curcumin and Non-alcoholic-Fatty-Liver-Disease

Metabolic diseases have become a serious threat to human health worldwide. It is crucial to look for effective drugs from natural products to treat metabolic diseases. Curcumin, a natural polyphenolic compound, is mainly obtained from the rhizomes of the genus

Topics: Curcumin; Diabetes Mellitus, Type 2; Humans; Metabolic Diseases; Non-alcoholic Fatty Liver Disease; Obesity

Metabolic (dysfunction)-associated fatty liver disease (MAFLD), previously known as non-alcoholic fatty liver disease (NAFLD), is the most common chronic liver disease. MAFLD is characterized by the excessive presence of lipids in liver cells and metabolic diseases/dysfunctions, e.g., obesity, diabetes, pre-diabetes, or hypertension. Due to the current lack of effective drug therapy, the potential for non-pharmacological treatments such as diet, supplementation, physical activity, or lifestyle changes is being explored. For the mentioned reason, we reviewed databases to identify studies that used curcumin supplementation or curcumin supplementation together with the use of the aforementioned non-pharmacological therapies. Fourteen papers were included in this meta-analysis. The results indicate that the use of curcumin supplementation or curcumin supplementation together with changes in diet, lifestyle, and/or physical activity led to statistically significant positive changes in alanine aminotransferase (ALT), aspartate aminotransferase (AST), fasting blood insulin (FBI), homeostasis model assessment of insulin resistance (HOMA-IR), total triglycerides (TG), total cholesterol (TC), and waist circumference (WC). It appears that these therapeutic approaches may be effective in alleviating MAFLD, but more thorough, better designed studies are needed to confirm this.

Topics: Anthropometry; Curcumin; Dietary Supplements; Humans; Non-alcoholic Fatty Liver Disease; Obesity

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a common cause of chronic liver disease and can progress to nonalcoholic steatohepatitis and cirrhosis. This study aims to summarize the evidence for the effects of curcumin on MAFLD progression. Studies were identified from Medline and Scopus databases until April 2022. Systematic reviews and meta-analyses (SRMA) and randomized controlled trials (RCT) were selected based on pre-specified criteria. Three reviewers independently extracted data and assessed quality of included studies. Of the 427 identified records, 6 SRMAs and 16 RCTs were included in the analysis. Very high overlap was observed among SRMAs with corrected covered area of 21.9%. From an updated meta-analysis, curcumin demonstrated significant improvement in aspartate and alanine aminotransferase with pooled mean difference [95% confidence interval (CI)] of -3.90 (-5.97, -1.82) and -5.61 (-9.37, -1.85) units/L, respectively. Resolution and improvement of hepatic steatosis was higher in curcumin than control group with pooled relative risk (95% CI) of 3.53 (2.01, 6.22) and 3.41 (1.36, 8.56), respectively. Curcumin supplementation also led to lower fasting blood sugar, body mass index, and total cholesterol. Further trials should be conducted to assess the effect of curcumin on liver histology, especially regarding non-invasive hepatic fibrosis and steatosis.

Topics: Curcumin; Humans; Iran; Liver Cirrhosis; Non-alcoholic Fatty Liver Disease; Thailand

Curcumin is one of the most commonly used indigenous molecules endowed with various shielding functionalities that protect the liver. In the present research, we aimed to investigate the effects of curcumin on metabolic factors and body mass index (BMI) in patients with non-alcoholic fatty liver disease (NAFLD) using a meta-analysis of randomized, controlled trials.. Online databases PubMed, Embase, Web of Science, and Science Direct were searched until April 2021 to identify eligible articles. Fourteen trials were included.. The results showed that curcumin consumption can significantly reduce AST (-0.35, (-0.57 to -0.14)), total cholesterol (-0.81, (-1.34 to -0.27)), TG (-0.49, (-0.71 to -0.27)), and FBS (-0.28, (-0.46 to -0.09)) in patients with NAFLD. However, the improvements in ALT (-0.29, (-0.58 to 0.00)), LDL (-0.48, (-0.97 to 0.01)), HDL (0.03, (-0.38 to 0.44)), and BMI (-0.13, (-0.29 to 0.02)) were not statistically significant. Furthermore, the findings revealed that the optimal dose and duration of curcumin consumption for patients with NAFLD is <500 mg/d for less than 10 weeks.. The present study suggests that consuming curcumin can improve liver enzymes, lipid profile, FBS, and BMI in patients with NAFLD. Moreover, curcumin supplementation may provide beneficial effects on metabolic biomarkers and body weight if used at the appropriate dose and duration. Further RCTs are required to confirm our findings.

Topics: Biomarkers; Body Mass Index; Curcumin; Dietary Supplements; Humans; Non-alcoholic Fatty Liver Disease; Randomized Controlled Trials as Topic

The aim of this review is to determine the effect of curcumin on the liver ultrasonographic morphology, and the effectiveness of curcumin as adjuvant treatment for NAFLD.. The Cochrane library and PubMed were searched systematically to identify randomized controlled trials from 2000 to January 2021. The primary outcomes were NAFLD severity, liver steatosis resolution, liver scarring, liver enzymes, also lipid profiles. 16 RCTs with a total of 1028 participants were included in the meta-analysis.. Curcumin improved NAFLD severity (RR: 3.52, 95 % CI 1.27-9.72; P = 0.02) and increased the liver steatosis resolution (RR 3.96, 95 % CI 1.54-10.17; P = 0.004) based on the liver ultrasonographic finding. Curcumin supplementation reduced aspartate aminotransferase (MD - 4.00, 95 % CI - 5.72 to - 2.28; P < 0.001), alanine aminotransferase (MD - 7.02, 95 % CI - 9.83 to - 4.20; P < 0.001), total cholesterol (MD - 11.86, 95 % CI - 19.25 to - 4.46; P = 0.002) and BMI (MD: - 0.41, 95 % CI - 0.75 to - 0.07; P = 0.02).. Curcumin supplementation has a favorable effect on liver ultrasonographic findings, reduced serum liver enzymes, total cholesterol, and BMI in participants with NAFLD. Therefore, promoting curcumin as adjuvant treatment on NAFLD patients might be justified.

Topics: Alanine Transaminase; Aspartate Aminotransferases; Cholesterol; Curcumin; Humans; Non-alcoholic Fatty Liver Disease

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.. 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.. 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. 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.

Topics: Alanine Transaminase; Anthocyanins; Aspartate Aminotransferases; Catechin; Cholesterol, HDL; Cholesterol, LDL; Curcumin; Dietary Supplements; Genistein; Hesperidin; Humans; Insulin Resistance; Non-alcoholic Fatty Liver Disease; Plant Extracts; Polyphenols; Resveratrol; Silymarin; Triglycerides

Oxidative stress and inflammation remain the major complications implicated in the development and progression of metabolic complications, including obesity, type 2 diabetes (T2D) and nonalcoholic fatty liver disease (NAFLD). In fact, due to their abundant antioxidant and anti-inflammatory properties, there is a general interest in understanding the therapeutic effects of some major food-derived bioactive compounds like curcumin against diverse metabolic diseases. Hence, a systematic search, through prominent online databases such as MEDLINE, Scopus, and Google Scholar was done focusing on randomized controlled trials (RCTs) reporting on the impact of curcumin supplementation in individuals with diverse metabolic complications, including obesity, T2D and NAFLD. Summarized findings suggest that curcumin supplementation can significantly reduce blood glucose and triglycerides levels, including markers of liver function like alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in patients with T2D and NAFLD. Importantly, this effect was consistent with the reduction of predominant markers of oxidative stress and inflammation, such as the levels of malonaldehyde (MDA), tumor necrosis factor-alpha (TNF-α), high sensitivity C-reactive protein (hs-CRP) and monocyte chemoattractant protein-1 (MCP-1) in these patients. Although RCTs suggest that curcumin is beneficial in ameliorating some metabolic complications, future research is still necessary to enhance its absorption and bioavailability profile, while also optimizing the most effective therapeutic doses.

Topics: Antioxidants; Biomarkers; Curcumin; Diabetes Mellitus, Type 2; Dietary Supplements; Functional Food; Humans; Inflammation; Non-alcoholic Fatty Liver Disease; Obesity; Oxidative Stress

In recent years, epidemiological studies have suggested that metabolic disorders are nutritionally dependent. A healthy diet that is rich in polyphenols may be beneficial in the treatment of metabolic diseases such as polycystic ovary syndrome, metabolic syndrome, non-alcoholic fatty liver disease, cardiovascular disease, and, in particular, atherosclerosis. Curcumin is a polyphenol found in turmeric and has been reported to have antioxidant, anti-inflammatory, hepatoprotective, anti-atherosclerotic, and antidiabetic properties, among others. This review summarizes the influence of supplementation with curcumin on metabolic parameters in selected metabolic disorders.

Topics: Anti-Inflammatory Agents; Antioxidants; Atherosclerosis; Cardiovascular Diseases; Curcuma; Curcumin; Dietary Supplements; Female; Humans; Hypoglycemic Agents; Male; Metabolic Diseases; Non-alcoholic Fatty Liver Disease; Phytotherapy; Polycystic Ovary Syndrome

Non-alcoholic fatty liver disease (NAFLD), which is emerging as a major public health issue worldwide, is characterized by a wide spectrum of liver disorders, ranging from simple fat accumulation in hepatocytes, also known as steatosis, to non-alcoholic steatohepatitis (NASH) and cirrhosis. At present, the pharmacological treatment of NAFLD is still debated and dietary strategies for the prevention and the treatment of this condition are strongly considered. Polyphenols are a group of plant-derived compounds whose anti-inflammatory and antioxidant properties are associated with a low prevalence of metabolic diseases, including obesity, hypertension, and insulin resistance. Since inflammation and oxidative stress are the main risk factors involved in the pathogenesis of NAFLD, recent studies suggest that the consumption of polyphenol-rich diets is involved in the prevention and treatment of NAFLD. However, few clinical trials are available on human subjects with NAFLD. Here, we reviewed the emerging existing evidence on the potential use of polyphenols to treat NAFLD. After introducing the physiopathology of NAFLD, we focused on the most investigated phenolic compounds in the setting of NAFLD and described their potential benefits, starting from basic science studies to animal models and human trials.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Curcumin; Diet; Dietary Supplements; Disease Models, Animal; Humans; Mice; Non-alcoholic Fatty Liver Disease; Polyphenols; Resveratrol; Silymarin

Non-alcoholic fatty liver disease (NAFLD) is a disorder of excessive fat accumulation in the liver, known as steatosis, without alcohol overconsumption. NAFLD can either manifest as simple steatosis or steatohepatitis, known as non-alcoholic steatohepatitis (NASH), which is accompanied by inflammation and possibly fibrosis. Furthermore, NASH might progress to hepatocellular carcinoma. NAFLD and NASH prevalence is in a continuous state of growth, and by 2018, NAFLD became a devastating metabolic disease with a global pandemic prevalence. The pathophysiology of NAFLD and NASH is not fully elucidated, but is known to involve the complex interplay between different metabolic, environmental, and genetic factors. In addition, unhealthy dietary habits and pre-existing metabolic disturbances together with other risk factors predispose NAFLD development and progression from simple steatosis to steatohepatitis, and eventually to fibrosis. Despite their growing worldwide prevalence, to date, there is no FDA-approved treatment for NAFLD and NASH. Several off-label medications are used to target disease risk factors such as obesity and insulin resistance, and some medications are used for their hepatoprotective effects. Unfortunately, currently used medications are not sufficiently effective, and research is ongoing to investigate the beneficial effects of different drugs and phytochemicals in NASH. In this review article, we outline the different risk factors and pathophysiological mechanisms involved in NAFLD, diagnostic procedures, and currently used management techniques.

Topics: Curcumin; Humans; Insulin Resistance; Liver; Liver Transplantation; Metabolic Syndrome; Non-alcoholic Fatty Liver Disease; Obesity; Plant Preparations; Resveratrol; Risk Factors

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.. 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.. 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.. 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.

Topics: Alanine Transaminase; Aspartate Aminotransferases; Chalcones; Chenodeoxycholic Acid; Cholesterol, HDL; Cholesterol, LDL; Curcumin; Enzyme Inhibitors; Humans; Network Meta-Analysis; Non-alcoholic Fatty Liver Disease; Plant Preparations; Propionates; Triglycerides

Metabolic-associated fatty liver disease (MAFLD), formerly non-alcoholic fatty liver disease (NAFLD), is characterized by excessive fat accumulation in hepatocytes. It is the most common chronic liver disease worldwide and is a significant public health problem. In the absence of pharmacological therapy, other treatments such as diet, physical activity, or supplementation are sought. Non-pharmacological therapies may include curcumin supplementation, which has been shown to have many health-promoting properties, including antioxidant, anti-inflammatory, and anti-cancer effects. For this reason, we reviewed available databases to analyze publications describing the effect of curcumin supplementation on biochemical parameters in MAFLD. Nine studies (eight RCTs and one CT) based solely on supplementation of patients with curcumin were included in this review. The results from the individual trials were varied and did not allow clear conclusions. Although they suggest that curcumin shows some potential in the treatment of MAFLD, further research is needed.

Topics: Curcumin; Databases, Factual; Dietary Supplements; Hepatocytes; Humans; Interleukins; Liver Diseases; Non-alcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) is a major cause of liver-related morbidity; its prevalence is elevating due to the rising epidemic of obesity. Several clinical trials have examined the effects of curcumin supplementation on anthropometric variables in NAFLD patients with inconclusive results. This dose-response meta-analysis aimed to evaluate the impact of curcumin supplementation on body mass index (BMI), body weight, and waist circumference (WC) in patients with NAFLD. A systematic review of the literature was conducted using PubMed/Medline, ISI Web of Science, Scopus, Cochrane Library, EMBASE, Google Scholar, Sid.ir, and Magiran.com to identify eligible studies up to March 2019. A meta-analysis of eligible studies was performed using the random-effects model to estimate the pooled effect size. Eight randomized controlled trials with 520 participants (curcumin group = 265 and placebo group = 255) were included. Supplementation dose and duration ranged from 70 to 3,000 mg/day and 8 to 12 weeks, respectively. Curcumin supplementation significantly reduced BMI (weighted mean difference [WMD] = -0.34 kg/m

Topics: Adult; Anthropometry; Body Mass Index; Body Weight; Curcumin; Dietary Supplements; Female; Humans; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Obesity; Randomized Controlled Trials as Topic; Waist Circumference; Weight Loss

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. Curcumin is the anti-inflammatory, antioxidant, anti-diabetic and also anti-hyperlipidemia agent and uses as herbal medicine for treating liver diseases.. The present systematic review and meta-analysis was conducted to investigate the effects of curcumin supplementation on metabolic markers and anthropometric parameters in patients with (NAFLD).. PubMed, Embase, Scopus, Web of Science and Cochrane Library were systematically searched to identify relevant randomized controlled trials (RCTs) investigating the effects of curcumin supplementation on the arms of this study in patients with NAFLD up to September 2019. Mean difference (MD) was pooled using a random effects model. Potential publication bias was assessed using Egger's weighted regression tests.. After excluding irrelevant records, 9 RCTs included in this meta-analysis. Pooled results of included studies indicated a significant reduction in alanine transaminase (ALT), aspartate transaminase (AST), serum total cholesterol (TC), low density lipoprotein (LDL), fasting blood sugar (FBS), HOMA-IR, serum insulin and waist circumference (WC), but not in serum triglyceride (TG), high density lipoprotein (HDL), HbA1c, body weight and body mass index (BMI) following curcumin supplementation. Additionally, age- and baseline TC-based subgroup analysis indicated a significant reduction in TG and also duration- and dosage-based showed a significant change in BMI.. The current study revealed that curcumin supplementation has favorable effect on metabolic markers and anthropometric parameters in patients with NAFLD.

