/2022] [Indexed: 01/27/2023] Open
Abstract
Polycystic ovarian syndrome (PCOS) is a complex endocrine disorder affecting females in their reproductive age. The early diagnosis of PCOS is complicated and complex due to overlapping symptoms of this disease. The most accepted diagnostic approach today is the Rotterdam Consensus (2003), which supports the positive diagnosis of PCOS when patients present two out of the following three symptoms: biochemical and clinical signs of hyperandrogenism, oligo, and anovulation, also polycystic ovarian morphology on sonography. Genetic variance, epigenetic changes, and disturbed lifestyle lead to the development of pathophysiological disturbances, which include hyperandrogenism, insulin resistance, and chronic inflammation in PCOS females. At the molecular level, different proteins and molecular and signaling pathways are involved in disease progression, which leads to the failure of a single genetic diagnostic approach. The genetic approach to elucidate the mechanism of pathogenesis of PCOS was recently developed, whereby four phenotypic variances of PCOS categorize PCOS patients into classic, ovulatory, and non-hyperandrogenic types. Genetic studies help to identify the root cause for the development of this PCOS. PCOS genetic inheritance is autosomal dominant but the latest investigations revealed it as a multigene origin disease. Different genetic loci and specific genes have been identified so far as being associated with this disease. Genome-wide association studies (GWAS) and related genetic studies have changed the scenario for the diagnosis and treatment of this reproductive and metabolic condition known as PCOS. This review article briefly discusses different genes associated directly or indirectly with disease development and progression.
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Affiliation(s)
- Himani Nautiyal
- Siddhartha Institute of Pharmacy, Near IT-Park, Sahastradhara Road, Dehradun 248001, India;
| | - Syed Sarim Imam
- Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia; (S.S.I.); (S.A.)
| | - Sultan Alshehri
- Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia; (S.S.I.); (S.A.)
| | - Mohammed M. Ghoneim
- Department of Pharmacy Practice, College of Pharmacy, AlMaarefa University, Ad Diriyah 13713, Saudi Arabia;
| | - Muhammad Afzal
- Department of Pharmacology, College of Pharmacy, Jouf University, Sakaka 72341, Saudi Arabia;
- Correspondence: (M.A.); (I.K.)
| | - Sami I. Alzarea
- Department of Pharmacology, College of Pharmacy, Jouf University, Sakaka 72341, Saudi Arabia;
| | - Emine Güven
- Biomedical Engineering Department, Faculty of Engineering, Düzce University, Düzce 81620, Turkey;
| | - Fahad A. Al-Abbasi
- Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia;
| | - Imran Kazmi
- Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia;
- Correspondence: (M.A.); (I.K.)
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Sadeghi HM, Adeli I, Calina D, Docea AO, Mousavi T, Daniali M, Nikfar S, Tsatsakis A, Abdollahi M. Polycystic Ovary Syndrome: A Comprehensive Review of Pathogenesis, Management, and Drug Repurposing. Int J Mol Sci 2022; 23:583. [PMID: 35054768 PMCID: PMC8775814 DOI: 10.3390/ijms23020583] [Citation(s) in RCA: 164] [Impact Index Per Article: 54.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2021] [Revised: 12/30/2021] [Accepted: 12/31/2021] [Indexed: 12/12/2022] Open
Abstract
Polycystic ovary syndrome (PCOS) is an endocrine-gynecology disorder affecting many women of childbearing age. Although a part of the involved mechanism in PCOS occurrence is discovered, the exact etiology and pathophysiology are not comprehensively understood yet. We searched PubMed for PCOS pathogenesis and management in this article and ClinicalTrials.gov for information on repurposed medications. All responsible factors behind PCOS were thoroughly evaluated. Furthermore, the complete information on PCOS commonly prescribed and repurposed medications is summarized through tables. Epigenetics, environmental toxicants, stress, diet as external factors, insulin resistance, hyperandrogenism, inflammation, oxidative stress, and obesity as internal factors were investigated. Lifestyle modifications and complementary and alternative medicines are preferred first-line therapy in many cases. Medications, including 3-hydroxy-3-methyl-3-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors, thiazolidinediones, sodium-glucose cotransporter-2 inhibitors, dipeptidyl peptidase-4 inhibitors, glucose-like peptide-1 receptor agonists, mucolytic agents, and some supplements have supporting data for being repurposed in PCOS. Since there are few completed clinical trials with a low population and mostly without results on PCOS repurposed medications, it would be helpful to do further research and run well-designed clinical trials on this subject. Moreover, understanding more about PCOS would be beneficial to find new medications implying the effect via the novel discovered routes.
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Affiliation(s)
- Hosna Mohammad Sadeghi
- Toxicology and Diseases Group (TDG), Pharmaceutical Sciences Research Center (PSRC), The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran 11369, Iran; (H.M.S.); (I.A.); (T.M.); (M.D.)
- Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 11369, Iran
| | - Ida Adeli
- Toxicology and Diseases Group (TDG), Pharmaceutical Sciences Research Center (PSRC), The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran 11369, Iran; (H.M.S.); (I.A.); (T.M.); (M.D.)
- Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 11369, Iran
| | - Daniela Calina
- Department of Clinical Pharmacy, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Anca Oana Docea
- Department of Toxicology, Faculty of Pharmacy, University of Medicine and Pharmacy, Petru Rares, 200349 Craiova, Romania;
| | - Taraneh Mousavi
- Toxicology and Diseases Group (TDG), Pharmaceutical Sciences Research Center (PSRC), The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran 11369, Iran; (H.M.S.); (I.A.); (T.M.); (M.D.)
- Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 11369, Iran
| | - Marzieh Daniali
- Toxicology and Diseases Group (TDG), Pharmaceutical Sciences Research Center (PSRC), The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran 11369, Iran; (H.M.S.); (I.A.); (T.M.); (M.D.)
- Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 11369, Iran
| | - Shekoufeh Nikfar
- Department of Pharmacoeconomics and Pharmaceutical Administration, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 11369, Iran;
- Personalized Medicine Research Center, Endocrinology and Metabolism Research Institute, Tehran University of Medical Sciences, Tehran 11369, Iran
- Evidence-Based Evaluation of Cost-Effectiveness and Clinical Outcomes Group, Pharmaceutical Sciences Research Center (PSRC), The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran 11369, Iran
| | - Aristidis Tsatsakis
- Department of Analytical and Forensic Medical Toxicology, Sechenov University, 119991 Moscow, Russia;
- Department of Forensic Sciences and Toxicology, Faculty of Medicine, University of Crete, 71003 Heraklion, Greece
- Laboratory of Toxicology, Medical School, University of Crete, 70013 Heraklion, Greece
| | - Mohammad Abdollahi
- Toxicology and Diseases Group (TDG), Pharmaceutical Sciences Research Center (PSRC), The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran 11369, Iran; (H.M.S.); (I.A.); (T.M.); (M.D.)
- Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 11369, Iran
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Tasinov O, Dincheva I, Badjakov I, Kiselova-Kaneva Y, Galunska B, Nogueiras R, Ivanova D. Phytochemical Composition, Anti-Inflammatory and ER Stress-Reducing Potential of Sambucus ebulus L. Fruit Extract. PLANTS (BASEL, SWITZERLAND) 2021; 10:plants10112446. [PMID: 34834808 PMCID: PMC8623228 DOI: 10.3390/plants10112446] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/07/2021] [Revised: 11/05/2021] [Accepted: 11/09/2021] [Indexed: 05/09/2023]
Abstract
Sambucus ebulus L. (SE) fruits are used for their immunostimulation, hematopoietic and antiviral potential. Recently, we focused on analyzing the mechanism underlying SE fruit aqueous extract's (FAE) immunomodulation and anti-inflammatory activities, with attention to its endoplasmic reticulum (ER) stress-reducing potential. J774A.1 macrophages were treated with SE FAE alone or in conditions of lipopolysaccharides (LPS) stimulation. Using GC-MS and LC-MS/MS, its phytochemical composition was analyzed. To measure transcription and protein levels, we used qPCR and Western blot, respectively. The prevailing phytochemicals in SE FAE were hydroxycinnamic acids, proanthocyanidins and anthocyanins. The content of some amino acids, organic acids, alcohols, fatty acids and esters were newly reported. Extracts exerted an immunostimulation potential by stimulating IL-6, TNFα, Ccl2, COX2 and iNOS transcription, without inducing ER stress. SE FAE suppressed the LPS-induced transcription of inflammation related genes (IL-1β, IL-6, TNFα, Ccl2, Icam-1, Fabp4, COX2, iNOS, Noxo1, IL-1ra, Sirt-1) and reduced the protein levels of iNOS, peIF2α, ATF6α and CHOP. The effects were comparable to that of salicylic acid. SE suppresses LPS-stimulated inflammatory markers on the transcription and translation levels. Targeting ER stress is possibly another mechanism underlying its anti-inflammatory potential. These findings reveal the potential of SE fruits as a beneficial therapeutic of inflammation and ER stress-related pathological conditions.
