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1
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Wang XC, Song L, Wang XH. Efficacy of dietary polyphenol supplement in patients with non-alcoholic fatty liver disease: a network meta-analysis. Front Nutr 2025; 12:1582861. [PMID: 40416369 PMCID: PMC12100629 DOI: 10.3389/fnut.2025.1582861] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2025] [Accepted: 04/24/2025] [Indexed: 05/27/2025] Open
Abstract
Background Non-alcoholic fatty liver disease (NAFLD) has become a public health issue worldwide. Dietary polyphenols are naturally occurring plant active ingredients and are widely employed in the treatment of NAFLD. However, the therapeutic effect is still controversial. In this study, a network meta-analysis (NMA) was performed to appraise the effects of various polyphenols on metabolic indices of NAFLD. Methods PubMed, Embase, the Cochrane Library, and Web of Science were retrieved for English studies on dietary polyphenols in the treatment of NAFLD. Outcome measures were extracted from the included studies and compared using a Bayesian NMA model, encompassing body mass index (BMI), alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and necrosis factor alpha (TNF-α). Results In total, 54 randomized controlled trials (RCTs) were included in this study, including 3,132 participants. It involved 13 single (or combined) dietary polyphenols. Naringenin could reduce serum TC (surface under the cumulative ranking curve: 94.59%) and TG (99.00%) in NAFLD patients. Catechin could decrease BMI (77.74%) and serum ALT (94.21%), AST (93.56%), TC (92.26%), and increase HDL-C (93.72%). Dihydromyricetin (DHM) was effective in reducing serum LDL-C (73.22%), and quercetin decreased serum TNF-α (99.47%). Conclusion Catechin may be the most appropriate dietary polyphenol supplement for NAFLD. Future studies should incorporate more RCTs to further validate the efficacy of dietary polyphenols (like DHM and quercetin), which are limited in sample sizes, in treating NAFLD. On the other hand, it is essential to investigate improvements in the bioavailability of these dietary polyphenols and to clarify their safety profiles.
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Affiliation(s)
- Xiao-cui Wang
- Ningxia Regional Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Regional High Incidence Disease, Ningxia Medical University, Yinchuan, China
- Key Laboratory of Ningxia Ethnomedicine Modernization, Ministry of Education, Ningxia Medical University, Yinchuan, China
| | - Li Song
- Department of Nephrology, Affiliated Hospital of Traditional Chinese Medicine, Ningxia Medical University, Yinchuan, China
| | - Xin-han Wang
- Ningxia Regional Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Regional High Incidence Disease, Ningxia Medical University, Yinchuan, China
- Key Laboratory of Ningxia Ethnomedicine Modernization, Ministry of Education, Ningxia Medical University, Yinchuan, China
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Ciobârcă D, Cătoi AF, Gavrilaș L, Banc R, Miere D, Filip L. Natural Bioactive Compounds in the Management of Type 2 Diabetes and Metabolic (Dysfunction)-Associated Steatotic Liver Disease. Pharmaceuticals (Basel) 2025; 18:279. [PMID: 40006091 PMCID: PMC11859434 DOI: 10.3390/ph18020279] [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: 11/18/2024] [Revised: 02/11/2025] [Accepted: 02/13/2025] [Indexed: 02/27/2025] Open
Abstract
Type 2 diabetes (T2D) and metabolic (dysfunction)-associated steatotic liver disease (MASLD) affect a growing number of individuals worldwide. T2D and MASLD often coexist and substantially elevate the risk of adverse hepatic and cardiovascular clinical outcomes. Several common pathogenetic mechanisms are responsible for T2D and MASLD onset and progression, including insulin resistance, oxidative stress, and low-grade inflammation, among others. The latter can also be induced by gut microbiota and its derived metabolites. Natural bioactive compounds (NBCs) have been reported for their therapeutic potential in both T2D and MASLD. A large amount of evidence obtained from clinical trials suggests that compounds like berberine, curcumin, soluble fibers, and omega-3 fatty acids exhibit significant hypoglycemic, hypolipidemic, and hepatoprotective activity in humans and may be employed as adjunct therapy in T2D and MASLD management. In this review, the role of the most studied NBCs in the management of T2D and MASLD is discussed, emphasizing recent clinical evidence supporting these compounds' efficacy and safety. Also, prebiotics that act against metabolic dysfunction by modulating gut microbiota are evaluated.
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Affiliation(s)
- Daniela Ciobârcă
- Department 2, Faculty of Nursing and Health Sciences, “Iuliu Hatieganu” University of Medicine and Pharmacy, 23 Gheorghe Marinescu Street, 400337 Cluj-Napoca, Romania; (D.C.); (L.G.)
| | - Adriana Florinela Cătoi
- Department of Pathophysiology, Faculty of Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, 2-4 Victor Babes Street, 400012 Cluj-Napoca, Romania
| | - Laura Gavrilaș
- Department 2, Faculty of Nursing and Health Sciences, “Iuliu Hatieganu” University of Medicine and Pharmacy, 23 Gheorghe Marinescu Street, 400337 Cluj-Napoca, Romania; (D.C.); (L.G.)
| | - Roxana Banc
- Department of Bromatology, Hygiene, Nutrition, Faculty of Pharmacy, “Iuliu Hatieganu” University of Medicine and Pharmacy, 6 Louis Pasteur Street, 400349 Cluj-Napoca, Romania; (R.B.); (D.M.); (L.F.)
| | - Doina Miere
- Department of Bromatology, Hygiene, Nutrition, Faculty of Pharmacy, “Iuliu Hatieganu” University of Medicine and Pharmacy, 6 Louis Pasteur Street, 400349 Cluj-Napoca, Romania; (R.B.); (D.M.); (L.F.)
| | - Lorena Filip
- Department of Bromatology, Hygiene, Nutrition, Faculty of Pharmacy, “Iuliu Hatieganu” University of Medicine and Pharmacy, 6 Louis Pasteur Street, 400349 Cluj-Napoca, Romania; (R.B.); (D.M.); (L.F.)
- Academy of Romanian Scientists (AOSR), 3 Ilfov Street, 050044 Bucharest, Romania
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Cai Y, Chen Q. Resveratrol: A Narrative Review Regarding Its Mechanisms in Mitigating Obesity-Associated Metabolic Disorders. Phytother Res 2025; 39:999-1019. [PMID: 39715730 DOI: 10.1002/ptr.8416] [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: 07/31/2024] [Revised: 12/04/2024] [Accepted: 12/07/2024] [Indexed: 12/25/2024]
Abstract
Resveratrol (RSV) is a naturally occurring astragalus-like polyphenolic compound with remarkable weight loss properties. However, the mechanism of RSV in treating obesity is unclear. In this narrative review, we explored electronic databases (PubMed) for research articles from 2021 to the present using the keywords "resveratrol" and "obesity". This article explores the mechanisms involved in the alleviation of obesity-related metabolic disorders by RSV. RSV affects obesity by modulating mitochondrial function, insulin signaling, and gut microbiota, regulating lipid metabolism, inhibiting oxidative stress, and regulating epigenetic regulation. Administering RSV to pregnant animals exhibits maternal and first-generation offspring benefits, and RSV administration to lactating animals has long-term benefits, which involve the epigenetic modulations by RSV. A comprehensive understanding of the epigenetic mechanisms of RSV regulation could help in developing drugs suitable for pregnancy preparation groups, pregnant women, and nursing infants.
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Affiliation(s)
- Yichen Cai
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Qiu Chen
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
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Handu D, Stote K, Piemonte T. Evaluating Bioactive-Substance-Based Interventions for Adults with MASLD: Results from a Systematic Scoping Review. Nutrients 2025; 17:453. [PMID: 39940310 PMCID: PMC11820841 DOI: 10.3390/nu17030453] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2024] [Revised: 01/17/2025] [Accepted: 01/20/2025] [Indexed: 02/14/2025] Open
Abstract
Objective: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a chronic condition affecting a broad population. This review aimed to identify and summarize the current evidence on bioactive-substance-based interventions for adults with MASLD, formerly known as nonalcoholic fatty liver disease (NAFLD), covering publications from 2000 to 2023. Methods: A search was conducted across six databases (MEDLINE, CINAHL, Cochrane CENTRAL, Cochrane Database of Systematic Reviews, Food Science Source, and SPORTDiscus) for randomized controlled trials and other study types (e.g., prospective cohort studies and systematic reviews), reflecting the scoping nature of this review. The search was limited to studies in adults (>18 years old), with an intervention of interest and at least one comparator group. Results: A total of 4572 articles were retrieved, with 201 full-text articles screened for eligibility. Of these, 131 primary studies and 49 systematic reviews were included in the scoping review. The most studied bioactive substances were Curcumin (Turmeric) (n = 25), Silymarin (Milk Thistle) (n = 17), Resveratrol (n = 10), Coffee (n = 7), Green Tea (n = 5), and Berberine (n = 5 each). Moreover, 46 studies reported on 36 other bioactive substances with 2 or fewer articles each. Among the included systematic reviews, 13 focused on Curcumin, 12 on Coffee or Tea, 10 on bioactive substance combinations, 6 on Resveratrol, and 2 each on Silymarin and Artichoke Leaf. The included studies showed substantial heterogeneity in reported outcomes, which primarily focused on hepatic health, body weight, adverse events, glycemic control, blood lipids, and body composition. Conclusions: This scoping review highlights a range of bioactive substances used in the treatment of MASLD. While evidence is abundant for bioactive substances like Curcumin and Silymarin, further research and synthesis of findings is necessary to establish the clinical efficacy of all bioactive substances.
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Affiliation(s)
- Deepa Handu
- Academy of Nutrition and Dietetics, Chicago, IL 60606, USA;
| | - Kim Stote
- Department of Allied Health Sciences, State University of New York, Empire State University, Saratoga Springs, NY 12866, USA;
| | - Tami Piemonte
- Academy of Nutrition and Dietetics, Chicago, IL 60606, USA;
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Amirkhizi F, Taghizadeh M, Khalese-Ranjbar B, Hamedi-Shahraki S, Asghari S. The clinical value of serum sirtuin-1 concentration in the diagnosis of metabolic dysfunction-associated steatotic liver disease. BMC Gastroenterol 2025; 25:27. [PMID: 39844087 PMCID: PMC11753077 DOI: 10.1186/s12876-025-03613-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2024] [Accepted: 01/14/2025] [Indexed: 01/24/2025] Open
Abstract
BACKGROUND Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease and can affect individuals without producing any symptoms. We aimed to explore the value of serum sirtuin-1 (Sirt-1) in the diagnosis of MASLD. METHODS This case-control study analyzed data collected from 190 individuals aged 20 to 60 years. Anthropometric parameters, demographic information, and serum biochemical variables-including glycemic parameters, lipid profiles, liver enzymes, and Sirt-1 levels-were assessed. The correlation between serum Sirt-1 and biochemical variables was examined using Pearson's correlation coefficient. Receiver operating characteristic (ROC) curve analysis was employed to evaluate the diagnostic value of serum Sirt-1 in the context of MASLD. RESULTS Serum Sirt-1 levels was significantly lower in the MASLD group (p < 0.001) and was inversely correlated with serum insulin (r = -0.163, p = 0.025), HOMA-IR (r = -0.169, p = 0.020) and triglyceride (r = -0.190, p = 0.009) and positively correlated with serum levels of high-density lipoprotein cholesterol (HDL-C) (r = 0.214, p = 0.003). The area under the curve (AUC) of Sirt-1 to predict the presence of MASLD was 0.76 (p < 0.001, 95% CI: 0.69, 0.82) with a sensitivity of 78.9, specificity of 61.1, positive predictive value (PPV) of 67.0%, and negative predictive value (NPV) of 74.0%. The optimal cutoff, determined using Youden's index, was 23.75 ng/mL. This indicates that serum Sirt-1 levels below 23.75 ng/mL may be indicative of MASLD. CONCLUSIONS The present study demonstrated that serum Sirt-1 levels were significantly lower in patients with MASLD. Furthermore, these levels were correlated with various metabolic parameters, including insulin resistance and the serum lipid profile. A serum Sirt-1 level below the cutoff of 23.75 ng/mL exhibited a significant association with the presence of MASLD, suggesting its potential utility in identifying patients with this condition.
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Affiliation(s)
- Farshad Amirkhizi
- Department of Nutrition, School of Public Health, Zabol University of Medical Sciences, Zabol, Iran
| | - Mahdiyeh Taghizadeh
- Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, No#44, Hojjatdoust St., Naderi St., Keshavarz Blvd, Tehran, 141556117, Iran
| | - Banafshe Khalese-Ranjbar
- Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, No#44, Hojjatdoust St., Naderi St., Keshavarz Blvd, Tehran, 141556117, Iran
| | - Soudabeh Hamedi-Shahraki
- Department of Epidemiology and Biostatistics, School of Public Health, Zabol University of Medical Sciences, Zabol, Iran
| | - Somayyeh Asghari
- Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, No#44, Hojjatdoust St., Naderi St., Keshavarz Blvd, Tehran, 141556117, Iran.
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Alanazi AZ, Alqinyah M, Alhamed AS, Mohammed H, Raish M, Aljerian K, Alsabhan JF, Alhazzani K. Cardioprotective effects of liposomal resveratrol in diabetic rats: unveiling antioxidant and anti-inflammatory benefits. Redox Rep 2024; 29:2416835. [PMID: 39496097 PMCID: PMC11536670 DOI: 10.1080/13510002.2024.2416835] [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] [Indexed: 11/06/2024] Open
Abstract
As a consequence of chronic hyperglycemia, diabetes complications and tissue damage are exacerbated. There is evidence that natural phytochemicals, including resveratrol, a bioactive polyphenol, may be able to reduce oxidative stress and improve insulin sensitivity. However, resveratrol's limited bioavailability hampers its therapeutic effectiveness. By using liposomes, resveratrol may be better delivered into the body and be more bioavailable. The objective of this study was to assess the cardioprotective potential of liposome-encapsulated resveratrol (LR) in a streptozotocin-induced (STZ) diabetic rat model. Adult male Wistar rats were categorized into five groups: control, diabetic, resveratrol-treated (40 mg/kg), liposomal resveratrol (LR)-treated (20 mg/kg) and liposomal resveratrol (LR)-treated (40 mg/kg) for a five-week study period. We compared the effects of LR to those of resveratrol (40 mg/kg) on various parameters, including serum levels of cardiac markers, tissue levels of pro-inflammatory cytokines, nuclear transcription factor, oxidative stress markers, and apoptotic markers. LR treatment in STZ-diabetic rats resulted in notable physiological improvements, including blood glucose regulation, inflammation reduction, oxidative stress mitigation, and apoptosis inhibition. LR effectively lowered oxidative stress and enhanced cardiovascular function. It also demonstrated a remarkable ability to suppress NF-kB-mediated inflammation by inhibiting the pro-inflammatory cytokines TNF-α and IL-6. Additionally, LR restored the antioxidant enzymes, catalase and glutathione peroxidase, thereby effectively counteracting oxidative stress. Notably, LR modulated apoptotic regulators, including caspase, Bcl2, and Bax, suggesting a role in regulating programmed cell death. These biochemical alterations were consistent with improved structural integrity of cardiac tissue as revealed by histological examination. In comparison, resveratrol exhibited lower efficacy at an equivalent dosage. Liposomal resveratrol shows promise in alleviating hyperglycemia-induced cardiac damage in diabetes. Further research is warranted to explore its potential as a therapeutic agent for diabetic cardiovascular complications and possible cardioprotective effects.