Topics: Body Composition; Curcumin; Dietary Supplements; Humans; Liver Function Tests; Metabolome; Non-alcoholic Fatty Liver Disease; Randomized Controlled Trials as Topic

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

Topics: Animals; Bilirubin; Biological Products; Curcumin; Heme Oxygenase (Decyclizing); Heme Oxygenase-1; Humans; Insulin Resistance; Liver; Non-alcoholic Fatty Liver Disease; Oxidoreductases Acting on CH-CH Group Donors; Reactive Oxygen Species

Evidence indicates that curcumin seems to improve outcomes in non-alcoholic fatty liver disease (NAFLD). A meta-analysis was performed to evaluate the effects of curcumin inNAFLD.. We searched PubMed, EMBASE, and the Cochrane Library from inception through March 2018 to identify randomized controlled trials (RCTs) evaluating the role of curcumin inNAFLD. The mean difference (MD) and 95% confidence interval (CI) were calculated.. Four RCTs with a total of 229 NAFLD patients were included. Curcumin was more likely to lower LDL-C, triglycerides, FBS, HOMA-IR, weight and AST levels compared with placebo, and the difference was statistically significant [MD = - 27.02, 95% CI (- 52.30, - 1.74); MD = - 33.20, 95% CI (- 42.30, - 24.09); MD = - 5.63, 95% CI (- 10.36, - 0.90); MD = - 0.53, 95% CI (- 1.00, - 0.05); MD = - 2.27, 95% CI (- 3.11, - 1.44); MD = - 7.43, 95% CI (- 11.31, - 3.54), respectively]. However, the beneficial effect of curcumin did not achieve statistical significance in lowering total cholesterol, HDL-C, HbA1c, ALT or insulin levels [MD = - 30.47,95% CI (- 60.89. - 0.06); MD = - 0.98, 95% CI (- 2.88, 0.92); MD = - 0.41, 95% CI (- 1.41, 0.59); MD = - 6.02, 95% CI (- 15.61, 3.57); MD = - 0.92, 95% CI (- 2.33, 0.49)].. Curcumin is effective in lowering LDL-C, triglycerides, FBS, HOMA-IR, weight, and AST levels in NAFLD patients, and it is well tolerated. Further RCTs are required to confirm our findings.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Curcumin; Humans; Non-alcoholic Fatty Liver Disease; Randomized Controlled Trials as Topic

We performed a meta-analysis to evaluate the efficacy of turmeric/curcumin supplementation on serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in patients with nonalcoholic fatty liver disease (NAFLD). We searched PubMed, Scopus, Cochrane Library, ISI Web of Science, and Google Scholar up to November 20, 2018. Studies that examined the effect of turmeric/curcumin on serum concentrations of ALT and AST among patients with NAFLD were included. The mean difference and standard deviation (SD) of changes in ALT and AST between intervention and control groups were used as effect size for the meta-analysis. A total of six randomized controlled trials (RCTs) were eligible for meta-analysis. Results from pooled analysis revealed that turmeric/curcumin supplementation reduced ALT (MD: -7.31 UL/L, 95% CI [-13.16, -1.47], p = 0.014) and AST (MD: -4.68 UL/L, 95% CI [-8.75 -0.60], p = 0.026). When RCTs stratified on the basis of their treatment duration, the significant reduction in serum concentrations of ALT and AST was observed only in studies lasting less than 12 weeks. This review suggests that turmeric/curcumin might have a favorable effect on serum concentrations of ALT and AST in patients with NAFLD. However, further clinical trials are needed to confirm these findings.

Topics: Alanine Transaminase; Aspartate Aminotransferases; Curcuma; Curcumin; Dietary Supplements; Humans; Liver; Liver Function Tests; Male; Non-alcoholic Fatty Liver Disease; Randomized Controlled Trials as Topic

Increasing prevalence of nonalcoholic fatty liver disease (NAFLD) in parallel with the obesity epidemic has been a major public health concern. NAFLD is the most common chronic liver disease in the United States, ranging from fatty liver to steatohepatitis, fibrosis and cirrhosis in the liver. In response to chronic liver injury, fibrogenesis in the liver occurs as a protective response; however, prolonged and dysregulated fibrogenesis can lead to liver fibrosis, which can further progress to cirrhosis and eventually hepatocellular carcinoma. Interplay of hepatocytes, macrophages and hepatic stellate cells (HSCs) in the hepatic inflammatory and oxidative milieu is critical for the development of NAFLD. In particular, HSCs play a major role in the production of extracellular matrix proteins. Studies have demonstrated that bioactive food components and natural products, including astaxanthin, curcumin, blueberry, silymarin, coffee, vitamin C, vitamin E, vitamin D, resveratrol, quercetin and epigallocatechin-3-gallate, have antifibrotic effects in the liver. This review summarizes current knowledge of the mechanistic insight into the antifibrotic actions of the aforementioned bioactive food components.

Topics: Blueberry Plants; Coffee; Curcumin; Food; Hepatic Stellate Cells; Hepatocytes; Humans; Liver Cirrhosis; Macrophages; Non-alcoholic Fatty Liver Disease; Oxidative Stress; Resveratrol; Vitamins; Xanthophylls

Non-alcoholic fatty liver disease (NAFLD) is a clinical condition characterized by lipid infiltration of the liver, highly prevalent in the general population affecting 25% of adults, with a doubled prevalence in diabetic and obese patients. Almost 1/3 of NAFLD evolves in Non-Alcoholic SteatoHepatitis (NASH), and this can lead to fibrosis and cirrhosis of the liver. However, the main causes of mortality of patients with NAFLD are cardiovascular diseases. At present, there are no specific drugs approved on the market for the treatment of NAFLD, and the treatment is essentially based on optimization of lifestyle. However, some nutraceuticals could contribute to the improvement of lipid infiltration of the liver and of the related anthropometric, haemodynamic, and/or biochemical parameters. The aim of this paper is to review the available clinical data on the effect of nutraceuticals on NAFLD and NAFLD-related parameters. Relatively few nutraceutical molecules have been adequately studied for their effects on NAFLD. Among these, we have analysed in detail the effects of silymarin, vitamin E, vitamin D, polyunsaturated fatty acids of the omega-3 series, astaxanthin, coenzyme Q10, berberine, curcumin, resveratrol, extracts of

Topics: Antioxidants; Berberine; Curcumin; Dietary Supplements; Fatty Acids, Omega-3; Fatty Acids, Unsaturated; Humans; Meta-Analysis as Topic; Non-alcoholic Fatty Liver Disease; Obesity; Observational Studies as Topic; Plant Extracts; Probiotics; Randomized Controlled Trials as Topic; Resveratrol; Salvia miltiorrhiza; Silymarin; Ubiquinone; Vitamin D; Vitamin E; Xanthophylls

Non-alcoholic fatty liver disease (NAFLD) is a common clinicopathological condition, encompassing a range of conditions caused by lipid deposition within liver cells. To date, no approved drugs are available for the treatment of NAFLD, despite the fact that it represents a serious and growing clinical problem in the Western world. Identification of the molecular mechanisms leading to NAFLD-related fat accumulation, mitochondrial dysfunction and oxidative balance impairment facilitates the development of specific interventions aimed at preventing the progression of hepatic steatosis. In this review, we focus our attention on the role of dysfunctions in mitochondrial bioenergetics in the pathogenesis of fatty liver. Major data from the literature about the mitochondrial targeting of some antioxidant molecules as a potential treatment for hepatic steatosis are described and critically analysed. There is ample evidence of the positive effects of several classes of antioxidants, such as polyphenols (

Topics: Animals; Anthocyanins; Antioxidants; Carotenoids; Catechin; Coumestrol; Curcumin; Energy Metabolism; Fatty Liver; Glucosinolates; Humans; Imidoesters; Isothiocyanates; Lipogenesis; Mitochondria; Non-alcoholic Fatty Liver Disease; Nutritional Sciences; Oxidative Stress; Oximes; Polyphenols; Quercetin; Resveratrol; Stilbenes; Sulfoxides; Xanthophylls

Nonalcoholic fatty liver disease (NAFLD) is the most common type of liver disease. NAFLD is considered a multifactorial disease and a clinically relevant hepatic manifestation of metabolic syndrome. NAFLD is often accompanied by a constellation of metabolic and non-metabolic alterations, like dyslipidemia, insulin resistance in the liver and peripheral tissues, inflammation and oxidative stress; therefore, treatment of NAFLD should be directed at correcting all of these disturbances. The natural polyphenol curcumin has been the subject of increasing research for the treatment of NAFLD due to its lipid-modifying, antioxidant, anti-inflammatory, insulinsensitizing, anti-steatotic, and anti-fibrotic properties. The therapeutic efficacy of curcumin has been demonstrated in several experimental models of NAFLD, however, clinical evidence is still scarce. The present review summarizes the current knowledge on the impact of curcumin supplementation on different biochemical and histopathological features of NAFLD.

Topics: Curcumin; Dietary Supplements; Humans; Mitochondria; Non-alcoholic Fatty Liver Disease; Oxidative Stress

As a sugar additive, fructose is widely used in processed foods and beverages. Excessive fructose consumption can cause hepatic steatosis and dyslipidemia, leading to the development of metabolic syndrome. Recent research revealed that fructose-induced nonalcoholic fatty liver disease (NAFLD) is related to several pathological processes, including: (1) augmenting lipogenesis; (2) leading to mitochondrial dysfunction; (3) stimulating the activation of inflammatory pathways; and (4) causing insulin resistance. Cellular signaling research indicated that partial factors play significant roles in fructose-induced NAFLD, involving liver X receptor (LXR)α, sterol regulatory element binding protein (SREBP)-1/1c, acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), stearoyl-CoA desaturase (SCD), peroxisome proliferator-activated receptor α (PPARα), leptin nuclear factor-erythroid 2-related factor 2 (Nrf2), nuclear factor kappa B (NF-κB), tumor necrosis factor α (TNF-α), c-Jun amino terminal kinase (JNK), phosphatidylinositol 3-kinase (PI3K) and adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK). Until now, a series of natural products have been reported as regulators of NAFLD in vivo and in vitro. This paper reviews the natural products (e.g., curcumin, resveratrol, and (-)-epicatechin) and their mechanisms of ameliorating fructose-induced NAFLD over the past years. Although, as lead compounds, natural products usually have fewer activities compared with synthesized compounds, it will shed light on studies aiming to discover new drugs for NAFLD.

Topics: Animals; Biological Products; Catechin; Curcumin; Fructose; Humans; Inflammation; Insulin Resistance; Lipogenesis; Mitochondria; Non-alcoholic Fatty Liver Disease; Resveratrol; Stilbenes

Nonalcoholic fatty liver disease (NAFLD) refers to a wide spectrum of liver disease that is not from excess alcohol consumption, but is often associated with obesity, type 2 diabetes, and metabolic syndrome. NAFLD pathogenesis is complicated and involves oxidative stress, lipotoxicity, mitochondrial damage, insulin resistance, inflammation, and excessive dietary fat intake, which increase hepatic lipid influx and de novo lipogenesis and impair insulin signaling, thus promoting hepatic triglyceride accumulation and ultimately NAFLD. Overproduction of proinflammatory adipokines from adipose tissue also affects hepatic metabolic function. Current NAFLD therapies are limited; thus, much attention has been focused on identification of potential dietary substances from fruits, vegetables, and edible plants to provide a new strategy for NAFLD treatment. Dietary natural compounds, such as carotenoids, omega-3-PUFAs, flavonoids, isothiocyanates, terpenoids, curcumin, and resveratrol, act through a variety of mechanisms to prevent and improve NAFLD. Here, we summarize and briefly discuss the currently known targets and signaling pathways as well as the role of dietary natural compounds that interfere with NAFLD pathogenesis.

Topics: Adipokines; Animals; Carotenoids; Curcumin; Fatty Acids, Omega-3; Fatty Liver; Flavonols; Humans; Insulin Resistance; Non-alcoholic Fatty Liver Disease; Obesity; Oxidative Stress; Polyphenols; Resveratrol; Stilbenes

Along with rising numbers of patients with metabolic syndrome, the prevalence of nonalcoholic fatty liver disease (NAFLD) has increased in proportion with the obesity epidemic. While there are no established treatments for NAFLD, current research is targeting new molecular mechanisms that underlie NAFLD and associated metabolic disorders. This review discusses some of these emerging molecular mechanisms and their therapeutic implications for the treatment of NAFLD. The basic research that has identified potential molecular targets for pharmacotherapy will be outlined.

Topics: Curcumin; Fatty Acid Synthase, Type I; Fatty Liver; Fibric Acids; Forkhead Box Protein O1; Forkhead Transcription Factors; Gene Expression Regulation; Humans; Lipid Metabolism; Liver; Mitochondria; Non-alcoholic Fatty Liver Disease; Peroxisomes; PPAR gamma; Pregnane X Receptor; Protective Agents; Receptors, Cytoplasmic and Nuclear; Receptors, Steroid; Thiazolidinediones

Non-alcoholic Fatty Liver Disease (NAFLD) is a global health problem that can progress to steatohepatitis and cirrhosis. The aim of this study was to determine the effect of curcumin + piperine on cardiometabolic risk factors, as well as hepatic steatosis and fibrosis in NAFLD patients with moderate-to-high hepatic steatosis. Patients diagnosed with moderate-to-high NAFLD by liver sonography were randomized to either curcumin + piperine (500 mg/day curcumin plus 5 mg/day piperine) for 12 weeks (n = 30) or placebo groups (n = 30). Liver fibroscan, anthropometric measurements, dietary intake, physical activity, blood pressure, lipid profile, high-sensitivity C-reactive protein, fasting blood glucose (FBG), and liver enzymes were assessed at baseline and after 12 weeks of follow-up. Intention-to-treat analysis was undertaken. Curcumin + piperine decreased waist circumference (p = 0.026), systolic blood pressure (p = 0.001), total cholesterol (p = 0.004), low-density lipoprotein-cholesterol (p = 0.006), FBG (p = 0.002), alanine transaminase (p = 0.007) and aspartate transaminase (p = 0.012) compared with placebo. However, fibroscan measurement did not differ between curcumin + piperine and placebo groups (p > 0.05). Fibroscan measurement as a marker of NAFLD improvement did not differ after 12 weeks of curcumin + piperine; however, curcumin + piperine may be considered as an adjunct therapy to improve anthropometric measures, blood pressure, lipid profile, blood glucose, and liver function in NAFLD patients.