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Affiliation(s)
- Oskan Tasinov
- Department of Biochemistry, Molecular Medicine and Nutrigenomics, Medical University of Varna, 84B Tzar Osvoboditel Blvd., 9002 Varna, Bulgaria; (Y.K.-K.); (B.G.); (D.I.)
- Correspondence: ; Tel.: +359-896-036961
| | - Ivayla Dincheva
- AgroBioInstitute, Agricultural Academy, 8 Dr. Tsankov Blvd., 1164 Sofia, Bulgaria; (I.D.); (I.B.)
| | - Ilian Badjakov
- AgroBioInstitute, Agricultural Academy, 8 Dr. Tsankov Blvd., 1164 Sofia, Bulgaria; (I.D.); (I.B.)
| | - Yoana Kiselova-Kaneva
- Department of Biochemistry, Molecular Medicine and Nutrigenomics, Medical University of Varna, 84B Tzar Osvoboditel Blvd., 9002 Varna, Bulgaria; (Y.K.-K.); (B.G.); (D.I.)
| | - Bistra Galunska
- Department of Biochemistry, Molecular Medicine and Nutrigenomics, Medical University of Varna, 84B Tzar Osvoboditel Blvd., 9002 Varna, Bulgaria; (Y.K.-K.); (B.G.); (D.I.)
| | - Ruben Nogueiras
- Center for Research in Molecular Medicine and Chronic Diseases (CiMUS), Department of Physiology, University of Santiago de Compostela-Instituto de Investigación Sanitaria, 15782 Santiago de Compostela, Spain;
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), 15706 Santiago de Compostela, Spain
| | - Diana Ivanova
- Department of Biochemistry, Molecular Medicine and Nutrigenomics, Medical University of Varna, 84B Tzar Osvoboditel Blvd., 9002 Varna, Bulgaria; (Y.K.-K.); (B.G.); (D.I.)
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Ribeiro R, Santos AC, Calazans MO, De Oliveira ACP, Vieira LB. Is resveratrol a prospective therapeutic strategy in the co-association of glucose metabolism disorders and neurodegenerative diseases? Nutr Neurosci 2021; 25:2442-2457. [PMID: 34514962 DOI: 10.1080/1028415x.2021.1972514] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Objectives: The mechanism behind the progression of Mild Cognitive Impairment (MCI) to Alzheimer's disease (AD) remains poorly understood. However some evidence pointed out that the co-occurrence of metabolic conditions affecting glucose homeostasis, as type 2 diabetes mellitus (T2DM), may be an important catalyst in this context. Notably, candidate drugs which modulate common pathways in the development of MCI-to-AD mediated by T2DM may offer likely therapy for AD. Nonetheless, limited pharmacological alternatives that modulate common pathways in T2DM, MCI, and AD are available. In the recent decades, studies have shown that resveratrol may act as a neuroprotective compound, but little is known about its potential in improving cognitive and metabolic aspects associated with AD progression mediated by the co-association between TDM2-MCI.Methods: In this review, we discuss possible protective mechanisms of resveratrol on shared pathways associated with AD progression mediated by T2DM-MCI co-occurrence.Results: Some studies indicated that insulin resistance and hyperglycemia may be also a T2DM risk factor for the progression of MCI-to-AD, promoting alterations in metabolic pathways associated with neuronal plasticity, and increasing pro-inflammatory environment. Interestingly, basic research and clinical trials indicate that resveratrol may modulate those pathways, showing a potential neuroprotective effect of this polyphenol.Conclusion: Therefore, there is not enough clinical data supporting the translational therapeutic use of resveratrol in this scenario.
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Affiliation(s)
- R Ribeiro
- Departamento de Farmacologia, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - A C Santos
- Departamento de Farmacologia, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - M O Calazans
- Departamento de Farmacologia, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - A C P De Oliveira
- Departamento de Farmacologia, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - L B Vieira
- Departamento de Farmacologia, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
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Ren B, Kwah MXY, Liu C, Ma Z, Shanmugam MK, Ding L, Xiang X, Ho PCL, Wang L, Ong PS, Goh BC. Resveratrol for cancer therapy: Challenges and future perspectives. Cancer Lett 2021; 515:63-72. [PMID: 34052324 DOI: 10.1016/j.canlet.2021.05.001] [Citation(s) in RCA: 240] [Impact Index Per Article: 60.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2021] [Revised: 05/05/2021] [Accepted: 05/05/2021] [Indexed: 12/20/2022]
Abstract
Resveratrol (3,4',5-trihydroxy-trans-stilbene) has been expected to ameliorate cancer and foster breakthroughs in cancer therapy. Despite thousands of preclinical studies on the anticancer activity of resveratrol, little progress has been made in translational research and clinical trials. Most studies have focused on its anticancer effects, cellular mechanisms, and signal transduction pathways in vitro and in vivo. In this review, we aimed to discern the causes that prevent resveratrol from being used in cancer treatment. Among the various limitations, poor pharmacokinetics and low potency seem to be the two main bottlenecks of resveratrol. In addition, resveratrol-induced nephrotoxicity in multiple myeloma patients hinders its further development as an anticancer drug. New insights and strategies have been proposed to accelerate the conversion of resveratrol from bench to bedside. In the interim, the most promising approach is to enhance the bioavailability of resveratrol with new formulations. Alternatively, more potent analogues of resveratrol could be developed to augment its anticancer potency. Given all the gaps mentioned, much work remains to be done. However, if remarkable progress can be made, resveratrol may finally be used for cancer therapy.
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Affiliation(s)
- Boxu Ren
- School of Basic Medicine, Health Science Center, Yangtze University, Jingzhou, 434023, China
| | - Marabeth Xin-Yi Kwah
- Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore, 117543, Singapore
| | - Cuiliu Liu
- School of Basic Medicine, Health Science Center, Yangtze University, Jingzhou, 434023, China
| | - Zhaowu Ma
- School of Basic Medicine, Health Science Center, Yangtze University, Jingzhou, 434023, China
| | - Muthu K Shanmugam
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117600, Singapore
| | - Lingwen Ding
- Department of Pathology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117600, Singapore
| | - Xiaoqiang Xiang
- Department of Clinical Pharmacy, School of Pharmacy, Fudan University, Shanghai, 201203, China
| | - Paul Chi-Lui Ho
- Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore, 117543, Singapore
| | - Lingzhi Wang
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117600, Singapore; Cancer Science Institute of Singapore, National University of Singapore, Singapore, 117599, Singapore.
| | - Pei Shi Ong
- Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore, 117543, Singapore.
| | - Boon Cher Goh
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117600, Singapore; Cancer Science Institute of Singapore, National University of Singapore, Singapore, 117599, Singapore; Department of Haematology-Oncology, National University Cancer Institute, Singapore, 119228, Singapore.
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Prospective Pharmacological Potential of Resveratrol in Delaying Kidney Aging. Int J Mol Sci 2021; 22:ijms22158258. [PMID: 34361023 PMCID: PMC8348580 DOI: 10.3390/ijms22158258] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2021] [Revised: 07/26/2021] [Accepted: 07/28/2021] [Indexed: 01/22/2023] Open
Abstract
Aging is an unavoidable part of life. The more aged we become, the more susceptible we become to various complications and damages to the vital organs, including the kidneys. The existing drugs for kidney diseases are mostly of synthetic origins; thus, natural compounds with minimal side-effects have attracted growing interest from the scientific community and pharmaceutical companies. A literature search was carried out to collect published research information on the effects of resveratrol on kidney aging. Recently, resveratrol has emerged as a potential anti-aging agent. This versatile polyphenol exerts its anti-aging effects by intervening in various pathologies and multi-signaling systems, including sirtuin type 1, AMP-activated protein kinase, and nuclear factor-κB. Researchers are trying to figure out the detailed mechanisms and possible resveratrol-mediated interventions in divergent pathways at the molecular level. This review highlights (i) the causative factors implicated in kidney aging and the therapeutic aspects of resveratrol, and (ii) the effectiveness of resveratrol in delaying the aging process of the kidney while minimizing all possible side effects.
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Mongioì LM, La Vignera S, Cannarella R, Cimino L, Compagnone M, Condorelli RA, Calogero AE. The Role of Resveratrol Administration in Human Obesity. Int J Mol Sci 2021; 22:ijms22094362. [PMID: 33921991 PMCID: PMC8122246 DOI: 10.3390/ijms22094362] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2021] [Revised: 04/19/2021] [Accepted: 04/20/2021] [Indexed: 01/10/2023] Open
Abstract
Obesity is a widespread disease that is associated with numerous and serious comorbidities. These include metabolic syndrome, diabetes mellitus, cardiovascular-cerebrovascular disease, hypertension, obstructive sleep apnea syndrome, cancer, and sexual and hormonal disorders. The treatment of obesity has therefore become a goal of great clinical and social relevance. Among the therapeutic strategies against obesity, resveratrol has aroused great interest. This polyphenol has anticancer and antioxidant properties and cytoprotective and anti-inflammatory effects. Other favorable effects attributed to resveratrol are anti-lipid, anti-aging, anti-bacterial, anti-viral, and neuroprotective actions. Administration of resveratrol appears to improve the metabolic profile in obese and/or insulin-resistant patients. This article aims to review the main results of clinical studies evaluating the effects of administering resveratrol alone in overweight/obese patients.