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Affiliation(s)
- Ahmed Z. Alanazi
- Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
| | - Mohammed Alqinyah
- Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
| | - Abdullah S. Alhamed
- Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
| | - Hanan Mohammed
- Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
| | - Mohammad Raish
- Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
| | - Khaldoon Aljerian
- Department of Pathology, College of Medicine, King Saud University, Riyadh, Saudi Arabia
| | - Jawza F. Alsabhan
- Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
| | - Khalid Alhazzani
- Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
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Sokal-Dembowska A, Jarmakiewicz-Czaja S, Filip R. Flavonoids and Their Role in Preventing the Development and Progression of MAFLD by Modifying the Microbiota. Int J Mol Sci 2024; 25:11187. [PMID: 39456969 PMCID: PMC11508831 DOI: 10.3390/ijms252011187] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2024] [Revised: 10/15/2024] [Accepted: 10/16/2024] [Indexed: 10/28/2024] Open
Abstract
With the increasing prevalence and serious health consequences of metabolic-associated fatty liver disease (MAFLD), early diagnosis and intervention are key to effective treatment. Recent studies highlight the important role of dietary factors, including the use of flavonoids, in improving liver health. These compounds possess anti-inflammatory, antioxidant, and liver-protective properties. Flavonoids have been shown to affect the gut microbiota, which plays a key role in liver function and disease progression. Therefore, their role in preventing the development and progression of MAFLD through modulation of the microbiome seems to be of interest. This narrative review aims to consolidate the current evidence on the effects of selected flavonoids on MAFLD progression, their potential mechanisms of action, and the implications for the development of personalized dietary interventions for the management of liver disease.
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Affiliation(s)
- Aneta Sokal-Dembowska
- Institute of Health Sciences, Medical College of Rzeszow University, 35-959 Rzeszow, Poland.; (S.J.-C.)
| | - Sara Jarmakiewicz-Czaja
- Institute of Health Sciences, Medical College of Rzeszow University, 35-959 Rzeszow, Poland.; (S.J.-C.)
| | - Rafał Filip
- Institute of Medicine, Medical College of Rzeszow University, 35-959 Rzeszow, Poland
- Department of Gastroenterology with IBD Unit, Clinical Hospital No. 2, 35-301 Rzeszow, Poland
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Ezhilarasan D, Langeswaran K. Hepatocellular Interactions of Potential Nutraceuticals in the Management of Inflammatory NAFLD. Cell Biochem Funct 2024; 42:e4112. [PMID: 39238138 DOI: 10.1002/cbf.4112] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2024] [Revised: 07/17/2024] [Accepted: 08/09/2024] [Indexed: 09/07/2024]
Abstract
Numerous studies highlight the potential of natural antioxidants, such as those found in foods and plants, to prevent or treat nonalcoholic fatty liver disease (NAFLD). Inflammation is a key factor in the progression from high-fat diet-induced NAFLD to nonalcoholic steatohepatitis (NASH). Injured liver cells and immune cells release inflammatory cytokines, activating hepatic stellate cells. These cells acquire a profibrogenic phenotype, leading to extracellular matrix accumulation and fibrosis. Persistent fibrosis can progress to cirrhosis. Fatty infiltration, oxidative stress, and inflammation exacerbate fatty liver diseases. Thus, many plant-derived antioxidants, like silymarin, silibinin, curcumin, resveratrol, berberine, and quercetin, have been extensively studied in experimental models and clinical patients with NAFLD. Experimentally, these compounds have shown beneficial effects in reducing lipid accumulation, oxidative stress, and inflammatory markers by modulating the ERK, NF-κB, AMPKα, and PPARγ pathways. They also help decrease metabolic endotoxemia, intestinal permeability, and gut inflammation. Clinically, silymarin and silibinin have been found to reduce transaminase levels, while resveratrol and curcumin help alleviate inflammation in NAFLD patients. However, these phytocompounds exhibit poor water solubility, leading to low oral bioavailability and hindering their biological efficacy. Additionally, inconclusive clinical results highlight the need for further trials with larger populations, longer durations, and standardized protocols.
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Affiliation(s)
- Devaraj Ezhilarasan
- Hepatology and Molecular Medicine Lab, Department of Pharmacology, Saveetha Dental College, Saveetha Institute of Medical and Technical Sciences (SIMATS), Chennai, Tamil Nadu, India
| | - Kulanthaivel Langeswaran
- Department of Biomedical Science, Science Campus, Alagappa University, Karaikudi, Tamil Nadu, India
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Cano R, Bermúdez V, Galban N, Garrido B, Santeliz R, Gotera MP, Duran P, Boscan A, Carbonell-Zabaleta AK, Durán-Agüero S, Rojas-Gómez D, González-Casanova J, Díaz-Vásquez W, Chacín M, Angarita Dávila L. Dietary Polyphenols and Gut Microbiota Cross-Talk: Molecular and Therapeutic Perspectives for Cardiometabolic Disease: A Narrative Review. Int J Mol Sci 2024; 25:9118. [PMID: 39201807 PMCID: PMC11354808 DOI: 10.3390/ijms25169118] [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: 06/11/2024] [Revised: 08/10/2024] [Accepted: 08/20/2024] [Indexed: 09/03/2024] Open
Abstract
The intricate interplay between the gut microbiota and polyphenols has emerged as a captivating frontier in understanding and potentially harnessing the therapeutic potential of these bioactive compounds. Phenolic compounds, renowned for their antioxidant, anti-inflammatory, antidiabetic, and anticancer properties, are subject to intricate transformations within the gut milieu, where the diverse microbial ecosystem exerts profound effects on their metabolism and bioavailability. Conversely, polyphenols exhibit a remarkable capacity to modulate the composition and activity of the gut microbiota, fostering a bidirectional relationship that extends beyond mere nutrient processing. This symbiotic interaction holds significant implications for human health, particularly in cardiometabolic diseases such as diabetes mellitus, metabolic-dysfunction-associated steatotic liver disease, and cardiovascular disease. Through a comprehensive exploration of molecular interactions, this narrative review elucidates the reciprocal dynamics between the gut microbiota and polyphenols, unveiling novel avenues for therapeutic intervention in cardiometabolic disorders. By unravelling the intricate cross-talk between these two entities, this review underscores the multifaceted roles of polyphenols in overall health and the pivotal role of gut microbiota modulation as a promising therapeutic strategy in mitigating the burden of cardiometabolic diseases.
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Affiliation(s)
- Raquel Cano
- Centro de Investigaciones Endocrino-Metabólicas, Escuela de Medicina, Universidad del Zulia, Maracaibo 4001, Venezuela; (R.C.); (N.G.); (R.S.); (P.D.)
| | - Valmore Bermúdez
- Facultad de Ciencias de la Salud, Universidad Simón Bolívar, Barranquilla 080002, Colombia
| | - Nestor Galban
- Centro de Investigaciones Endocrino-Metabólicas, Escuela de Medicina, Universidad del Zulia, Maracaibo 4001, Venezuela; (R.C.); (N.G.); (R.S.); (P.D.)
| | - Bermary Garrido
- Centro de Investigaciones Endocrino-Metabólicas, Escuela de Medicina, Universidad del Zulia, Maracaibo 4001, Venezuela; (R.C.); (N.G.); (R.S.); (P.D.)
| | - Raquel Santeliz
- Centro de Investigaciones Endocrino-Metabólicas, Escuela de Medicina, Universidad del Zulia, Maracaibo 4001, Venezuela; (R.C.); (N.G.); (R.S.); (P.D.)
| | - Maria Paula Gotera
- Centro de Investigaciones Endocrino-Metabólicas, Escuela de Medicina, Universidad del Zulia, Maracaibo 4001, Venezuela; (R.C.); (N.G.); (R.S.); (P.D.)
| | - Pablo Duran
- Centro de Investigaciones Endocrino-Metabólicas, Escuela de Medicina, Universidad del Zulia, Maracaibo 4001, Venezuela; (R.C.); (N.G.); (R.S.); (P.D.)
| | - Arturo Boscan
- Escuela de Medicina, Facultad de Medicina, Universidad del Zulia, Maracaibo 4001, Venezuela;
| | | | - Samuel Durán-Agüero
- Escuela de Nutrición y Dietética, Facultad de Ciencias para el Cuidado de la Salud, Universidad San Sebastián, Santiago 7511111, Chile
| | - Diana Rojas-Gómez
- Escuela de Nutrición y Dietética, Facultad de Medicina, Universidad Andres Bello, Santiago 8370321, Chile;
| | - Jorge González-Casanova
- Facultad de Ciencias de la Salud, Instituto de Ciencias Biomédicas, Universidad Autónoma de Chile, Santiago 8910060, Chile
| | - Waldo Díaz-Vásquez
- Escuela de Nutrición y Dietética, Facultad de Ciencias para el Cuidado de la Salud, Universidad San Sebastián, Santiago 7511111, Chile
| | - Maricarmen Chacín
- Facultad de Ciencias de la Salud, Universidad Simón Bolívar, Barranquilla 080002, Colombia
| | - Lissé Angarita Dávila
- Escuela de Nutrición y Dietética, Facultad de Medicina, Universidad Andres Bello, Concepción 4260000, Chile
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Ahmed DH, Fateh HL. Impact of flaxseed supplementation on lipid profile and liver enzymes in patients with non-alcoholic fatty liver disease: Systematic review and meta-analysis of randomized controlled trials. Prostaglandins Other Lipid Mediat 2024; 173:106838. [PMID: 38663513 DOI: 10.1016/j.prostaglandins.2024.106838] [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: 02/03/2024] [Revised: 04/18/2024] [Accepted: 04/21/2024] [Indexed: 05/07/2024]
Abstract
Since the effects of flaxseed supplementation on lipid profile and liver enzymes are still controversial, a meta-analysis of randomized controlled trials was conducted in the present study to assess the effect of flaxseed supplementation on lipid profile and liver enzymes. The study was designed, conducted, and reported according to the guidelines of the 2020 preferred reporting items for systematic reviews and meta-analysis (PRISMA) statement. A systematic and comprehensive search was performed in several databases from inception up to January 10, 2024. The meta-analysis on the impact of flaxseed supplementation on lipid profile and liver enzymes indicates that the overall effect of flaxseed supplementation on triglycerides, combining different doses, revealed a significant reduction with a WMD of - 230.72 (-53.95, - 27.49) and a P-value of 0.010. High-density lipoprotein (HDL) demonstrated a positive effect, with an overall WMD of 1.82 (0.27, 3.38) and a P-value of 0.021, indicating an increase in HDL levels. The liver enzymes AST and ALT displayed reductions in their levels, with overall WMDs of - 21.18 (-2.95, 0.59) and - 24.83 (-8.74, - 20.91), respectively. Subgroup analysis based on dosage revealed more pronounced reductions in ALT levels for doses below 2000 mg/day. Findings from this study suggest that a flaxseed supplement might be beneficial to modulate the blood lipid profile and liver enzymes.
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Affiliation(s)
- Dyari H Ahmed
- Nursing Department, Halabja Technical Institute, Sulaimani Polytechnic University, Sulaimani, Iraq
| | - Hawal Lateef Fateh
- Nursing Department, Kalar Technical Institute, Garmian Polytechnic University, Kalar, Iraq.
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Rathnayake DW, Sooriyaarachchi P, Niriella MA, Ediriweera D, Perera J. Herbal treatments for non-alcoholic fatty liver disease: A systematic review and meta-analysis of randomized controlled trials. ADVANCES IN INTEGRATIVE MEDICINE 2024. [DOI: 10.1016/j.aimed.2024.08.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Liu H, Li Y, Jin Y, Li X, Wang D, Yu X, Jiang Z, Yin G, Chen S, Zhang X, Meng D, Yu W, Jiang W, Zhang F. Effects of different natural products in patients with non-alcoholic fatty liver disease-A network meta-analysis of randomized controlled trials. Phytother Res 2024; 38:3801-3824. [PMID: 38886838 DOI: 10.1002/ptr.8182] [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: 07/31/2023] [Revised: 02/06/2024] [Accepted: 02/23/2024] [Indexed: 06/20/2024]
Abstract
Due to a scarcity of appropriate therapeutic approaches capable of ameliorating or eliminating non-alcoholic fatty liver disease (NAFLD), many researchers have come to focus on natural products based on traditional medicine that can be utilized to successfully treat NAFLD. In this study, we aimed to evaluate the effects exerted by seven natural products (curcumin, silymarin, resveratrol, artichoke leaf extract, berberine, catechins, and naringenin) on patients with NAFLD. For this purpose, PubMed, Embase, Cochrane Library, and Web of Science, were searched for randomized controlled trials (RCTs) exclusively. The selected studies were evaluated for methodological quality via the Cochrane bias risk assessment tool, and data analysis software was used to analyze the data accordingly. The RCTs from the earliest available date until September 2022 were collected. This process resulted in 37 RCTs with a total sample size of 2509 patients being included. The results of the network meta-analysis showed that artichoke leaf extract confers a relative advantage in reducing the aspartate aminotransferase (AST) levels (SUCRA: 99.1%), alanine aminotransferase (ALT) levels (SUCRA: 88.2%) and low-density lipoprotein cholesterol (LDL-C) levels (SUCRA: 88.9%). Naringenin conferred an advantage in reducing triglyceride (TG) levels (SUCRA: 97.3%), total cholesterol (TC) levels (SUCRA: 73.9%), and improving high-density lipoprotein cholesterol (HDL-C) levels (SUCRA: 74.9%). High-density catechins significantly reduced body mass index (BMI) levels (SUCRA: 98.5%) compared with the placebo. The Ranking Plot of the Network indicated that artichoke leaf extract and naringenin performed better than the other natural products in facilitating patient recovery. Therefore, we propose that artichoke leaf extract and naringenin may exert a better therapeutic effect on NAFLD. This study may help guide clinicians and lead to further detailed studies.
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Affiliation(s)
- Hongshuai Liu
- Shandong University of Traditional Chinese Medicine, Jinan, People's Republic of China
| | - Yufei Li
- Shandong University of Traditional Chinese Medicine, Jinan, People's Republic of China
| | - Yan Jin
- Shandong University of Traditional Chinese Medicine, Jinan, People's Republic of China
| | - Xin Li
- Department of Neurology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, People's Republic of China
| | - Dongxian Wang
- Shandong University of Traditional Chinese Medicine, Jinan, People's Republic of China
| | - Xiaowen Yu
- Department of Neurology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, People's Republic of China
| | - Zhenyuan Jiang
- Department of Neurology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, People's Republic of China
| | - Guoliang Yin
- Shandong University of Traditional Chinese Medicine, Jinan, People's Republic of China
| | - Suwen Chen
- Shandong University of Traditional Chinese Medicine, Jinan, People's Republic of China
| | - Xin Zhang
- Shandong University of Traditional Chinese Medicine, Jinan, People's Republic of China
| | - Decheng Meng
- Shandong University of Traditional Chinese Medicine, Jinan, People's Republic of China
| | - Wenfei Yu
- Shandong University of Traditional Chinese Medicine, Jinan, People's Republic of China
| | - Wenyin Jiang
- Shandong University of Traditional Chinese Medicine, Jinan, People's Republic of China
| | - Fengxia Zhang
- Department of Neurology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, People's Republic of China
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13
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Batista-Jorge GC, Barcala-Jorge AS, Lelis DF, Santos DE, Jorge AH, Monteiro-Junior RS, Santos SHS. Resveratrol Effects on Metabolic Syndrome Features: A Systematic Review and Meta-Analysis. ENDOCRINES 2024; 5:225-243. [DOI: 10.3390/endocrines5020016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2025] Open
Abstract
Resveratrol is a natural polyphenol with important anti-inflammatory and antioxidant properties for treating cardiometabolic disorders. Therefore, the present meta-analysis aimed to review and investigate the oral resveratrol supplementation effects on metabolic syndrome (MetS) components. The bibliographic search was carried out in 2023 in the following databases: PubMed, Web of Science, and Scopus. Studies that investigated the oral resveratrol effects on the MetS parameters were included. Statistical analyses were performed using RevMan Software V.5.3. The main findings showed that resveratrol significantly decreased systolic and diastolic blood pressure while having no significant effects on waist circumference and high-density lipoprotein levels. In addition, glucose level was significantly decreased in the subgroup of studies reporting change from baseline means, although the overall effect was not statistically significant (p = 0.81), while triglyceride levels were increased after the treatment period. In conclusion, the present meta-analysis evidenced the potential therapeutic effect of resveratrol on improving some MetS features, especially regarding systolic blood pressure, diastolic blood pressure, and glucose reduction; however, the results are still borderline and sometimes controversial, which might be justified by the methodological and statistical heterogeneity of the studies, with the latter varying from 17 to 57%.