Topics: Blood Glucose; Cholesterol; Curcumin; Dietary Supplements; Double-Blind Method; Humans; Lipids; Non-alcoholic Fatty Liver Disease

Cardiovascular disease (CVD) is the leading cause of death in patients with non-alcoholic fatty liver disease (NAFLD). Curcumin has been shown to exert glucose-lowering and anti-atherosclerotic effects in type 2 diabetes. Hence, we investigated curcumin's effects on atherogenesis markers, fatty liver, insulin resistance, and adipose tissue-related indicators in patients with NAFLD. In this secondary analysis of a 12-week randomized controlled trial, fifty-two patients with NAFLD received lifestyle modification. In addition, they were randomly allocated to either the curcumin group (1.5 g/day) or the matching placebo. Outcome variables (assessed before and after the study) were: the fatty liver index (FLI), hepatic steatosis index (HSI), fatty liver score (FLS), BMI, age, ALT, TG score (BAAT), triglyceride glucose (TyG) index, Castelli risk index-I (CRI-I), Castelli risk index-II (CRI-II), TG/HDL-C ratio, atherogenic coefficient (AC), atherogenic index of plasma (AIP), lipoprotein combine index (LCI), cholesterol index (CHOLINDEX), lipid accumulation product (LAP), body adiposity index (BAI), visceral adiposity index (VAI), metabolic score for visceral fat (METS-VF), visceral adipose tissue (VAT), and waist-to-height ratio (WHtR) values. The TyG index decreased in the curcumin group and increased in the placebo group, with a significant difference between the groups (

Topics: Atherosclerosis; Body Mass Index; Cardiovascular Diseases; Curcumin; Diabetes Mellitus, Type 2; Glucose; Humans; Life Style; Non-alcoholic Fatty Liver Disease; Triglycerides

Experimental and clinical studies have revealed that curcumin may be an effective therapy for non-alcoholic fatty liver disease (NAFLD). Hence, the aim of this study was to assess the effect of curcumin plus piperine administration on NAFLD.. Adults 18-65 years-old diagnosed with NAFLD by liver sonography were randomly allocated to curcumin (500 mg/day) or placebo groups for 2 months. All participants received both dietary and exercise advice. Anthropometric and biochemical measurements as well as hepatic ultrasound were performed at baseline and final conditions.. Seventy-nine participants were recruited and randomly allocated into the curcumin (n = 39) or placebo (n = 40) groups. There were no significant differences between placebo and curcumin groups for demographic and clinical characteristics and NAFLD grade at baseline. After the treatment period, the curcumin group exhibited lower alkaline phosphatase (-16.2 ± 22.8 versus -6.0 ± 22.5 mg/dL, p = 0.04) concentrations and severity of NAFLD compared with the placebo group (p = 0.04).. Results of this clinical trial suggest that short-term treatment with curcumin plus piperine administration improves NAFLD severity.

Topics: Adolescent; Adult; Aged; Alkaloids; Benzodioxoles; Curcumin; Dietary Supplements; Double-Blind Method; Humans; Liver; Middle Aged; Non-alcoholic Fatty Liver Disease; Piperidines; Polyunsaturated Alkamides; Young Adult

Topics: Body Mass Index; Body Weight; Curcumin; Double-Blind Method; Humans; Non-alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is a global health problem with increasing prevalence among overweight and obese patients. It is strongly associated with conditions of insulin resistance including type 2 diabetes mellitus (T2DM) and obesity. It has detrimental consequences ranged from simple steatosis to irreversible hepatic fibrosis and cirrhosis. Curcumin is a dietary polyphenol with potential effect in improving NAFLD. Therefore, the aim of this trial was to examine the effect of curcumin supplementation on various aspects of NAFLD. In this trial, a total number of 80 patients were randomised to receive either curcumin at 250 mg daily or placebo for 2 months. Lipid profiles, hepatic enzymes, anthropometric indices and hepatic fat mass were assessed at the baseline and the end of the trial, and compared within the groups. The grade of hepatic steatosis, and serum aspartate aminotransferase (AST) levels were significantly reduced in the curcumin group (p = 0.015 and p = 0.007, respectively) compared to the placebo. There was also a significant reduction in high density lipoprotein (HDL) levels and anthropometric indices in both groups with no significant differences between the two groups. Low dose phospholipid curcumin supplementation each day for 2 months showed significant reduction in hepatic steatosis and enzymes in patients with NAFLD compared to placebo. Further studies of longer duration and higher dosages are needed to assess its effect on other parameters of NAFLD including cardiovascular risk.

Topics: Aspartate Aminotransferases; Curcumin; Diabetes Mellitus, Type 2; Double-Blind Method; Humans; Non-alcoholic Fatty Liver Disease

A mixture of natural ingredients, namely, DHA, phosphatidylcholine, silymarin, choline, curcumin and d-α-tocopherol, was studied in subjects with non-alcoholic fatty liver disease (NAFLD). Primary endpoints were serum levels of hepatic enzymes, and other parameters of liver function, the metabolic syndrome and inflammation were the secondary endpoints. The coagulation-fibrinolysis balance was also thoroughly investigated, as NAFLD is associated with haemostatic alterations, which might contribute to increased cardiovascular risk of this condition. The present study involved a double-blind, randomised, multicentre controlled trial of two parallel groups. Subjects with NAFLD (18-80 years, either sex) received the active or control treatment for 3 months. All assays were performed on a total of 113 subjects before and at the end of supplementation. The hepatic enzymes aspartate aminotransferase (AST), alanine aminotransferase and γ-glutamyl transpeptidase decreased from 23·2 to 3·7 % after treatment, only the AST levels reaching statistical significance. However, no differences were found between control and active groups. Metabolic and inflammatory variables were unchanged, except for a slight (less than 10 %) increase in cholesterol and glucose levels after the active treatment. Coagulation-fibrinolytic parameters were unaffected by either treatment. In conclusion, chronic supplementation with the mixture of dietary compounds was well tolerated and apparently safe in NAFLD subjects. The trial failed to demonstrate any efficacy on relevant physiopathological markers, but its protocol and results may be useful to design future studies with natural compounds.

Topics: Adult; Aged; Alanine Transaminase; Aspartate Aminotransferases; Biomarkers; Choline; Curcumin; Dietary Supplements; Docosahexaenoic Acids; Double-Blind Method; Drug Combinations; Female; Fibrinolysis; gamma-Glutamyltransferase; Humans; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Phosphatidylcholines; Silymarin; Tocopherols

Nonalcoholic fatty liver diseases (NAFLD) is a highly prevalent disease that is closely associated with several cardiometabolic complications. The potential anti-inflammatory role of curcuminoids that have already been reported to reduce hepatic steatosis, in patients with NAFLD was explored in this study.. This double-blind, randomized placebo-controlled trial was conducted for a period of 8 weeks in patients with NAFLD. Subjects (n = 55) were randomly allocated to receive either curcuminoids or placebo. The curcuminoids group received one capsule containing 500 mg curcuminoids (plus 5 mg piperine to increase intestinal absorption) per day for 8 weeks and the control group received matched placebo capsules for the same period. Liver ultrasonography was performed to assess the severity of hepatic steatosis at baseline and the study end. Serum levels of cytokines including interleukin-1α, interleukin-1β, interleukin-2, interleukin-4, interleukin-6, interleukin-8, interleukin-10, tumor necrosis factor-α, monocyte chemoattractant protein-1, interferon γ, vascular endothelial growth factor and epidermal growth factor were measured before and after the intervention.. The two groups were comparable in demographic features at baseline. The results showed that supplementation with curcuminoids could decrease weight compared to the placebo group (p = 0.016) in patients with NAFLD. Curcuminoids supplementation improved the severity of NAFLD according to the ultrasound results (p = 0.002). Moreover, serum concentrations of TNF-α (p = 0.024), MCP-1 (p = 0.008) and EGF (p = 0.0001) were improved by curcuminoids in NAFLD patients.. The results of our study showed that curcumin supplementation can improve serum levels of inflammatory cytokines in subjects with NAFLD and this might be at least partly responsible for the anti-steatotic effects of curcuminoids.

Topics: Adolescent; Adult; Aged; Alkaloids; Benzodioxoles; Curcumin; Diarylheptanoids; Double-Blind Method; Female; Humans; Inflammation; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Piperidines; Polyunsaturated Alkamides; Young Adult

The enhancement of oxidative stress in non-alcoholic fatty liver disease (NAFLD) patients may cause mutation in DNA by deamination of cytosine to 5-hydroxyuracil or uracil. This study aimed to discover the effects of curcumin on NAFLD progress, DNA damage caused by oxidative stress, and promoter methylation of mismatch repair enzymes.. in this study, 54 NAFLD patients were randomly devided into two groups, according to a double blind parallel design either phytosomal curcumin (250 mg/day) or placebo for 8 weeks. Fasting blood samples and anthropometric measures were taken twice, once at the baseline and once at the end of the study. Promoter methylation and 8-hydroxy-2' -deoxyguanosine (8-OHdG) concentration as DNA damage mediator were measured by restriction enzymes and enzyme-linked immunosorbent assay, respectively.. Analysis was performed on 44 patients. According to our between groups analysis, curcumin significantly reduced the methylation in MutL homolog 1 (MLH1) and MutS homolog 2 (MSH2) promoter regions. The within-group comparison revealed that anthropometric variables significantly decreased. However, the result of the between groups comparison indicated no significant changes in the anthropometric variables except for BMI. Liver enzymes and 8-OHdG did not significantly change at the end of the study, neither in curcumin group nor in placebo group.. Curcumin might be able to reduce the risk of mismatch base pair in DNA among the NAFLD patients. However, it did not change the DNA damage mediator and liver enzymes. For confirming these results, more studies with longer duration, more numbers of examined genes, higher dose of curcumin, and larger sample size are required.

Topics: Adult; Curcumin; DNA Damage; Double-Blind Method; Epigenesis, Genetic; Female; Humans; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Oxidative Stress; Pilot Projects

With increasing age, non-alcoholic fatty liver disease is very common among women with low levels of physical activity. Nonlinear resistance training is one of the new methods to help patients who have low levels of physical activity. Curcumin is an herbal supplement that has anti-inflammatory effects. The present study aimed to examine the effects of nonlinear resistance training and curcumin supplementation on the liver structure and biochemical markers in obese older women with non-alcoholic fatty liver disease.. Forty-five obese women with non-alcoholic fatty liver disease were randomly assigned into resistance training (RT), curcumin supplement (C), resistance training with curcumin supplement (RTC), and placebo (P) groups. The RT and RTC groups received 12-weeks of nonlinear resistance training while the C and P groups had a normal sedentary lifestyle. Daily, the C and RTC groups received a curcumin capsule while the P and RT groups were given a placebo capsule. Blood sampling and ultrasonography were taken before and after the protocol.. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels significantly decreased in the RT and RTC groups (P ≤ 0.05) but not in the C and P groups (P > 0.05). Alkaline phosphatase (ALP), total bilirubin (TB) levels, platelet counts (PLT), and liver structure did not significantly change in all groups (P > 0.05). Resistance training alone and with curcumin supplementation could significantly improve liver function while taking curcumin alone did not have any significant effect on it.. 12-week non-linear resistance training has beneficial effects on non-alcoholic fatty liver disease in older obese women.

Topics: Aged; Biomarkers; Curcumin; Dietary Supplements; Female; Humans; Non-alcoholic Fatty Liver Disease; Resistance Training

Curcumin has shown to exert a positive impact on human glucose metabolism, even if its bioavailability is usually very low. The present study aimed to explore the effect of phosphatidylserine- and piperine-containing curcumin phytosomes on a large number of metabolic parameters related to insulin resistance, in the context of a randomized double-blind placebo-controlled trial involving 80 overweight subjects with suboptimal fasting plasma glucose.. Subjects were randomized to be treated with indistinguishable tablets (2 per day, to be taken after dinner) containing 800 mg phytosomal curcumin (Curserin®: 200 mg curcumin, 120 mg phosphatidylserine, 480 mg phosphatidylcholine and 8 mg piperine from Piper nigrum L. dry extract) for 8 weeks.. After 56-day treatment, the curcumin-treated group experienced a significant improvement in fasting plasma insulin (FPI), HOMA index, waist circumference, blood pressure, triglycerides (TG), HDL-C, liver transaminases, gamma-GT, index of liver steatosis and serum cortisol compared to the baseline. FPI, TG, liver transaminases, fatty liver index and serum cortisol level also significantly improved compared with the placebo-treated group. Compared to the baseline, at the end of the study placebo group experienced an improvement only in FPG and TG.. In conclusion, the present trial shows that supplementation with a phytosomal preparation of curcumin containing phosphatidylserine and piperine could improve glycemic factors, hepatic function and serum cortisol levels in subjects with overweight and impaired fasting glucose.

Topics: Curcumin; Double-Blind Method; Female; Humans; Hydrocortisone; Insulin; Insulin Resistance; Male; Middle Aged; Non-alcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) is a major global health problem. The most common cause of death in these patients is due to cardiovascular disorders. The aim of this study was to examine the effects of curcumin supplementation on cardiovascular risk factors in patients with NAFLD.. In this randomized, placebo-controlled, clinical trial, fifty two patients with NAFLD were randomly assigned to receive life style recommendations plus either 1500 mg curcumin or placebo for 12 weeks. Anthropometric indices, blood lipid profile, insulin resistance, as well as hepatic steatosis and fibrosis scores were measured at the beginning and the end of the study, and compared between and within groups.. Hepatic fibrosis, serum cholesterol, glucose and alanin aminotransferase (ALT) reduced significantly only in curcumin group (p < 0.05). Anthropometric indices, blood lipid profile, insulin resistance, and hepatic steatosis decreased significantly in both groups (p < 0.05), without any significant difference between two groups.. Our results showed that daily intake of 1500 mg curcumin plus weight loss is not superior to weight loss alone in amelioration of cardiovascular risk factors in patients with NAFLD. Further studies with different dosages of curcumin are needed to be able to conclude about the effects of this dietary supplement on cardiovascular risk factors and NAFLD characteristics.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Blood Glucose; Curcumin; Dietary Supplements; Double-Blind Method; Female; Homeostasis; Humans; Insulin Resistance; Iran; Lipids; Liver; Liver Cirrhosis; Male; Middle Aged; Non-alcoholic Fatty Liver Disease

Curcumin, a natural polyphenol compound in the spice turmeric, has been found to have potent anti-oxidative and anti-inflammatory activity. Curcumin may treat non-alcoholic fatty liver disease (NAFLD) through its beneficial effects on biomarkers of oxidative stress (OS) and inflammation, which are considered as two feature of this disease. However, the effects of curcumin on NAFLD have been remained poorly understood. This investigation evaluated the effects of administrating curcumin on metabolic status in NAFLD patients.. Fifty-eight NAFLD patients participated in a randomized, double-blind, placebo-controlled parallel design of study. The subjects were allocated randomly into two groups, which either received 250 mg phospholipid curcumin or placebo, one capsule per day for a period of 8 weeks. Fasting blood samples were taken from each subject at the start and end of the study period. Subsequently, metabolomics analysis was performed for serum samples using NMR.. Compared with the placebo, supplementing phospholipid curcumin resulted in significant decreases in serum including 3- methyl-2-oxovaleric acid, 3-hydroxyisobutyrate, kynurenine, succinate, citrate, α-ketoglutarate, methylamine, trimethylamine, hippurate, indoxyl sulfate, chenodeoxycholic acid, taurocholic acid, and lithocholic acid. This profile of metabolic biomarkers could distinguish effectively NAFLD subjects who were treated with curcumin and placebo groups, achieving value of 0.99 for an area under receiver operating characteristic curve (AUC).. Characterizing the serum metabolic profile of the patients with NAFLD at the end of the intervention using NMR-based metabolomics method indicated that the targets of curcumin treatment included some amino acids, TCA cycle, bile acids, and gut microbiota.

Topics: Adult; Anti-Inflammatory Agents; Antioxidants; Biomarkers; Curcumin; Dietary Supplements; Double-Blind Method; Female; Humans; Iran; Magnetic Resonance Spectroscopy; Male; Metabolomics; Middle Aged; Non-alcoholic Fatty Liver Disease; Pilot Projects; Placebos

Background The main causes of the progression of non-alcoholic fatty liver disease (NAFLD) are enhanced levels of reactive oxygen species and lipid peroxidation products. Therefore, the usage of antioxidant agents for the prevention and remedy of this disorder was recommended. Curcumin is proposed to treat NAFLD due to its high antioxidative activity. The aim of this study was to examine the effect of curcumin with piperine supplementation on oxidative stress in subjects with NAFLD. Methods In this double-blind, placebo-controlled trial, 55 subjects were randomly divided into two groups (curcumin with piperine and placebo). The participants received administrations of curcumin (500 mg) in combination with piperine (5 mg) and placebo daily for 8 weeks. Oxidative stress was assessed by measuring serum pro-oxidant and antioxidant balance (PAB) assay before and after the intervention. Results The serum PAB values did not significantly change between the treatment group vs. age and gender-matched placebo group after 8 weeks of supplementation. Also, curcumin in combination with piperine did not show a significant decrease (p = 0.06) in PAB levels compared to baseline. Conclusions The present study demonstrated that a dose of curcumin, co-supplied with piperine might be less than a dose in which curcumin can significantly decrease PAB values in these patients.

