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Fluorescence of intracellular lipids by Nile Red staining. Effect of resveratrol on lipid accumulation in HepG2 cells treated with high glucose concentrations for 24 h (magnification x 100). Lipid vacuoles in cells showed a yellowgold fluorescence. Control group-HepG2 cells without tested substances (normal glucose concentration-5.5 mM), RSV-resveratrol. The procedure was repeated three times (n = 3) and representative photographs were chosen.
Source publication
Purpose:
The aim of this study was to evaluate the effect of resveratrol on de novo lipogenesis in HepG2 cells caused by high glucose concentrations. Increased lipogenesis in the liver is the main reason for the development of nonalcoholic fatty liver disease (NAFLD) - currently one of the most common chronic liver diseases. In developed countries...
Contexts in source publication
Context 1
... glucose concentrations were used to induce de novo lipogenesis and steatosis of cells in in vitro models (29)(30)(31). The study revealed that high glucose concentrations (25 or 33 mM) induced steatosis in HepG2 cells (cytoplasm of these cells contains numerous fluorescent bodies corresponding to lipid accumulation, classified as microvacuolar steatosis -small lipid droplets) (Figures 2, 5). Steatosis of HepG2 cells was visualized by Nile red staining. ...
Context 2
... et al. demonstrated the utility of Nile red as a stain to detect lipid droplets by fluorescence microscopy but this dye can also interact and exhibit fluorescence in the presence of phospholipid, cholesterol and cholesteryl esters (26). Because, especially in the group of cells treated with 25 mM glucose and 20 μM resveratrol, increased background fluorescence after Nile red staining was observed (Figure 2), we decided to take images in three different color channels (for Nile Red, MitoTracker Green FM, and Hoechst 33342) superimposed by NIS-Elements, Nikon Microscope Imaging Software. These three dyes (staining colours) were used to differentiate the background noise (fluorescence of mitochondrial membrane phospholipids from stimulated mitochondria) from actual vacuoles' lipids ( Figure 5). ...
Context 3
... glucose concentrations were used to induce de novo lipogenesis and steatosis of cells in in vitro models (29)(30)(31). The study revealed that high glucose concentrations (25 or 33 mM) induced steatosis in HepG2 cells (cytoplasm of these cells contains numerous fluorescent bodies corresponding to lipid accumulation, classified as microvacuolar steatosis -small lipid droplets) (Figures 2, 5). Steatosis of HepG2 cells was visualized by Nile red staining. ...
Context 4
... et al. demonstrated the utility of Nile red as a stain to detect lipid droplets by fluorescence microscopy but this dye can also interact and exhibit fluorescence in the presence of phospholipid, cholesterol and cholesteryl esters (26). Because, especially in the group of cells treated with 25 mM glucose and 20 μM resveratrol, increased background fluorescence after Nile red staining was observed (Figure 2), we decided to take images in three different color channels (for Nile Red, MitoTracker Green FM, and Hoechst 33342) superimposed by NIS-Elements, Nikon Microscope Imaging Software. These three dyes (staining colours) were used to differentiate the background noise (fluorescence of mitochondrial membrane phospholipids from stimulated mitochondria) from actual vacuoles' lipids ( Figure 5). ...
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One of the most important threats to global human health is the increasing incidences of metabolic pathologies (including obesity, type 2 diabetes and non-alcoholic fatty liver disease), which is paralleled by increasing consumptions of hypercaloric diets enriched in simple sugars. The challenge is to identify the metabolic pathways affected by the...
Citations
... In a study conducted by Izdebska et al. [84] on HepG2 lines, resveratrol at doses of 10 and 20 µM after 24 h of treatment reduced the degree of steatosis and mitochondrial oxidative stress (induced by oleic/palmitic acid) in HepG2 cells. The same investigators confirmed that resveratrol at a dose of 20 µM can mitigate glucose-induced steatosis and improve mitochondrial function in HepG2 cells [85]. Using the same cells, other researchers demonstrated that resveratrol (1-10 µM) can protect against the production of reactive oxygen species (ROS) produced by oleic acid intervention [86]. ...