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Affiliation(s)
- Gislaine C. Batista-Jorge
- Postgraduate Program in Health Sciences, Universidade Estadual de Montes Claros (Unimontes), Montes Claros 39401-089, Minas Gerais, Brazil
| | - Antônio S. Barcala-Jorge
- Postgraduate Program in Health Sciences, Universidade Estadual de Montes Claros (Unimontes), Montes Claros 39401-089, Minas Gerais, Brazil
| | - Deborah F. Lelis
- Postgraduate Program in Health Sciences, Universidade Estadual de Montes Claros (Unimontes), Montes Claros 39401-089, Minas Gerais, Brazil
| | - Daniel E. Santos
- Nursing Department, Universidade Estadual de Montes Claros (Unimontes), Montes Claros 39401-089, Minas Gerais, Brazil
| | - Antônio H. Jorge
- Medicine Department, Centro Universitário FIPMoc (UNIFIPMOC), Montes Claros 39408-007, Minas Gerais, Brazil
| | - Renato S. Monteiro-Junior
- Postgraduate Program in Health Sciences, Universidade Estadual de Montes Claros (Unimontes), Montes Claros 39401-089, Minas Gerais, Brazil
| | - Sérgio H. S. Santos
- Institute of Agricultural Sciences, Food Engineering College, Universidade Federal de Minas Gerais (UFMG), Montes Claros 39404-547, Minas Gerais, Brazil
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14
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Tian C, Huang R, Xiang M. SIRT1: Harnessing multiple pathways to hinder NAFLD. Pharmacol Res 2024; 203:107155. [PMID: 38527697 DOI: 10.1016/j.phrs.2024.107155] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2024] [Revised: 03/04/2024] [Accepted: 03/21/2024] [Indexed: 03/27/2024]
Abstract
Non-alcoholic fatty liver disease (NAFLD) encompasses hepatic steatosis, non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and hepatocellular carcinoma. It is the primary cause of chronic liver disorders, with a high prevalence but no approved treatment. Therefore, it is indispensable to find a trustworthy therapy for NAFLD. Recently, mounting evidence illustrates that Sirtuin 1 (SIRT1) is strongly associated with NAFLD. SIRT1 activation or overexpression attenuate NAFLD, while SIRT1 deficiency aggravates NAFLD. Besides, an array of therapeutic agents, including natural compounds, synthetic compounds, traditional Chinese medicine formula, and stem cell transplantation, alleviates NALFD via SIRT1 activation or upregulation. Mechanically, SIRT1 alleviates NAFLD by reestablishing autophagy, enhancing mitochondrial function, suppressing oxidative stress, and coordinating lipid metabolism, as well as reducing hepatocyte apoptosis and inflammation. In this review, we introduced the structure and function of SIRT1 briefly, and summarized the effect of SIRT1 on NAFLD and its mechanism, along with the application of SIRT1 agonists in treating NAFLD.
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Affiliation(s)
- Cheng Tian
- Department of Pharmacology, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Rongrong Huang
- Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Ming Xiang
- Department of Pharmacology, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
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15
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Godos J, Romano GL, Gozzo L, Laudani S, Paladino N, Dominguez Azpíroz I, Martínez López NM, Giampieri F, Quiles JL, Battino M, Galvano F, Drago F, Grosso G. Resveratrol and vascular health: evidence from clinical studies and mechanisms of actions related to its metabolites produced by gut microbiota. Front Pharmacol 2024; 15:1368949. [PMID: 38562461 PMCID: PMC10982351 DOI: 10.3389/fphar.2024.1368949] [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: 01/11/2024] [Accepted: 02/19/2024] [Indexed: 04/04/2024] Open
Abstract
Cardiovascular diseases are among the leading causes of mortality worldwide, with dietary factors being the main risk contributors. Diets rich in bioactive compounds, such as (poly)phenols, have been shown to potentially exert positive effects on vascular health. Among them, resveratrol has gained particular attention due to its potential antioxidant and anti-inflammatory action. Nevertheless, the results in humans are conflicting possibly due to interindividual different responses. The gut microbiota, a complex microbial community that inhabits the gastrointestinal tract, has been called out as potentially responsible for modulating the biological activities of phenolic metabolites in humans. The present review aims to summarize the main findings from clinical trials on the effects of resveratrol interventions on endothelial and vascular outcomes and review potential mechanisms interesting the role of gut microbiota on the metabolism of this molecule and its cardioprotective metabolites. The findings from randomized controlled trials show contrasting results on the effects of resveratrol supplementation and vascular biomarkers without dose-dependent effect. In particular, studies in which resveratrol was integrated using food sources, i.e., red wine, reported significant effects although the resveratrol content was, on average, much lower compared to tablet supplementation, while other studies with often extreme resveratrol supplementation resulted in null findings. The results from experimental studies suggest that resveratrol exerts cardioprotective effects through the modulation of various antioxidant, anti-inflammatory, and anti-hypertensive pathways, and microbiota composition. Recent studies on resveratrol-derived metabolites, such as piceatannol, have demonstrated its effects on biomarkers of vascular health. Moreover, resveratrol itself has been shown to improve the gut microbiota composition toward an anti-inflammatory profile. Considering the contrasting findings from clinical studies, future research exploring the bidirectional link between resveratrol metabolism and gut microbiota as well as the mediating effect of gut microbiota in resveratrol effect on cardiovascular health is warranted.
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Affiliation(s)
- Justyna Godos
- Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy
| | | | - Lucia Gozzo
- Clinical Pharmacology Unit/Regional Pharmacovigilance Centre, Azienda Ospedaliero Universitaria Policlinico “G. Rodolico-S. Marco”, Catania, Italy
| | - Samuele Laudani
- Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy
| | - Nadia Paladino
- Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy
| | - Irma Dominguez Azpíroz
- Research Group on Food, Nutritional Biochemistry and Health, Universidad Europea del Atlántico, Santander, Spain
- Universidade Internacional do Cuanza, Cuito, Angola
- Universidad de La Romana, La Romana, Dominican Republic
| | - Nohora Milena Martínez López
- Research Group on Food, Nutritional Biochemistry and Health, Universidad Europea del Atlántico, Santander, Spain
- Universidad Internacional Iberoamericana, Campeche, Mexico
- Fundación Universitaria Internacional de Colombia, Bogotá, Colombia
| | - Francesca Giampieri
- Research Group on Food, Nutritional Biochemistry and Health, Universidad Europea del Atlántico, Santander, Spain
- Department of Clinical Sciences, Università Politecnica delle Marche, Ancona, Italy
| | - José L. Quiles
- Research Group on Food, Nutritional Biochemistry and Health, Universidad Europea del Atlántico, Santander, Spain
- Department of Physiology, Institute of Nutrition and Food Technology “José Mataix”, Biomedical Research Center, University of Granada, Parque Tecnologico de la Salud, Granada, Spain
- Research and Development Functional Food Centre (CIDAF), Health Science Technological Park, Granada, Spain
| | - Maurizio Battino
- Research Group on Food, Nutritional Biochemistry and Health, Universidad Europea del Atlántico, Santander, Spain
- Department of Clinical Sciences, Università Politecnica delle Marche, Ancona, Italy
- International Joint Research Laboratory of Intelligent Agriculture and Agri-products Processing, Jiangsu University, Zhenjiang, Jiangsu, China
| | - Fabio Galvano
- Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy
| | - Filippo Drago
- Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy
| | - Giuseppe Grosso
- Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy
- Center for Human Nutrition and Mediterranean Foods (NUTREA), University of Catania, Catania, Italy
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16
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Moretti JB, Drouin A, Truong C, Youn E, Cloutier A, Alvarez F, Paganelli M, Grzywacz K, Jantchou P, Dubois J, Levy E, El Jalbout R. Effects of polyphenol supplementation on hepatic steatosis, intima-media thickness and non-invasive vascular elastography in obese adolescents: a pilot study protocol. BMJ Open 2024; 14:e074882. [PMID: 38296273 PMCID: PMC10828866 DOI: 10.1136/bmjopen-2023-074882] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2023] [Accepted: 12/21/2023] [Indexed: 02/03/2024] Open
Abstract
INTRODUCTION Non-alcoholic fatty liver disease (NAFLD) is increasingly prevalent in obese adolescents. Increased systemic inflammation and decreased gut microbial diversity linked to obesity affect the liver and are also associated with cardiovascular diseases in adulthood. However, NAFLD and vascular alterations are reversible. METHODS AND ANALYSIS This pilot study evaluated the feasibility of a prospective open-label randomised controlled trial evaluating the effects of polyphenols on NAFLD and vascular parameters in obese adolescents. Children aged 12-18 years with hepatic steatosis (n=60) will be recruited. The participants will be randomised with a 1:1 allocation ratio to receive polyphenol supplementation one time per day for 8 weeks along with the clinician-prescribed treatment (group B, n=30) or to continue the prescribed treatment without taking any polyphenols (group A, n=30). The outcome measures will be collected from both the groups at day 1 before starting polyphenol supplementation, at day 60 after 8 weeks of supplementation and at day 120, that is, 60 days after supplementation. The changes in hepatic steatosis and vascular parameters will be measured using liver and vascular imaging. Furthermore, anthropometric measures, blood tests and stool samples for gut microbiome analysis will be collected. After evaluating the study's feasibility, we hypothesise that, as a secondary outcome, compared with group A, the adolescents in group B will have improved NAFLD, vascular parameters, systemic inflammation and gut microbiome. ETHICS AND DISSEMINATION This study is approved by Health Canada and the hospital ethics. Participants and their parents/tutors will both provide consent. Trial results will be communicated to the collaborating gastroenterologists who follow the enrolled participants. Abstracts and scientific articles will be submitted to high-impact radiological societies and journals. CLINICALTRIALS gov ID: NCT03994029. Health Canada authorisation referral number: 250 811. Protocole version 13, 2 June 2023. TRIAL REGISTRATION NUMBER NCT03994029.
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Affiliation(s)
| | | | | | | | - Anik Cloutier
- CHU Sainte-Justine Centre de Recherche, Montreal, Québec, Canada
| | | | | | | | | | | | - Emile Levy
- CHU Sainte-Justine, Montreal, Québec, Canada
| | - Ramy El Jalbout
- Medical Imaging Department, CHU Sainte-Justine, Montreal, Québec, Canada
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17
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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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18
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Ghaeini Hesarooeyeh Z, Basham A, Sheybani-Arani M, Abbaszadeh M, Salimi Asl A, Moghbeli M, Saburi E. Effect of resveratrol and curcumin and the potential synergism on hypertension: A mini-review of human and animal model studies. Phytother Res 2024; 38:42-58. [PMID: 37784212 DOI: 10.1002/ptr.8023] [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: 03/20/2023] [Revised: 09/12/2023] [Accepted: 09/15/2023] [Indexed: 10/04/2023]
Abstract
Resveratrol (RES) and curcumin (CUR) are two of the most extensively studied bioactive compounds in cardiovascular research from the past until today. These compounds have effectively lowered blood pressure by downregulating the renin-angiotensin system, exerting antioxidant effects, and exhibiting antiproliferative activities on blood vessels. This study aims to summarize the results of human and animal studies investigating the effects of CUR, RES, and their combination on hypertension and the molecular mechanisms involved. The published trials' results are controversial regarding blood pressure reduction with different doses of RES and CUR, highlighting the need to address this issue.
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Affiliation(s)
- Zahra Ghaeini Hesarooeyeh
- Student Research Committee, Faculty of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
| | - Ayoub Basham
- Student Research Committee, Faculty of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
| | | | - Mahshid Abbaszadeh
- Student Research Committee, School of Dentistry, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
| | - Ali Salimi Asl
- Student Research Committee, Faculty of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
| | - Meysam Moghbeli
- Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Ehsan Saburi
- Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Medical Genetics and Molecular Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
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19
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Datta S, Aggarwal D, Sehrawat N, Yadav M, Sharma V, Sharma A, Zghair AN, Dhama K, Sharma A, Kumar V, Sharma AK, Wang H. Hepatoprotective effects of natural drugs: Current trends, scope, relevance and future perspectives. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2023; 121:155100. [PMID: 37801892 DOI: 10.1016/j.phymed.2023.155100] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/12/2023] [Revised: 09/02/2023] [Accepted: 09/17/2023] [Indexed: 10/08/2023]
Abstract
BACKGROUND The liver is a well-known player in the metabolism and removal of drugs. Drug metabolizing enzymes in the liver detoxify drugs and xenobiotics, ultimately leading to the acquisition of homeostasis. However, liver toxicity and cell damage are not only related to the nature and dosage of a particular drug but are also influenced by other factors such as aging, immune status, environmental contaminants, microbial metabolites, gender, obesity, and expression of individual genes Furthermore, factors such as drugs, alcohol, and environmental contaminants could induce oxidative stress, thereby impairing the regenerative potential of the liver and causing several diseases. Persons suffering from other ailments and those with comorbidities are found to be more prone to drug-induced toxicities. Moreover, drug composition and drug-drug interactions could further aggravate the risk of drug-induced hepatotoxicity. A plethora of mechanisms are responsible for initiating liver cell damage and further aggravating liver cell injury, followed by impairment of homeostasis, ultimately leading to the generation of reactive oxygen species, immune-suppression, and oxidative stress. OBJECTIVE To summarize the potential of phytochemicals and natural bioactive compounds to treat hepatotoxicity and other liver diseases. STUDY DESIGN A deductive qualitative content analysis approach was employed to assess the overall outcomes of the research and review articles pertaining to hepatoprotection induced by natural drugs, along with analysis of the interventions. METHODS An extensive literature search of bibliographic databases, including Web of Science, PUBMED, SCOPUS, GOOGLE SCHOLAR, etc., was carried out to understand the role of hepatoprotective effects of natural drugs. RESULTS Bioactive natural products, including curcumin, resveratrol, etc., have been seen as neutralizing agents against the side effects induced by the drugs. Moreover, these natural products are dietary and are readily available; thus, could be supplemented along with drugs to reduce toxicity to cells. Probiotics, prebiotics, and synbiotics have shown promise of improving overall liver functioning, and these should be evaluated more extensively for their hepatoprotective potential. Therefore, selecting an appropriate natural product or a bioactive compound that is free of toxicity and offers a reliable solution for drug-induced liver toxicity is quintessential. CONCLUSIONS The current review highlights the role of natural bioactive products in neutralizing drug-induced hepatotoxicity. Efforts have been made to delineate the possible underlying mechanism associated with the neutralization process.