Topics: Adolescent; Adult; Aged; Alkaloids; Antioxidants; Benzodioxoles; Curcumin; Dietary Supplements; Double-Blind Method; Female; Humans; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Oxidative Stress; Piperidines; Polyunsaturated Alkamides; Young Adult

Non-alcoholic fatty liver disease (NAFLD) is associated with insulin resistance and changes in serum adipocytokine levels. The aim of the current study was to evaluate the effect of phytosomal curcumin on serum adiponectin and leptin levels in patients with NAFLD.. In this randomized double-blind, placebo-controlled trial, 65 eligible patients were randomly allocated into curcumin and placebo recipient groups using a blocked randomized technique. Parameters of weight, height, body mass index (BMI), fasting blood sugar (FBS), lipid profile, aspartate aminotransferase (AST), alanine aminotransferase (ALT), adiponectin, leptin, and the leptin:adiponectin ratio were measured at baseline and eight weeks after intervention.. High-density lipoprotein cholesterol (HDL-C) levels increased significantly in the curcumin group compared to the placebo group (p=0.01). Serum adiponectin levels increased significantly (p<0.001) and serum leptin levels decreased significantly (p<0.001) with a decrease in the leptin: adiponectin ratio in the curcumin group compared to the placebo group after 8 weeks of intervention.. Non-alcoholic fatty liver disease was associated with changes in serum adipokines levels. Phytosomal curcumin effectively improved leptin and adiponectin levels. It is possible that curcumin efficacy will increase with long-term use of higher doses of this substance.

Topics: Adiponectin; Adult; Alanine Transaminase; Anti-Inflammatory Agents, Non-Steroidal; Aspartate Aminotransferases; Blood Glucose; Body Mass Index; Body Weight; Curcumin; Dietary Supplements; Double-Blind Method; Female; Humans; Leptin; Lipids; Male; Middle Aged; Non-alcoholic Fatty Liver Disease

The aim of the present study was to evaluate the effects of curcumin supplementation on inflammatory indices, and hepatic features in patients with non-alcoholic fatty liver disease (NAFLD).. Fifty patients with NAFLD were randomized to receive lifestyle modification advice plus either 1500 mg curcumin or the same amount of placebo for 12 weeks.. Curcumin supplementation was associated with significant decrease in hepatic fibrosis (p < 0.001), and nuclear factor-kappa B activity (p < 0.05) as compared with the baseline. Hepatic steatosis and serum level of liver enzymes, and tumor necrosis-α (TNF-α) significantly reduced in both groups (p < 0.05). None of the changes were significantly different between two groups.. Our results indicated that curcumin supplementation plus lifestyle modification is not superior to lifestyle modification alone in amelioration of inflammation.. IRCT20100524004010N24, this trial was retrospectively registered on May 14, 2018.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Curcumin; Female; Humans; Inflammation; Liver; Liver Function Tests; Male; Middle Aged; NF-kappa B; Non-alcoholic Fatty Liver Disease; Risk Reduction Behavior; Treatment Outcome; Tumor Necrosis Factor-alpha

Different studies have been conducted on the role of curcumin in health since having multiple properties, including antioxidant and anti-inflammatory effects. Due to the lack of studies regarding curcumin effects on obese patients with non-alcoholic fatty liver disease (NAFLD), our protocol was designed to assess nanocurcumin impacts on blood sugar, lipids, inflammatory indices, insulin resistance and liver function, especially by nesfatin.. This trial will be conducted in the Oil Company central hospital of Tehran, Iran with a primary level of care.. 84 obese patients with NAFLD diagnosed using ultrasonography will be employed according to the eligibility criteria‎.. The patients will be randomly divided into two equal groups (nanocurcumin and placebo, two 40 mg capsules per day with meals for 3 months, follow-up monthly). Also, lifestyle changes (low-calorie diet and physical activity) will be advised.. A general questionnaire, 24 hours food recall (at the beginning, middle and end) and short-form International Physical Activity Questionnaire will be completed. Blood pressure, anthropometrics, serum sugar indices (fasting blood sugar and insulin, insulin resistance and sensitivity and glycosylated haemoglobin), lipids (triglyceride, total cholesterol and low-density and high-density lipoprotein-cholesterol, inflammatory profiles (interleukin-6, high-sensitivity C-reactive protein, and tumour necrosis factor-alpha), liver function (alanine and aspartate transaminase) and nesfatin will be measured at the beginning and end of the study.. This trial would be the first experiment to determine nanocurcumin efficacy on certain blood factors among obese patients with NAFLD. Nevertheless, studying the potential consequences of curcumin in various diseases, especially NAFLD, is required for clinical use.. IRCT2016071915536N3; pre-results.

Topics: Adult; Body Mass Index; Curcumin; Dietary Supplements; Exercise; Female; Humans; Insulin; Insulin Resistance; Iran; Lipids; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Obesity; Research Design

Non-alcoholic fatty liver disease (NAFLD) is a common liver disease characterized by excess lipid deposition in the hepatic tissue and subsequent oxidative and inflammatory damage. Curcumin is a dietary polyphenol with lipid-modifying, antioxidant and anti-inflammatory properties. This study aimed to evaluate the efficacy and safety of supplementation with phytosomal curcumin in subjects with NAFLD.Patients diagnosed with NAFLD (grades 1-3 according to liver ultrasonography) were randomly assigned to the curcumin (phytosomal form; 1 000 mg/day in 2 divided doses) (n=50) or placebo group (n=52) for a period of 8 weeks. All patients received dietary and lifestyle advises before the start of trial. Anthropometric measurements, hepatic enzymes, and liver ultrasonography were assessed at baseline and after 8 weeks of follow-up.87 subjects (n=44 and 43 in the curcumin and control group, respectively) completed the trial. Supplementation with curcumin was associated with a reduction in body mass index (-0.99±1.25

Topics: Adult; Alanine Transaminase; Anti-Inflammatory Agents; Antioxidants; Aspartate Aminotransferases; Body Mass Index; Curcumin; Dietary Supplements; Dosage Forms; Female; Humans; Lipid Metabolism; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Polyphenols; Treatment Outcome; Waist Circumference

Nonalcoholic fatty liver disease (NAFLD) is one of the most common hepatic diseases in the general adult population. Dyslipidemia, hyperuricemia, and insulin resistance are common risk factors and accompanying features of NAFLD. Curcumin is a dietary natural product with beneficial metabolic effects relevant to the treatment of NAFLD.. To assess the effects of curcumin on metabolic profile in subjects with NAFLD.. Patients diagnosed with NAFLD (grades 1-3; according to liver sonography) were randomly assigned to curcumin (1000 mg/d in 2 divided doses) (n = 50) or control (n = 52) group for a period of 8 weeks. All patients received dietary and lifestyle advises before the start of trial. Anthropometric measurements, lipid profile, glucose, insulin, glycated hemoglobin, and uric acid concentrations were measured at baseline and after 8 weeks of follow-up.. Eighty-seven subjects (n = 44 and 43 in the curcumin and control group, respectively) completed the trial. Supplementation with curcumin was associated with a reduction in serum levels of total cholesterol (P < 0.001), low-density lipoprotein cholesterol (P < 0.001), triglycerides (P < 0.001), non-high-density lipoprotein cholesterol (P < 0.001), and uric acid (P < 0.001), whereas serum levels of high-density lipoprotein cholesterol and glucose control parameters remained unaltered. Curcumin was safe and well tolerated during this study.. Results of the present trial suggest that curcumin supplementation reduces serum lipids and uric acid concentrations in patients with NAFLD.

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Biomarkers; Cholesterol, HDL; Cholesterol, LDL; Curcumin; Dietary Supplements; Female; Humans; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Uric Acid

Non-alcoholic fatty liver disease (NAFLD) is a global health problem. Although many aspects of NAFLD pathogenesis have been understood, there is a paucity of effective treatments to be used as the second line when lifestyle modification is insufficient. Curcumin, a natural polyphenol from turmeric, has been shown to be effective against development of hepatic steatosis and its progression to steatohepatitis, yet these beneficial effects have not been explored in clinical practice. The aim of this study is to investigate the effects of curcumin on hepatic fat content as well as biochemical and anthropometric features of patients with NAFLD. In this randomized double-blind placebo-controlled trial, patients with ultrasonographic evidence of NAFLD were randomly assigned to receive an amorphous dispersion curcumin formulation (500 mg/day equivalent to 70-mg curcumin) or matched placebo for a period of 8 weeks. Liver fat content (assessed through ultrasonography), glycemic and lipid profile, transaminase levels, and anthropometric indices were evaluated at baseline and at the end of follow-up period. The clinical trial protocol was registered under the Iranian Registry of Clinical Trials ID: IRCT2014110511763N18. Compared with placebo, curcumin was associated with a significant reduction in liver fat content (78.9% improvement in the curcumin vs 27.5% improvement in the placebo group). There were also significant reductions in body mass index and serum levels of total cholesterol, low-density lipoprotein cholesterol, triglycerides, aspartate aminotransferase, alanine aminotransferase, glucose, and glycated hemoglobin compared with the placebo group. Curcumin was safe and well tolerated during the course of trial. Findings of the present proof-of-concept trial suggested improvement of different features of NAFLD after a short-term supplementation with curcumin. Copyright © 2016 John Wiley & Sons, Ltd.

Topics: Curcumin; Double-Blind Method; Female; Humans; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Treatment Outcome

Non-alcoholic fatty liver disease (NAFLD) is an emerging chronic liver disease worldwide. Curcumin and andrographolide are famous for improving hepatic functions, being able to reverse oxidative stress and release pro-inflammatory cytokines, and they are implicated in hepatic stellate cell activation and in liver fibrosis development. Thus, we tested curcumin and andrographolide separately and in combination to determine their effect on triglyceride accumulation and ROS production, identifying the differential expression of genes involved in fatty liver and oxidative stress development. In vitro steatosis was induced in HepG2 cells and the protective effect of curcumin, andrographolide, and their combination was observed evaluating cell viability, lipid and triglyceride content, ROS levels, and microarray differential gene expression. Curcumin, andrographolide, and their association were effective in reducing steatosis, triglyceride content, and ROS stress, downregulating the genes involved in lipid accumulation. Moreover, the treatments were able to protect the cytotoxic effect of steatosis, promoting the expression of survival and anti-inflammatory genes. The present study showed that the association of curcumin and andrographolide could be used as a therapeutic approach to counter high lipid content and ROS levels in steatosis liver, avoiding the possible hepatotoxic effect of curcumin. Furthermore, this study improved our understanding of the antisteatosis and hepatoprotective properties of a curcumin and andrographolide combination.

Topics: Curcumin; Hep G2 Cells; Humans; Liver; Non-alcoholic Fatty Liver Disease; Reactive Oxygen Species; Triglycerides

Mesenchymal stem cells (MSCs) derived exosomes (MSCs/Exo) is considered a new strategy in cell free regenerative therapy. Curcumin preconditioning of MSCs reported to improve the anti- inflammatory and immunomodulatory properties of MSCs. We investigated the efficacy of exosome (Exo) obtained from curcumin-preconditioned MSCs (MSCs/Exo-Cur) vs. MSC/Exo without curcumin to ameliorate and prevent recurrence of non-alcoholic fatty liver (NASH) disease.. In-vivo, methionine/choline-deficient diet (MCD) induced mice non-alcoholic fatty liver disease (NASH) were injected with MSCs/Exo without curcumin or MSCs/Exo-Cur with curcumin. We found that mice treated with MSCs/Exo-Cur had significantly ameliorated steatosis, inflammation, as evaluated by the reduced fibrosis in histopathological examination, decreased the serum level of liver enzymes (p < 0.001), liver triglycerides (TG) (p < 0.001) and cholesterol (Ch) (p < 0.001) and increased the lipid peroxidation (p < 0.001) compared to MSCs/Exo-treated mice. These effects remained for 3 months after treatment in MSCs/Exo-Cur-treated mice while features of NASH returned in MSCs/Exo-treated group. In vitro, HepG2 cells were cultured with palmitic acid (PA) and treated with MSCs/Exo or MSCs/Exo-Cur: the MSCs/Exo-Cur exposure reversed the lipotoxic effect from 4.5 to 1.7 fold vs 4.0 fold in MSCs/Exo and oxidative stress in PA-treated HepG2 cells (p < 0.001). We found that MSCs/Exo-Cur regulated the key markers of inflammatory and oxidative stress, genes responsible for fibrogenesis of the liver, key genes of lipid synthesis and transport. Interestingly, MSCs/Exo-Cur significantly down regulated the ASK-JNK-BAX genes involved in mitochondrial stress and apoptosis compared to MSCs/Exo (p < 0.001).. Our study indicated that exosomes derived from curcumin preconditioned MSCs were able to ameliorate and protect against recurrence of NASH and regulated inflammatory, oxidative stress and mitochondrial-dependent apoptosis ASK-JNK-BAX genes.

Topics: Animals; bcl-2-Associated X Protein; Curcumin; Exosomes; Fatty Liver, Alcoholic; Inflammation; Mesenchymal Stem Cells; Mice; Non-alcoholic Fatty Liver Disease; Oxidative Stress

Curcumin 2005-8 (Cur5-8), a derivative of curcumin, improves fatty liver disease via AMP-activated protein kinase activation and autophagy regulation. EW-7197 (vactosertib) is a small molecule inhibitor of transforming growth factor β (TGF-β) receptor I and may scavenge reactive oxygen species and ameliorate fibrosis through the SMAD2/3 canonical pathway. This study aimed to determine whether co-administering these two drugs having different mechanisms is beneficial.. Hepatocellular fibrosis was induced in mouse hepatocytes (alpha mouse liver 12 [AML12]) and human hepatic stellate cells (LX-2) using TGF-β (2 ng/mL). The cells were then treated with Cur5-8 (1 μM), EW-7197 (0.5 μM), or both. In animal experiments were also conducted during which, methionine-choline deficient diet, Cur5-8 (100 mg/kg), and EW-7197 (20 mg/kg) were administered orally to 8-week-old C57BL/6J mice for 6 weeks.. TGF-β-induced cell morphological changes were improved by EW-7197, and lipid accumulation was restored on the administration of EW-7197 in combination with Cur5-8. In a nonalcoholic steatohepatitis (NASH)-induced mouse model, 6 weeks of EW-7197 and Cur5-8 co-administration alleviated liver fibrosis and improved the nonalcoholic fatty liver disease (NAFLD) activity score.. Co-administering Cur5-8 and EW-7197 to NASH-induced mice and fibrotic hepatocytes reduced liver fibrosis and steatohepatitis while maintaining the advantages of both drugs. This is the first study to show the effect of the drug combination against NASH and NAFLD. Similar effects in other animal models will confirm its potential as a new therapeutic agent.

Topics: Animals; Curcumin; Fibrosis; Humans; Liver Cirrhosis; Mice; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Transforming Growth Factor beta; Transforming Growth Factors

Hepatic endothelial function is central to the development of nonalcoholic steatohepatitis (NASH). Curcumin (Cur) is reportedly hepatoprotective, however, it remains unknown whether Cur improves hepatic endothelial function in NASH. Additionally, the poor bioavailability of Cur renders it difficult to elucidate its hepatoprotective effect, hence, its biotransformation should be considered. Herein, we investigated the effects and mechanisms of Cur and its bioconversion on hepatic endothelial function against high-fat diet-induced NASH in rats. The results revealed that Cur improved hepatic lipid accumulation, inflammation, and endothelial dysfunction by inhibiting NF-κB and PI3K/Akt/HIF-1α pathways, however, these effects were weakened via antibiotic addition, which was closely related to reduced tetrahydrocurcumin (THC) produce in the liver and intestinal content. Moreover, THC exerted a better effect than Cur on restoring liver sinusoidal endothelial cells function to attenuate steatosis and injury in L02 cells. Thus, these findings indicate that the effect of Cur on NASH is closely related to hepatic endothelial function improvement with intestinal microbial biotransformation.