Metabolic dysfunction-associated steatotic liver disease (MASLD) is influenced by a variety of factors, including environmental and genetic factors. The most significant outcome is the alteration of free fatty acid and triglyceride metabolism. Lipotoxicity, impaired autophagy, chronic inflammation, and oxidative stress, as well as coexisting insulin resistance, obesity, and changes in the composition of gut microbiota, are also considered crucial factors in the pathogenesis of MASLD. Resveratrol is a polyphenolic compound that belongs to the stilbene subgroup. This review summarises the available information on the therapeutic effects of resveratrol against MASLD. Resveratrol has demonstrated promising antisteatotic, antioxidant, and anti-inflammatory activities in liver cells in in vitro and animal studies. Resveratrol has been associated with inhibiting the NF-κB pathway, activating the SIRT-1 and AMPK pathways, normalizing the intestinal microbiome, and alleviating intestinal inflammation. However, clinical studies have yielded inconclusive results regarding the efficacy of resveratrol in alleviating hepatic steatosis or reducing any of the parameters found in MASLD in human patients. The lack of homogeneity between studies, low bioavailability of resveratrol, and population variability when compared to animal models could be the reasons for this.
... RSV has pharmacological effects such as inhibiting adipogenesis and promoting mitochondrial biogenesis to enhance mitochondrial activity (Kim et al., 2014). Studies have shown that resveratrol (20 μM) can inhibit glucose-induced steatosis in HepG2 cells and improve its mitochondrial activity without affecting the cell viability, suggesting the beneficial role of RSV in the treatment of mitochondrial dysfunction (Izdebska et al., 2018). Indeed, RSV can reduce HFD-induced high triglyceride and restore the core component of mitochondrial electron transport chain gene expression, such as COQs. ...
Non-alcoholic fatty liver disease (NAFLD) has become one of the most common chronic liver diseases worldwide, and its prevalence is still growing rapidly. However, the efficient therapies for this liver disease are still limited. Mitochondrial dysfunction has been proven to be closely associated with NAFLD. The mitochondrial injury caused reactive oxygen species (ROS) production, and oxidative stress can aggravate the hepatic lipid accumulation, inflammation, and fibrosis. which contribute to the pathogenesis and progression of NAFLD. Therefore, pharmacological therapies that target mitochondria could be a promising way for the NAFLD intervention. Recently, natural products targeting mitochondria have been extensively studied and have shown promising pharmacological activity. In this review, the recent research progress on therapeutic effects of natural-product-derived compounds that target mitochondria and combat NAFLD was summarized, aiming to provide new potential therapeutic lead compounds and reference for the innovative drug development and clinical treatment of NAFLD.
... eir findings showed that resveratrol inhibited oleic acid/palmitic acidinduced steatosis in HepG2 cells and reduced oxidative stress [85]. In another study, they showed resveratrol reduced the glucose-induced steatosis in HepG2 cells and increased the mitochondrial activity of cells [86]. However, in both studies, resveratrol did not affect the viability of HepG2 cells. ...
Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease that can lead to end-stage liver disease needing a liver transplant. Many pharmacological approaches are used to reduce the disease progression in NAFLD. However, current strategies remain ineffective to reverse the progression of NAFLD completely. Employing nanoparticles as a drug delivery system has demonstrated significant potential for improving the bioavailability of drugs in the treatment of NAFLD. Various types of nanoparticles are exploited in this regard for the management of NAFLD. In this review, we cover the current therapeutic approaches to manage NAFLD and provide a review of recent up-to-date advances in the uses of nanoparticles for the treatment of NAFLD.
... In the brain, resveratrol induces HO-1 to protect against ischemic stroke [108,109]. Resveratrol also protects the heart in models of diabetic-induced cardiomyopathy as well as ischemia-reperfusion injury [110,111]. Resveratrol induces HO-1 through activation of the Nrf2 pathway in both cultured PC12 cells and in Hep G2 liver cells through activation of the extracellular signal-regulated kinase (ERK) pathway [112,113]. Resveratrol also acts epigenetically to alter methylation of the Nrf2 promoter in the liver as treatment of HepG2 cells with 5-aza, a demethylating agent, prevents resveratrol induced Nfr2 gene induction and subsequent increases in HO-1 [114]. ...