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Delmas D, Cornebise C, Courtaut F, Xiao J, Aires V. New Highlights of Resveratrol: A Review of Properties against Ocular Diseases. Int J Mol Sci 2021; 22:1295. [PMID: 33525499 PMCID: PMC7865717 DOI: 10.3390/ijms22031295] [Citation(s) in RCA: 42] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2020] [Revised: 01/22/2021] [Accepted: 01/24/2021] [Indexed: 02/06/2023] Open
Abstract
Eye diseases are currently a major public health concern due to the growing number of cases resulting from both an aging of populations and exogenous factors linked to our lifestyles. Thus, many treatments including surgical pharmacological approaches have emerged, and special attention has been paid to prevention, where diet plays a preponderant role. Recently, potential antioxidants such as resveratrol have received much attention as potential tools against various ocular diseases. In this review, we focus on the mechanisms of resveratrol against ocular diseases, in particular age-related macular degeneration, glaucoma, cataract, diabetic retinopathy, and vitreoretinopathy. We analyze, in relation to the different steps of each disease, the resveratrol properties at multiple levels, such as cellular and molecular signaling as well as physiological effects. We show and discuss the relationship to reactive oxygen species, the regulation of inflammatory process, and how resveratrol can prevent ocular diseases through a potential epigenetic action by the activation of sirtuin-1. Lastly, various new forms of resveratrol delivery are emerging at the same time as some clinical trials are raising more questions about the future of resveratrol as a potential tool for prevention or in therapeutic strategies against ocular diseases. More preclinical studies are required to provide further insights into RSV's potential adjuvant activity.
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Affiliation(s)
- Dominique Delmas
- Université de Bourgogne Franche-Comté, F-21000 Dijon, France; (C.C.); (F.C.); (V.A.)
- INSERM Research Center U1231, Cancer and Adaptive Immune Response Team, Bioactive Molecules and Health Research Group, F-21000 Dijon, France
- Centre Anticancéreux Georges François Leclerc, F-21000 Dijon, France
| | - Clarisse Cornebise
- Université de Bourgogne Franche-Comté, F-21000 Dijon, France; (C.C.); (F.C.); (V.A.)
- INSERM Research Center U1231, Cancer and Adaptive Immune Response Team, Bioactive Molecules and Health Research Group, F-21000 Dijon, France
| | - Flavie Courtaut
- Université de Bourgogne Franche-Comté, F-21000 Dijon, France; (C.C.); (F.C.); (V.A.)
- INSERM Research Center U1231, Cancer and Adaptive Immune Response Team, Bioactive Molecules and Health Research Group, F-21000 Dijon, France
| | - Jianbo Xiao
- Nutrition and Bromatology Group, Department of Analytical Chemistry and Food Science, Faculty of Food Science and Technology, University of Vigo-Ourense Campus, E-32004 Ourense, Spain;
- College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China
- International Research Center for Food Nutrition and Safety, Jiangsu University, Zhenjiang 212013, China
| | - Virginie Aires
- Université de Bourgogne Franche-Comté, F-21000 Dijon, France; (C.C.); (F.C.); (V.A.)
- INSERM Research Center U1231, Cancer and Adaptive Immune Response Team, Bioactive Molecules and Health Research Group, F-21000 Dijon, France
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García-Martínez BI, Ruiz-Ramos M, Pedraza-Chaverri J, Santiago-Osorio E, Mendoza-Núñez VM. Hypoglycemic Effect of Resveratrol: A Systematic Review and Meta-Analysis. Antioxidants (Basel) 2021; 10:69. [PMID: 33430470 PMCID: PMC7827898 DOI: 10.3390/antiox10010069] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2020] [Revised: 12/30/2020] [Accepted: 01/04/2021] [Indexed: 02/06/2023] Open
Abstract
Resveratrol (RV) is a polyphenolic compound with antioxidant, anti-inflammatory, and hypoglycemic properties. Several in vitro and animal model studies have demonstrated the beneficial effects of RV; however, the results in humans are not conclusive. After a search of different databases, 32 studies were selected for this systematic review and 30 were included in the meta-analysis. Studies that evaluated the effect of RV on glucose, insulin, HbA1c, and insulin resistance (HOMA-IR) levels were included. A significant decrease of glucose (-5.24 mg/dL, p = 0.002) and insulin levels (-1.23 mIU/L, p = 0.0003) was observed. HbA1c and HOMA-IR did not show significant changes. Due to heterogeneity, sub-analyzes were performed. Sub-analysis by dose revealed that glucose levels improve significantly after the administration of 500-1000 mg/day of RV (-7.54 mg/dL, p = 0.002), while insulin improves with doses lower than 500 mg/day (-1.43 mIU/L, p = 0.01) and greater than 1000 mg/day (-2.12 mIU/L, p = 0.03). HbA1c and HOMA-IR remained unchanged after sub-analysis by dose. Our findings suggest that RV improves glucose and insulin levels in subjects with type 2 diabetes mellitus (T2DM) and aged 45-59 years, regardless of the duration of the intervention. HbA1c improves with interventions ≥3 months. HOMA-IR does not exhibit significant changes after RV administration.
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Affiliation(s)
- Beatriz Isabel García-Martínez
- Research Unit on Gerontology, FES Zaragoza, National Autonomous University of Mexico, Mexico City 09230, Mexico; (B.I.G.-M.); (M.R.-R.)
| | - Mirna Ruiz-Ramos
- Research Unit on Gerontology, FES Zaragoza, National Autonomous University of Mexico, Mexico City 09230, Mexico; (B.I.G.-M.); (M.R.-R.)
| | - José Pedraza-Chaverri
- Department of Biology, Faculty of Chemistry, National Autonomous University of Mexico (UNAM), Mexico City 04510, Mexico;
| | - Edelmiro Santiago-Osorio
- Hematopoiesis and Leukemia Laboratory, Research Unit on Cell Differentiation and Cancer, FES Zaragoza, National Autonomous University of Mexico, Mexico City 09230, Mexico;
| | - Víctor Manuel Mendoza-Núñez
- Research Unit on Gerontology, FES Zaragoza, National Autonomous University of Mexico, Mexico City 09230, Mexico; (B.I.G.-M.); (M.R.-R.)
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Delpino FM, Figueiredo LM, Caputo EL, Mintem GC, Gigante DP. What is the effect of resveratrol on obesity? A systematic review and meta-analysis. Clin Nutr ESPEN 2020; 41:59-67. [PMID: 33487308 DOI: 10.1016/j.clnesp.2020.11.025] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2020] [Revised: 11/21/2020] [Accepted: 11/28/2020] [Indexed: 12/22/2022]
Abstract
BACKGROUND & AIMS Obesity is increasing worldwide. Resveratrol appears as a substance capable of helping with weight loss. This study aimed to investigate the resveratrol effect in the treatment of obesity in general population. METHODS An online search was conducted in the following databases: Pubmed, LILACS, Scielo, Scopus and Web of Science. Experimental studies that investigated the effects between resveratrol supplementation for weight loss treatment, as well as its relationship with overweight and obesity were included. Observational and non-human studies were excluded. The Cochrane scale was used to assess the quality of the studies. RESULTS Nineteen studies were included, of which only three demonstrated some type of positive effect. In the meta-analysis, there was no significant effect on weight loss [SMD: 0.03; CI95%: -0,44, 0,49; p = 0,01; I2 = 82%], and body mass index (BMI) [SMD: 0.01; CI95%: -0,39, 0,41; p = 0,01; I2 = 72%]. A small effect was found on the waist circumference [SMD: -1.04; CI95%: -1,86, -0,27; p = 0,01; I2 = 87%]. CONCLUSION This systematic review with meta-analysis demonstrated that supplementation with resveratrol does not have an anti-obesity effect.