Topics: Animals; Biotransformation; Curcumin; Diet, High-Fat; Endothelial Cells; Liver; Mice; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Phosphatidylinositol 3-Kinases; Rats

Metabolic associated fatty liver disease (MAFLD) is the most common chronic liver disease that has no viable treatment. Curcumin (Cur) and resveratrol (Res) are two natural products that have been studied for their potential to ameliorate MAFLD. However, while these compounds have been investigated individually, their combined use and the potential for a synergistic or augmented effect remain unexplored. This study aims to investigate the effect of curcumin (Cur) and resveratrol (Res) as a potential combination therapy on MAFLD. Cur, Res and Cur+Res were tested in palmitic acid (PA)-induced-HepG2 cells. MAFLD model was established using Goto-Kakizaki rats. The animals were treated with vehicle control (model group), Cur (150 mg/kg), Res (150 mg/kg), Cur+Res (150 mg/kg, 8:2, w/w), or metformin (Met, positive control, 400 mg/kg/day) via oral gavage for 4 weeks. Wistar rats were used as the control group. Network pharmacology was conducted to elucidate the molecular actions of Cur and Res, followed by q-PCR and immunoblotting in vivo. Cur+Res exhibited synergistic effects in reducing triglyceride, total cholesterol and lipid accumulation in PA-induced HepG2 cells. The combination also markedly attenuated hepatic steatosis in the MAFLD rats. Network pharmacology illustrated that the interaction of Cur and Res was associated with the modulation of multiple molecular targets associated with the PI3K/AKT/mTOR and HIF-1 signaling pathways. Experimental results confirmed that Cur+Res nomalised the gene targets and protein expressions in the PI3K/AKT/mTOR and HIF-1 signaling pathways, including PI3K, mTOR, STAT-3, HIF-1α, and VEGF. The present study demonstrated an advanced effect of Cur and Res in combination to attenuate MAFLD, and the mechanism is at least partly associated with the modulation of the PI3K/AKT/mTOR and HIF-1 signaling pathways.

Topics: Animals; Curcumin; Non-alcoholic Fatty Liver Disease; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Rats; Rats, Wistar; Resveratrol; TOR Serine-Threonine Kinases; Vascular Endothelial Growth Factor A

Erhuang Quzhi Granules (EQG), the Chinese herbal compound, has demonstrated significant clinical efficacy in treating non-alcoholic fatty liver disease (NAFLD). The mechanism of this treatment has been shown to involve the nuclear factor kappa B (NF-κB)/nod-like receptor thermal protein domain associated protein 3 (NLRP3) pathway. However, research on the material basis of EQG against NAFLD is still in its primary stages. Following these considerations, this study predicted and screened the active ingredients of EQG using the absorption, distribution, metabolism, and excretion (ADME) property evaluation tool and molecular docking. Then the levels of these active ingredients in EQG were measured using ultra-high-performance liquid chromatography (UHPLC). The efficacy of the active ingredients and their mechanisms were validated through both in vivo and in vitro experiments. The results indicate that the collected 12 components have favorable metabolic stability, are safe, and have drug-like properties. Aloe-emodin (AE), rhein (RH), curcumin (CUR), emodin (EM), and chrysophanol (CP) showed better binding affinity with TNF-α and Caspase-1 proteins. UHPLC analysis revealed that EQG contains AE, RH, CUR, EM, and CP. Cellular experiments proved that all these five ingredients reduce the accumulation of lipids and reactive oxygen species. In animal models of NAFLD, AE, and RH significantly improved the pathological symptoms of steatosis and fibrosis and reduced the levels of pro-inflammatory factors via the NF-κB/NLRP3 pathway. The results reveal the active ingredients of EQG for treating NAFLD based on the NF-κB/NLRP3 pathway and lay the foundation for the clinical promotion of EQG.

Topics: Animals; Curcumin; Emodin; Inflammasomes; Molecular Docking Simulation; Molecular Structure; NF-kappa B; NLR Family, Pyrin Domain-Containing 3 Protein; Non-alcoholic Fatty Liver Disease

In this study, the fraction extracted from turmeric powder with 50% ethanol and fractionated with n-hexane were administered to diet-induced NASH model rats. NASH model was prepared with SD rats by feeding an originally designed choline-deficient, high-fat, high-fructose (HFF-CD) diet for 10 weeks. To the HFF-CD diet, hexane fraction and 50% ethanol fraction after hexane fractionation were added at 100 mg/kg body weight. 10 weeks later, blood samples and liver were collected for the following parameters: lipid weights, serum ALT, AST, TG, liver TG, TBARS levels, lipid metabolism-related gene expression and histopathological examination of the liver. As the results, the hexane fraction and 50% ethanol fraction showed a decrease in lipid weight, a decrease in hepatic TG, and activation of PPAR-α in the lipid metabolism-related gene test. These results suggest that the hexane fraction of turmeric has an inhibitory effect on fat accumulation in the liver by promoting lipid metabolism in NASH model rats.

Topics: Animals; Curcuma; Diet, High-Fat; Ethanol; Hexanes; Lipid Metabolism; Lipids; Liver; Liver Cirrhosis; Non-alcoholic Fatty Liver Disease; Rats; Rats, Sprague-Dawley

Topics: Animals; Animals, Newborn; Antioxidants; Curcumin; Diet, High-Fat; Disease Models, Animal; Feeding Behavior; Male; Mitochondria; Non-alcoholic Fatty Liver Disease; Phytotherapy; Rats; Rats, Sprague-Dawley; Sirtuin 3

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a prevalent metabolic disorder. Defects in function/expression of genes/proteins are critical in initiation/progression of NAFLD. Natural products may modulate these genes/proteins. Curcumin improves steatosis, inflammation, and fibrosis progression. Here, bioinformatic tools, gene−drug and gene-disease databases were utilized to explore targets, interactions, and pathways through which curcumin could impact NAFLD. METHODS: Significant curcumin−protein interaction was identified (high-confidence:0.7) in the STITCH database. Identified proteins were investigated to determine association with NAFLD. gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were analyzed for significantly involved targets (p < 0.01). Specificity of obtained targets with NAFLD was estimated and investigated in Tissue/Cells−gene associations (PanglaoDB Augmented 2021, Mouse Gene Atlas) and Disease−gene association-based EnrichR algorithms (Jensen DISEASES, DisGeNET). RESULTS: Two collections were constructed: 227 protein−curcumin interactions and 95 NAFLD-associated genes. By Venn diagram, 14 significant targets were identified, and their biological pathways evaluated. Based on gene ontology, most targets involved stress and lipid metabolism. KEGG revealed chemical carcinogenesis, the AGE-RAGE signaling pathway in diabetic complications and NAFLD as the most common significant pathways. Specificity to diseases database (EnrichR algorithm) revealed specificity for steatosis/steatohepatitis. CONCLUSION: Curcumin may improve, or inhibit, progression of NAFLD through activation/inhibition of NAFLD-related genes.

Topics: Animals; Computational Biology; Curcumin; Gene Ontology; Mice; Non-alcoholic Fatty Liver Disease; Signal Transduction

We investigated the effect of an 11β-HSD1 inhibitor (H8) on hepatic steatosis and its mechanism of action. Although H8, a curcumin derivative, has been shown to alleviate insulin resistance, its effect on non-alcoholic fatty liver disease (NAFLD) remains unknown. Rats were fed a high-fat diet (HFD) for 8 weeks, intraperitoneally injected with streptozotocin (STZ) to induce NAFLD, and, then, treated with H8 (3 or 6 mg/kg/day) or curcumin (6 mg/kg/day) for 4 weeks, to evaluate the effects of H8 on NAFLD. H8 significantly alleviated HFD+STZ-induced lipid accumulation, fibrosis, and inflammation as well as improved liver function. Moreover, 11β-HSD1 overexpression was established by transfecting animals and HepG2 cells with lentivirus, carrying the 11β-HSD1 gene, to confirm that H8 improved NAFLD, by reducing 11β-HSD1. An AMP-activated protein kinase (AMPK) inhibitor (Compound C, 10 μM for 2 h) was used to confirm that H8 increased AMPK, by inhibiting 11β-HSD1, thereby restoring lipid metabolic homeostasis. A silencing-related enzyme 1 (SIRT1) inhibitor (EX572, 10 μM for 4 h) and a SIRT1 activator (SRT1720, 1 μM for 4 h) were used to confirm that H8 exerted anti-inflammatory effects, by elevating SIRT1 expression. Our findings demonstrate that H8 alleviates hepatic steatosis, by inhibiting 11β-HSD1, which activates the AMPK/SIRT1 signaling pathway.

Topics: 11-beta-Hydroxysteroid Dehydrogenase Type 1; AMP-Activated Protein Kinases; Animals; Curcumin; Enzyme Inhibitors; Lipids; Liver; Non-alcoholic Fatty Liver Disease; Rats; Signal Transduction; Sirtuin 1

Chronic exposure to low-dose bisphenol A (BPA) has become a global problem of public health. Our previous work showed that low-dose BPA exposure caused gut microbial dysbiosis and hepatic steatosis. Curcumin, a polyphenol extracted from turmeric, has an inhibitory effect on liver lipid accumulation, whether curcumin can alleviate BPA-induced hepatic steatosis through improving intestinal flora and modulating gut-liver axis remains to be elucidated. Male CD-1 mice were fed with BPA-contaminated diet supplemented with or not with curcumin for 24 weeks. Curcumin supplementation markedly ameliorated liver fat accumulation and hepatic steatosis induced by BPA. Gut microbiota analysis via 16S rRNA sequencing revealed that the relative abundance of Proteobacteria and Firmicutes/Bacteroidetes ratio were increased in BPA-fed mice, and this alteration was reversed by curcumin treatment. Akkermansia, which was recognized as a potential probiotic, was significantly reduced after BPA exposure and was restored to the control level with curcumin addition. Furthermore, curcumin supplementation reversed the down-regulation of intestinal tight junction protein expressions (zona occludens-1 and occludin), improved increased gut permeability, reduced serum lipopolysaccharide level and suppressed the activation of hepatic toll-like receptor 4 / nuclear factor-κB (TLR4/NF-κB) pathway induced by BPA. These results indicated that the protective effect of curcumin against hepatic steatosis induced by BPA and further revealed that its mechanism might be its prebiotic effect on maintaining intestinal flora homeostasis and improving intestinal barrier function, consequently reducing serum lipopolysaccharide-triggered inflammatory response in the liver. Our work provides evidence for curcumin as a potential nutritional therapy for BPA-mediated hepatic steatosis.

Topics: Animals; Benzhydryl Compounds; Curcumin; Diet, High-Fat; Dysbiosis; Gastrointestinal Microbiome; Lipopolysaccharides; Liver; Male; Mice; Mice, Inbred C57BL; NF-kappa B; Non-alcoholic Fatty Liver Disease; Occludin; Phenols; Polyphenols; RNA, Ribosomal, 16S; Toll-Like Receptor 4

The relationship between the incidence of cardiovascular abnormalities and non-alcoholic fatty liver disease (NAFLD) has long been postulated. Curcumin (CUR) is a potential anti-atherosclerotic agent but its poor water solubility hinders its pharmacological use. Therefore, the present study aimed to investigate the effect of formulation of CUR nanoemulsion prepared using the spontaneous emulsification technique on high fat high fructose (HFHF)-induced hepatic and cardiac complications. Fifty Wistar rats were divided into five groups. CUR nanoemulsion at doses of 5 and 10 mg/kg and conventional powdered CUR at a dose of 50 mg/kg were orally administered daily to rats for two weeks, and compared with normal control and HFHF control. Results revealed that the high dose level of CUR nanoemulsion was superior to conventional CUR in ameliorating the HFHF-induced insulin resistance status and hyperlipidemia, with beneficial impact on rats' recorded electrocardiogram (ECG), serum aspartate aminotransferase (ALT) and alanine aminotransferase (AST) levels, leptin, adiponectin, creatine phosphokinase, lactate dehydrogenase and cardiac troponin-I. In addition, hepatic and cardiac oxidative and nitrosative stresses, oxidative DNA damage and disrupted cellular energy statuses were counteracted. Results were also confirmed by histopathological examination. PRACTICAL APPLICATIONS: The use of curcumin nanoemulsion could be beneficial in combating hepatic and cardiac complications resulting from HFHF diets.

Topics: Animals; Curcumin; Fructose; Non-alcoholic Fatty Liver Disease; Rats; Rats, Wistar

Comorbidity of Opisthorchis viverrini (OV) infection and nonalcoholic fatty-liver disease (NAFLD) enhances NAFLD progression to nonalcoholic steatohepatitis (NASH) by promoting severe liver inflammation and fibrosis. Here, we investigated the effect of supplementation with curcumin-loaded nanocomplexes (CNCs) on the severity of NASH in hamsters.. Hamsters were placed in experimental groups as follows: fed standard chow diet (normal control, NC); fed only high-fat and high-fructose (HFF) diet; O. viverrini-infected and fed HFF diet (HFFOV); group fed with blank nanocomplexes (HFFOV+BNCs); groups fed different doses of CNCs (25, 50 and 100 mg/kg body weight: HFFOV+CNCs25; HFFOV+CNCs50; HFFOV+CNCs100, respectively) and a group given native curcumin (HFFOV+CUR). All treatment were for three months.. The HFF group revealed NAFLD as evidenced by hepatic fat accumulation, ballooning, mild inflammation and little or no fibrosis. These changes were more obvious in the HFFOV group, indicating development of NASH. In contrast, in the HFFOV+CNCs50 group, histopathological features indicated that hepatic fat accumulation, cell ballooning, cell inflammation and fibrosis were lower than in other treatment groups. Relevantly, the expression of lipid-uptake genes, including fatty-acid uptake (cluster of differentiation 36), was reduced, which was associated with the lowering of alanine aminotransferase, total cholesterol and triglyceride (TG) levels. Reduced expression of an inflammation marker (high-mobility group box protein 1) and a fibrosis marker (alpha smooth-muscle actin) were also observed in the HFFOV+CNCs50 group.. CNCs treatment attenuates the severity of NASH by decreasing hepatic steatosis, inflammation, and fibrosis as well as TG synthesis. CNCs mitigate the severity of NASH in this preclinical study, which indicates promise for future use in patients.

Topics: Actins; Alanine Transaminase; Animals; Cholesterol; Cricetinae; Curcumin; Diet, High-Fat; Disease Models, Animal; Fructose; Humans; Inflammation; Lipids; Liver; Non-alcoholic Fatty Liver Disease; Opisthorchiasis; Opisthorchis; Triglycerides

Non-alcoholic steatohepatitis (NASH) is a global medical problem and macrophages' activation is closely related to the pathogenesis of NASH. Curcumin is a polyphenol from turmeric with significant anti-inflammatory activity.. The objective of present study was to observe the effect of curcumin on macrophages' activation and secretion of pro-inflammatory cytokines in NASH.. Hematoxylin and eosin and TUNEL staining were used to observe the hepatic function. RT-PCR was conducted to evaluate the hepatic mRNA expression of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). Flow cytometry was adopted to detect the M1 polarization of macrophages. The RAW264.7 macrophage was pretreated with different doses of curcumin, and then lipopolysaccharide (LPS) and interferon-γ (IFN-γ) were given to activate the M1 macrophage. The activation ratio of M1 macrophage was observed by flow cytometry, and IL-1β and TNF-α expression was detected by RT-PCR and ELISA.. After treatment with curcumin, the activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), the mRNA expression of TNF-α and IL-1β, and M1 polarization of macrophages were significantly decreased. Hematoxylin and eosin and TUNEL staining showed that inflammation and apoptosis in the liver were improved. What is more, curcumin can effectively inhibit M1 macrophage activation induced by lipopolysaccharide and IFN-γ and reduce the secretion of IL-1β and TNF-α.. Curcumin can effectively improve NASH and reduce hepatic cell necrosis by inhibiting the M1 polarization of macrophages and the secretion of inflammatory factors.