Heme oxygenase (HO) is a critical component of the defense mechanism to a wide variety of cellular stressors. HO induction affords cellular protection through the breakdown of toxic heme into metabolites, helping preserve cellular integrity. Nonalcoholic fatty liver disease (NAFLD) is a pathological condition by which the liver accumulates fat. The incidence of NAFLD has reached all-time high levels driven primarily by the obesity epidemic. NALFD can progress to nonalcoholic steatohepatitis (NASH), advancing further to liver cirrhosis or cancer. NAFLD is also a contributing factor to cardiovascular and metabolic diseases. There are currently no drugs to specifically treat NAFLD, with most treatments focused on lifestyle modifications. One emerging area for NAFLD treatment is the use of dietary supplements such as curcumin, pomegranate seed oil, milk thistle oil, cold-pressed Nigella Satvia oil, and resveratrol, among others. Recent studies have demonstrated that several of these natural dietary supplements attenuate hepatic lipid accumulation and fibrosis in NAFLD animal models. The beneficial actions of several of these compounds are associated with the induction of heme oxygenase-1 (HO-1). Thus, targeting HO-1 through dietary-supplements may be a useful therapeutic for NAFLD either alone or with lifestyle modifications.
... 27 Resveratrol (Polygonum cuspidatum) and the extract from fermented Cordyceps militaris decrease the expression and activity of SREBP-1c and decrease fat synthesis. 28,29 Curcumin increases the phosphorylation of acetyl-CoA carboxylase (p-ACC) and decreases the ratelimiting enzyme acetyl-CoA carboxylase (ACC) of fatty acid synthesis, which inhibits lipogenesis. 30 Traditional Chinese medicine can also inhibit lipid synthesis and metabolism by activating AMPK. ...
Obesity is the lipid deposition caused by the imbalance between energy intake and consumption caused by a variety of factors. Obesity can lead to multiple systemic complications. At present, the treatment of obesity is mainly lifestyle intervention, drug weight loss, and weight loss surgery, but the curative effect is limited or the side effects are serious. Traditional Chinese medicine plays a unique role in the treatment of obesity. Existing studies have found that traditional Chinese medicine can treat obesity in a variety of ways, such as regulating intestinal microflora, enhancing hormone level, regulating fat metabolism, and so on. In this review, we will introduce and summarize the mechanism of traditional Chinese medicine in the treatment of obesity.
... The increase of serum TC, TG, LDL-C, ALT, and AST content and the reduction of HDL-C were as serum markers of NAFLD, and RES could return them to normality effectively due to the hepatoprotective and lipid metabolic activity [105-107, 111, 113]. In addition, in FFA-, PA-, OA-, or HG-induced HepG2 cell models, RES reduced lipid droplet accumulation indirectly [108,110,112]. Sirtuin 1 (SIRT1) was an important regulator associated with glucose and fat acid metabolism in the liver. ...
Nonalcoholic fatty liver disease, a type of metabolic syndrome, continues to rise globally. Currently, there is no approved drug for its treatment. Improving lifestyle and exercise can alleviate symptoms, but patients’ compliance is poor. More and more studies have shown the potential of Polygoni Multiflori Radix (PMR) in the treatment of NAFLD and metabolic syndrome. Therefore, this paper reviews the pharmacological effects of PMR and its main chemical components (tetrahydroxystilbene glucoside, emodin, and resveratrol) on NAFLD. PMR can inhibit the production of fatty acids and promote the decomposition of triglycerides, reduce inflammation, and inhibit the occurrence of liver fibrosis. At the same time, it maintains an oxidation equilibrium status in the body, to achieve the therapeutic purpose of NAFLD and metabolic syndrome. Although more standardized studies and clinical trials are needed to confirm its efficacy, PMR may be a potential drug for the treatment of NAFLD and its complications. However, the occurrence of adverse reactions of PMR has affected its extensive clinical application. Therefore, it is necessary to further study its toxicity mechanism, enhance efficacy and control toxicity, and even reduce toxicity, which will contribute to the safe clinical use of PMR.
... In an in vitro study carried out by Izdebska et al., [84], RSV (10 and 20 µM) reduced the levels of steatosis and mitochondrial oxidative stress in HepG2 hepatocytes induced by oleic acid, palmitic acid and mixtures of both fatty acids after 24-h treatment. The same group of researchers also reported that RSV (20 µM) reduced steatosis induced by glucose and improved the mitochondrial function in HepG2 cells [85]. In the same HepG2 model, Rafiei et al., [86] evidenced that RSV (1-10 µM) protected against oleic acid-induced ROS production. ...