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Affiliation(s)
- Felipe Mendes Delpino
- Department of Nursing in Public Health, Federal University of Pelotas, Rio Grande do Sul, Brazil.
| | | | - Eduardo L Caputo
- Postgraduate Program in Physical Education, Federal University of Pelotas. Pelotas, Brazil
| | - Gicele Costa Mintem
- Postgraduate Program in Nutrition and Food, Faculty of Nutrition, Federal University of Pelotas. Pelotas, Brazil
| | - Denise Petrucci Gigante
- Postgraduate Program in Nutrition and Food, Faculty of Nutrition, Federal University of Pelotas. Pelotas, Brazil
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Ullah H, De Filippis A, Santarcangelo C, Daglia M. Epigenetic regulation by polyphenols in diabetes and related complications. MEDITERRANEAN JOURNAL OF NUTRITION AND METABOLISM 2020; 13:289-310. [DOI: 10.3233/mnm-200489] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Diabetes mellitus (DM) is a chronic metabolic disorder and one of the most challenging health problems worldwide. Left untreated, it may progress causing serious complications. Genetics, epigenetics, and environmental factors are known to play an overlapping role in the pathogenesis of DM. Growing evidence suggests the hypothesis that the environment induces changes in the early phases of growth and development, influencing health and disease in the adulthood through the alteration in genetic expression of an individual, at least in part. DNA methylation, histone modifications and miRNAs are three mechanisms responsible for epigenetic alterations. The daily diet contains a number of secondary metabolites, with polyphenols being highest in abundance, which contribute to overall health and may prevent or delay the onset of many chronic diseases. Polyphenols have the ability to alter metabolic and signaling pathways at various levels, such as gene expression, epigenetic regulation, protein expression and enzyme activity. The potential efficacy of polyphenolic compounds on glucose homeostasis has been evidenced from in vitro, in vivo and clinical studies. The present review is designed to focus on epigenetic regulation exerted by polyphenolic compounds in DM and their complications, as well as to summarize clinical trials involving polyphenols in DM.
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Affiliation(s)
- Hammad Ullah
- Department of Pharmacy, University of Naples Federico II, Naples, Italy
| | - Anna De Filippis
- Department of Pharmacy, University of Naples Federico II, Naples, Italy
| | | | - Maria Daglia
- Department of Pharmacy, University of Naples Federico II, Naples, Italy
- International Research Center for Food Nutrition and Safety, Jiangsu University, Zhenjiang, China
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Huang CC, Liu CC, Tsao JP, Hsu CL, Cheng IS. Effects of Oral Resveratrol Supplementation on Glycogen Replenishment and Mitochondria Biogenesis in Exercised Human Skeletal Muscle. Nutrients 2020; 12:nu12123721. [PMID: 33276518 PMCID: PMC7760965 DOI: 10.3390/nu12123721] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2020] [Revised: 11/28/2020] [Accepted: 11/29/2020] [Indexed: 12/11/2022] Open
Abstract
The present study aimed to investigate the effect of oral resveratrol supplementation on the key molecular gene expressions involved in mitochondria biogenesis and glycogen resynthesis in human skeletal muscle. Nine young male athletes participated in the single-blind and crossover designed study. All subjects completed a 4-day resveratrol and placebo supplement in a randomized order while performing a single bout of cycling exercise. Immediately after the exercise challenge, the subjects consumed a carbohydrate (CHO) meal (2 g CHO/Kg body mass) with either resveratrol or placebo capsules. Biopsied muscle samples, blood samples and expired gas samples were obtained at 0 h and 3 h after exercise. The muscle samples were measured for gene transcription factor expression by real-time PCR for glucose uptake and mitochondria biogenesis. Plasma glucose, insulin, glycerol, non-esterified fatty acid concentrations and respiratory exchange ratio were analyzed during post-exercise recovery periods. The results showed that the muscle glycogen concentrations were higher at 3 h than at 0 h; however, there were no difference between resveratrol trial and placebo trial. There were no significantly different concentrations in plasma parameters between the two trials. Similarly, no measured gene expressions were significant between the two trials. The evidence concluded that the 4-day oral resveratrol supplementation did not improve post-exercise muscle glycogen resynthesis and related glucose uptake and mitochondrial biosynthesis gene expression in men.
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Affiliation(s)
- Chun-Ching Huang
- Department of Exercise and Health Sciences, National Taipei University of Nursing and Health Science, Taipei City 112, Taiwan;
| | - Chia-Chen Liu
- Department of Physical Education, National Taichung University of Education, Taichung City 403, Taiwan; (C.-C.L.); (J.-P.T.)
| | - Jung-Piao Tsao
- Department of Physical Education, National Taichung University of Education, Taichung City 403, Taiwan; (C.-C.L.); (J.-P.T.)
| | - Chin-Lin Hsu
- Department of Nutrition, Chung Shan Medical University Hospital, Taichung 404, Taiwan
- School of Nutrition, Chung Shan Medical University, Taichung 404, Taiwan
- Correspondence: (C.-L.H.); (I.-S.C.); Tel.: +886-4-2218-3459 (I.-S.C.)
| | - I-Shiung Cheng
- Department of Physical Education, National Taichung University of Education, Taichung City 403, Taiwan; (C.-C.L.); (J.-P.T.)
- Correspondence: (C.-L.H.); (I.-S.C.); Tel.: +886-4-2218-3459 (I.-S.C.)
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Resveratrol and exercise combined to treat functional limitations in late life: A pilot randomized controlled trial. Exp Gerontol 2020; 143:111111. [PMID: 33068691 DOI: 10.1016/j.exger.2020.111111] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2020] [Revised: 09/17/2020] [Accepted: 10/04/2020] [Indexed: 12/26/2022]
Abstract
PURPOSE To evaluate the safety and feasibility of combining exercise (EX) and resveratrol to treat older adults with physical function limitations. METHODS Three-arm, two-site pilot randomized, controlled trial (RCT) for community-dwelling adults (N = 60), 71.8 ± 6.3 years of age with functional limitations. Participants were randomized to receive either 12 weeks of (1) EX + placebo [EX0], (2) EX + 500 mg/day resveratrol [EX500], or (3) EX + 1000 mg/day resveratrol [EX1000]. EX consisted of two sessions a week for 12 weeks of center-based walking and whole-body resistance training. Safety was assessed through adverse events and feasibility through exercise session and supplement (placebo, or resveratrol) protocol adherence. Outcome measures included a battery of indices of physical function as well as skeletal muscle mitchondrial function. Data were adjusted for age and gender using the Intent-To-Treat approach. RESULTS Adverse event frequency and type were similar between groups (n = 8 EX0, n = 12 EX500, and n = 7 EX1000). Overall, 85% of participants met the supplement adherence via pill counts while 82% met the exercise session adherence. Adjusted within group mean differences (95% confidence interval) from week 0 to 12 for gait speed ranged from -0.04 (EX0: -0.1, 0.03) m/s to 0.04 (EX1000: -0.02, 0.11) and the six-minute walk test mean differences were 9.45 (EX0: -9.02, 27.7), 22.9 (EX500: 4.18, 41.6), and 33.1 (EX1000: 13.8, 52.4) meters. Unadjusted mean differences for citrate synthase were -0.80 (EX0: -15.45, 13.84), -1.38 (EX500: -12.16, 9.39), and 7.75 (EX1000: -4.68, 20.18) mU/mg. COX activity mean within group changes ranged from -0.05 (EX0) to 0.06 (EX500) k/s/mg. Additional outcomes are detailed in the text. CONCLUSION The pilot RCT indicated that combined EX + resveratrol was safe and feasible for older adults with functional limitations and may improve skeletal muscle mitochondrial function and mobility-related indices of physical function. A larger trial appears warranted and is needed to formally test these hypotheses.
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Pyo IS, Yun S, Yoon YE, Choi JW, Lee SJ. Mechanisms of Aging and the Preventive Effects of Resveratrol on Age-Related Diseases. Molecules 2020; 25:molecules25204649. [PMID: 33053864 PMCID: PMC7587336 DOI: 10.3390/molecules25204649] [Citation(s) in RCA: 109] [Impact Index Per Article: 21.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2020] [Revised: 09/29/2020] [Accepted: 10/03/2020] [Indexed: 02/06/2023] Open
Abstract
Aging gradually decreases cellular biological functions and increases the risk of age-related diseases. Cancer, type 2 diabetes mellitus, cardiovascular disease, and neurological disorders are commonly classified as age-related diseases that can affect the lifespan and health of individuals. Aging is a complicated and sophisticated biological process involving damage to biochemical macromolecules including DNA, proteins, and cellular organelles such as mitochondria. Aging causes multiple alterations in biological processes including energy metabolism and nutrient sensing, thus reducing cell proliferation and causing cellular senescence. Among the polyphenolic phytochemicals, resveratrol is believed to reduce the negative effects of the aging process through its multiple biological activities. Resveratrol increases the lifespan of several model organisms by regulating oxidative stress, energy metabolism, nutrient sensing, and epigenetics, primarily by activating sirtuin 1. This review summarizes the most important biological mechanisms of aging, and the ability of resveratrol to prevent age-related diseases.