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Affiliation(s)
- Sonal Datta
- Department of Bio-Sciences and Technology, Maharishi Markandeshwar (Deemed to be University), Mullana, Ambala, Haryana 133207, India
| | - Diwakar Aggarwal
- Department of Bio-Sciences and Technology, Maharishi Markandeshwar (Deemed to be University), Mullana, Ambala, Haryana 133207, India
| | - Nirmala Sehrawat
- Department of Bio-Sciences and Technology, Maharishi Markandeshwar (Deemed to be University), Mullana, Ambala, Haryana 133207, India
| | - Mukesh Yadav
- Department of Bio-Sciences and Technology, Maharishi Markandeshwar (Deemed to be University), Mullana, Ambala, Haryana 133207, India
| | - Varruchi Sharma
- Department of Biotechnology & Bioinformatics, Sri Guru Gobind Singh College, Chandigarh 160019, India
| | - Ajay Sharma
- Department of Chemistry, Career Point University, Tikker - Kharwarian, Hamirpur, Himachal Pradesh 176041, India
| | - Abdulrazzaq N Zghair
- College of Health and Medical Techniques, Middle Technical University, Baghdad, Iraq
| | - Kuldeep Dhama
- Division of Pathology, ICAR-Indian Veterinary Research Institute, Izatnagar, UP, India
| | - Aanchal Sharma
- University Centre for Research and Development, University Institute of Biotechnology Chandigarh University, Gharuan, Mohali, India
| | - Vikas Kumar
- Department of Bio-Sciences and Technology, Maharishi Markandeshwar (Deemed to be University), Mullana, Ambala, Haryana 133207, India
| | - Anil K Sharma
- Department of Biotechnology, Amity University, Sector-82-A, IT City Road, Mohali, Punjab 140306, India.
| | - Hailian Wang
- Institute of Organ Transplantation, Sichuan Academy of Medical Science and Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
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20
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Park JS, Rustamov N, Roh YS. The Roles of NFR2-Regulated Oxidative Stress and Mitochondrial Quality Control in Chronic Liver Diseases. Antioxidants (Basel) 2023; 12:1928. [PMID: 38001781 PMCID: PMC10669501 DOI: 10.3390/antiox12111928] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2023] [Revised: 10/24/2023] [Accepted: 10/27/2023] [Indexed: 11/26/2023] Open
Abstract
Chronic liver disease (CLD) affects a significant portion of the global population, leading to a substantial number of deaths each year. Distinct forms like non-alcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease (ALD), though they have different etiologies, highlight shared pathologies rooted in oxidative stress. Central to liver metabolism, mitochondria are essential for ATP production, gluconeogenesis, fatty acid oxidation, and heme synthesis. However, in diseases like NAFLD, ALD, and liver fibrosis, mitochondrial function is compromised by inflammatory cytokines, hepatotoxins, and metabolic irregularities. This dysfunction, especially electron leakage, exacerbates the production of reactive oxygen species (ROS), augmenting liver damage. Amidst this, nuclear factor erythroid 2-related factor 2 (NRF2) emerges as a cellular protector. It not only counters oxidative stress by regulating antioxidant genes but also maintains mitochondrial health by overseeing autophagy and biogenesis. The synergy between NRF2 modulation and mitochondrial function introduces new therapeutic potentials for CLD, focusing on preserving mitochondrial integrity against oxidative threats. This review delves into the intricate role of oxidative stress in CLD, shedding light on innovative strategies for its prevention and treatment, especially through the modulation of the NRF2 and mitochondrial pathways.
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Affiliation(s)
| | | | - Yoon-Seok Roh
- College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju 28160, Republic of Korea; (J.-S.P.); (N.R.)
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Cogorno L, Formisano E, Vignati A, Prigione A, Tramacere A, Borgarelli C, Sukkar SG, Pisciotta L. Non-alcoholic fatty liver disease: Dietary and nutraceutical approaches. LIVER RESEARCH 2023; 7:216-227. [PMID: 39958388 PMCID: PMC11791914 DOI: 10.1016/j.livres.2023.08.005] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Revised: 07/20/2023] [Accepted: 08/24/2023] [Indexed: 02/18/2025]
Abstract
Non-alcoholic fatty liver disease (NAFLD), defined as the presence of fat accumulation in imaging or histology in more than 5% of hepatocytes and exclusion of other causes for secondary hepatic fat accumulation, is one of the major causes of chronic liver disease worldwide. Metabolic syndrome is associated with an increased risk of progression from NAFLD to non-alcoholic steatohepatitis (NASH), fibrosis, and forthcoming liver failure. Also, genetic predisposition contributes to the risk of NAFLD development. This review explores the role of diets and nutraceuticals in delaying the development and the evolution of NAFLD to chronic liver disease. The Mediterranean diet, high-protein diet, low-carbohydrate/high-fat diet, high-carbohydrate/low-fat diet, and intermittent fasting are the dietary approaches investigated given the presence of relevant literature data. Moreover, this review focused on nutraceuticals with proven efficacy in ameliorating NAFLD and grouped them into four different categories: plant-based nutraceuticals (Ascophyllum nodosum and Fucus vesiculosus, Silymarin, Berberine, Curcumin, Resveratrol, Nigella sativa, Quercetin), vitamin-like substances (vitamin E, vitamin D, vitamin C, coenzyme Q10, inositol), fatty acids (omega-3), and microbiota-management tools (probiotics).
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Affiliation(s)
- Ludovica Cogorno
- Department of Experimental Medicine-Medical Pathophysiology, Food Science and Endocrinology Section, Sapienza University of Rome, Rome, Italy
| | - Elena Formisano
- Department of Internal Medicine, University of Genoa, Genoa, Italy
- Dietetics and Clinical Nutrition Unit, IRCCS Policlinic Hospital San Martino, Genoa, Italy
| | - Andrea Vignati
- Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Amalia Prigione
- Department of Internal Medicine, University of Genoa, Genoa, Italy
| | | | | | - Samir Giuseppe Sukkar
- Dietetics and Clinical Nutrition Unit, IRCCS Policlinic Hospital San Martino, Genoa, Italy
| | - Livia Pisciotta
- Department of Internal Medicine, University of Genoa, Genoa, Italy
- Dietetics and Clinical Nutrition Unit, IRCCS Policlinic Hospital San Martino, Genoa, Italy
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22
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Vrânceanu M, Hegheş SC, Cozma-Petruţ A, Banc R, Stroia CM, Raischi V, Miere D, Popa DS, Filip L. Plant-Derived Nutraceuticals Involved in Body Weight Control by Modulating Gene Expression. PLANTS (BASEL, SWITZERLAND) 2023; 12:2273. [PMID: 37375898 DOI: 10.3390/plants12122273] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/11/2023] [Revised: 06/09/2023] [Accepted: 06/09/2023] [Indexed: 06/29/2023]
Abstract
Obesity is the most prevalent health problem in the Western world, with pathological body weight gain associated with numerous co-morbidities that can be the main cause of death. There are several factors that can contribute to the development of obesity, such as diet, sedentary lifestyle, and genetic make-up. Genetic predispositions play an important role in obesity, but genetic variations alone cannot fully explain the explosion of obesity, which is why studies have turned to epigenetics. The latest scientific evidence suggests that both genetics and environmental factors contribute to the rise in obesity. Certain variables, such as diet and exercise, have the ability to alter gene expression without affecting the DNA sequence, a phenomenon known as epigenetics. Epigenetic changes are reversible, and reversibility makes these changes attractive targets for therapeutic interventions. While anti-obesity drugs have been proposed to this end in recent decades, their numerous side effects make them not very attractive. On the other hand, the use of nutraceuticals for weight loss is increasing, and studies have shown that some of these products, such as resveratrol, curcumin, epigallocatechin-3-gallate, ginger, capsaicin, and caffeine, can alter gene expression, restoring the normal epigenetic profile and aiding weight loss.
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Affiliation(s)
- Maria Vrânceanu
- Department of Toxicology, "Iuliu Haţieganu" University of Medicine and Pharmacy, 6 Pasteur Street, 400349 Cluj-Napoca, Romania
| | - Simona-Codruţa Hegheş
- Department of Drug Analysis, "Iuliu Haţieganu" University of Medicine and Pharmacy, 6 Pasteur Street, 400349 Cluj-Napoca, Romania
| | - Anamaria Cozma-Petruţ
- Department of Bromatology, Hygiene, Nutrition, "Iuliu Haţieganu" University of Medicine and Pharmacy, 6 Pasteur Street, 400349 Cluj-Napoca, Romania
| | - Roxana Banc
- Department of Bromatology, Hygiene, Nutrition, "Iuliu Haţieganu" University of Medicine and Pharmacy, 6 Pasteur Street, 400349 Cluj-Napoca, Romania
| | - Carmina Mariana Stroia
- Department of Pharmacy, Oradea University, 1 Universităţii Street, 410087 Oradea, Romania
| | - Viorica Raischi
- Laboratory of Physiology of Stress, Adaptation and General Sanocreatology, Institute of Physiology and Sanocreatology, 1 Academiei Street, 2028 Chișinău, Moldova
| | - Doina Miere
- Department of Bromatology, Hygiene, Nutrition, "Iuliu Haţieganu" University of Medicine and Pharmacy, 6 Pasteur Street, 400349 Cluj-Napoca, Romania
| | - Daniela-Saveta Popa
- Department of Toxicology, "Iuliu Haţieganu" University of Medicine and Pharmacy, 6 Pasteur Street, 400349 Cluj-Napoca, Romania
| | - Lorena Filip
- Department of Bromatology, Hygiene, Nutrition, "Iuliu Haţieganu" University of Medicine and Pharmacy, 6 Pasteur Street, 400349 Cluj-Napoca, Romania
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23
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Machado IF, Miranda RG, Dorta DJ, Rolo AP, Palmeira CM. Targeting Oxidative Stress with Polyphenols to Fight Liver Diseases. Antioxidants (Basel) 2023; 12:1212. [PMID: 37371941 DOI: 10.3390/antiox12061212] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2023] [Revised: 05/26/2023] [Accepted: 05/31/2023] [Indexed: 06/29/2023] Open
Abstract
Reactive oxygen species (ROS) are important second messengers in many metabolic processes and signaling pathways. Disruption of the balance between ROS generation and antioxidant defenses results in the overproduction of ROS and subsequent oxidative damage to biomolecules and cellular components that disturb cellular function. Oxidative stress contributes to the initiation and progression of many liver pathologies such as ischemia-reperfusion injury (LIRI), non-alcoholic fatty liver disease (NAFLD), and hepatocellular carcinoma (HCC). Therefore, controlling ROS production is an attractive therapeutic strategy in relation to their treatment. In recent years, increasing evidence has supported the therapeutic effects of polyphenols on liver injury via the regulation of ROS levels. In the current review, we summarize the effects of polyphenols, such as quercetin, resveratrol, and curcumin, on oxidative damage during conditions that induce liver injury, such as LIRI, NAFLD, and HCC.
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Affiliation(s)
- Ivo F Machado
- CNC-Center for Neuroscience and Cell Biology, CIBB-Center for Innovative Biomedicine and Biotechnology, University of Coimbra, 3000 Coimbra, Portugal
- IIIUC-Institute of Interdisciplinary Research, University of Coimbra, 3000 Coimbra, Portugal
| | - Raul G Miranda
- School of Pharmaceutical Science of Ribeirão Preto, University of São Paulo, São Paulo 14040, Brazil
| | - Daniel J Dorta
- Department of Chemistry, Faculty of Philosophy, Sciences and Letters of Ribeirão Preto, University of São Paulo, Ribeirão Preto 14040, Brazil
| | - Anabela P Rolo
- CNC-Center for Neuroscience and Cell Biology, CIBB-Center for Innovative Biomedicine and Biotechnology, University of Coimbra, 3000 Coimbra, Portugal
- Department of Life Sciences, University of Coimbra, 3000 Coimbra, Portugal
| | - Carlos M Palmeira
- CNC-Center for Neuroscience and Cell Biology, CIBB-Center for Innovative Biomedicine and Biotechnology, University of Coimbra, 3000 Coimbra, Portugal
- Department of Life Sciences, University of Coimbra, 3000 Coimbra, Portugal
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24
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Yang M, Shen Y, Zhao S, Zhang R, Dong W, Lei X. Protective effect of resveratrol on mitochondrial biogenesis during hyperoxia-induced brain injury in neonatal pups. BMC Neurosci 2023; 24:27. [PMID: 37098490 PMCID: PMC10127954 DOI: 10.1186/s12868-023-00797-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2022] [Accepted: 04/14/2023] [Indexed: 04/27/2023] Open
Abstract
BACKGROUND Neonatal hyperoxic brain injury is caused by exposure to hyperphysiological oxygen content during the period of incomplete development of the oxidative stress defence system, resulting in a large number of reactive oxygen species (ROS) and causing damage to brain tissue. Mitochondrial biogenesis refers to the synthesis of new mitochondria from existing mitochondria, mostly through the PGC-1α/Nrfs/TFAM signalling pathway. Resveratrol (Res), a silencing information regulator 2-related enzyme 1 (Sirt1) agonist, has been shown to upregulate the level of Sirt1 and the expression of peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α). We speculate that Res has a protective effect on hyperoxia-induced brain injury through mitochondrial biogenesis. METHODS Sprague-Dawley (SD) pups were randomly divided into the nonhyperoxia (NN) group, the nonhyperoxia with dimethyl sulfoxide (ND) group, the nonhyperoxia with Res (NR) group, the hyperoxia (HN) group, the hyperoxia with dimethyl sulfoxide (HD) group, and the hyperoxia with Res (HR) group within 12 h after birth. The HN, HD, and HR groups were placed in a high-oxygen environment (80‒85%), and the other three groups were placed in the standard atmosphere. The NR and HR groups were given 60 mg/kg Res every day, the ND and HD groups were given the same dose of dimethyl sulfoxide (DMSO) every day, and the NN and HN groups were given the same dose of normal saline every day. On postnatal day (PN) 1, PN7, and PN14, brain samples were acquired for HE staining to assess pathology, TUNEL to detect apoptosis, and real-time quantitative polymerase chain reaction and immunoblotting to detect the expression levels of Sirt1, PGC-1α, nuclear respiratory factor 1 (Nrf1), nuclear respiratory factor 2 (Nrf2) and mitochondrial transcription factor A (TFAM) in brain tissue. RESULTS Hyperoxia induced brain tissue injury; increased brain tissue apoptosis; inhibited Sirt1, PGC-1α, Nrf1, Nrf2, TFAM mRNA expression in mitochondria; diminished the ND1 copy number and ND4/ND1 ratio; and decreased Sirt1, PGC-1α, Nrf1, Nrf2, and TFAM protein levels in the brain. In contrast, Res reduced brain injury and attenuated brain tissue apoptosis in neonatal pups and increased the levels of the corresponding indices. CONCLUSION Res has a protective effect on hyperoxia-induced brain injury in neonatal SD pups by upregulating Sirt1 and stimulating the PGC-1α/Nrfs/TFAM signalling pathway for mitochondrial biogenesis.