Background
Non-alcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease worldwide directly related to the progressive increase in overweight and obesity. The accumulation of lipids in patients with NAFLD contributes to the development of insulin resistance, inflammatory response and oxidative stress in hepatocytes and an alteration of the circulating lipid and glycaemic profile. However, to date there are no effective pharmacological treatments for patients with NAFLD. Lifestyle changes and dietary modifications aimed to weight loss are the best current alternatives, therefore, new approaches should be considered. Resveratrol, a natural polyphenol of the stilbene group, is a potential candidate to be aware of the management of NAFLD for its anti-inflammatory, antioxidant properties, and calorie restriction-like effects.
Methods
In this review, the available information on the potential therapeutic effects of resveratrol on NAFLD developed mainly in animal models and in some clinical trials are summarize.
Results
In vitro and animal model studies have shown beneficial effects of resveratrol treatment on NAFLD. Resveratrol reduces hepatic accumulation of lipids and improves lipid and glycaemic metabolism. Some of the mechanisms of action are the signalling pathways of AMP-activated protein kinase, sirtuin 1 and nuclear factor κB. However, the results obtained in clinical trials are inconclusive.
Conclusion
Although preclinical trials have shown promising results of resveratrol against NALFD, the lack of clear results in clinical trials makes necessary more studies with a larger number of patients and for a longer time.
... To confirm our finding from In-vivo experiments, we treated HepG2 cells with glucose 33mM and RSV 20 µM for 24 h. The doses of the treatments were selected based on the previous studies (24,25). The alterations of cellular lipid accumulation were evaluated using Oil Red O (ORO) staining. ...
MicroRNAs have been shown to regulate lipogenesis in liver. The aim of the present study was to investigate whether the effects of resveratrol (RSV) on lipogenesis are associated with the changes in the expression of two miRNAs (miR-107 and miR-10b) that regulate lipogenic pathways. 30 wild type C57BL/6j male mice were randomly fed three diets: a standard chow diet (ND), a high fat diet (HFD, 60% fat) and the high fat diet supplemented with 0.4% RSV (HFD-RSV) for 16 weeks. HepG2 cells were treated with high glucose (33 mM) and RSV (20 µM) for 24 h. The expression of the genes and miRNAs were measured by real-time PCR. Triglyceride level was increased in the liver of mice and HepG2 cells. In both animal and In-vitro experiments, triglyceride level was significantly decreased in groups treated with RSV. The expression of the miR-107 and miR-10b was significantly upregulated in the liver of HFD mice, whereas HFD-RSV group demonstrated a significant lower expression of both miRNAs compared to HFD group. In addition, RSV treatment significantly upregulated the expression of CPT-1a and PPARα genes in the liver of HFD mice. Moreover, treatment with RSV could reduce the expression of miR-107 and miR-10b and increase the expression of CPT-1a and PPARα in HG-treated HepG2 cells. These evidence, as a whole, suggest that RSV could exert its anti-lipogenic effect partially through alterations in the expression of miR-107 and miR-10b in liver cells.
Non-alcoholic fatty liver disease (NAFLD) is a global health problem, and its prevalence has been on the rise in recent years. Traditional Chinese Medicine (TCM) contains a wealth of therapeutic resources and has been in use for thousands of years regarding the prevention of liver disease and has been shown to be effective in the treatment of NAFLD in China. but the molecular mechanisms behind it have not been elucidated. In this article, we have updated and summarized the research and evidence concerning herbs and their active ingredients for the treatment in vivo and vitro models of NAFLD or NASH, by searching PubMed, Web of Science and SciFinder databases. In particular, we have found that most of the herbs and active ingredients reported so far have the effect of clearing heat and dispelling dampness, which is consistent with the concept of dampness-heat syndrome, in TCM theory. we have attempted to establish the TCM theory and modern pharmacological mechanisms links between herbs and monomers according to their TCM efficacy, experiment models, targets of modulation and amelioration of NAFLD pathology. Thus, we provide ideas and perspectives for further exploration of the pathogenesis of NAFLD and herbal therapy, helping to further the scientific connotation of TCM theories and promote the modernization of TCM.