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Karaman Mayack B, Sippl W, Ntie-Kang F. Natural Products as Modulators of Sirtuins. Molecules 2020; 25:molecules25143287. [PMID: 32698385 PMCID: PMC7397027 DOI: 10.3390/molecules25143287] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2020] [Revised: 07/12/2020] [Accepted: 07/15/2020] [Indexed: 02/07/2023] Open
Abstract
Natural products have been used for the treatment of human diseases since ancient history. Over time, due to the lack of precise tools and techniques for the separation, purification, and structural elucidation of active constituents in natural resources there has been a decline in financial support and efforts in characterization of natural products. Advances in the design of chemical compounds and the understanding of their functions is of pharmacological importance for the biomedical field. However, natural products regained attention as sources of novel drug candidates upon recent developments and progress in technology. Natural compounds were shown to bear an inherent ability to bind to biomacromolecules and cover an unparalleled chemical space in comparison to most libraries used for high-throughput screening. Thus, natural products hold a great potential for the drug discovery of new scaffolds for therapeutic targets such as sirtuins. Sirtuins are Class III histone deacetylases that have been linked to many diseases such as Parkinson`s disease, Alzheimer’s disease, type II diabetes, and cancer linked to aging. In this review, we examine the revitalization of interest in natural products for drug discovery and discuss natural product modulators of sirtuins that could serve as a starting point for the development of isoform selective and highly potent drug-like compounds, as well as the potential application of naturally occurring sirtuin inhibitors in human health and those in clinical trials.
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Affiliation(s)
- Berin Karaman Mayack
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Istanbul University, Istanbul 34116, Turkey
- Correspondence:
| | - Wolfgang Sippl
- Institute of Pharmacy, Martin-Luther University of Halle-Wittenberg, Kurt-Mothes-Str. 3, 06120 Halle (Saale), Germany; (W.S.); (F.N.-K.)
| | - Fidele Ntie-Kang
- Institute of Pharmacy, Martin-Luther University of Halle-Wittenberg, Kurt-Mothes-Str. 3, 06120 Halle (Saale), Germany; (W.S.); (F.N.-K.)
- Department of Chemistry, University of Buea, P.O. Box 63, Buea CM-00237, Cameroon
- Institute of Botany, Technical University of Dresden, 01217 Dresden, Germany
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Attenuation of Free Fatty Acid (FFA)-Induced Skeletal Muscle Cell Insulin Resistance by Resveratrol is Linked to Activation of AMPK and Inhibition of mTOR and p70 S6K. Int J Mol Sci 2020; 21:ijms21144900. [PMID: 32664532 PMCID: PMC7404286 DOI: 10.3390/ijms21144900] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2020] [Revised: 07/03/2020] [Accepted: 07/09/2020] [Indexed: 12/13/2022] Open
Abstract
Insulin resistance, a main characteristic of type 2 diabetes mellitus (T2DM), is linked to obesity and excessive levels of plasma free fatty acids (FFA). Studies indicated that significantly elevated levels of FFAs lead to skeletal muscle insulin resistance, by dysregulating the steps in the insulin signaling cascade. The polyphenol resveratrol (RSV) was shown to have antidiabetic properties but the exact mechanism(s) involved are not clearly understood. In the present study, we examined the effect of RSV on FFA-induced insulin resistance in skeletal muscle cells in vitro and investigated the mechanisms involved. Parental and GLUT4myc-overexpressing L6 rat skeletal myotubes were used. [3H]2-deoxyglucose (2DG) uptake was measured, and total and phosphorylated levels of specific proteins were examined by immunoblotting. Exposure of L6 cells to FFA palmitate decreased the insulin-stimulated glucose uptake, indicating insulin resistance. Palmitate increased ser307 (131% ± 1.84% of control, p < 0.001) and ser636/639 (148% ± 10.1% of control, p < 0.01) phosphorylation of IRS-1, and increased the phosphorylation levels of mTOR (174% ± 15.4% of control, p < 0.01) and p70 S6K (162% ± 20.2% of control, p < 0.05). Treatment with RSV completely abolished these palmitate-induced responses. In addition, RSV increased the activation of AMPK and restored the insulin-mediated increase in (a) plasma membrane GLUT4 glucose transporter levels and (b) glucose uptake. These data suggest that RSV has the potential to counteract the FFA-induced muscle insulin resistance.
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Hendley MA, Isely C, Murphy KP, Hall HE, Annamalai P, Gower RM. Scaffold Implant Into the Epididymal Adipose Tissue Protects Mice From High Fat Diet Induced Ectopic Lipid Accumulation and Hyperinsulinemia. Front Bioeng Biotechnol 2020; 8:562. [PMID: 32612981 PMCID: PMC7308717 DOI: 10.3389/fbioe.2020.00562] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2020] [Accepted: 05/11/2020] [Indexed: 12/18/2022] Open
Abstract
Ectopic lipid accumulation, the deposition of lipids in lean tissue, is linked to type 2 diabetes through an association with insulin resistance. It occurs when adipose tissue fails to meet lipid storage needs and there is lipid spillover into tissues not equipped to store them. Ectopic lipid contributes to organ dysfunction because lipids can interfere with insulin signaling and other signaling pathways. Clinical studies indicate that decreasing ectopic lipids through diet and exercise is effective in treating type 2 diabetes; however, its prevalence continues to rise. We propose that strategies to improve lipid handling in the adipose tissue would be adjunctive to healthy lifestyle modification and may address difficulties in treating type 2 diabetes and other syndromes spurred by ectopic lipid. Herein, we investigate biomaterial implants as a means to increase lipid utilization in adipose tissue through the recruitment of highly metabolic cells. Poly(lactide-co-glycolide) scaffolds were implanted into the epididymal fat of mice fed a high fat diet that overwhelms the adipose tissue and promotes ectopic lipid accumulation. Over 5 weeks, mice with scaffolds gained less weight compared to mice without scaffolds and were protected from hyperinsulinemia. These effects correlated with a 53% decrease in triglyceride in the gastrocnemius and a 25% decrease in the liver. Scaffolds increased CPT1A protein levels in the epididymal fat and histology revealed high expression of CTP1A in the cells infiltrating the scaffold relative to the rest of the fat pad. In addition, lacing the scaffold with resveratrol increased CPT1A expression in the epididymal fat over scaffolds with no drug; however, this did not result in further decreases in weight gain or ectopic lipid. Mechanistically, we propose that the cellular activity caused by scaffold implant mitigates the lipid load imposed by the high fat diet and leads to a substantial decrease in lipid accumulation in the muscle and liver. In conclusion, this study establishes that a tissue engineering approach to modulate lipid utilization in the epididymal fat tissue can mitigate ectopic lipid accumulation in mice fed a high fat diet with positive effects on weight gain and whole-body insulin resistance.
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Affiliation(s)
- Michael A Hendley
- Biomedical Engineering Program, University of South Carolina, Columbia, SC, United States
| | - Christopher Isely
- Department of Chemical Engineering, University of South Carolina, Columbia, SC, United States
| | - Kendall P Murphy
- Department of Chemical Engineering, University of South Carolina, Columbia, SC, United States
| | - Hayley E Hall
- Biomedical Engineering Program, University of South Carolina, Columbia, SC, United States
| | - Prakasam Annamalai
- Department of Chemical Engineering, University of South Carolina, Columbia, SC, United States
| | - R Michael Gower
- Biomedical Engineering Program, University of South Carolina, Columbia, SC, United States.,Department of Chemical Engineering, University of South Carolina, Columbia, SC, United States
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Si L, Zhang M, Guan E, Han Q, Liu Y, Long X, Long F, Zhao RCH, Huang J, Liu Z, Zhao R, Zhang H, Wang X. Resveratrol inhibits proliferation and promotes apoptosis of keloid fibroblasts by targeting HIF-1α. J Plast Surg Hand Surg 2020; 54:290-296. [PMID: 32493094 DOI: 10.1080/2000656x.2020.1771719] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
A keloid is characterized by red, tickling, hard, and irregular raised tissues, and it tends to outgrow its origin. It frequently occurs in young adults and appears to be refractory to prevailing therapies. Resveratrol is a new drug that has anti-proliferative effect. In this study, keloid-derived fibroblasts were cultured under hypoxia environment and was treated by resveratrol. CCK-8 assay and Annexin V-FITC were used to evaluate cell activity and apoptosis level. Western blot and RT-qPCR were also used to assess the expression of HIF-α, Collagen I and Collagen III. Besides, siRNA was also used to explore the mechanisms of resveratrol's effect. In this study, hypoxia promotes proliferation and inhibits apoptosis of keloid fibroblasts. These findings highlight the potential obstacle in treating keloids. Furthermore, we demonstrated that resveratrol could reverse the effect of hypoxia on keloids through down-regulation of HIF-1α. Moreover, collagen synthesis in keloid fibroblasts was also inhibited by resveratrol, which corresponded with HIF-1α suppression. These results provide evidence for resveratrol's treatment effect against keloids through inhibiting cell proliferation and promoting cell apoptosis, while, HIF-1α may play the key role in this process.