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Affiliation(s)
- Menghan Yang
- Division of Neonatology, Department of Pediatrics, The Affiliated Hospital of Southwest Medical University, No. 8, Section 2, Kangcheng Road, Luzhou, Sichuan, 646000, China
- Department of Perinatology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China
- Sichuan Clinical Research Center for Birth Defects, Luzhou, Sichuan, China
| | - Yunchuan Shen
- Division of Neonatology, Department of Pediatrics, The Affiliated Hospital of Southwest Medical University, No. 8, Section 2, Kangcheng Road, Luzhou, Sichuan, 646000, China
- Department of Perinatology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China
- Sichuan Clinical Research Center for Birth Defects, Luzhou, Sichuan, China
| | - Shuai Zhao
- Division of Neonatology, Department of Pediatrics, The Affiliated Hospital of Southwest Medical University, No. 8, Section 2, Kangcheng Road, Luzhou, Sichuan, 646000, China
- Department of Perinatology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China
- Sichuan Clinical Research Center for Birth Defects, Luzhou, Sichuan, China
| | - Rong Zhang
- Division of Neonatology, Department of Pediatrics, The Affiliated Hospital of Southwest Medical University, No. 8, Section 2, Kangcheng Road, Luzhou, Sichuan, 646000, China
- Department of Perinatology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China
- Sichuan Clinical Research Center for Birth Defects, Luzhou, Sichuan, China
| | - Wenbin Dong
- Division of Neonatology, Department of Pediatrics, The Affiliated Hospital of Southwest Medical University, No. 8, Section 2, Kangcheng Road, Luzhou, Sichuan, 646000, China.
- Department of Perinatology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China.
- Sichuan Clinical Research Center for Birth Defects, Luzhou, Sichuan, China.
| | - Xiaoping Lei
- Division of Neonatology, Department of Pediatrics, The Affiliated Hospital of Southwest Medical University, No. 8, Section 2, Kangcheng Road, Luzhou, Sichuan, 646000, China.
- Department of Perinatology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China.
- Sichuan Clinical Research Center for Birth Defects, Luzhou, Sichuan, China.
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Nemati A, Nikniaz Z, Mota A. Effects of Resveratrol Supplementation on Nonalcoholic Fatty Liver Disease Management. TOP CLIN NUTR 2023. [DOI: 10.1097/tin.0000000000000314] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/30/2023]
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Soltani S, Sharifi-Zahabi E, Sangsefidi ZS, Ahmadi Vasmehjani A, Meshkini F, Clayton ZS, Abdollahi S. The effect of resveratrol supplementation on biomarkers of liver health: A systematic review and meta-analysis of randomized controlled trials. Phytother Res 2023; 37:1153-1166. [PMID: 36642444 DOI: 10.1002/ptr.7719] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2022] [Revised: 10/25/2022] [Accepted: 12/18/2022] [Indexed: 01/17/2023]
Abstract
This study aimed to evaluate the effect of resveratrol on liver biomarkers in adult participants, using systematic review and meta-analysis of randomized controlled trials. PubMed, Scopus, Web of Science and Cochran Library was searched, up to October 2021. The pooled effects were calculated using a random-effects model and expressed as weighted mean difference and 95% confidence interval. The methodological quality of studies as well as certainty of evidence were assessed by standard tools. Thirty-seven relevant trials were found. Although overall analysis found no significant change, subgroup analysis showed a significant improvement in alanine aminotransferase (ALT; -7.79 U/L) and glutamyl transferase (-6.0 U/L) in patients with liver disorders, and ALT (-2.22 U/L) in younger adults; however, high-dose supplementation (>1,000 mg/day) appeared to increase alkaline phosphatase concentration (+5.07 U/L). ALT also increased in older adults (+2.33 U/L) following resveratrol supplementation. We found resveratrol did not have a significant effect on liver health in the general population. However, resveratrol could be effective in patients with liver disorders. Our findings also suggest that high-dose resveratrol administration and supplementation in older adults should be performed with caution. Further high-quality clinical trials are also needed to firmly establish the clinical efficacy of resveratrol.
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Affiliation(s)
- Sepideh Soltani
- Yazd Cardiovascular Research Center, Non-Communicable Diseases Research Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Elham Sharifi-Zahabi
- School of Nutrition Sciences and Food Technology, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Zohreh Sadat Sangsefidi
- Department of Nutrition, School of Public Health, North Khorasan University of Medical Sciences, Bojnurd, Iran
| | - Azam Ahmadi Vasmehjani
- Department of Nutrition, School of Public Health, Shahid Sadughi University of Medical Sciences, Yazd, Iran
| | - Fatemeh Meshkini
- Department of Biochemistry, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.,Student Research Committee, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Zachary Stephen Clayton
- Department of Integrative Physiology, University of Colorado Boulder, Boulder, Colorado, USA
| | - Shima Abdollahi
- Department of Nutrition, School of Public Health, North Khorasan University of Medical Sciences, Bojnurd, Iran
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Dark Sweet Cherry ( Prunus avium) Supplementation Reduced Blood Pressure and Pro-Inflammatory Interferon Gamma (IFNγ) in Obese Adults without Affecting Lipid Profile, Glucose Levels and Liver Enzymes. Nutrients 2023; 15:nu15030681. [PMID: 36771387 PMCID: PMC9920461 DOI: 10.3390/nu15030681] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2022] [Revised: 01/24/2023] [Accepted: 01/24/2023] [Indexed: 01/31/2023] Open
Abstract
Dark sweet cherries (DSC) are rich in fiber and polyphenols that decrease risk factors associated with obesity. This single-blind randomized placebo-controlled study investigated DSC effects on inflammation, cardiometabolic, and liver health biomarkers in obese adults. Participants (>18 years, body mass index (BMI) = 30-40 kg/m2) consumed 200 mL of DSC drink (juice supplemented with DSC powder) (n = 19) or a placebo drink (n = 21) twice/day for 30 days. Anthropometric and physiological biomarkers were monitored at baseline (D1), mid-point (D15), and endpoint (D30) visits. Blood inflammatory biomarkers were assessed at D1, D15, and D30, and blood lipids, glucose, and liver enzymes at D1 and D30. DSC consumption lowered systolic blood pressure (SBP) (p = 0.05) and decreased diastolic blood pressure (DBP) compared to placebo (p = 0.04). Stratification of participants by BMI revealed a greater (p = 0.008) SBP reduction in BMI > 35 participants. DSC lowered pro-inflammatory interferon-gamma (IFNγ) (p = 0.001), which correlated with SBP changes. The interleukin (IL)-1RA and SBP changes were correlated in the placebo group, as well as triglycerides (TG) with DBP. The increased IL-10 levels in the placebo group suggested a compensatory mechanism to counteract elevated IFNγ levels. No significant between-group differences were detected for blood lipids, glucose, and liver enzymes. In conclusion, DSC helped to decrease blood pressure levels and inflammation in obese adults.
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Anggreini P, Kuncoro H, Sumiwi SA, Levita J. Role of the AMPK/SIRT1 pathway in non‑alcoholic fatty liver disease (Review). Mol Med Rep 2022; 27:35. [PMID: 36562343 PMCID: PMC9827347 DOI: 10.3892/mmr.2022.12922] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Accepted: 10/26/2022] [Indexed: 12/24/2022] Open
Abstract
Non‑alcoholic fatty liver disease (NAFLD) is an increasingly prevalent ailment worldwide. Moreover, de novo lipogenesis (DNL) is considered a critical factor in the development of NAFLD; hence, its inhibition is a promising target for the prevention of fatty liver disease. There is evidence to indicate that AMP‑activated protein kinase (AMPK) and sirtuin 1 (SIRT1) may play a crucial role in DNL and are the regulatory proteins in type 2 diabetes mellitus, obesity and cardiovascular disease. Therefore, AMPK and SIRT1 may be promising targets for the treatment of NAFLD. The present review article thus aimed to summarize the findings of clinical studies published during the past decade that suggested the beneficial effects of AMPK and SIRT1, using their specific activators and their combined effects on fatty liver disease.
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Affiliation(s)
- Putri Anggreini
- Doctoral Program in Pharmacy, Faculty of Pharmacy, Padjadjaran University, Sumedang, West Java 46363, Indonesia,Laboratory of Pharmaceutical Research and Development, Faculty of Pharmacy, Mulawarman University, Samarinda, East Borneo 75119, Indonesia
| | - Hadi Kuncoro
- Laboratory of Pharmaceutical Research and Development, Faculty of Pharmacy, Mulawarman University, Samarinda, East Borneo 75119, Indonesia,Correspondence to: Dr Hadi Kuncoro, Laboratory of Pharmaceutical Research and Development, Faculty of Pharmacy, Mulawarman University, Muara Muntai Street, Gunung Kelua, Samarinda, East Borneo 75119, Indonesia, E-mail:
| | - Sri Adi Sumiwi
- Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Padjadjaran University, Sumedang, West Java 46363, Indonesia
| | - Jutti Levita
- Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Padjadjaran University, Sumedang, West Java 46363, Indonesia
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Yang K, Chen J, Zhang T, Yuan X, Ge A, Wang S, Xu H, Zeng L, Ge J. Efficacy and safety of dietary polyphenol supplementation in the treatment of non-alcoholic fatty liver disease: A systematic review and meta-analysis. Front Immunol 2022; 13:949746. [PMID: 36159792 PMCID: PMC9500378 DOI: 10.3389/fimmu.2022.949746] [Citation(s) in RCA: 36] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2022] [Accepted: 07/21/2022] [Indexed: 11/23/2022] Open
Abstract
Background Dietary polyphenol treatment of non-alcoholic fatty liver disease (NAFLD) is a novel direction, and the existing clinical studies have little effective evidence for its therapeutic effect, and some studies have inconsistent results. The effectiveness of dietary polyphenols in the treatment of NAFLD is still controversial. The aim of this study was to evaluate the therapeutic efficacy of oral dietary polyphenols in patients with NAFLD. Methods The literature (both Chinese and English) published before 30 April 2022 in PubMed, Cochrane, Medline, CNKI, and other databases on the treatment of NAFLD with dietary polyphenols was searched. Manual screening, quality assessment, and data extraction of search results were conducted strictly according to the inclusion and exclusion criteria. RevMan 5.3 software was used to perform the meta-analysis. Results The RCTs included in this study involved dietary supplementation with eight polyphenols (curcumin, resveratrol, naringenin, anthocyanin, hesperidin, catechin, silymarin, and genistein) and 2,173 participants. This systematic review and meta-analysis found that 1) curcumin may decrease body mass index (BMI), Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Triglycerides (TG) total cholesterol (TC), and Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) compared to placebo; and curcumin does not increase the occurrence of adverse events. 2) Although the meta-analysis results of all randomized controlled trials (RCTs) did not reveal significant positive changes, individual RCTs showed meaningful results. 3) Naringenin significantly decreased the percentage of NAFLD grade, TG, TC, and low-density lipoprotein cholesterol (LDL-C) and increased high-density lipoprotein cholesterol (HDL-C) but had no significant effect on AST and ALT, and it is a safe supplementation. 4) Only one team presents a protocol about anthocyanin (from Cornus mas L. fruit extract) in the treatment of NAFLD. 5) Hesperidin may decrease BMI, AST, ALT, TG, TC, HOMA-IR, and so on. 6) Catechin may decrease BMI, HOMA-IR, and TG level, and it was well tolerated by the patients. 7) Silymarin was effective in improving ALT and AST and reducing hepatic fat accumulation and liver stiffness in NAFLD patients. Conclusion Based on current evidence, curcumin can reduce BMI, TG, TC, liver enzymes, and insulin resistance; catechin can reduce BMI, insulin resistance, and TG effectively; silymarin can reduce liver enzymes. For resveratrol, naringenin, anthocyanin, hesperidin, and catechin, more RCTs are needed to further evaluate their efficacy and safety.
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Affiliation(s)
- Kailin Yang
- Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, Hunan University of Chinese Medicine, Changsha, China
| | - Junpeng Chen
- School of Mechanical Engineering, Hunan University of Science and Technology, Xiangtan, China
| | - Tianqing Zhang
- The First Affiliated Hospital, Department of Cardiovascular Medicine, Hengyang Medical School, University of South China, Hengyang, China
| | - Xiao Yuan
- Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, Hunan University of Chinese Medicine, Changsha, China
| | - Anqi Ge
- The First Hospital of Hunan University of Chinese Medicine, Changsha, China
| | - Shanshan Wang
- Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, Hunan University of Chinese Medicine, Changsha, China
| | - Hao Xu
- Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, Hunan University of Chinese Medicine, Changsha, China
| | - Liuting Zeng
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Jinwen Ge
- Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, Hunan University of Chinese Medicine, Changsha, China
- Hunan Academy of Chinese Medicine, Changsha, China
- *Correspondence: Jinwen Ge,
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Xu X, Liu Q, Li J, Xiao M, Gao T, Zhang X, Lu G, Wang J, Guo Y, Wen P, Gu J. Co-Treatment With Resveratrol and FGF1 Protects Against Acute Liver Toxicity After Doxorubicin Treatment via the AMPK/NRF2 Pathway. Front Pharmacol 2022; 13:940406. [PMID: 36110535 PMCID: PMC9468578 DOI: 10.3389/fphar.2022.940406] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2022] [Accepted: 06/22/2022] [Indexed: 11/13/2022] Open
Abstract
Doxorubicin (DOX), an anthracycline type of chemotherapy, is an effective therapy for several types of cancer, but serious side effects, such as severe hepatotoxicity, limit its use currently. Accordingly, an effective therapeutic strategy to prevent DOX-related hepatotoxicity is urgently needed. Through the inhibition of oxidative stress, fibroblast growth factor 1 (FGF1) is an effect therapy for a variety of liver diseases, but its use is limited by an increased risk of tumorigenesis due to hyperproliferation. Resveratrol (RES), a natural product, inhibits the growth of many cancer cell lines, including liver, breast, and prostate cancer cells. Therefore, this study explored whether and how RES in combination with FGF1 can alleviate DOX-induced hepatotoxicity. The results showed that RES or FGF1 alone improved DOX-induced hepatic inflammation, apoptosis and oxidative stress, and these adverse effects were further attenuated after treatment with both RES and FGF1. Mechanistically, both in vivo and in vitro results showed that RES/FGF1 reduced oxidative stress and thereby alleviated liver injury by promoting nuclear translocation of nuclear factor erythroid 2-related factor 2 (NRF2) and subsequently upregulating expression of antioxidant proteins in an adenosine monophosphate-activated protein kinase (AMPK)-dependent manner. Together, our results not only demonstrate that co-treatment with RES and FGF1 significantly inhibited DOX-induced hepatic inflammation and apoptosis, but also that co-treatment with RES and FGF1 markedly suppressed DOX-induced hepatic oxidative stress, via targeting the AMPK/NRF2 pathway and subsequently ameliorating hepatic dysfunction. Thus, the combination of RES and FGF1 may provide a new therapeutic strategy for limiting DOX-induced hepatotoxicity.
