Therapeutic effects of curcumin and ursodexycholic acid on non-alcoholic fatty liver disease

The growth of adipose tissues is considered angiogenesis-dependent during non-alcoholic fatty liver disease (NAFLD). We have recently reported that our standardized 50% methanolic extract (ME) of Phyllanthus niruri (50% ME of P. niruri) has alleviated NAFLD in Sprague–Dawley rats. This study aimed to assess the molecular mechanisms of action, and to further evaluate the antiangiogenic effect of this extract. NAFLD was induced by eight weeks of high-fat diet, and treatment was applied for four weeks. Antiangiogenic activity was assessed by aortic ring assay and by in vitro tests. Our findings demonstrated that the therapeutic effects of 50% ME among NAFLD rats, were associated with a significant increase in serum adiponectin, reduction in the serum levels of RBP4, vaspin, progranulin, TNF-α, IL-6, and significant downregulation of the hepatic gene expression of PPARγ, SLC10A2, and Collα1. Concomitantly, 50% ME of P. niruri has exhibited a potent antiangiogenic activity on ring assay, cell migration, vascular endothelial growth factor (VEGF), and tube formation, without any cytotoxic effect. Together, our findings revealed that the protective effects of P. niruri against NAFLD might be attributed to its antiangiogenic effect, as well as to the regulation of adipocytokines and reducing the expression of adipogenic genes.

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Integrative lipidomic and transcriptomic study unravels the therapeutic effects of saikosaponins A and D on non-alcoholic fatty liver disease

Acta Pharmaceutica Sinica B ◽

10.1016/j.apsb.2021.03.018 ◽

2021 ◽

Author(s):

Xiaojiaoyang Li ◽

Junde Ge ◽

Yajing Li ◽

Yajie Cai ◽

Qi Zheng ◽

...

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Therapeutic Effects ◽

Alcoholic Fatty Liver ◽

Alcoholic Fatty Liver Disease

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Hepatoprotective effects of Cassiae Semen on mice with non-alcoholic fatty liver disease based on gut microbiota

Communications Biology ◽

10.1038/s42003-021-02883-8 ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Hanyan Luo ◽

Hongwei Wu ◽

Lixia Wang ◽

Shuiming Xiao ◽

Yaqi Lu ◽

...

Keyword(s):

Liver Disease ◽

Gut Microbiota ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Intestinal Barrier ◽

Therapeutic Effects ◽

Alcoholic Fatty Liver ◽

Hepatoprotective Effects ◽

Underlying Mechanisms ◽

Alcoholic Fatty Liver Disease

AbstractCassiae Semen (CS), the seeds of Cassia obtusifolia L. and C. tora L, have a long medicinal history in China, with suggestions for it to relieve constipation and exert hepatoprotective effects. However, the underlying mechanisms are still unclear. In this study, mice with high-fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) were used to study the hepatoprotective effects of CS. The relationship between gut microbiota and hepatoprotective effect mechanisms mediated by CS extracts, the total aglycone extracts of CS, rubrofusarin-6-β-gentiobioside, and aurantio-obtusin were examined. Our data indicate that CS extracts and components confer a protective effect by ameliorating lipid accumulation, intestinal barrier damage, liver damage, and inflammation on HFD-induced liver injury. Meanwhile, fecal microbe transplantation exerted the pharmacological effect of CS on HFD-fed mice; however, the efficacy of CS was inhibited or eliminated by antibiotic-induced dysbiosis. In conclusion, the therapeutic effects of CS on NAFLD were closely related to the gut microbiota, suggesting a role for TCM in treating disease.

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The Evaluation of Effective Drugs for the Treatment of Non-Alcoholic Fatty Liver Disease: A Aystematic Review and Network Meta-Analysis

Advanced Pharmaceutical Bulletin ◽

10.34172/apb.2020.065 ◽

2020 ◽

Vol 10 (4) ◽

pp. 542-555

Author(s):

Ramin Jalili ◽

Mohammad Hossein Somi ◽

Hossein Hosseinifard ◽

Fatemeh Salehnia ◽

Morteza Ghojazadeh ◽

...