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Affiliation(s)
- Loubin Si
- Department of Plastic Surgery, Peking Union Medical College Hospital, Beijing, China
| | - Mingzi Zhang
- Department of Plastic Surgery, Peking Union Medical College Hospital, Beijing, China
| | - Enling Guan
- Department of Ear-Nose-Throat, Qingdao Huangdao District Hospital of Traditional Chinese Medicine, Shandong, China
| | - Qin Han
- Department of Ear-Nose-Throat, Qingdao Huangdao District Hospital of Traditional Chinese Medicine, Shandong, China
| | - Yifang Liu
- International Education College, Beijing Vocational College of Agriculture, Beijing, China
| | - Xiao Long
- Department of Plastic Surgery, Peking Union Medical College Hospital, Beijing, China
| | - Fei Long
- Department of Plastic Surgery, Peking Union Medical College Hospital, Beijing, China
| | - Robert Chun-Hua Zhao
- Center of Excellence in Tissue Engineering, Institute of Basic Medical Sciences and School of Basic Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jiuzuo Huang
- Department of Plastic Surgery, Peking Union Medical College Hospital, Beijing, China
| | - Zhifei Liu
- Department of Plastic Surgery, Peking Union Medical College Hospital, Beijing, China
| | - Ru Zhao
- Department of Plastic Surgery, Peking Union Medical College Hospital, Beijing, China
| | - Hailin Zhang
- Department of Plastic Surgery, Peking Union Medical College Hospital, Beijing, China
| | - Xiaojun Wang
- Department of Plastic Surgery, Peking Union Medical College Hospital, Beijing, China
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de Ligt M, Bergman M, Fuentes RM, Essers H, Moonen-Kornips E, Havekes B, Schrauwen-Hinderling VB, Schrauwen P. No effect of resveratrol supplementation after 6 months on insulin sensitivity in overweight adults: a randomized trial. Am J Clin Nutr 2020; 112:1029-1038. [PMID: 32492138 PMCID: PMC7528554 DOI: 10.1093/ajcn/nqaa125] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2020] [Accepted: 05/07/2020] [Indexed: 12/03/2022] Open
Abstract
BACKGROUND Effects of resveratrol on metabolic health have been studied in several short-term human clinical trials, with conflicting results. Next to dose, the duration of the clinical trials may explain the lack of effect in some studies, but long-term studies are still limited. OBJECTIVES The objective of this study was to investigate the effects of 6-mo resveratrol supplementation on metabolic health outcome parameters. METHODS Forty-one overweight men and women (BMI: 27-35 kg/m2; aged 40-70 y) completed the study. In this parallel-group, double-blind clinical trial, participants were randomized to receive either 150 mg/d of resveratrol (n = 20) or placebo (n = 21) for 6 mo. The primary outcome of the study was insulin sensitivity, using the Matsuda index. Secondary outcome measures were intrahepatic lipid (IHL) content, body composition, resting energy metabolism, blood pressure, plasma markers, physical performance, quality of life, and quality of sleep. Postintervention differences between the resveratrol and placebo arms were evaluated by ANCOVA adjusting for corresponding preintervention variables. RESULTS Preintervention, no differences were observed between the 2 treatment arms. Insulin sensitivity was not affected after 6 mo of resveratrol treatment (adjusted mean Matsuda index: 5.18 ± 0.35 in the resveratrol arm compared with 5.50 ± 0.34 in the placebo arm), although there was a significant difference in postintervention glycated hemoglobin (HbA1c) between the arms (P = 0.007). The adjusted means showed that postintervention HbA1c was lower on resveratrol (35.8 ± 0.43 mmol/mol) compared with placebo (37.6 ± 0.44 mmol/mol). No postintervention differences were found in IHL, body composition, blood pressure, energy metabolism, physical performance, or quality of life and sleep between treatment arms. CONCLUSIONS After 6 mo of resveratrol supplementation, insulin sensitivity was unaffected in the resveratrol arm compared with the placebo arm. Nonetheless, HbA1c was lower in overweight men and women in the resveratrol arm. This trial was registered at Clinicaltrials.gov as NCT02565979.
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Affiliation(s)
- Marlies de Ligt
- Department of Nutrition and Movement Sciences, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht, Netherlands
| | - Maaike Bergman
- Department of Nutrition and Movement Sciences, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht, Netherlands
| | - Rodrigo Mancilla Fuentes
- Department of Nutrition and Movement Sciences, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht, Netherlands
| | - Hans Essers
- Department of Nutrition and Movement Sciences, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht, Netherlands
| | - Esther Moonen-Kornips
- Department of Nutrition and Movement Sciences, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht, Netherlands
| | - Bas Havekes
- Department of Internal Medicine, Division of Endocrinology, Maastricht University Medical Center, Maastricht, Netherlands
| | - Vera B Schrauwen-Hinderling
- Department of Radiology and Nuclear Medicine, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht, Netherlands
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Mollo N, Cicatiello R, Aurilia M, Scognamiglio R, Genesio R, Charalambous M, Paladino S, Conti A, Nitsch L, Izzo A. Targeting Mitochondrial Network Architecture in Down Syndrome and Aging. Int J Mol Sci 2020; 21:E3134. [PMID: 32365535 PMCID: PMC7247689 DOI: 10.3390/ijms21093134] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2020] [Revised: 04/26/2020] [Accepted: 04/27/2020] [Indexed: 12/12/2022] Open
Abstract
Mitochondria are organelles that mainly control energy conversion in the cell. In addition, they also participate in many relevant activities, such as the regulation of apoptosis and calcium levels, and other metabolic tasks, all closely linked to cell viability. Functionality of mitochondria appears to depend upon their network architecture that may dynamically pass from an interconnected structure with long tubular units, to a fragmented one with short separate fragments. A decline in mitochondrial quality, which presents itself as an altered structural organization and a function of mitochondria, has been observed in Down syndrome (DS), as well as in aging and in age-related pathologies. This review provides a basic overview of mitochondrial dynamics, from fission/fusion mechanisms to mitochondrial homeostasis. Molecular mechanisms determining the disruption of the mitochondrial phenotype in DS and aging are discussed. The impaired activity of the transcriptional co-activator PGC-1α/PPARGC1A and the hyperactivation of the mammalian target of rapamycin (mTOR) kinase are emerging as molecular underlying causes of these mitochondrial alterations. It is, therefore, likely that either stimulating the PGC-1α activity or inhibiting mTOR signaling could reverse mitochondrial dysfunction. Evidence is summarized suggesting that drugs targeting either these pathways or other factors affecting the mitochondrial network may represent therapeutic approaches to improve and/or prevent the effects of altered mitochondrial function. Overall, from all these studies it emerges that the implementation of such strategies may exert protective effects in DS and age-related diseases.
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Affiliation(s)
- Nunzia Mollo
- Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, 80131 Naples, Italy
| | - Rita Cicatiello
- Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, 80131 Naples, Italy
| | - Miriam Aurilia
- Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, 80131 Naples, Italy
| | - Roberta Scognamiglio
- Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, 80131 Naples, Italy
| | - Rita Genesio
- Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, 80131 Naples, Italy
| | - Maria Charalambous
- Institute of Experimental Endocrinology and Oncology “G. Salvatore”, National Research Council, 80131 Naples, Italy
| | - Simona Paladino
- Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, 80131 Naples, Italy
| | - Anna Conti
- Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, 80131 Naples, Italy
| | - Lucio Nitsch
- Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, 80131 Naples, Italy
- Institute of Experimental Endocrinology and Oncology “G. Salvatore”, National Research Council, 80131 Naples, Italy
| | - Antonella Izzo
- Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, 80131 Naples, Italy
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Feeding brown fat: dietary phytochemicals targeting non-shivering thermogenesis to control body weight. Proc Nutr Soc 2020; 79:338-356. [PMID: 32290888 PMCID: PMC7663322 DOI: 10.1017/s0029665120006928] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Excessive adipose accumulation, which is the main driver for the development of secondary metabolic complications, has reached epidemic proportions and combined pharmaceutical, educational and nutritional approaches are required to reverse the current rise in global obesity prevalence rates. Brown adipose tissue (BAT) is a unique organ able to dissipate energy and thus a promising target to enhance BMR to counteract a positive energy balance. In addition, active BAT might support body weight maintenance after weight loss to prevent/reduce relapse. Natural products deliver valuable bioactive compounds that have historically helped to alleviate disease symptoms. Interest in recent years has focused on identifying nutritional constituents that are able to induce BAT activity and thereby enhance energy expenditure. This review provides a summary of selected dietary phytochemicals, including isoflavones, catechins, stilbenes, the flavonoids quercetin, luteolin and resveratrol as well as the alkaloids berberine and capsaicin. Most of the discussed phytochemicals act through distinct molecular pathways e.g. sympathetic nerve activation, AMP-kinase signalling, SIRT1 activity or stimulation of oestrogen receptors. Thus, it might be possible to utilise this multitude of pathways to co-activate BAT using a fine-tuned combination of foods or combined nutritional supplements.