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Affiliation(s)
- Xianchou Xu
- Department of Breast Surgery, General Surgery, Qilu Hospital of Shandong University, Jinan, China
- Department of Gastrointestinal Surgery, Pingyang Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Qingbo Liu
- School of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Jiahao Li
- School of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Mengjie Xiao
- School of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Ting Gao
- School of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Xiaohui Zhang
- School of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Guangping Lu
- School of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Jie Wang
- School of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Yuanfang Guo
- School of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Peinan Wen
- Department of Gastrointestinal Surgery, Pingyang Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
- *Correspondence: Junlian Gu, ; Peinan Wen,
| | - Junlian Gu
- School of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong University, Jinan, China
- *Correspondence: Junlian Gu, ; Peinan Wen,
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Ferro Y, Pujia R, Mazza E, Lascala L, Lodari O, Maurotti S, Pujia A, Montalcini T. A new nutraceutical (Livogen Plus®) improves liver steatosis in adults with non-alcoholic fatty liver disease. Lab Invest 2022; 20:377. [PMID: 35986358 PMCID: PMC9392294 DOI: 10.1186/s12967-022-03579-1] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2022] [Accepted: 08/07/2022] [Indexed: 11/10/2022]
Abstract
Abstract
Background
Currently, there is no approved medication for non-alcoholic fatty liver disease management. Pre-clinical and clinical studies showed that several bioactive molecules in plants or foods (i.e., curcumin complex, bergamot polyphenol fraction, artichoke leaf extract, black seed oil, concentrate fish oil, picroliv root, glutathione, S-adenosyl-l-methionine and other natural ingredients) have been associated with improved fatty liver disease. Starting from these evidences, our purpose was to evaluate the effects of a novel combination of abovementioned nutraceuticals as a treatment for adults with fatty liver disease.
Methods
A total of 140 participants with liver steatosis were enrolled in a randomized, double-blind, placebo controlled clinical trial. The intervention group received six softgel capsules daily of a nutraceutical (namely Livogen Plus®) containing a combination of natural bioactive components for 12 weeks. The control group received six softgel capsules daily of a placebo containing maltodextrin for 12 weeks. The primary outcome measure was the change in liver fat content (CAP score). CAP score, by transient elastography, serum glucose, lipids, transaminases, and cytokines were measured at baseline and after intervention.
Results
After adjustment for confounding variables (i.e., CAP score and triglyceride at baseline, and changes of serum γGT, and vegetable and animal proteins, cholesterol intake at the follow-up), we found a greater CAP score reduction in the nutraceutical group rather than placebo (− 34 ± 5 dB/m vs. − 20 ± 5 dB/m, respectively; p = 0.045). The CAP score reduction (%) was even greater in those with aged 60 or less, low baseline HDL-C, AST reduction as well as in men.
Conclusion
Our results showed that a new combination of bioactive molecules as nutraceutical was safe and effective in reducing liver fat content over 12 weeks in individuals with hepatic steatosis.
Trial registration ISRCTN, ISRCTN70887063. Registered 03 August 2021—retrospectively registered, https://doi.org/10.1186/ISRCTN70887063
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Aggarwal S, Trehanpati N, Nagarajan P, Ramakrishna G. The Clock-NAD + -Sirtuin connection in nonalcoholic fatty liver disease. J Cell Physiol 2022; 237:3164-3180. [PMID: 35616339 DOI: 10.1002/jcp.30772] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2022] [Revised: 04/27/2022] [Accepted: 05/02/2022] [Indexed: 11/10/2022]
Abstract
Nonalcoholic or metabolic associated fatty liver disease (NAFLD/MAFLD) is a hepatic reflection of metabolic derangements characterized by excess fat deposition in the hepatocytes. Identifying metabolic regulatory nodes in fatty liver pathology is essential for effective drug targeting. Fatty liver is often associated with circadian rhythm disturbances accompanied with alterations in physical and feeding activities. In this regard, both sirtuins and clock machinery genes have emerged as critical metabolic regulators in maintaining liver homeostasis. Knockouts of either sirtuins or clock genes result in obesity associated with the fatty liver phenotype. Sirtuins (SIRT1-SIRT7) are a highly conserved family of nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases, protecting cells from metabolic stress by deacetylating vital proteins associated with lipid metabolism. Circadian rhythm is orchestrated by oscillations in expression of master regulators (BMAL1 and CLOCK), which in turn regulate rhythmic expression of clock-controlled genes involved in lipid metabolism. The circadian metabolite, NAD+ , serves as a crucial link connecting clock genes to sirtuin activity. This is because, NAMPT which is a rate limiting enzyme in NAD+ biosynthesis is transcriptionally regulated by the clock genes and NAD+ in turn is a cofactor regulating the deacetylation activity of sirtuins. Intriguingly, on one hand the core circadian clock regulates the sirtuin activity and on the other hand the activated sirtuins regulate the acetylation status of clock proteins thereby affecting their transcriptional functions. Thus, the Clock-NAD+-Sirtuin connection represents a novel "feedback loop" circuit that regulates the metabolic machinery. The current review underpins the importance of NAD+ on the sirtuin and clock connection in preventing fatty liver disorder.
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Affiliation(s)
- Savera Aggarwal
- Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Nirupma Trehanpati
- Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Perumal Nagarajan
- Department of Experimental Animal Facility, National Institute of Immunology, New Delhi, India
| | - Gayatri Ramakrishna
- Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India
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Liudvytska O, Kolodziejczyk-Czepas J. A Review on Rhubarb-Derived Substances as Modulators of Cardiovascular Risk Factors—A Special Emphasis on Anti-Obesity Action. Nutrients 2022; 14:nu14102053. [PMID: 35631194 PMCID: PMC9144273 DOI: 10.3390/nu14102053] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Revised: 05/09/2022] [Accepted: 05/11/2022] [Indexed: 02/06/2023] Open
Abstract
The currently available anti-obesity therapies encounter many associated risks and side effects often causing the ineffectiveness of treatment. Therefore, various plant-derived substances have been extensively studied as a promising support or even an alternative for existing anti-obesity therapies. This review is dealing with the anti-obesity potential of edible and ethnomedicinal rhubarb species and emerging possible role of the rhubarb-derived extracts or individual compounds in the prevention of obesity and perspectives for their use in an anti-obesity treatment. A special emphasis is put on the most popular edible specimens, i.e., Rheum rhabarbarum L. (garden rhubarb) and Rheum rhaponticum L. (rhapontic rhubarb, Siberian rhubarb); however, the anti-obesity potential of other rhubarb species (e.g., R. officinale, R. palmatum, and R. emodi) is presented as well. The significance of rhubarb-derived extracts and low-molecular specialized rhubarb metabolites of diversified chemical background, e.g., anthraquinones and stilbenes, as potential modulators of human metabolism is highlighted, including the context of cardiovascular disease prevention. The available reports present multiple encouraging rhubarb properties starting from the anti-lipidemic action of rhubarb fibre or its use as purgative medicines, through various actions of rhubarb-derived extracts and their individual compounds: inhibition of enzymes of cholesterol and lipid metabolism, targeting of key molecular regulators of adipogenesis, regulators of cell energy metabolism, the ability to inhibit pro-inflammatory signalling pathways and to regulate glucose and lipid homeostasis contributing to overall in vivo and clinical anti-obesity effects.
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A Molecular Insight into the Role of Antioxidants in Nonalcoholic Fatty Liver Diseases. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2022; 2022:9233650. [PMID: 35602098 PMCID: PMC9117022 DOI: 10.1155/2022/9233650] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/05/2022] [Accepted: 04/26/2022] [Indexed: 12/12/2022]
Abstract
Nonalcoholic fatty liver disease (NAFLD) defines fat accumulation in the liver, and it is commonly associated with metabolic syndromes like diabetes and obesity. Progressive NAFLD leads to nonalcoholic steatohepatitis (NASH) and ultimately causes cirrhosis and hepatocellular carcinoma, and NASH is currently a frequent cause of liver transplantation. Oxidative stress is often contributed to the progression of NAFLD, and hence, antioxidants such as silymarin, silybin, or silibinin, pentoxifylline, resveratrol, and vitamins A, C, and E are used in clinical trials against NAFLD. Silymarin induces the peroxisome proliferator-activated receptor α (PPARα), a fatty acid sensor, which promotes the transcription of genes that are required for the enzymes involved in lipid oxidation in hepatocytes. Silybin inhibits sterol regulatory element-binding protein 1 and carbohydrate response element-binding protein to downregulate the expression of genes responsible for de novo lipogenesis by activating AMP-activated protein kinase phosphorylation. Pentoxifylline inhibits TNF-α expression and endoplasmic reticulum stress-mediated inflammatory nuclear factor kappa B (NF-κB) activation. Thus, it prevents NAFLD to NASH progression. Resveratrol inhibits methylation at Nrf-2 promoters and NF-κB activity via SIRT1 activation in NAFLD conditions. However, clinically, resveratrol has not shown promising beneficial effects. Vitamin C is beneficial in NAFLD patients. Vitamin E is not effectively regressing hepatic fibrosis. Hence, its combination with antifibrotic agents is used as an adjuvant to produce a synergistic antifibrotic effect. However, to date, none of these antioxidants have been used as a definite therapeutic agent in NAFLD patients. Further, these antioxidants should be studied in NAFLD patients with larger populations and multiple endpoints in the future.
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Ali Sangouni A, Abdollahi S, Mozaffari-Khosravi H. Effect of resveratrol supplementation on hepatic steatosis and cardiovascular indices in overweight subjects with type 2 diabetes: a double-blind, randomized controlled trial. BMC Cardiovasc Disord 2022; 22:212. [PMID: 35538431 PMCID: PMC9088077 DOI: 10.1186/s12872-022-02637-2] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2021] [Accepted: 04/18/2022] [Indexed: 11/23/2022] Open
Abstract
BACKGROUND Patients with type 2 diabetes mellitus (T2DM) are prone to develop non-alcoholic fatty liver disease (NAFLD) and cardiovascular diseases (CVD). We aimed to investigate whether the resveratrol supplementation improves novel hepatic and cardiovascular indices in these patients. METHODS We conducted a double-blind, randomized controlled trial for 8 weeks. Seventy-six patients with T2DM were randomly assigned to receive 1000 mg/day resveratrol or placebo. Levels of lipid accumulation product (LAP), visceral adiposity index (VAI), Castelli risk index I (CRI-I), CRI-II and atherogenic coefficient (AC) were measured at the beginning and after intervention. RESULTS A total of 71 participants completed the trial. After adjusting for confounding factors including medications, diabetes duration, energy intake and physical activity, no significant difference was found between the intervention group and the control group in LAP (mean change: - 2.46 ± 23.3 vs. 1.43 ± 14.3; P = 0.43), VAI (mean change: - 0.25 ± 1.1 vs. - 0.02 ± 0.6; P = 0.47), CRI-I (mean change: - 0.25 ± 0.9 vs. - 0.09 ± 0.5; P = 0.79), CRI-II (mean change: - 0.23 ± 0.7 vs. - 0.06 ± 0.6; P = 0.38) and AC (mean change: - 0.25 ± 0.9 vs. - 0.09 ± 0.5; P = 0.79). CONCLUSIONS Resveratrol supplementation had no effect on hepatic steatosis and cardiovascular indices. Further clinical trials, especially among subjects with dyslipidemia are needed to reach a firm conclusion. In addition, taking all medications should be controlled in future studies. Trial registration The protocol was registered on 29/12/2017 at the Iranian clinical trials website (IRCT20171118037528N1) with URL: https://en.irct.ir/trial/27734 .
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Affiliation(s)
- Abbas Ali Sangouni
- 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
| | - Shima Abdollahi
- Department of Nutrition, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
- Department of Nutrition, School of Public Health, North Khorasan University of Medical Sciences, Bojnurd, Iran
| | - Hassan Mozaffari-Khosravi
- 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.
- Yazd Diabetic Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
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Kong N, Yang G, Wang L, Li Y. CALISTHENICS EXERCISES TO INTERVENE IN OBESITY AND DIABETES IN MIDDLE-AGED PEOPLE. REV BRAS MED ESPORTE 2022. [DOI: 10.1590/1517-8692202228022021_0457] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
ABSTRACT Introduction: There is an annual increase in type 2 diabetes (T2DM) incidence in middle-aged people. Aerobic exercise is known to influence glucose metabolic pathways positively. Few studies concerning calisthenic aerobic exercise and its influence on elderly patients with T2DM. Objective: To measure the therapeutic effect of calisthenic exercise in obese Middle-aged people with T2DM. Methods: A total of 86 patients with T2DM were selected from the physical examination of employees of the same unit. They were randomly divided into the exercise group and the control group. The exercise intervention lasted for 16 weeks, with sessions held 3-5 times per week, varying from 60 to 90 minutes per session. The markers evaluated were defined according to the literature and statistically verified. Results: After 16 weeks of calisthenic exercise intervention, compared to the control group or before the experiment, we observed significant reductions in variables VFA (visceral fat area), FPG (fasting glucose), Fins (fasting insulin), HOMA-IR (homeostasis model evaluation of insulin resistance), 2hPBG (postprandial two hours glucose) and HbAlc (hemoglobin Alc) of the exercise group were significantly reduced (P<0.01). Conclusion: Calisthenic exercise intervention can reduce the levels of VFA, FPG. FIns, HOMA-HR, 2hPBG and HbAlc in patients with T2DM. It was also found to reduce the visceral fat content of obese elderly patients with T2DM, reducing obesity risks. Level of evidence II; Therapeutic studies - investigation of treatment results.
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Affiliation(s)
| | | | | | - Yang Li
- HeBei Sport University, China
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Zhou Q, Wang Y, Han X, Fu S, Zhu C, Chen Q. Efficacy of Resveratrol Supplementation on Glucose and Lipid Metabolism: A Meta-Analysis and Systematic Review. Front Physiol 2022; 13:795980. [PMID: 35431994 PMCID: PMC9009313 DOI: 10.3389/fphys.2022.795980] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2022] [Accepted: 02/25/2022] [Indexed: 02/05/2023] Open
Abstract
Background Lipids are ubiquitous metabolites with diverse functions. Excessive lipid accumulation can trigger lipid redistribution among metabolic organs such as adipose, liver and muscle, thus altering the lipid metabolism. It has been revealed that disturbed lipid metabolism would cause multiple disease complications and is highly correlated with human morbidity. Resveratrol (RSV), a phytoestrogen with antioxidant, can modulate insulin resistance and lipid profile. Recently, research on RSV supplementation to improve glucose and lipid metabolism has been controversial. A meta-analysis may provide a scientific reference for the relationship between lipid metabolism and RSV supplementation. Methods and Analysis We searched the PubMed, Cochrane Library, Web of Science, and Embase databases from inception to October 2021 using relevant keywords. A comprehensive search for randomized controlled trials (RCTs) was performed. For calculating pooled effects, continuous data were pooled by mean difference (MD) and 95% confidence interval (CI). Adopting the method of inverse-variance with a random-effect, all related statistical analyses were performed using the Rev Man V.5.3 and STATA V.15 software. Results A total of 25 articles were incorporated into the final meta-analysis after removal of duplicates by checking titles and abstracts and excluding non-relevant articles. The selected articles had a total of 1,171 participants, including 578 in the placebo group and 593 in the intervention group. According to the current meta-analysis, which demonstrated that there was a significant decrease in waist circumference (SMD = –0.36; 95% CI: –0.59, –0.14; P = 0.002; I2 = 88%), hemoglobin A1c (–0.48; –0.69, –0.27; P ≤ 0.001; I2 = 94%), total cholesterol (–0.15; –0.3, –0.01; P = 0.003; I2 = 94%), low density lipoprotein cholesterol (–0.42; –0.57, –0.27; P ≤ 0.001; I2 = 92%), high density lipoprotein cholesterol (0.16; –0.31, –0.02; P = 0.03; I2 = 81%) following resveratrol administration. Conclusion These results suggest that RSV has a dramatic impact on regulating lipid and glucose metabolism, and the major clinical value of resveratrol intake is for obese and diabetic patients. We hope that this study could provide more options for clinicians using RSV. Furthermore, in the future, large-scale and well-designed trials will be warranted to confirm these results. Systematic Review Registration Website [https://www.crd.york.ac.uk/prospero/#recordDetails], identifier [CRD42021244904].