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Meta Analysis ◽

Therapeutic Effects ◽

Omega 3 ◽

Alcoholic Fatty Liver ◽

Remarkable Effect ◽

Increased Risk ◽

Alcoholic Fatty Liver Disease

Purpose : Non-alcoholic fatty liver disease (NAFLD) and steatohepatitis are two forms of fatty liver disease with benign and malignant nature, respectively. These two conditions can cause an increased risk of liver cirrhosis and hepatocellular carcinoma. Given the importance and high prevalence of NAFLD, it is necessary to investigate the results of different studies in related scope to provide a clarity guarantee of effectiveness. Therefore, this systematic review and metaanalysis aim to study the efficacy of various medications used in the treatment of NAFLD. Methods: A systematic search of medical databases identified 1963 articles. After exclusion of duplicated articles and those which did not meet our inclusion criteria, eta-analysis was performed on 84 articles. Serum levels of alanine aminotransferase (ALT), aspartate amino transferase (AST) were set as primary outcomes and body mass index (BMI), hepatic steatosis, and NAFLD activity score (NAS) were determined as secondary outcomes. Results: Based on the P-score of the therapeutic effects on the non-alcoholic steatohepatitis (NASH), we observed the highest efficacy for atorvastatin, tryptophan, orlistat, omega-3 and obeticholic acid for reduction of ALT, AST, BMI, steatosis and NAS respectively. Conclusion: This meta-analysis showed that atorvastatin. life-style modification, weight loss, and BMI reduction had a remarkable effect on NAFLD-patients by decreasing aminotransferases.

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Garcinia cambogia Ameliorates Non-Alcoholic Fatty Liver Disease by Inhibiting Oxidative Stress-Mediated Steatosis and Apoptosis through NRF2-ARE Activation

Antioxidants ◽

10.3390/antiox10081226 ◽

2021 ◽

Vol 10 (8) ◽

pp. 1226

Author(s):

Joo-Hui Han ◽

Min-Ho Park ◽

Chang-Seon Myung

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Parp Cleavage ◽

Ros Generation ◽

Therapeutic Effects ◽

Ros Production ◽

Alcoholic Fatty Liver ◽

Garcinia Cambogia ◽

Alcoholic Fatty Liver Disease

Excessive free fatty acids (FFAs) causes reactive oxygen species (ROS) generation and non-alcoholic fatty liver disease (NAFLD) development. Garcinia cambogia (G. cambogia ) is used as an anti-obesity supplement, and its protective potential against NAFLD has been investigated. This study aims to present the therapeutic effects of G. cambogia on NAFLD and reveal underlying mechanisms. High-fat diet (HFD)-fed mice were administered G. cambogia for eight weeks, and steatosis, apoptosis, and biochemical parameters were examined in vivo. FFA-induced HepG2 cells were treated with G. cambogia, and lipid accumulation, apoptosis, ROS level, and signal alterations were examined. The results showed that G. cambogia inhibited HFD-induced steatosis and apoptosis and abrogated abnormalities in serum chemistry. G. cambogia increased in NRF2 nuclear expression and activated antioxidant responsive element (ARE), causing induction of antioxidant gene expression. NRF2 activation inhibited FFA-induced ROS production, which suppressed lipogenic transcription factors, C/EBPα and PPARγ. Moreover, the ability of G. cambogia to inhibit ROS production suppressed apoptosis by normalizing the Bcl-2/BAX ratio and PARP cleavage. Lastly, these therapeutic effects of G. cambogia were due to hydroxycitric acid (HCA). These findings provide new insight into the mechanism by which G. cambogia regulates NAFLD progression.

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Geniposide and Chlorogenic Acid Combination Improves Non-Alcoholic Fatty Liver Disease Involving the Potent Suppression of Elevated Hepatic SCD-1

Frontiers in Pharmacology ◽

10.3389/fphar.2021.653641 ◽

2021 ◽

Vol 12 ◽

Author(s):

Cheng Chen ◽

Xin Xin ◽

Qian Liu ◽

Hua-Jie Tian ◽

Jing-Hua Peng ◽

...