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Mediterranean Diet Nutrients to Turn the Tide against Insulin Resistance and Related Diseases. Nutrients 2020; 12:nu12041066. [PMID: 32290535 PMCID: PMC7230471 DOI: 10.3390/nu12041066] [Citation(s) in RCA: 160] [Impact Index Per Article: 32.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2020] [Revised: 04/06/2020] [Accepted: 04/10/2020] [Indexed: 12/11/2022] Open
Abstract
Insulin resistance (IR), defined as an attenuated biological response to circulating insulin, is a fundamental defect in obesity and type 2 diabetes (T2D), and is also linked to a wide spectrum of pathological conditions, such as non-alcoholic fatty liver disease (NAFLD), cognitive impairment, endothelial dysfunction, chronic kidney disease (CKD), polycystic ovary syndrome (PCOS), and some endocrine tumors, including breast cancer. In obesity, the unbalanced production of pro- and anti-inflammatory adipocytokines can lead to the development of IR and its related metabolic complications, which are potentially reversible through weight-loss programs. The Mediterranean diet (MedDiet), characterized by high consumption of extra-virgin olive oil (EVOO), nuts, red wine, vegetables and other polyphenol-rich elements, has proved to be associated with greater improvement of IR in obese individuals, when compared to other nutritional interventions. Also, recent studies in either experimental animal models or in humans, have shown encouraging results for insulin-sensitizing nutritional supplements derived from MedDiet food sources in the modulation of pathognomonic traits of certain IR-related conditions, including polyunsaturated fatty acids from olive oil and seeds, anthocyanins from purple vegetables and fruits, resveratrol from grapes, and the EVOO-derived, oleacein. Although the pharmacological properties and clinical uses of these functional nutrients are still under investigation, the molecular mechanism(s) underlying the metabolic benefits appear to be compound-specific and, in some cases, point to a role in gene expression through an involvement of the nuclear high-mobility group A1 (HMGA1) protein.
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Vlavcheski F, Den Hartogh DJ, Giacca A, Tsiani E. Amelioration of High-Insulin-Induced Skeletal Muscle Cell Insulin Resistance by Resveratrol Is Linked to Activation of AMPK and Restoration of GLUT4 Translocation. Nutrients 2020; 12:E914. [PMID: 32230718 PMCID: PMC7230755 DOI: 10.3390/nu12040914] [Citation(s) in RCA: 53] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2020] [Revised: 03/17/2020] [Accepted: 03/23/2020] [Indexed: 12/14/2022] Open
Abstract
Insulin resistance, the hallmark of type 2 diabetes mellitus (T2DM), is linked to hyperinsulinemia, which develops to counterbalance initial peripheral hormone resistance. Studies indicate that chronically elevated levels of insulin lead to skeletal muscle insulin resistance by deregulating steps within the insulin signaling cascade. The polyphenol resveratrol (RSV) has been shown to have antidiabetic properties in vitro and in vivo. In the present study, we examined the effect of RSV on high insulin (HI)-induced insulin resistance in skeletal muscle cells in vitro and investigated the mechanisms involved. Parental and GLUT4myc-overexpressing L6 rat skeletal muscle cells were used. [3H]2-deoxyglucose (2DG) uptake was measured, and total and phosphorylated levels of specific proteins were examined by immunoblotting. Exposure of L6 cells to HI levels (100 nM) for 24 h decreased the acute-insulin-stimulated 2DG uptake, indicating insulin resistance. HI increased ser307 and ser636/639 phosphorylation of IRS-1 (to 184% ± 12% and 225% ± 28.9% of control, with p < 0.001 and p < 0.01, respectively) and increased the phosphorylation levels of mTOR (174% ± 6.7% of control, p < 0.01) and p70 S6K (228% ± 33.5% of control, p < 0.01). Treatment with RSV abolished these HI-induced responses. Furthermore, RSV increased the activation of AMPK and restored the insulin-mediated increase in plasma membrane GLUT4 glucose transporter levels. These data suggest that RSV has a potential to counteract the HI-induced muscle insulin resistance.
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Affiliation(s)
- Filip Vlavcheski
- Department of Health Sciences, Brock University, St. Catharines, ON L2S 3A1, Canada; (F.V.); (D.J.D.H.)
- Centre for Bone and Muscle Health, Brock University, St. Catharines, ON L2S 3A1, Canada
| | - Danja J. Den Hartogh
- Department of Health Sciences, Brock University, St. Catharines, ON L2S 3A1, Canada; (F.V.); (D.J.D.H.)
- Centre for Bone and Muscle Health, Brock University, St. Catharines, ON L2S 3A1, Canada
| | - Adria Giacca
- Department of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada;
- Department of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada
- Institute of Medical Sciences, University of Toronto, Toronto, ON M5S 1A8T, Canada
- Banting and Best Diabetes Centre, University of Toronto, Toronto, ON M5G 2C4, Canada
| | - Evangelia Tsiani
- Department of Health Sciences, Brock University, St. Catharines, ON L2S 3A1, Canada; (F.V.); (D.J.D.H.)
- Centre for Bone and Muscle Health, Brock University, St. Catharines, ON L2S 3A1, Canada
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Barbalho SM, Bueno Ottoboni AMM, Fiorini AMR, Guiguer ÉL, Nicolau CCT, Goulart RDA, Flato UAP. Grape juice or wine: which is the best option? Crit Rev Food Sci Nutr 2020; 60:3876-3889. [PMID: 31920107 DOI: 10.1080/10408398.2019.1710692] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Grapes used in the wine or juice production are mainly Vitis vinifera and Vitis labrusca and possess high amounts of polyphenolic compounds. These compounds are associated with the reduction of the inflammatory processes, oxidative stress, and protection against cardiovascular diseases. The industrial processes used for juice and wine production may interfere with the antioxidant composition of these products and the effects on human health. The aim of this review is to compare the effects of the consumption of wine or grape juice on cardiovascular risk factors. We used PRISMA guidelines and Medline/PUBMED and EMBASE to perform our search. The main effects of red wine and grape juice in humans were a reduction of body mass index, waist circumference, glycemia, plasma lipid peroxidation, total cholesterol, LDL-c, triglycerides, blood pressure, and homocysteine levels. Both wine and grape juice possess numerous bioactive compounds that are potentially responsible for many beneficial effects on human health. Nevertheless, there is a need for more double-blind, randomized controlled studies comparing the effects of juice and wine consumption without the biases that occur when comparisons are made with different populations, ages, doses, and different types of wine or juice.
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Affiliation(s)
- Sandra Maria Barbalho
- Medical School of Marília, UNIMAR, Marília, São Paulo, Brazils.,Food Technology School, Marília, São Paulo, Brazil
| | | | | | - Élen Landgraf Guiguer
- Medical School of Marília, UNIMAR, Marília, São Paulo, Brazils.,Food Technology School, Marília, São Paulo, Brazil
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Mankowski RT, You L, Buford TW, Leeuwenburgh C, Manini TM, Schneider S, Qiu P, Anton SD. Higher dose of resveratrol elevated cardiovascular disease risk biomarker levels in overweight older adults - A pilot study. Exp Gerontol 2019; 131:110821. [PMID: 31891746 DOI: 10.1016/j.exger.2019.110821] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2019] [Revised: 12/06/2019] [Accepted: 12/26/2019] [Indexed: 02/05/2023]
Abstract
Older adults are at high risk of developing cardiovascular disease (CVD). Pre-clinical studies indicate that resveratrol (RSV), a polyphenol commonly found in grapes and red wine, may help prevent development of CVD. Based on our previous reports where the 300 mg and 1000 mg doses appeared safe and improved psychomotor function in a dose-dependent manner, our hypothesis was that RSV would reduce biomarkers of CVD risk in overweight, but otherwise healthy older adults and that 1000 mg would lower CVD biomarkers >300 mg. This analysis was performed on samples from older participants (65 years and older) who were randomized to a 90 day RSV treatment with 300 mg (n = 10), 1000 mg (n = 9) or placebo (n = 10). We measured levels of CVD risk biomarkers i.e. oxidized low-density lipoprotein (oxLDL), soluble E-selectin-1 (sE-selectin), soluble Intercellular Adhesion Molecule-1 (sICAM-1), Soluble Vascular Cell Adhesion Molecule-1 (sVCAM-1), total plasminogen activator inhibitor (tPAI-1). Statistical significance was set at p < 0.05. Both sVCAM-1 and tPAI increased significantly more in the 1000 mg vs. 300 mg and placebo groups. Other biomarkers (300 mg vs. 1000 mg vs. placebo: oxLDL, sEselectin-1 and sICAM-1) followed the same trend toward higher levels in the 1000 mg group compared to the 300 mg and placebo groups, without reaching statistical significance. This pilot project suggests that a higher dose of RSV may increase the levels of CVD risk biomarkers in overweight older adults. Given no change in the CVD risk biomarkers in response to a lower dose, future studies should test the effects of different doses of RSV to evaluate potential detrimental effects of higher doses on CVD biomarkers and measures of cardiovascular function in older adults at risk for CVD.