Topics: Animals; Anti-Inflammatory Agents; Cell Polarity; Curcumin; Cytokines; Inflammation Mediators; Macrophage Activation; Macrophages; Male; Mice; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; RAW 264.7 Cells

Modern dietary habits have been associated with Nonalcoholic Steatohepatitis (NASH). Curcumin is a natural herbal found to suppress cellular oxidative states and could be beneficial in NASH. This study investigates the effect of curcumin in an animal model of NASH.. Fifty rats were allocated into five groups. Control, High Fat Diet (HFD), curcumin prophylactic (CP) and therapeutic (CT) groups. HFD regimen was given for 16 weeks. Curcumin was given along with HFD (prophylactic) or after establishment of the model for two weeks (therapeutic). Livers and blood samples were harvested for histological, biochemical, and molecular studies.. Livers from HFD groups showed vascular, inflammatory, cellular degenerative and fibrotic changes. The hepatic damage was reflected by the increased serum liver enzymes. HFD groups showed excessive fibrotic change. Interestingly, curcumin administration as prophylactic or therapeutic significantly preserved and/or restored liver structure. This was evidenced by the normalization of the liver enzymes, preservation and/or reversibility of cellular changes and the decrease of the stage of fibrosis. Nuclear factor E2-related factor 2 gene (Nrf2) expression showed no changes in the HFD groups, however it showed upregulation in curcumin treated groups. Thus, the protective and therapeutic effect of curcumin could be induced through upregulation of the Nrf2 gene. Curcumin has a beneficial prophylactic and therapeutic effect that could hinder the development and/or treat NASH in susceptible livers.. Curcumin has a beneficial prophylactic and therapeutic effect that could hinder the development and/or treat NASH in susceptible livers.

Topics: Animals; Body Weight; Collagen; Curcumin; Diet, High-Fat; Liver; Male; Microscopy, Electron; NF-E2-Related Factor 2; Non-alcoholic Fatty Liver Disease; Rats; Rats, Sprague-Dawley

Upregulated de novo lipogenesis (DNL) plays a pivotal role in the progress of the nonalcoholic fatty liver disease (NAFLD). Cytoplasmic citrate flux, mediated by plasma membrane citrate transporter (SLC13A5), mitochondrial citrate carrier (SLC25A1), and ATP-dependent citrate lyase (ACLY), determines the central carbon source for acetyl-CoA required in DNL. Curcumin, a widely accepted dietary polyphenol, can attenuate lipid accumulation in NAFLD. Here, we first investigated the lipid-lowering effect of curcumin against NAFLD in oleic and palmitic acid (OPA)-induced primary mouse hepatocytes and high-fat plus high-fructose diet (HFHFD)-induced mice. Curcumin profoundly attenuated OPA- or HFHFD-induced hyperlipidemia and aberrant hepatic lipid deposition via modulating the expression and function of SLC13A5 and ACLY. The possible mechanism of curcumin on the citrate pathway was investigated using HepG2 cells, HEK293T cells transfected with human SLC13A5, and recombinant human ACLY. In OPA-stimulated HepG2 cells, curcumin rectified the dysregulated expression of SLC13A5/ACLY possibly via the AMPK-mTOR signaling pathway. Besides, curcumin also functionally inhibited both citrate transport and metabolism mediated by SLC13A5 and ACLY, respectively. These findings confirm that curcumin improves the lipid accumulation in the liver by blocking citrate disposition and hence may be used to prevent NAFLD.

Topics: Animals; ATP Citrate (pro-S)-Lyase; Citric Acid; Curcumin; Dicarboxylic Acid Transporters; HEK293 Cells; Humans; Lipid Metabolism; Mice; Mitochondrial Proteins; Non-alcoholic Fatty Liver Disease; Organic Anion Transporters; Symporters

The combination of berberine (BER) and curcumin (CUR) has been verified with ameliorative effects on non-alcohol fatty liver disease (NAFLD). However, discrepant bioavailability and biodistribution of BER and CUR remained an obstacle to achieve synergistic effects. Multilayer nanovesicles have great potential for the protection and oral delivery of drug combinations. Therein lies bile salts inserted liposomes, named as bilosomes, that possesses long residence time in the gastrointestinal tract (GIT) and permeability across the small intestine. Diethylaminoethyl dextran (DEAE-DEX) is generally used as an outside layer on the nanovesicles to increase the mucinous stability and promote oral absorption. Herein, we developed a DEAE-DEX-coated bilosome with BER and CUR encapsulated (DEAE-DEX@LSDBC) for the treatment of NAFLD.. DEAE-DEX@LSDBC with 150 nm size exhibited enhanced permeation across mucus and Caco-2 monolayer. In vivo pharmacokinetics study demonstrated that DEAE-DEX@LSDBC profoundly prolonged the circulation time and improved the oral absorption of both BER and CUR. Intriguingly, synchronized biodistribution of BER and CUR and highest biodistribution at liver was achieved by DEAE-DEX@LSDBC, which contributed to the optimal ameliorative effects on NAFLD. It was further verified to be mainly mediated by anti-oxidation and anti-inflammation related pathways CONCLUSION: DEAE-DEX coated bilosome displayed promoted oral absorption, prolonged circulation and synchronized biodistribution of BER and CUR, leading to improved ameliorative effects on NAFLD in mice, which provided a promising strategy for oral administration of drug combinations.

Topics: Administration, Oral; Animals; Berberine; Biological Availability; Caco-2 Cells; Curcumin; Dextrans; Drug Carriers; Drug Combinations; Humans; Liposomes; Liver; Male; Mice; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Tissue Distribution

Nonalcoholic fatty liver disease (NAFLD) occurs when excess fat storage in the liver and it is strongly linked with metabolic syndrome including obesity, insulin resistance, dyslipidemia and hypertension. Curcumin5-8 (CUR5-8) is a synthetic derivative of naturally active curcumin (CUR) that has anti-oxidative and anti-inflammatory properties. In the present study, we investigated the effects of CUR5-8, a novel CUR analog, on hepatic steatosis in mice with high-fat diet (HFD)-induced obesity.. Based on their diets for 13 weeks, the mice were categorized into the following six groups: regular diet (RD, n = 10), RD with CUR (RD + CUR, 100 mg/kg/day, n = 10), RD with CUR5-8 (RD + CUR5-8, 100 mg/kg/day, n = 10), high-fat diet-induced obese mice (HFD, n = 10), HFD with CUR (HFD + CUR, 100 mg/kg/day, n = 10), and HFD with CUR5-8 (HFD + CUR5-8, 100 mg/kg/day, n = 10) for 13 weeks. Hematoxylin and eosin (H&E) staining of the sections revealed hepatic steatosis.. CUR5-8 administration prevented increase in body and liver weights in mice with HFD-induced obesity. Compared to the HFD group, insulin resistance was significantly improved in the HFD + CUR5-8 group. Serum alanine aminotransferase level, which is an indicator of liver damage, was also decreased after CUR5-8 administration. H&E staining revealed that CUR5-8 treatment decreased hepatic steatosis in mice with HFD-induced obesity. Interestingly, CUR5-8, and not CUR, decreased the elevated liver triglyceride level induced by the HFD.. These findings suggest that CUR5-8 ameliorates insulin resistance and hepatic steatosis in mice with HFD-induced obesity.

Topics: Animals; Autophagy; Cells, Cultured; Curcumin; Cytoprotection; Diet, High-Fat; Lipid Metabolism; Liver; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Non-alcoholic Fatty Liver Disease; Obesity; Weight Gain

The prevalence of nonalcoholic fatty liver is increasing due to modern lifestyle. Germinated and dehulled Macrotyloma uniflorum and Vigna radiate were shown to have enhanced nutrients. Curcuma longa and Trigonella foenum graecum were proven hepatoprotective.The supplementation of the nutrient herbal mixture to the MCD diet-induced steatosis shows reduced hepatic fat accumulation and lipid profile, and liver injury markers in serum also reserved in normal. Increased serum albumin in the treatment group indicates that the liver function is enhanced than that of steatosis. The supplementation of the herbal mixture has preserved the hepatic antioxidant. Zymographic analysis of matrix metalloproteinase, western blot determination of α-SMA, and histological evolution (H&E, Sirius red) depicted reduced fibrosis and reveled management of hepatic stellate cells in quiescent form. The present study concludes that the herbal mixture has reduced hepatocyte fat accumulation in steatotic animals, and curtailed the oxidative stress, further it prevents the progression of steatohepatitis. PRACTICAL APPLICATIONS: Fatty liver diseases can be treated by modulating the diet composition such as consuming food rich in the nutrient herbal mixture. In this study, the nutrient mixture was made with dynamic food processing techniques such as germination, dehulling, and milling to augment the nutritional contents. Besides, Macrotyloma uniflorum, Vigna radiate, Curcuma longa, and Trigonella foenum graecum were used to improve the medicinal value and antioxidant. This formulation could target the various stages of NAFLD. This study revealed that the nutrient herbal mixture reduces the steatosis of the liver and curtailed the progression of steatohepatitis from hepatic steatosis. Since the edible foodstuff was used to make the nutrient mixture, it has excellent clinical application.

Topics: Animals; Curcuma; Non-alcoholic Fatty Liver Disease; Nutrients; Rats; Trigonella; Vigna

24 cytokines/chemokines were assayed. IL-2 (+ 80%) and IL-13 (+ 83%) were greater with curcumin supplementation in the prevention arm. IL-2 (+ 192%), IL-13 (+ 87%), IL-17A (+ 81%) and fractalkine (+ 121%) were higher while RANTES was lower (- 22%) with curcumin supplementation in the treatment arm (p < 0.05 for all). RANTES concentrations also correlated significantly with hepatic pathology scores of inflammation (r = 0.417, p = 0.008). Select serum cytokines/chemokines were affected with curcumin supplementation in this female rat model of NASH. Moreover, curcumin's effect(s) on RANTES and its association with liver disease pathogenesis and progression may warrant further investigation.

Topics: Animals; Anti-Inflammatory Agents; Carbon Tetrachloride; Chemokine CCL5; Chemokine CX3CL1; Curcumin; Diet, Western; Dietary Supplements; Disease Models, Animal; Drug Administration Schedule; Female; Gene Expression Regulation; Humans; Interleukin-13; Interleukin-17; Interleukin-2; Liver; Non-alcoholic Fatty Liver Disease; Rats; Rats, Wistar; Treatment Outcome

The cause of progression to non-alcoholic fatty liver disease (NAFLD) is not fully understood. In the present study, we aimed to investigate how curcumin, a natural phytopolyphenol pigment, ameliorates NAFLD. Initially, we demonstrated that curcumin dramatically suppresses fat accumulation and hepatic injury induced in methionine and choline-deficient (MCD) diet mice. The severity of hepatic inflammation was alleviated by curcumin treatment. To identify the proteins involved in the pathogenesis of NAFLD, we also characterized the hepatic proteome in MCD diet mice. As a result of two-dimensional proteomic analysis, it was confirmed that thirteen proteins including antioxidant protein were differentially expressed in hepatic steatosis. However, the difference in expression was markedly improved by curcumin treatment. Interestingly, eight of the identified proteins are known to undergo

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Cell Line; Choline Deficiency; Curcumin; Disease Models, Animal; Endoplasmic Reticulum Stress; Glycosylation; Hexosamines; Inflammation Mediators; Liver; Male; Methionine; Mice, Inbred C57BL; N-Acetylglucosaminyltransferases; NF-kappa B; Non-alcoholic Fatty Liver Disease; Signal Transduction; Sirtuin 1; Superoxide Dismutase-1

Curcumin is a safe and dietary phytochemical that can improve different pathophysiologic features of non-alcoholic fatty liver disease (NAFLD). Here, we investigated the efficacy of phospholipidated curcumin supplementation in NAFLD patients. In this single-arm study, 36 patients were recruited. Each patient received three capsules a day (each containing 500 mg of phospholipidated curcumin [overall content of curcuminoids per capsule: 100 mg]) for a period of 8 weeks. The results indicated that phospholipidated curcumin supplementation reduced NAFLD severity and ameliorated ultrasonographic and biochemical measures (including liver transaminases and lipid profile) associated with disease progression.

Topics: Adult; Blood Pressure; Curcumin; Female; Humans; Liver; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Phospholipids; Ultrasonography, Doppler

Both inflammation and fibrosis are essential in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Taking inflammatory cytokines and signaling pathways as vital mediators, the inhibition of inflammation response may be an effective approach for treating NAFLD. a19, a resveratrol-curcumin hybrid, has been confirmed to exhibit a good anti-inflammatory activity by preventing LPS-induced inflammatory response in macrophages. The study aims to evaluate the protective effect of a19 on high fat diet (HFD)-induced NAFLD. In the present study, compound a19 significantly inhibited the HFD-induced lipid accumulation, liver injury, liver inflammation and fibrosis in mouse model. In vitro, a19 obviously suppressed the expression of PA-induced inflammatory cytokines and fibrosis markers mRNA. Meanwhile, the anti-inflammatory effect of a19 was found to be associated with the inhibition of ERK signal pathway. These results indicated that a19 can be potentially used as a protective agent for NAFLD.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Curcumin; Diet, High-Fat; Dose-Response Relationship, Drug; Drug Combinations; Hep G2 Cells; Humans; Male; Mice; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Resveratrol

Topics: Administration, Oral; Anti-Inflammatory Agents, Non-Steroidal; Curcumin; Humans; Non-alcoholic Fatty Liver Disease

Topics: Age Factors; AMP-Activated Protein Kinases; Animals; Animals, Newborn; Anti-Inflammatory Agents; Curcumin; Cytoprotection; Dietary Sugars; Drug Administration Schedule; Female; Fructose; Lipid Metabolism; Liver; Liver Cirrhosis, Experimental; Male; Non-alcoholic Fatty Liver Disease; Rats, Sprague-Dawley; Sex Factors; Time Factors; Tumor Necrosis Factor-alpha

Fatty liver disease is commonly associated with inflammation, oxidative stress and apoptosis of hepatocytes. This study was designed to investigate the combinational therapeutic effects of curcumin (CMN) and Ursodeoxycholic acid (UDCA) on non-alcoholic fatty liver disease (NAFLD). Male Wistar rats were divided into 8 groups: NAFLD-induced rats, NAFLD-induced rats + CMN, NAFLD-induced rats + UDCA, and NAFLD-induced rats that received CMN + UDCA. CMN (200 mg/kg) and UDCA (80 mg/kg) was administered orally for 14 and 28 consecutive days. Biochemical and histopathological analysis were conducted in all the groups. It was seen that co-administration of CMN and UDCA significantly reduced fatty degeneration, cellular necrosis, edema, and immune cell infiltration compared to non-treated NAFLD-induced rats. Whereas, combinational therapy caused a significant decrease in levels of SGOT and SGPT enzymes and expression of p53, caspase III, iNOS and bcl-2 mRNA and proteins, in variant with the treatment of CMN and UDCA, respectively. Co-administration of CMN and UDCA was also associated with the restoration of the levels of serum TG and HDL-C however, had no effect on LDL-C. It also resulted in an in TAC, GSH- PX, and SOD and decrease in MDA level. Our study concludes that combinational therapy of CMN and UDCA is effective for the treatment of NAFLD, as compared to their solo treatment.