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Chlorogenic Acid ◽

High Fat Diet ◽

Fatty Liver Disease ◽

Liver Enzymes ◽

Therapeutic Effects ◽

High Fat ◽

Alcoholic Fatty Liver ◽

Alcoholic Fatty Liver Disease

Background: Non-alcoholic fatty liver disease (NAFLD), characterized by the excessive accumulation of hepatic triglycerides (TGs), has become a worldwide chronic liver disease. But efficient therapy keeps unsettled. Our previous works show that geniposide and chlorogenic acid combination (namely the GC combination), two active chemical components combined with a unique ratio (67.16:1), presents beneficial effects on high-fat diet-induced NAFLD rodent models. Notably, microarray highlighted the more than 5-fold down-regulated SCD-1 gene in the GC combination group. SCD-1 is an essential lipogenic protein for monounsaturated fatty acids’ biosynthesis and serves as a key regulatory enzyme in the last stage of hepatic de novo lipogenesis (DNL).Methods: NAFLD mice model was fed with 16 weeks high-fat diet (HFD). The pharmacological effects, primarily on hepatic TG, TC, FFA, and liver enzymes, et al. of the GC combination and two individual components were evaluated. Furthermore, hepatic SCD-1 expression was quantified with qRT-PCR, immunoblotting, and immunohistochemistry. Finally, the lentivirus-mediated over-expressed cell was carried out to confirm the GC combination’s influence on SCD-1.Results: The GC combination could significantly reduce hepatic TG, TC, and FFA in NAFLD rodents. Notably, the GC combination presented synergetic therapeutic effects, compared with two components, on normalizing murine hepatic lipid deposition and disordered liver enzymes (ALT and AST). Meanwhile, the robust SCD-1 induction induced by HFD and FFA in rodents and ALM-12 cells was profoundly blunted, and this potent suppression was recapitulated in lentivirus-mediated SCD-1 over-expressed cells.Conclusion: Taken together, our data prove that the GC combination shows a substantial and synergetic anti-lipogenesis effect in treating NAFLD, and these amelioration effects are highly associated with the potent suppressed hepatic SCD-1 and a blunted DNL process.

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Mitochondrial Targeting Therapeutics: Promising Role of Natural Products in Non-alcoholic Fatty Liver Disease

Frontiers in Pharmacology ◽

10.3389/fphar.2021.796207 ◽

2021 ◽

Vol 12 ◽

Author(s):

Jingqi Xu ◽

Jiayan Shen ◽

Ruolan Yuan ◽

Bona Jia ◽

Yiwen Zhang ◽

...

Keyword(s):

Natural Products ◽

Liver Disease ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Research Progress ◽

Therapeutic Effects ◽

Innovative Drug ◽

Alcoholic Fatty Liver ◽

Hepatic Lipid Accumulation ◽

Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) has become one of the most common chronic liver diseases worldwide, and its prevalence is still growing rapidly. However, the efficient therapies for this liver disease are still limited. Mitochondrial dysfunction has been proven to be closely associated with NAFLD. The mitochondrial injury caused reactive oxygen species (ROS) production, and oxidative stress can aggravate the hepatic lipid accumulation, inflammation, and fibrosis. which contribute to the pathogenesis and progression of NAFLD. Therefore, pharmacological therapies that target mitochondria could be a promising way for the NAFLD intervention. Recently, natural products targeting mitochondria have been extensively studied and have shown promising pharmacological activity. In this review, the recent research progress on therapeutic effects of natural-product-derived compounds that target mitochondria and combat NAFLD was summarized, aiming to provide new potential therapeutic lead compounds and reference for the innovative drug development and clinical treatment of NAFLD.

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Lycopene Modulates Pathophysiological Processes of Non-Alcoholic Fatty Liver Disease in Obese Rats

Antioxidants ◽

10.3390/antiox8080276 ◽

2019 ◽

Vol 8 (8) ◽

pp. 276 ◽

Cited By ~ 6

Author(s):

Mariane Róvero Costa ◽

Jéssica Leite Garcia ◽

Carol Cristina Vágula de Almeida Silva ◽

Artur Junio Togneri Ferron ◽

Fabiane Valentini Francisqueti-Ferron ◽

...

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Obese Group ◽

Control Group ◽

Therapeutic Effects ◽

Alcoholic Fatty Liver ◽

Tnf Α ◽

Hypercaloric Diet ◽

Alcoholic Fatty Liver Disease

Background: The higher consumption of fat and sugar are associated with obesity development and its related diseases such as non-alcoholic fatty liver disease (NAFLD). Lycopene is an antioxidant whose protective potential on fatty liver degeneration has been investigated. The aim of this study was to present the therapeutic effects of lycopene on NAFLD related to the obesity induced by a hypercaloric diet. Methods: Wistar rats were distributed in two groups: Control (Co, n = 12) and hypercaloric (Ob, n = 12). After 20 weeks, the animals were redistributed into the control group (Co, n = 6), control group supplemented with lycopene (Co+Ly, n = 6), obese group (Ob, n = 6), and obese group supplemented with lycopene (Ob+Ly, n = 6). Ob groups also received water + sucrose (25%). Animals received lycopene solution (10 mg/kg/day) or vehicle (corn oil) via gavage for 10 weeks. Results: Animals which consumed the hypercaloric diet had higher adiposity index, increased fasting blood glucose, hepatic and blood triglycerides, and also presented in the liver macro and microvesicular steatosis, besides elevated levels of tumor necrosis factor-α (TNF-α). Lycopene has shown therapeutic effects on blood and hepatic lipids, increased high-density lipoprotein cholesterol (HDL), mitigated TNF-α, and malondialdehyde (MDA) and further improved the hepatic antioxidant capacity. Conclusion: Lycopene shows therapeutic potential to NAFLD.

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