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Affiliation(s)
- R T Mankowski
- Department of Aging and Geriatric Research, University of Florida, Gainesville, FL, USA.
| | - L You
- Department of Biostatistics, University of Florida, Gainesville, FL, USA
| | - T W Buford
- Department of Medicine, UAB School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
| | - C Leeuwenburgh
- Department of Aging and Geriatric Research, University of Florida, Gainesville, FL, USA
| | - T M Manini
- Department of Aging and Geriatric Research, University of Florida, Gainesville, FL, USA
| | - S Schneider
- Department of Aging and Geriatric Research, University of Florida, Gainesville, FL, USA
| | - P Qiu
- Department of Biostatistics, University of Florida, Gainesville, FL, USA
| | - S D Anton
- Department of Aging and Geriatric Research, University of Florida, Gainesville, FL, USA
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The Fluid Aspect of the Mediterranean Diet in the Prevention and Management of Cardiovascular Disease and Diabetes: The Role of Polyphenol Content in Moderate Consumption of Wine and Olive Oil. Nutrients 2019; 11:nu11112833. [PMID: 31752333 PMCID: PMC6893438 DOI: 10.3390/nu11112833] [Citation(s) in RCA: 134] [Impact Index Per Article: 22.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2019] [Revised: 11/10/2019] [Accepted: 11/13/2019] [Indexed: 12/20/2022] Open
Abstract
A growing interest has emerged in the beneficial effects of plant-based diets for the prevention of cardiovascular disease, diabetes and obesity. The Mediterranean diet, one of the most widely evaluated dietary patterns in scientific literature, includes in its nutrients two fluid foods: olive oil, as the main source of fats, and a low-to-moderate consumption of wine, mainly red, particularly during meals. Current mechanisms underlying the beneficial effects of the Mediterranean diet include a reduction in inflammatory and oxidative stress markers, improvement in lipid profile, insulin sensitivity and endothelial function, as well as antithrombotic properties. Most of these effects are attributable to bioactive ingredients including polyphenols, mono- and poly-unsaturated fatty acids. Polyphenols are a heterogeneous group of phytochemicals containing phenol rings. The principal classes of red wine polyphenols include flavonols (quercetin and myricetin), flavanols (catechin and epicatechin), anthocyanin and stilbenes (resveratrol). Olive oil has at least 30 phenolic compounds. Among them, the main are simple phenols (tyrosol and hydroxytyrosol), secoroids and lignans. The present narrative review focuses on phenols, part of red wine and virgin olive oil, discussing the evidence of their effects on lipids, blood pressure, atheromatous plaque and glucose metabolism.
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Jia E, Yan Y, Zhou M, Li X, Jiang G, Liu W, Zhang D. Combined effects of dietary quercetin and resveratrol on growth performance, antioxidant capability and innate immunity of blunt snout bream (Megalobrama amblycephala). Anim Feed Sci Technol 2019. [DOI: 10.1016/j.anifeedsci.2019.114268] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
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Abdollahi S, Salehi-Abargouei A, Toupchian O, Sheikhha MH, Fallahzadeh H, Rahmanian M, Tabatabaie M, Mozaffari-Khosravi H. The Effect of Resveratrol Supplementation on Cardio-Metabolic Risk Factors in Patients with Type 2 Diabetes: A Randomized, Double-Blind Controlled Trial. Phytother Res 2019; 33:3153-3162. [PMID: 31475415 DOI: 10.1002/ptr.6487] [Citation(s) in RCA: 36] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2019] [Revised: 07/28/2019] [Accepted: 08/06/2019] [Indexed: 12/15/2022]
Abstract
The aim of the present randomized controlled trial was to evaluate the effect of a micronized resveratrol supplement on glycemic status, lipid profile, and body composition in patients with type 2 diabetes mellitus (T2DM). A total of 71 overweight patients with T2DM (body mass index ranged 25-30) were randomly assigned to receive 1000 mg/day trans-resveratrol or placebo (methyl cellulose) for 8 weeks. Anthropometric indices and biochemical indices including lipid and glycemic profile were measured before and after the intervention. In adjusted model (age, sex, and baseline body mass index), resveratrol decreased fasting blood sugar (-7.97±13.6 mg/dL, p=0.05) and increased high density lipoprotein (3.62±8.75 mg/dL, p=0.01) levels compared with placebo. Moreover, the mean difference in insulin levels reached significance (-0.97±1.91, μIU/mL, p= 0.02). However, no significant differences were observed for anthropometric measures. It was found that 8-week resveratrol supplementation produced useful effects on some cardio-metabolic parameters in patients with T2DM. More studies are needed to confirm these findings.
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Affiliation(s)
- Shima Abdollahi
- Department of Nutrition, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.,Nutrition and Food Security Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.,Department of Nutrition and Public Health, School of Public Health, North Khorasan University of Medical Sciences, Bojnurd, Iran
| | - Amin Salehi-Abargouei
- Department of Nutrition, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.,Nutrition and Food Security Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Omid Toupchian
- Department of Nutrition and Public Health, School of Public Health, North Khorasan University of Medical Sciences, Bojnurd, Iran
| | - Mohammad Hasan Sheikhha
- Department of Genetics, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.,Yazd Clinical and Research Center for Infertility, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Hossein Fallahzadeh
- Department of Biostatistics and Epidemiology, Research Center of Prevention and Epidemiology of Non-Communicable Disease, School of Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Masoud Rahmanian
- Yazd Diabetic Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Mahtab Tabatabaie
- Department of Nutrition, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.,Nutrition and Food Security Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Hassan Mozaffari-Khosravi
- Department of Nutrition, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.,Yazd Diabetic Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
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Effect of Resveratrol on In Vitro and In Vivo Models of Diabetic Retinophathy: A Systematic Review. Int J Mol Sci 2019; 20:ijms20143503. [PMID: 31319465 PMCID: PMC6678653 DOI: 10.3390/ijms20143503] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2019] [Revised: 06/19/2019] [Accepted: 07/11/2019] [Indexed: 12/21/2022] Open
Abstract
A large number of preclinical studies suggest the involvement of resveratrol in the prevention and treatment of eye diseases induced by oxidative stress and inflammation. We tested the hypothesis that resveratrol influences many pathways of in vitro and in vivo models of diabetic retinopathy through a systematic literature review of original articles. The review was conducted in accordance with the PRISMA guidelines. A literature search of all original articles published until April 2019 was performed. The terms “resveratrol” in combination with “retina”, “retinal pathology”, “diabetic retinopathy” and “eye” were searched. Possible biases were identified with the adopted SYRCLE’s tool. Eighteen articles met inclusion/exclusion criteria for full-text review. Eleven of them included in vitro experiments, 11 studies reported in vivo data and 3 studies described both in vitro and in vivo experiments. Most of the in vivo studies did not include data that would allow exclusion of bias risks, according to SYRCLE’s risk of bias tool. Both in vitro and in vivo data suggest anti-apoptotic, anti-inflammatory and anti-oxidative actions of resveratrol in models of diabetic retinopathy. However, results on its anti-angiogenic effects are contradictory and need more rigorous studies.
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Bashir SO. Concomitant administration of resveratrol and insulin protects against diabetes mellitus type-1-induced renal damage and impaired function via an antioxidant-mediated mechanism and up-regulation of Na +/K +-ATPase. Arch Physiol Biochem 2019; 125:104-113. [PMID: 29436859 DOI: 10.1080/13813455.2018.1437752] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
This study investigated if a combination of resveratrol (RES) and insulin could reverse type 1 diabetic mellitus-induced (T1DM) nephropathy and illustrates mechanism of action. Rats were divided into six groups (n = 10/group) as follows: control, control + RES (20 mg/kg), T1DM, T1DM + RES, T1DM + insulin (1 U/g), and T1DM + RES + insulin and treated for eight weeks. While individual administrations of both drugs significantly but partially restored renal function and cortex architectures, combination therapy of both RES and insulin produced the maximum improvements. Mechanism of actions revealed a synergist effect of both drugs due to hypoglycaemic effect of insulin and the ability of both drugs to increase renal cortex antioxidant enzymes activities, inhibit lipid peroxidation, and up-regulate Na+/K+-ATPase, independent of each others. In conclusion, these data suggest the combined therapy with insulin and RES could provide an excellent combined drug therapy against T1DM-induced nephropathy.
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Affiliation(s)
- Salah O Bashir
- a Department of Physiology, College of Medicine , King Khalid University , Abha , Saudi Arabia
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