Topics: Animals; Antioxidants; Biomarkers; Curcumin; Diet, High-Fat; Disease Models, Animal; Drug Therapy, Combination; Liver; Male; Non-alcoholic Fatty Liver Disease; Rats, Wistar; Ursodeoxycholic Acid

Topics: Animals; Antioxidants; Biomarkers; Curcuma; Diet, High-Fat; Fatty Acids; Fatty Acids, Nonesterified; Hep G2 Cells; Humans; Lipid Metabolism; Liver; Male; Mice; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Oxidative Stress; Plant Extracts; Reactive Oxygen Species; RNA, Messenger

Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic macrophage inflammation, steatosis and fibrosis. Liposomes injected intravenously passively target hepatic myeloid cells and have potential to deliver immunomodulatory compounds and treat disease. We investigated targeting, delivery, immunomodulation and efficacy of liposomes in mice with diet-induced NASH.. Liposome-encapsulated lipophilic curcumin or 1,25-dihydroxy-vitamin D3 (calcitriol) were injected intravenously into mice with diet-induced NASH. Liver and cell liposome uptake was assessed by in vivo imaging and flow cytometry. Immunomodulation of targeted cells were assessed by RNA transcriptome sequencing. NASH was assessed by histological scoring, serum liver enzymes and fasting glucose/insulin and liver RNA transcriptome sequencing.. Liposomes targeted lipid containing MHC class-II. Liposomes are a new strategy to target lipid rich inflammatory dendritic cells and have potential to deliver immunomodulatory compounds to treat NASH.

Topics: Animals; Curcumin; Diet, High-Fat; Disease Progression; Female; Fibrosis; Hepatocytes; Immunologic Factors; Inflammation; Insulin Resistance; Liposomes; Liver; Liver Cirrhosis; Macrophages; Mice; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Transcriptome; Vitamin D

Studies have shown that satins and herbal products have potential to treat non-alcohol fatty liver disease (NAFLD) in clinic. However, no study has compared their effects, and their mechanisms remain unresolved. Here, we choose lovastatin and two herbal products including berberine and curcumin to compare their effects in treating NAFLD. NAFLD model was established by high fat food, and rats were administrated with lovastatin, berberine, curcumin, berberine + curcumin at the dosage of 100, 100, 100, 50 + 50 mg/kg bw, respectively. The body weight, visceral fat gain, histological inspection and serum parameters were studied to exam the curative effects. In addition, mediators including SREBP-1c, caveolin-1, pERK, NF-κB, TNF-α, and pJNK were studied. Results showed that berberine + curcumin group exhibited lower body and fat weigh compared with lovastatin group. Biochemical assays showed that LDL-c, ALT, AST, ALP, MDA, LSP level were lower in berberine + curcumin group compared with lovastatin group. Lower expression of SREBP-1c, pERK, TNF-α, and pJNK were also observed in berberine + curcumin group. We conclude that combination of curcumin and berberine exhibited better ameliorative effects in treating NAFLD than lovastatin, and this enhanced effect is associated with oxidative stress, hepatic inflammation and lipid metabolism.

Topics: Alanine Transaminase; Alkaline Phosphatase; Animals; Aspartate Aminotransferases; Berberine; Biological Products; Blood Glucose; Body Weight; Curcumin; Gene Expression Regulation; Inflammation; Insulin; Intra-Abdominal Fat; Lipid Metabolism; Lipids; Lipopolysaccharides; Liver; Lovastatin; Male; Non-alcoholic Fatty Liver Disease; Organ Size; Oxidative Stress; Rats, Sprague-Dawley

Our studies in vitro and in vivo aimed to investigate the influence of DNA methylation of peroxisome proliferator activated receptor-α (PPAR-α) gene in non-alcoholic fatty liver disease (NAFLD) pathogenesis and to observe whether the DNA methylation inhibitor 5-Aza-2'-deoxycytidine (5-Aza-CdR) and the herbal medicine curcumin might reverse the effect both in vivo and in vitro.. Steatotic hepatocyte model of cell lines and NAFLD rat models were established following protocols documented in previous studies. Subsequently, the models received 5-Aza-CdR and curcumin treatment. Morphological, histological and laboratory variables in each group were determined by routine methods, including PPAR-α mRNA expression by polymerase chain reaction (PCR), PPAR-α protein expression by Western blot and DNA methylation by pyrosequencing.. The steatotic hepatocyte model and NAFLD rat model were completely established. The expressions of PPAR-α mRNA and protein were significantly lower in the steatotic hepatocyte and NAFLD rat model groups than in the controls (P < 0.05). The mean DNA methylation levels of the PPAR-α gene were significantly higher in the two steatotic model groups than in the controls, especially at several CpG sites (P < 0.05). 5-Aza-CdR and curcumin treatment significantly reversed the DNA methylation levels, increased PPAR-α mRNA and protein expression, and improved lipid accumulation in the two steatotic models (P < 0.05).. DNA methylation at the PPAR-α gene is involved in the pathogenesis of NAFLD and is possibly reversible by 5-Aza-CdR and curcumin. Curcumin may be a promising candidate for NAFLD therapy.

Topics: Animals; Cell Line; Curcumin; Decitabine; Disease Models, Animal; DNA Methylation; Enzyme Inhibitors; Hepatocytes; Humans; Non-alcoholic Fatty Liver Disease; PPAR alpha; Rats

Curcumin is a natural polyphenol with beneficial effects on NAFLD patients and NAFLD is accompanied by metabolism decompensation.. This study was focused on the effect of curcumin on the relationship between endogenous bile acids metabolism pathway and exogenous xenobiotics metabolism pathway in C57BL/6 mice of non-alcoholic fatty liver disease induced by high-fat and high-fructose diet (HFHFr) and in cultured mice hepatocytes.. Our results showed curcumin treatment apparently attenuated the hepatic steatosis and reversed the abnormalities of serum biochemical parameters in HFHFr-fed mice. Curcumin effectively reversed the expression of CYP3A and CYP7A in fatty liver status to restore metabolism capability. In the meantime, lipid synthesis has been controlled by curcumin, evidenced by the expression of CD36, SREBP-1c and FAS. Further, FXR, SHP and Nrf2 expressions were remarkably dropped in HFHFr-fed mice and LXRα expression was significantly enhanced, while curcumin treatment was quite effective to restore this pathway. In addition, LXRα antagonist GGPP pretreatment weakened the curcumin effects on CYP3A, CYP7A and SREBP-1c.. These findings indicate that the Nrf2/FXR/LXRα pathway might synergistically regulate both endogenous and exogenous metabolism in NAFLD mice and LXRα may be a novel therapeutic target of curcumin for the prevention and treatment of NAFLD.

Topics: Animals; Curcumin; Cytochrome P-450 Enzyme System; Diet, High-Fat; Fructose; Hepatocytes; Lipids; Liver; Liver X Receptors; Male; Mice; Mice, Inbred C57BL; NF-E2-Related Factor 2; Non-alcoholic Fatty Liver Disease; Polyisoprenyl Phosphates; Protective Agents; Receptors, Cytoplasmic and Nuclear; Signal Transduction; Sterol Regulatory Element Binding Protein 1

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Apolipoprotein B-100; Collagen; Curcumin; Diet, High-Fat; Female; Glutathione; Non-alcoholic Fatty Liver Disease; Osteopontin; Rats; Rats, Wistar; Tumor Necrosis Factor-alpha

Salidroside and curcumin (SC) formula could alleviate lipid deposition in high fat diet-induced nonalcoholic fatty liver disease (NAFLD). However, the mechanisms are still unknown, and the magnitude of potential therapeutic benefit remains understudied.. The rats were treated with high fat diet for 14 weeks to induce NAFLD. The experiment was divided into control, model (NAFLD), SC formula and rosiglitazone groups (n = 7 in each group). Hematoxylin-eosin (H&E) staining was applied to detect liver morphological changes. Biochemical, metabolic indices and inflammation factors in liver tissue and serum were detected. Additionally, the activities of related enzymes were detected by enzyme-linked immunosorbent assay.. In the established rat model, typical lipid deposition and liver steatosis were observed. Liver triglyceride, free fatty acids, sera alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, fasting insulin, fasting blood glucose and homeostasis model assessment of insulin resistance were elevated in model group. Liver malondialdehyde was significantly elevated, while superoxide dismutase was significantly decreased in model group, compared with control. Moreover, tumor necrosis factor-α and Interleukin-1 were significantly produced in model group, compared with control. As a mechanism, high fat diet decreased tissue AMP-activated protein kinase (AMPK), phosphorylated AMPK, carnitine palmitoyltransferase 1 and increased inacetyl-CoA carboxylase (ACCase), phosphorylated ACCase. Importantly, these abnormal changes caused by high fat diet were reduced by SC formula administration.. SC formula could ameliorate the injury caused by high fat diet. The effect was likely mediated via its influence on insulin resistance, lipid peroxidation injury and AMPK signaling pathway.

Topics: AMP-Activated Protein Kinases; Animals; Biomarkers; Blood Glucose; Curcumin; Diet, High-Fat; Disease Models, Animal; Drug Combinations; Glucosides; Insulin; Insulin Resistance; Lipid Metabolism; Lipid Peroxidation; Liver; Male; Non-alcoholic Fatty Liver Disease; Phenols; Rats, Sprague-Dawley; Signal Transduction

Diet-induced obesity is strongly associated with nonalcoholic fatty-liver disease (NAFLD) and insulin resistance. We aimed to investigate the in vivo therapeutic value of tetrahydrocurcumin (THC) intervention in high-fat-diet (HFD)-induced obesity and hepatic steatosis. C57BL/6 mice were fed an HFD for 10 weeks, and then they received 20 or 100 mg/kg THC along with the HFD for another 10 weeks. Mice fed an HFD for 20 weeks experienced obesity, hepatic steatosis, hyperlipidemia, and insulin resistance. Tetrahydrocurcumin (THC) intervention for 10 weeks significantly reduced adiposity (epididymal-fat weights of 6.6 ± 0.4 g for the HFD-only group and 5.3 ± 0.8 and 5.6 ± 0.7 g for the HFD with 20 mg/kg THC and HFD with 100 mg/kg THC groups, respectively; p < 0.05) via downregulation of adipogenic factors. Inflammatory macrophage infiltration and polarization were decreased by THC in mouse epididymal adipose tissues. In the liver, THC markedly alleviated steatosis by approximately 28-37% ( p < 0.05) via the downregulation of lipogenesis, the activation of AMP-activated protein kinase (AMPK), and the increase of fatty acid oxidation. Elevated blood glucose and insulin resistance were also improved by THC, which might be caused by regulation of the hepatic insulin signaling cascade, gene transcription involved in glucose metabolism, and reduced macrophage infiltration in the liver and adipose tissue. Our results demonstrated the beneficial effects of THC-mediated intervention against obesity and NAFLD as well as other metabolic syndromes, revealing a novel therapeutic use of THC in obese populations.

Topics: Adipose Tissue; Adiposity; Animals; Curcumin; Diet, High-Fat; Glucose; Humans; Insulin; Lipid Metabolism; Lipogenesis; Liver; Male; Mice; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Obesity

Structural disruption of gut microbiota contributes to the development of non-alcoholic fatty liver disease (NAFLD) and modulating the gut microbiota represents a novel strategy for NAFLD prevention. Although previous studies have demonstrated that curcumin alleviates hepatic steatosis, its effect on the gut microbiota modulation has not been investigated.. Next generation sequencing and multivariate analysis were utilized to evaluate the structural changes of gut microbiota in a NAFLD rat model induced by high fat-diet (HFD) feeding.. We found that curcumin attenuated hepatic ectopic fat deposition, improved intestinal barrier integrity, and alleviated metabolic endotoxemia in HFD-fed rats. More importantly, curcumin dramatically shifted the overall structure of the HFD-disrupted gut microbiota toward that of lean rats fed a normal diet and altered the gut microbial composition. The abundances of 110 operational taxonomic units (OTUs) were altered by curcumin. Seventy-six altered OTUs were significantly correlated with one or more hepatic steatosis associated parameters and designated 'functionally relevant phylotypes'. Thirty-six of the 47 functionally relevant OTUs that were positively correlated with hepatic steatosis associated parameters were reduced by curcumin.. These results indicate that curcumin alleviates hepatic steatosis in part through stain-specific impacts on hepatic steatosis associated phylotypes of gut microbiota in rats.. Compounds with antimicrobial activities should be further investigated as novel adjunctive therapies for NAFLD.

Topics: Animals; Curcumin; Diet, High-Fat; Gastrointestinal Microbiome; High-Throughput Nucleotide Sequencing; Male; Non-alcoholic Fatty Liver Disease; Rats; Rats, Sprague-Dawley

Topics: Administration, Oral; Angiotensin II; Angiotensinogen; Animals; Atherosclerosis; Chlorogenic Acid; Commiphora; Curcumin; Diet, High-Fat; Dietary Supplements; Fatty Acid-Binding Proteins; Gene Expression Regulation; Inulin; Lipid Metabolism; Male; Mice; Mice, Inbred C57BL; Neoplasm Proteins; Non-alcoholic Fatty Liver Disease; Plant Extracts; Plant Gums; RNA, Messenger; Silymarin; Suppressor of Cytokine Signaling 3 Protein

Developing confirmation recommends that in patients with dynamic type of NAFLD, particularly nonalcoholic steatohepatitis (NASH) may have the pathogenic parts in the advancement of kidney damage. In this study we have examined the impact of curcumin on NASH instigated chronic kidney damage (CKD) and the putative mechanisms. To prepare this NASH model, neonatal C57BL/6J male mice were exposed to low-dose streptozotocin (STZ) and were fed high-fat diet (HFD) at the age of 4weeks and continued up to 14weeks, curcumin was given at 100mg/kg dose by oral gavage daily after 10weeks of STZ injection and continued for 4weeks along with HFD feeding. NASH incited mice demonstrated nephrotoxicity as proved by declining renal capacity, which was evaluated by measuring blood urea nitrogen and creatinine in serum and histopathological variations from the norm. These progressions were switched by curcumin treatment, which brought about huge change in renal capacity. Furthermore, curcumin markedly decreased NAD(P)H oxidase subunits (p67phox, p47phox, p22phox), nitrotyrosine and CYP2E1 renal protein expression as well as reduced pro-inflammatory cytokine expression (TNFα, IL-1β, IFNγ). Renal protein expression of mitogen activated protein kinases (MAPKs) (p-JNK, p-ERK1/2) and glucose regulated protein 78, CHOP were increased in NASH induced mice and curcumin treatment attenuated these increased expressions. In addition, curcumin treatment also decreased the apoptosis signaling proteins (cleaved caspase-3, cleaved caspase-12) in the NASH kidney. Taken together, our results suggest that curcumin preserves the renal function, probably by attenuating the ER stress mediated MAPK signaling.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Apoptosis; Blood Urea Nitrogen; Creatinine; Curcumin; Diet, High-Fat; Extracellular Signal-Regulated MAP Kinases; Humans; Kidney; Male; Mice; Mice, Inbred C57BL; NADPH Oxidases; Non-alcoholic Fatty Liver Disease; Renal Insufficiency, Chronic; Signal Transduction; Streptozocin

Topics: Animals; Body Weight; CD36 Antigens; Curcumin; Cyclic AMP Response Element-Binding Protein; Diet, High-Fat; Fatty Liver; Lipid Metabolism; Liver; Male; Mice; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Obesity; PPAR gamma; Signal Transduction

Curcumin, a phenolic compound, has a wide spectrum of therapeutic effects such as antitumor, anti-inflammatory, anti-cancer and so on. The study aimed to investigate the underlying mechanisms of curcumin to protect liver damage and progression of non-alcoholic steatohepatitis (NASH) in a novel NASH-hepatocellular carcinoma (HCC) mouse model. To induce this model neonatal C57BL/6J male mice were exposed to low-dose streptozotocin and were fed a high-fat diet (HFD) from the age of 4weeks to 14weeks. Curcumin was given at 100mg/kg dose daily by oral gavage started at the age of 10weeks and continued until 14weeks along with HFD feeding. We found that curcumin improved the histopathological changes of the NASH liver via reducing the level of steatosis, fibrosis associated with decreasing serum aminotransferases. In addition, curcumin treatment markedly reduced the hepatic protein expression of oxidative stress, pro-inflammatory cytokines, and chemokines including interferon (IFN) γ, interleukin-1β and IFNγ-inducible protein 10, in NASH mice. Furthermore, curcumin treatment significantly reduced the cytoplasmic translocation of high mobility group box 1 (HMGB1) and the protein expression of toll like receptor 4. Nuclear translocation of nuclear factor kappa B (NF-κB) was also dramatically attenuated by the curcumin in NASH liver. Curcumin treatment effectively reduced the progression of NASH to HCC by suppressing the protein expression of glypican-3, vascular endothelial growth factor, and prothrombin in the NASH liver. Our data suggest that curcumin reduces the progression of NASH and liver damage, which may act via inhibiting HMGB1-NF-κB translocation.