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Abstract
ABSTRACT Introduction: Heart rate and blood pressure are important physiological indicators that reflect cardiovascular function, and they are widely used because they are convenient and practical to measure. Objective: To study the characteristics of cardiovascular changes in athletes under different training conditions. Methods: Thirty-four male students majoring in physical education in universities (group A) and 22 male non-sports majors (group B) with no formal training history were randomly selected. Heart rate before and after exercise and heart rate recovery rate at different stages of the recovery period were compared. Results: As regards heart rate changes in the recovery phase after loading, both groups showed a continuous decline, although the drop in heart rate of group A was slightly lower than that of group B (153.03± 15.88 beats/min, dropped to 110.69± 15.78 beats/minute, 171.00± 14.67 beats/minute dropped to 122. 82± 13.77 beats/min, respectively). However, the heart rate recovery rate of group A (59.40%) was significantly higher than that of group B (49.42%) (P<0.05). Conclusions: Physical exercise plays a significant role in promoting physical fitness and its effect on improving cardiovascular function is especially evident. Level of evidence II; Therapeutic studies - investigation of treatment results.
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Curcumin and Weight Loss: Does It Work? Int J Mol Sci 2022; 23:ijms23020639. [PMID: 35054828 PMCID: PMC8775659 DOI: 10.3390/ijms23020639] [Citation(s) in RCA: 42] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2021] [Revised: 12/29/2021] [Accepted: 01/06/2022] [Indexed: 01/27/2023] Open
Abstract
Obesity is a global health problem needing urgent research. Synthetic anti-obesity drugs show side effects and variable effectiveness. Thus, there is a tendency to use natural compounds for the management of obesity. There is a considerable body of knowledge, supported by rigorous experimental data, that natural polyphenols, including curcumin, can be an effective and safer alternative for managing obesity. Curcumin is a is an important compound present in Curcuma longa L. rhizome. It is a lipophilic molecule that rapidly permeates cell membrane. Curcumin has been used as a pharmacological traditional medicinal agent in Ayurvedic medicine for ∼6000 years. This plant metabolite doubtless effectiveness has been reported through increasingly detailed in vitro, in vivo and clinical trials. Regarding its biological effects, multiple health-promoting, disease-preventing and even treatment attributes have been remarkably highlighted. This review documents the status of research on anti-obesity mechanisms and evaluates the effectiveness of curcumin for management of obesity. It summarizes different mechanisms of anti-obesity action, associated with the enzymes, energy expenditure, adipocyte differentiation, lipid metabolism, gut microbiota and anti-inflammatory potential of curcumin. However, there is still a need for systematic and targeted clinical studies before curcumin can be used as the mainstream therapy for managing obesity.
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Fakhri M, Fatahian A, Yousefi S, Moosazadeh M, Azadbakht M. The effect of natural products use on blood pressure in Iran: Systematic review and meta-analysis. JOURNAL OF NURSING AND MIDWIFERY SCIENCES 2022. [DOI: 10.4103/jnms.jnms_74_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
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Salami M, Salami R, Mafi A, Aarabi MH, Vakili O, Asemi Z. Therapeutic potential of resveratrol in diabetic nephropathy according to molecular signaling. Curr Mol Pharmacol 2021; 15:716-735. [PMID: 34923951 DOI: 10.2174/1874467215666211217122523] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2021] [Revised: 08/23/2021] [Accepted: 08/31/2021] [Indexed: 11/22/2022]
Abstract
BACKGROUND Diabetic nephropathy (DN) as a severe complication of diabetes mellitus (DM), is a crucial menace for human health and survival and remarkably elevates the healthcare systems' costs. Therefore, it is worth noting to identify novel preventive and therapeutic strategies to alleviate the disease conditions. Resveratrol, as a well-defined anti-diabetic/ antioxidant agent has capabilities to counteract diabetic complications. It has been predicted that resveratrol will be a fantastic natural polyphenol for diabetes therapy in the next few years. OBJECTIVE Accordingly, the current review aims to depict the role of resveratrol in the regulation of different signaling pathways that are involved in the reactive oxygen species (ROS) production, inflammatory processes, autophagy, and mitochondrial dysfunction, as critical contributors to DN pathophysiology. RESULTS The pathogenesis of DN can be multifactorial; hyperglycemia is one of the prominent risk factors of DN development that is closely related to oxidative stress. Resveratrol, as a well-defined polyphenol, has various biological and medicinal properties, including anti-diabetic, anti-inflammatory, and anti-oxidative effects. CONCLUSION Resveratrol prevents kidney damages that are caused by oxidative stress, enhances antioxidant capacity, and attenuates the inflammatory and fibrotic responses. For this reason, resveratrol is considered an interesting target in DN research due to its therapeutic possibilities during diabetic disorders and renal protection.
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Affiliation(s)
- Marziyeh Salami
- Department of biochemistry, Faculty of medicine, Semnan University of medical sciences, Semnan, Iran
| | - Raziyeh Salami
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran
| | - Alireza Mafi
- Department of Clinical Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mohammad-Hossein Aarabi
- Department of Clinical Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Omid Vakili
- Department of Clinical Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Zatollah Asemi
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran
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Stadler JT, Marsche G. Dietary Strategies to Improve Cardiovascular Health: Focus on Increasing High-Density Lipoprotein Functionality. Front Nutr 2021; 8:761170. [PMID: 34881279 PMCID: PMC8646038 DOI: 10.3389/fnut.2021.761170] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2021] [Accepted: 10/28/2021] [Indexed: 12/12/2022] Open
Abstract
Cardiovascular disease is one of the leading causes of morbidity and mortality worldwide, with increasing incidence. A cornerstone of cardiovascular disease prevention is lifestyle modification through dietary changes to influence various risk factors such as obesity, hypertension and diabetes. The effects of diet on cardiovascular health are complex. Some dietary components and metabolites directly affect the composition and structure of high-density lipoproteins (HDL) and increase anti-inflammatory and vasoprotective properties. HDLs are composed of distinct subpopulations of particles of varying size and composition that have several dynamic and context-dependent functions. The identification of potential dietary components that improve HDL functionality is currently an important research goal. One of the best-studied diets for cardiovascular health is the Mediterranean diet, consisting of fish, olive oil, fruits, vegetables, whole grains, legumes/nuts, and moderate consumption of alcohol, most commonly red wine. The Mediterranean diet, especially when supplemented with extra virgin olive oil rich in phenolic compounds, has been shown to markedly improve metrics of HDL functionality and reduce the burden, or even prevent the development of cardiovascular disease. Particularly, the phenolic compounds of extra virgin olive oil seem to exert the significant positive effects on HDL function. Moreover, supplementation of anthocyanins as well as antioxidants such as lycopene or the omega-3 fatty acid eicosapentaenoic acid improve parameters of HDL function. In this review, we aim to highlight recent discoveries on beneficial dietary patterns as well as nutritional components and their effects on cardiovascular health, focusing on HDL function.
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Affiliation(s)
- Julia T. Stadler
- Division of Pharmacology, Otto Loewi Research Center, Medical University of Graz, Graz, Austria
| | - Gunther Marsche
- Division of Pharmacology, Otto Loewi Research Center, Medical University of Graz, Graz, Austria
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Effect of resveratrol supplementation on biomarkers associated with atherosclerosis in humans. Complement Ther Clin Pract 2021; 46:101491. [PMID: 34731768 DOI: 10.1016/j.ctcp.2021.101491] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2021] [Revised: 09/08/2021] [Accepted: 10/03/2021] [Indexed: 12/16/2022]
Abstract
Previous studies have suggested the beneficial effects of resveratrol against cardiovascular disease (CVD). However, there are inconsistent results on cardiovascular-related biomarkers mainly because of variable dosage, intervention time and baseline characteristics of the population. Thus, the exact effect of resveratrol remains unclear. We conducted a review to classify the studies that applied resveratrol to supplement humans according to the major biomarkers and identify which protocol characteristics would be associated with each result profile. Randomized clinical trials that assessed resveratrol effect on biomarkers related to atherosclerosis were searched in databases. Biochemical data were collected from 27 studies on the baseline and post-intervention time. We selected 12 biomarkers to compose the matrix, based on their clinical relevance and higher variation level. A total of 32 assays were obtained from these 27 studies. The net change (%) was calculated for each biomarker. Applying multivariate analysis, the assays were grouped into 3 clusters. Studies that composed Cluster II were characterized by a mean dose of 454.14 mg/day for 74.21 days and showed higher reduction of triglyceride concentration and blood pressure, while those composing Cluster III applied doses around 273.75 mg/day for about 175.33 days and showed the highest HDL increase. Thus, interventions with resveratrol could be customized according to the patient condition, in terms of "dose/time of intervention". This information can be applied to combine resveratrol with drugs to reduce blood pressure or improve lipid profile in further clinical studies.
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Komolafe O, Buzzetti E, Linden A, Best LM, Madden AM, Roberts D, Chase TJ, Fritche D, Freeman SC, Cooper NJ, Sutton AJ, Milne EJ, Wright K, Pavlov CS, Davidson BR, Tsochatzis E, Gurusamy KS. Nutritional supplementation for nonalcohol-related fatty liver disease: a network meta-analysis. Cochrane Database Syst Rev 2021; 7:CD013157. [PMID: 34280304 PMCID: PMC8406904 DOI: 10.1002/14651858.cd013157.pub2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
BACKGROUND The prevalence of non-alcohol-related fatty liver disease (NAFLD) varies between 19% and 33% in different populations. NAFLD decreases life expectancy and increases risks of liver cirrhosis, hepatocellular carcinoma, and the requirement for liver transplantation. Uncertainty surrounds relative benefits and harms of various nutritional supplements in NAFLD. Currently no nutritional supplement is recommended for people with NAFLD. OBJECTIVES • To assess the benefits and harms of different nutritional supplements for treatment of NAFLD through a network meta-analysis • To generate rankings of different nutritional supplements according to their safety and efficacy SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, Science Citation Index Expanded, Conference Proceedings Citation Index-Science, the World Health Organization International Clinical Trials Registry Platform, and trials registers until February 2021 to identify randomised clinical trials in people with NAFLD. SELECTION CRITERIA We included only randomised clinical trials (irrespective of language, blinding, or status) for people with NAFLD, irrespective of method of diagnosis, age and diabetic status of participants, or presence of non-alcoholic steatohepatitis (NASH). We excluded randomised clinical trials in which participants had previously undergone liver transplantation. DATA COLLECTION AND ANALYSIS We performed a network meta-analysis with OpenBUGS using Bayesian methods whenever possible and calculated differences in treatments using hazard ratios (HRs), odds ratios (ORs), and rate ratios with 95% credible intervals (CrIs) based on an available-case analysis, according to National Institute of Health and Care Excellence Decision Support Unit guidance. MAIN RESULTS We included in the review a total of 202 randomised clinical trials (14,200 participants). Nineteen trials were at low risk of bias. A total of 32 different interventions were compared in these trials. A total of 115 trials (7732 participants) were included in one or more comparisons. The remaining trials did not report any of the outcomes of interest for this review. Follow-up ranged from 1 month to 28 months. The follow-up period in trials that reported clinical outcomes was 2 months to 28 months. During this follow-up period, clinical events related to NAFLD such as mortality, liver cirrhosis, liver decompensation, liver transplantation, hepatocellular carcinoma, and liver-related mortality were sparse. We did not calculate effect estimates for mortality because of sparse data (zero events for at least one of the groups in the trial). None of the trials reported that they measured overall health-related quality of life using a validated scale. The evidence is very uncertain about effects of interventions on serious adverse events (number of people or number of events). We are very uncertain about effects on adverse events of most of the supplements that we investigated, as the evidence is of very low certainty. However, people taking PUFA (polyunsaturated fatty acid) may be more likely to experience an adverse event than those not receiving an active intervention (network meta-analysis results: OR 4.44, 95% CrI 2.40 to 8.48; low-certainty evidence; 4 trials, 203 participants; direct evidence: OR 4.43, 95% CrI 2.43 to 8.42). People who take other supplements (a category that includes nutritional supplements other than vitamins, fatty acids, phospholipids, and antioxidants) had higher numbers of adverse events than those not receiving an active intervention (network meta-analysis: rate ratio 1.73, 95% CrI 1.26 to 2.41; 6 trials, 291 participants; direct evidence: rate ratio 1.72, 95% CrI 1.25 to 2.40; low-certainty evidence). Data were sparse (zero events in all groups in the trial) for liver transplantation, liver decompensation, and hepatocellular carcinoma. So, we did not perform formal analysis for these outcomes. The evidence is very uncertain about effects of other antioxidants (antioxidants other than vitamins) compared to no active intervention on liver cirrhosis (HR 1.68, 95% CrI 0.23 to 15.10; 1 trial, 99 participants; very low-certainty evidence). The evidence is very uncertain about effects of interventions in any of the remaining comparisons, or data were sparse (with zero events in at least one of the groups), precluding formal calculations of effect estimates. Data were probably because of the very short follow-up period (2 months to 28 months). It takes follow-up of 8 to 28 years to detect differences in mortality between people with NAFLD and the general population. Therefore, it is unlikely that differences in clinical outcomes are noted in trials providing less than 5 to 10 years of follow-up. AUTHORS' CONCLUSIONS The evidence indicates considerable uncertainty about effects of nutritional supplementation compared to no additional intervention on all clinical outcomes for people with non-alcohol-related fatty liver disease. Accordingly, high-quality randomised comparative clinical trials with adequate follow-up are needed. We propose registry-based randomised clinical trials or cohort multiple randomised clinical trials (study design in which multiple interventions are trialed within large longitudinal cohorts of patients to gain efficiencies and align trials more closely to standard clinical practice) comparing interventions such as vitamin E, prebiotics/probiotics/synbiotics, PUFAs, and no nutritional supplementation. The reason for the choice of interventions is the impact of these interventions on indirect outcomes, which may translate to clinical benefit. Outcomes in such trials should be mortality, health-related quality of life, decompensated liver cirrhosis, liver transplantation, and resource utilisation measures including costs of intervention and decreased healthcare utilisation after minimum follow-up of 8 years (to find meaningful differences in clinically important outcomes).