Topics: Active Transport, Cell Nucleus; Animals; Animals, Newborn; Carcinoma, Hepatocellular; Curcumin; Disease Models, Animal; Fibrosis; HMGB1 Protein; Humans; Liver; Liver Neoplasms; Male; Mice; Mice, Inbred C57BL; NF-kappa B; Non-alcoholic Fatty Liver Disease; Oxidative Stress; Streptozocin

The immune system acts on different metabolic tissues that are implicated in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Leptin and linoleic acid have the ability to potentially affect immune cells, whereas curcumin is a known natural polyphenol with antioxidant and anti-inflammatory properties.. This study was designed to evaluate the pro-inflammatory and pro-oxidant effects of leptin and linoleic acid on immune cells from patients with NAFLD and to corroborate the modulatory effects of curcumin and its preventive properties against the progression of NAFLD using a high-fat diet (HFD)-induced NAFLD/nonalcoholic steatohepatitis mouse model.. The ex vivo experiments showed that linoleic acid increased the production of reactive oxygen species in monocytes and liver macrophages, whereas leptin enhanced tumor necrosis factor-α (TNF-α) production in monocytes and interferon-γ production in circulating CD4+ cells. Conversely, oral administration of curcumin prevented HFD-induced liver injury, metabolic alterations, intrahepatic CD4+ cell accumulation and the linoleic acid- and leptin- induced pro-inflammatory and pro-oxidant effects on mouse liver macrophages.. Our findings provide new evidence for the therapeutic potential of curcumin to treat human NAFLD. However, the development of a preventive treatment targeting human circulating monocytes and liver macrophages as well as peripheral and hepatic CD4+ cells requires additional research.

Topics: Animals; Antioxidants; CD4-Positive T-Lymphocytes; Curcumin; Diet, High-Fat; Disease Models, Animal; Fatty Liver; Hepatocytes; Humans; Leptin; Linoleic Acid; Liver; Mice; Non-alcoholic Fatty Liver Disease; Reactive Oxygen Species

Nonalcoholic fatty liver disease (NAFLD), the hepatic manifestation of the metabolic syndrome, has become one of the most common causes of chronic liver disease over the last decade in developed countries. NAFLD includes a spectrum of pathological hepatic changes, such as steatosis, steatohepatitis, advanced fibrosis, and cirrhosis. Bisdemethoxycurcumin (BDMC) is polyphenolic compounds with a diarylheptanoid skeleton, curcumin close analogues, which is derived from the Curcumae Longae Rhizoma. While the rich bioavailability research of curcumin, BDMC is the poor studies. We investigated whether BDMC has the hepatoprotective effect and combinatory preventive effect with silymarin on methionine choline deficient (MCD)-diet-induced NAFLD in C57BL/6J mice. C57BL/6J mice were divided into five groups of normal (normal diet without any treatment), MCD diet (MCD diet only), MCD + silymarin (SIL) 100 mg/kg group, MCD + BDMC 100 mg/kg group, MCD + SIL 50 mg/kg + BDMC 50 mg/kg group. Body weight, liver weight, liver function tests, histological changes were assessed and quantitative real-time polymerase chain reaction and Western blot analyses were conducted after 4 weeks. Mice lost body weight on the MCD-diet, but BDMC did not lose less than the MCD-diet group. Liver weights decreased from BDMC, but they increased significantly in the MCD-diet groups. All liver function test values decreased from the MCD-diet, whereas those from the BDMC increased significantly. The MCD- diet induced severe hepatic fatty accumulation, but the fatty change was reduced in the BDMC. The BDMC showed an inhibitory effect on liver lipogenesis by reducing associated gene expression caused by the MCD-diet. In all experiments, the combinations of BDMC with SIL had a synergistic effect against MCD-diet models. In conclusion, our findings indicate that BDMC has a potential suppressive effect on NAFLD. Therefore, our data suggest that BDMC may act as a novel and potent therapeutic agent against NAFLD.

Topics: Alanine Transaminase; Animals; Aspartate Aminotransferases; Body Weight; Cholesterol; Choline; Choline Deficiency; Curcuma; Curcumin; Diarylheptanoids; Drug Synergism; Food, Formulated; Lipogenesis; Liver; Liver Function Tests; Male; Methionine; Mice; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Organ Size; Protective Agents; Silymarin; Triglycerides

Diabetic patients frequently suffer from non-alcoholic steatohepatitis. The current study aimed to investigate the role of curcumin and the response of hepatic stellate cells in streptozotocin (STZ)-induced hepatic damage. Sixty male rats were divided into three groups. The normal control injected with a citrate buffer vehicle and the diabetic control group which was injected intraperitoneally (IP) with a single-dose of streptozotocin (50mg/kg body weight) and a diabetic group was treated with an oral dose of curcumin at 80 mg/kg body weight daily for 60 days. Curcumin effectively counteracts oxidative stress-mediated hepatic damage and improves biochemical parameters. Alpha-smooth muscle actin (α-SMA) was significantly reduced, and insulin antibodies showed strong positive immunoreactivity with curcumin administration. These results optimistically demonstrate the potential use of curcumin, which is attributed to its antiradical/antioxidant activities and its potential β-cell regenerative properties. Also, it has the capability to encourage the trans-differentiation of hepatic stellate cells into insulin-producing cells for a period of time. In addition, as it is an anti-fibrotic mediator that inhibits hepatic stellate cell activation and the transition to myofibroblast-like cells, this suggests the possibility of considering curcumin's novel therapeutic effects in reducing hepatic dysfunction in diabetic patients.

Topics: Actins; Animals; Cell Transdifferentiation; Curcumin; Diabetes Complications; Diabetes Mellitus; Hepatic Stellate Cells; Humans; Insulin; Liver; Non-alcoholic Fatty Liver Disease; Oxidation-Reduction; Oxidative Stress; Rats; Streptozocin

To investigate the role of adiponectin precursor (ADIPOQ) DNA methylation in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) and the effect of curcumin on the development of NAFLD using rat models.. Male Sprague-Dawley rats were divided into the control, NAFLD and curcumin-treated groups. The genetic and epigenetic features of each rat were measured and recorded. Real-time polymerase chain reaction (PCR), Western blot and bisulfite sequencing PCR (BSP) were used to quantify the ADIPOQ mRNA and protein expressions, and DNA methylation status, respectively.. Serum levels of alanine aminotransferase (ALT), triglyceride (TG), total cholesterol (TC) and fasting blood glucose in the NAFLD group were significantly increased compared with the control group. The genetic and epigenetic features were reversed after curcumin treatment. The ADIPOQ mRNA and protein expressions in the livers of the NAFLD rats was lower compared with the control and the curcumin-treated groups. ADIPOQ methylation rate in the NAFLD group was significantly higher than in the control group, which was declined slightly following curcumin treatment. A negative correlation was found between the degrees of DNA methylation and ADIPOQ mRNA expression. ALT, TC, TG and homeostatic model assessment insulin resistance index had a positive correlation with ADIPOQ DNA methylation, showing that curcumin might affect the gene expression involved in lipid and glucose metabolism by influencing ADIPOQ DNA methylation modifications, which contributed to alleviation of NAFLD.. Altering the DNA methylation of ADIPOQ is one of the mechanisms by which curcumin executes its hepatoprotective function in NAFLD.

Topics: Adiponectin; Animals; Anti-Inflammatory Agents, Non-Steroidal; Curcumin; DNA Methylation; Gene Expression; Male; Non-alcoholic Fatty Liver Disease; Rats; Rats, Sprague-Dawley; RNA, Messenger

To investigate the effect of curcumin on visfatin and zinc-α2-glycoprotein (ZAG) expression levels in rats with non-alcoholic fatty liver disease (NAFLD).. Fifty-six male rats were randomly divided into a control group (n=16) and model group (n=40) and were fed on a normal diet or a high-fat diet, respectively. Equal volumes of sodium carboxymethyl cellulose (CMC) were intragastrically administered to the control group for 4 weeks. At the end of the 12th week, visfatin and ZAG protein expression levels were examined by immunohistochemistry. Visfatin mRNA levels were measured by semi-quantitative reverse transcription polymerase chain reaction.. Compared with the control group, the model group showed significantly increased expression of visfatin in liver tissue (P < 0.01) and significantly decreased expression of ZAG (P < 0.01). These effects were ameliorated by curcumin treatment.. Visfatin and zinc-α2-glycoprotein may be involved in the pathogenesis of NAFLD. Treatment of NAFLD in rats by curcumin may be mediated by the decrease of visfatin and the increase of non-alcoholic fatty liver disease.

Topics: Alanine Transaminase; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Cholesterol; Curcumin; Disease Models, Animal; Drug Evaluation, Preclinical; Fatty Acids; Liver; Male; Nicotinamide Phosphoribosyltransferase; Non-alcoholic Fatty Liver Disease; Random Allocation; Rats; Rats, Sprague-Dawley; Seminal Plasma Proteins; Triglycerides; Zn-Alpha-2-Glycoprotein

Non-alcoholic fatty hepatitis (NASH) is highly prevalent, mitochondria damage is the main pathophysiological characteristic of NASH. However, treatment for mitochondria damage is rarely reported.. NASH model was established in rats, the protective effects of curcumin were evaluated by histological observation; structure and function assessments of mitochondria; and apoptotic genes expression.. NASH rats treated with curcumin displayed relatively slight liver damage when compared with NASH livers. The average mitochondrial length and width of NASH (12.0 ± 3.2 and 5.1 ± 1.1 micrometers) were significantly longer than that of normal (6.2 ± 2.1 and 2.1 ± 1.5 micrometers) and NASH treated with curcumin (7.4 ± 1.2 and 3.2 ± 1.5 micrometers) rats. The average malondialdehyde (MDA) and 4-hydroxy nonyl alcohol (HNE) levels in liver homogenates of NASH rats (4.23 ± 0.22 and 19.23 ± 2.3 nmol/Ml) were significantly higher than these in normal (1.32 ± 0.12 and 3.52 ± 0.43 nmol/mL) and NASH treated with curcumin (1.74 ± 0.11 and 4.66 ± 0.99 nmol/mL) rats. The expression levels of CytC, Casp3 and Casp8 of the NASH livers were significantly higher than normal and NASH treated with curcumin rats livers.. Our data demonstrated that curcumin prevents the NASH by mitochondria protection and apoptosis reduction and provided a possible novel treatment for NASH.

Topics: Animals; Antioxidants; Apoptosis; Curcumin; Disease Models, Animal; Male; Microscopy, Electron, Transmission; Mitochondria; Non-alcoholic Fatty Liver Disease; Polymerase Chain Reaction; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species

Obesity contributes to the increased risk of liver- related morbidity and mortality. The accumulation of macrophages in adipose tissue in an inflammatory state is a hallmark of obesity-induced hepatic steatosis. In this study, we reveal the role of curcumin in the molecular mechanisms underlying inflammatory events in a model consisting of obese mice with hepatic steatosis. Obese mice fed with curcumin experienced significant weight loss and significantly reduced serum triglyceride (TG) levels. The adipose tumor necrocis factor-α, interleukin-6 (IL-6) and monocyte chemotactic protein-1 levels were significantly higher in obese mice compared to mice fed with curcumin. Compared to the obese mice, curcumin decreased the number of F4/80-positive macrophages in epididymal adipose and liver tissue. The induction of signal transducer and activator of transcription 3 phosphorylation by curcumin resulted in the downregulation of the suppressor of cytokine signaling 3 in the liver of obese mice. Curcumin decreased hepatic TG in obese mice by downregulating the gene expression of sterol regulatory element-binding protein-1c in the liver. The hepatic expression of several mitochondrial biogenesis genes decreased in the obese mice, including mitochondrial DNA (mtDNA), nuclear respiratory factor 1 (NRF1) and mitochondrial transcription factor A (Tfam), which are responsible for the lower mitochondrial respiratory chain (MRC) complex I activity and adenosine triphosphate production. By contrast, obese mice treated with curcumin showed normalized mtDNA, NRF1 and Tfam gene expression, reduced hepatic nuclear factor-κB activities and levels of thiobarbituric acid reactive substances (TBARS) and restored mitochondrial oxidative metabolism and biogenesis. The results from the present sudy show that curcumin prevents fatty liver disease through multiple mechanisms, and suggest that curcumin may be used to prevent the development and progression of non-alcoholic fatty liver disease (NAFLD).

Topics: Adipose Tissue; Animals; Body Weight; Curcumin; Cytokines; Fatty Liver; Gene Expression Regulation; Inflammation; Inflammation Mediators; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Mitochondria; Non-alcoholic Fatty Liver Disease; Obesity; Signal Transduction

Topics: Animals; Curcumin; Fatty Liver; Feeding Behavior; Fructose; Humans; Liver Cirrhosis; Non-alcoholic Fatty Liver Disease; Rats; Treatment Outcome

To observe the effects of curcumin derivative on non-alcoholic steatohepatitis (NASH).. 60 SD male rats were randomly divided into 5 groups. The NASH model was induced by high fat diet combined with carbon tetrachloride. These rats were then treated with curcumin and curcumin derivative, saline treating group as control. The serum biochemical parameters and liver histological examinations were observed. The TNF alpha, NF-kappa B and HMG-CoA reductase mRNA transcriptions of liver tissue were detected with RT-PCR. The protein expressions of TNF alpha and NF-kappa B were detected by western blot.. Compared with the saline group, A remarkable reduction was observed in serum ALT (U/L), AST (U/L) and TC (mmol/L) in rats treated with curcumin derivatives [(69.20 +/- 27.58) vs (102.43 +/- 47.29), (158.00 +/- 39.15) vs (229.50 +/- 105.20) and (2.08 +/- 0.30) vs (2.58 +/- 1.02), P < 0.05]. The degrees of fibrosis were significantly alleviated; Compared with curcumin group, liver index and serum ALT, AST of curcumin derivative group were also significantly decreased [(4.88 +/- 0.62) vs (5.16 +/- 0.61); (69.20 +/- 27.58) vs (82.5 +/- 33.23); (158.00 +/- 39.15) vs (211.75 +/- 106.30), P < 0.05]; The liver steatosis and inflammation grade were also significantly improved .The gene transcriptions of TNF alpha, NF-kappa B and HMG-CoA reductase in curcumin derivative group were significantly lower than those in curcumin and saline group (P < 0.05).. These results indicate that the water-soluble curcumin derivative displays superior bioavailability to the parent curcumin, which can effectively improve the lipid metabolism and delay the progression of hepatic fibrosis in rats with steatohepatitis.

Topics: Animals; Curcumin; Fatty Liver; Hydroxymethylglutaryl CoA Reductases; Liver; Male; NF-kappa B; Non-alcoholic Fatty Liver Disease; Phytotherapy; Rats; Rats, Sprague-Dawley; Tumor Necrosis Factor-alpha