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Affiliation(s)
| | - Elena Buzzetti
- Sheila Sherlock Liver Centre, Royal Free Hospital and the UCL Institute of Liver and Digestive Health, London, UK
| | - Audrey Linden
- Division of Surgery and Interventional Science, University College London, London, UK
| | - Lawrence Mj Best
- Division of Surgery and Interventional Science, University College London, London, UK
| | - Angela M Madden
- School of Life and Medical Sciences, University of Hertfordshire, Hatfield, UK
| | - Danielle Roberts
- Division of Surgery and Interventional Science, University College London, London, UK
| | - Thomas Jg Chase
- Department of General Surgery, Homerton University Hospital NHS Foundation Trust, London, UK
| | | | - Suzanne C Freeman
- Department of Health Sciences, University of Leicester, Leicester, UK
| | - Nicola J Cooper
- Department of Health Sciences, University of Leicester, Leicester, UK
| | - Alex J Sutton
- Department of Health Sciences, University of Leicester, Leicester, UK
| | | | - Kathy Wright
- Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, Centre for Clinical Intervention Research, The Capital Region of Denmark, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| | - Chavdar S Pavlov
- Department of Therapy, I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation
| | - Brian R Davidson
- Division of Surgery and Interventional Science, University College London, London, UK
| | - Emmanuel Tsochatzis
- Sheila Sherlock Liver Centre, Royal Free Hospital and the UCL Institute of Liver and Digestive Health, London, UK
| | - Kurinchi Selvan Gurusamy
- Division of Surgery and Interventional Science, University College London, London, UK
- Department of Therapy, I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation
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Murugan DD, Balan D, Wong PF. Adipogenesis and therapeutic potentials of antiobesogenic phytochemicals: Insights from preclinical studies. Phytother Res 2021; 35:5936-5960. [PMID: 34219306 DOI: 10.1002/ptr.7205] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2021] [Revised: 05/21/2021] [Accepted: 06/17/2021] [Indexed: 12/11/2022]
Abstract
Obesity is one of the most serious public health problems in both developed and developing countries in recent years. While lifestyle and diet modifications are the most important management strategies of obesity, these may be insufficient to ensure long-term weight reduction in certain individuals and alternative strategies including pharmacotherapy need to be considered. However, drugs option remains limited due to low efficacy and adverse effects associated with their use. Hence, identification of safe and effective alternative therapeutic agents remains warranted to combat obesity. In recent years, bioactive phytochemicals are considered as valuable sources for the discovery of new pharmacological agents for the treatment of obesity. Adipocyte hypertrophy and hyperplasia increases with obesity and undergo molecular and cellular alterations that can affect systemic metabolism giving rise to metabolic syndrome and comorbidities such as type 2 diabetes and cardiovascular diseases. Many phytochemicals have been reported to target adipocytes by inhibiting adipogenesis, inducing lipolysis, suppressing the differentiation of preadipocytes to mature adipocytes, reducing energy intake, and boosting energy expenditure mainly in vitro and in animal studies. Nevertheless, further high-quality studies are needed to firmly establish the clinical efficacy of these phytochemicals. This review outlines common pathways involved in adipogenesis and phytochemicals targeting effector molecules of these pathways, the challenges faced and the way forward for the development of phytochemicals as antiobesity agents.
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Affiliation(s)
- Dharmani Devi Murugan
- Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Dharvind Balan
- Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Pooi-Fong Wong
- Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
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Zhang S, Xu M, Zhang W, Liu C, Chen S. Natural Polyphenols in Metabolic Syndrome: Protective Mechanisms and Clinical Applications. Int J Mol Sci 2021; 22:ijms22116110. [PMID: 34204038 PMCID: PMC8201163 DOI: 10.3390/ijms22116110] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Revised: 05/29/2021] [Accepted: 06/02/2021] [Indexed: 12/14/2022] Open
Abstract
Metabolic syndrome (MetS) is a chronic disease, including abdominal obesity, dyslipidemia, hyperglycemia, and hypertension. It should be noted that the occurrence of MetS is closely related to oxidative stress-induced mitochondrial dysfunction, ectopic fat accumulation, and the impairment of the antioxidant system, which in turn further aggravates the intracellular oxidative imbalance and inflammatory response. As enriched anti-inflammatory and antioxidant components in plants, natural polyphenols exhibit beneficial effects, including improving liver fat accumulation and dyslipidemia, reducing blood pressure. Hence, they are expected to be useful in the prevention and management of MetS. At present, epidemiological studies indicate a negative correlation between polyphenol intake and MetS incidence. In this review, we summarized and discussed the most promising natural polyphenols (including flavonoid and non-flavonoid drugs) in the precaution and treatment of MetS, including their anti-inflammatory and antioxidant properties, as well as their regulatory functions involved in glycolipid homeostasis.
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Affiliation(s)
| | | | | | | | - Siyu Chen
- Correspondence: ; Tel./Fax: +86-25-86185645
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Thapa K, Grewal AS, Kanojia N, Rani L, Sharma N, Singh S. Alcoholic and Non-Alcoholic Liver Diseases: Promising Molecular Drug Targets and their Clinical Development. Curr Drug Discov Technol 2021; 18:333-353. [PMID: 31965945 DOI: 10.2174/1570163817666200121143959] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2019] [Revised: 11/25/2019] [Accepted: 12/04/2019] [Indexed: 11/22/2022]
Abstract
Alcoholic and non-alcoholic fatty liver diseases have become a serious concern worldwide. Both these liver diseases have an identical pathology, starting from simple steatosis to cirrhosis and, ultimately to hepatocellular carcinoma. Treatment options for alcoholic liver disease (ALD) are still the same as they were 50 years ago which include corticosteroids, pentoxifylline, antioxidants, nutritional support and abstinence; and for non-alcoholic fatty liver disease (NAFLD), weight loss, insulin sensitizers, lipid-lowering agents and anti-oxidants are the only treatment options. Despite broad research in understanding the disease pathophysiology, limited treatments are available for clinical use. Some therapeutic strategies based on targeting a specific molecule have been developed to lessen the consequences of disease and are under clinical investigation. Therefore, focus on multiple molecular targets will help develop an efficient therapeutic strategy. This review comprises a brief overview of the pathogenesis of ALD and NAFLD; recent molecular drug targets explored for ALD and NAFLD that may prove to be effective for multiple therapeutic regimens and also the clinical status of these promising drug targets for liver diseases.
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Affiliation(s)
- Komal Thapa
- Chitkara University School of Basic Sciences, Chitkara University, Himachal Pradesh, India
| | - Ajmer Singh Grewal
- Chitkara University School of Basic Sciences, Chitkara University, Himachal Pradesh, India
| | - Neha Kanojia
- Chitkara College of Pharmacy, Chitkara University, Punjab, India
| | - Lata Rani
- Chitkara University School of Basic Sciences, Chitkara University, Himachal Pradesh, India
| | - Neelam Sharma
- Chitkara College of Pharmacy, Chitkara University, Punjab, India
| | - Sukhbir Singh
- Chitkara College of Pharmacy, Chitkara University, Punjab, India
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Zhou J, Chen Y, Yu J, Li T, Lu Z, Chen Y, Zhang X, Ye F. The efficacy of novel metabolic targeted agents and natural plant drugs for nonalcoholic fatty liver disease treatment: A PRISMA-compliant network meta-analysis of randomized controlled trials. Medicine (Baltimore) 2021; 100:e24884. [PMID: 33761646 PMCID: PMC9282112 DOI: 10.1097/md.0000000000024884] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2020] [Accepted: 02/03/2021] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is a highly prevalent chronic liver disease characterized by excess accumulation of fat in hepatocytes. Because no drug has been approved for NAFLD treatment, this work analyzed the effects of agents resulting from 2 research hotspots, metabolic target agents, and natural plant drugs, on NAFLD with network meta-analysis. METHODS Public databases were searched through August 14, 2020. Randomized controlled trials that compared obeticholic acid, elafibranor, cenicriviroc, selonsertib, curcumin, silymarin, and resveratrol to placebo were included. Liver pathology improvement, hepatic biochemical indicators, and lipid metabolism indicators were analyzed. RESULTS Thirty-five studies were included in the meta-analysis. Obeticholic acid was found to significantly increase the frequency of liver biopsy improvement compared to placebo (OR: 2.10; 95% CI: 1.60, 2.77). The ranking results among the hepatic biochemical indicators showed that obeticholic acid (94.9%) and elafibranor (86.3%) have a relative advantage in reducing alanine aminotransferase (ALT) levels, and obeticholic acid also had an advantage (95.4%) in reducing aspartate aminotransferase (AST) levels. Considering lipid metabolic indicators, elafibranor (expSMD: 0.01; 95% CI: 0.00, 0.05; SUCRA: 100%), and obeticholic acid (expSMD: 0.48; 95% CI: 0.28,0.84; SUCRA: 75.6%) significantly reduced triglyceride (TG) levels compared with placebo; moreover, obeticholic acid, but not elafibranor, caused a serious increase in total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels and a decrease in high-density lipoprotein cholesterol (HDL-C) levels. CONCLUSIONS Novel metabolic targeted agents generally have better effects than natural plant drugs, especially obeticholic acid, and elafibranor. However, obeticholic acid showed serious adverse effects such as increasing LDL-C levels and decreasing HDL-C levels. Curcumin showed potential advantages for NAFLD but lacked statistical significance.
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Affiliation(s)
- Jingwen Zhou
- Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine
| | - Yidi Chen
- School of Medicine & Holistic Integrative Medicine, Medical College of Nanjing University of Chinese Medicine
| | - Jun Yu
- The First Clinical Medical College of Nanjing University of Chinese Medicine, Nanjing
| | - Tianci Li
- The First Clinical Medical College of Nanjing University of Chinese Medicine, Nanjing
| | - Ziyu Lu
- School of Medicine & Holistic Integrative Medicine, Medical College of Nanjing University of Chinese Medicine
| | - Yan Chen
- Taizhou Hospital of Traditional Chinese Medicine, Taizhou, China
| | - Xiaolong Zhang
- Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine
| | - Fang Ye
- The First Clinical Medical College of Nanjing University of Chinese Medicine, Nanjing
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Darand M, Farrokhzad A, Ghavami A, Hadi A, Karimi E, Fadel A, Askari G. Effects of resveratrol supplementation on liver enzymes: A systematic review and meta-analysis of randomised controlled trials. Int J Clin Pract 2021; 75:e13692. [PMID: 32869460 DOI: 10.1111/ijcp.13692] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2020] [Accepted: 08/21/2020] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND The available evidence regarding the possible effects of resveratrol on liver function is inconsistent. Therefore, the present meta-analysis was performed to investigate the overall effects of resveratrol supplementation on liver enzymes in adults. METHODS A systematic and comprehensive search of the online medical databases including PubMed, Scupos, Web of Science and Cochran Library was performed up to February 2020. All RCTs using resveratrol supplements in adults were included in this systematic review and meta-analysis. The overall effect was presented as weighted mean difference (WMD) and 95% confidence interval (CI) in a random-effects meta-analysis model. RESULTS Finally, 15 randomised trials including 714 participants were selected for the present meta-analysis. Pooled analysis did not show any significant changes in alanine aminotransferase (ALT) (WMD: 0 IU/L, 95% CI: -3.17 to 3.17, P = .99; I2 = 74.2%), aspartate aminotransferase (AST) (WMD: -2.40 IU/L, 95% CI: -5.45 to 0.65, P = .11; I2 = 82.9%), gamma-glutamyl transferase (GGT) (WMD: -1.26 IU/L, 95% CI: -4.64 to 2.13, P = .64; I2 = 23.7%), alkaline phosphatase (ALP) (WMD: 3.80 IU/L, 95% CI: -4.65 to 12.25, P = .37; I2 = 29.9%) and bilirubin (WMD: 0.13 IU/L, 95% CI: -0.43 to 0.17, P = .39; I2 = 8.9%) after supplementation with resveratrol. CONCLUSION Overall, in our study, resveratrol does not affect liver enzyme levels significantly, but subgroup analysis indicates that these results may be influenced by resveratrol dose, duration of the study and population status, so future high-quality studies are necessary to get definitive results.
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Affiliation(s)
- Mina Darand
- Student Research Committee, Department of Clinical Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
| | | | - Abed Ghavami
- Student Research Committee, Department of Clinical Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Amir Hadi
- Halal Research Center of IRI, FDA, Tehran, Iran
| | - Elham Karimi
- Student Research Committee, Department of Clinical Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
- Research Development Center, Arash Women's Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Abdulmnannan Fadel
- School of Sport and Exercise Sciences, Liverpool John Moores University, Liverpool, UK
| | - Gholamreza Askari
- Department of Community Nutrition, School of Nutrition and Food Science, Food Security Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
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50
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Du F, Huang R, Lin D, Wang Y, Yang X, Huang X, Zheng B, Chen Z, Huang Y, Wang X, Chen F. Resveratrol Improves Liver Steatosis and Insulin Resistance in Non-alcoholic Fatty Liver Disease in Association With the Gut Microbiota. Front Microbiol 2021; 12:611323. [PMID: 33708180 PMCID: PMC7942199 DOI: 10.3389/fmicb.2021.611323] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2020] [Accepted: 01/11/2021] [Indexed: 12/12/2022] Open
Abstract
Resveratrol (RSV) is a potential alternative therapy for non-alcoholic fatty liver disease (NAFLD) that has been evaluated in many clinical trials, but the mechanisms of RSV action have not been fully elucidated. Recent studies suggested that the gut microbiota is an important RSV target; therefore, we speculated that the gut microbiota might mediate the beneficial effects of RSV in NAFLD. To verify this hypothesis, we established a high-fat diet (HFD)-induced NAFLD mouse model, which was subjected to RSV gavage to evaluate the therapeutic effects. We observed that RSV reduced liver steatosis and insulin resistance in NAFLD. RSV significantly changed the diversity and composition of the gut microbiota according to 16S rRNA sequencing. Gut microbiota gene function prediction showed that the enrichment of pathways related to lipid and glucose metabolism decreased after RSV treatment. Furthermore, correlation analysis indicated that the improvements in NAFLD metabolic indicators were closely related to the altered gut microbiota. We further fermented RSV with the gut microbiota in vitro to verify that RSV directly affected the gut microbiota. Our data suggested that the gut microbiota might be an important target through which RSV exerts its anti-NAFLD effect.
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Affiliation(s)
- Fan Du
- Department of Gastroenterology, Fujian Medical University Union Hospital, Fuzhou, China.,Fujian Medical University Cancer Center, Fujian Medical University, Fuzhou, China
| | - Rongfeng Huang
- Department of Gastroenterology, Fujian Medical University Union Hospital, Fuzhou, China.,Fujian Medical University Cancer Center, Fujian Medical University, Fuzhou, China
| | - Dan Lin
- Department of Gastroenterology, Fujian Medical University Union Hospital, Fuzhou, China.,Fujian Medical University Cancer Center, Fujian Medical University, Fuzhou, China
| | - Yuying Wang
- Department of Gastroenterology, Fujian Medical University Union Hospital, Fuzhou, China.,Fujian Medical University Cancer Center, Fujian Medical University, Fuzhou, China
| | - Xiaohuang Yang
- Department of Gastroenterology, Fujian Medical University Union Hospital, Fuzhou, China.,Fujian Medical University Cancer Center, Fujian Medical University, Fuzhou, China
| | - Xiaoyun Huang
- Department of Gastroenterology, Fujian Medical University Union Hospital, Fuzhou, China.,Fujian Medical University Cancer Center, Fujian Medical University, Fuzhou, China
| | - Biyun Zheng
- Department of Gastroenterology, Fujian Medical University Union Hospital, Fuzhou, China.,Fujian Medical University Cancer Center, Fujian Medical University, Fuzhou, China
| | - Zhixin Chen
- Department of Gastroenterology, Fujian Medical University Union Hospital, Fuzhou, China.,Fujian Medical University Cancer Center, Fujian Medical University, Fuzhou, China
| | - Yuehong Huang
- Department of Gastroenterology, Fujian Medical University Union Hospital, Fuzhou, China.,Fujian Medical University Cancer Center, Fujian Medical University, Fuzhou, China
| | - Xiaozhong Wang
- Department of Gastroenterology, Fujian Medical University Union Hospital, Fuzhou, China.,Fujian Medical University Cancer Center, Fujian Medical University, Fuzhou, China
| | - Fenglin Chen
- Department of Gastroenterology, Fujian Medical University Union Hospital, Fuzhou, China.,Fujian Medical University Cancer Center, Fujian Medical University, Fuzhou, China
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