Protective effects of glycyrrhizic acid against non-alcoholic fatty liver disease in mice

2017 ◽  
Vol 806 ◽  
pp. 75-82 ◽  
Author(s):  
Xue Sun ◽  
Xingping Duan ◽  
Changyuan Wang ◽  
Zhihao Liu ◽  
Pengyuan Sun ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Glycyrrhizic Acid ◽  
Protective Effects ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Efficacy and Safety of a Fixed Combination of Glycyrrhizic Acid and Essential Phospholipids in Non-Alcoholic Fatty and Alcoholic Liver Disease: Results from Randomized Placebo-Controlled Trials

2021 ◽  
Vol 76 (6) ◽  
pp. 595-603
Author(s):  
Igor V. Maev ◽  
Alexey O. Bueverov ◽  
Artem V. Volnukhin
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Alcoholic Liver Disease ◽  
Fatty Liver Disease ◽  
Glycyrrhizic Acid ◽  
Fixed Combination ◽  
Efficacy And Safety ◽  
Alcoholic Fatty Liver ◽  
Essential Phospholipids ◽  
Alcoholic Fatty Liver Disease

Background. Drug treatment of non-alcoholic fatty and alcoholic liver disease remains an urgent, unsolved problem. Due to the commonality of many pathogenetic mechanisms and predictors of progression, a universal approach to the search for a therapeutic agent can be considered. Aims pooled analysis of the results of two multicenter, randomized, double-blind, placebo-controlled studies of a fixed combination of glycyrrhizic acid and essential phospholipids in two dosage forms to study its efficacy and safety in non-alcoholic fatty and alcoholic liver disease, in the presence and absence of predictors of disease progression. Methods. The pooled analysis included 180 patients with non-alcoholic fatty liver disease (Gepard study) and 120 patients with alcoholic liver disease (Jaguar study). Patients of the main group received a fixed combination of 5.0 g intravenous jet 3 times a week for the first 2 weeks; then 2 capsules 3 times a day for the next 10 weeks. Patients in the control group received placebo according to the same scheme. The total duration of treatment was 12 weeks in the Gepard study (1 course of stepwise therapy) and 24 weeks in the Jaguar study (2 courses of stepwise therapy). A comparative analysis of the efficacy and safety of a fixed combination and a placebo was carried out, in the presence and absence of predictors of progression, separately for each nosology and in a mixed sample. Results. In patients with non-alcoholic fatty and alcoholic liver disease who received the fixed combination, in contrast to the placebo group, there was a statistically more significant decrease in the level of biochemical markers of inflammation alanine aminotransferase, aspartate aminotransferase, adiponectin, and the value of the AktiTest index. There was no negative trend in the NAFLD fibrosis score; more significant positive dynamics of FibroTest is shown. Predictors of disease progression hyperglycemia, hyperlipidemia, age did not have a negative impact on the results in the study group. The efficacy of the study drug was noted in patients with non-alcoholic fatty liver disease and normal body weight; data were obtained indicating its possible effectiveness with a high activity of the inflammatory process associated with alcoholic liver damage. The frequency of adverse events in the study and control groups was comparable. Conclusions. Based on a generalized analysis of the results of two studies, promising directions for the study and use of a fixed combination of glycyrrhizic acid and essential phospholipids were identified: non-alcoholic fatty liver disease without obesity, alcoholic steatohepatitis of high activity (as an adjuvant); steatohepatitis of non-alcoholic and alcoholic etiology, combined with hyperglycemia and hyperlipidemia.

scholarly journals Hepatoprotective properties of glycyrrhizic acid

2020 ◽  
pp. 96-108
Author(s):  
S. V. Okovity ◽  
K. L. Raikhelson ◽  
A. V. Volnukhin ◽  
D. A. Kudlai
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Intrahepatic Cholestasis ◽  
Fatty Liver Disease ◽  
Glycyrrhizic Acid ◽  
Evidence Base ◽  
Alcoholic Fatty Liver ◽  
Organ Systems ◽  
Wide Range ◽  
Alcoholic Fatty Liver Disease

The review is devoted to the problem of treatment of non-alcoholic fatty liver disease, which is the most common pathology of the hepato-biliary system worldwide and is characterized by an increasing frequency, including of more severe forms. A wide range of pathogenetic relationships of non-alcoholic fatty liver disease with diseases of other organ systems, primarily with diseases of the cardiovascular system, type 2 diabetes mellitus, chronic kidney disease and diseases of the biliary tract, is presented. The main mechanisms of comorbidity are insulin resistance, oxidative stress, inflammation, disorders of carbohydrate and fat metabolism. An approach to the therapy of this disease based on the concept of comorbidity has been substantiated. As a rational therapeutic choice, a molecule of glycyrrhizic acid is presented, which has pleiotropic effects, including anti-inflammatory, antioxidant, antifibrotic and immunomodulatory effects. The evidence base for glycyrrhizic acid is formed by a large array of clinical trials, including randomized placebo-controlled trials conducted both in Russia and abroad, in infectious and non-infectious liver diseases, including non-alcoholic fatty liver disease. Attention is focused on non-alcoholic fatty liver disease with intrahepatic cholestasis associated with a more severe course and high rates of disease progression. A theoretical justification for the use of a combination of glycyrrhizic acid and ursodeoxycholic acid in such patients is presented. The reason for this is the potential synergy of the two molecules, based on the induction of CYP3A4, and associated with the effect on inflammation, as a factor in the development of intrahepatic cholestasis and cholestasis itself.

scholarly journals Protective effects of the herbal medicine goshajinkigan in a rat model of non-alcoholic fatty liver disease

2012 ◽  
Vol 33 (6) ◽  
pp. 373-376 ◽  
Author(s):  
Yoshihiko Hirotani ◽  
Ayae Doi ◽  
Tomoki Takahashi ◽  
Hanako Umezawa ◽  
Yoko Urashima ◽  
...  
Keyword(s):  
Liver Disease ◽  
Herbal Medicine ◽  
Fatty Liver ◽  
Rat Model ◽  
Fatty Liver Disease ◽  
Protective Effects ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Vanillic Acid and Non-Alcoholic Fatty Liver Disease: A Focus on AMPK in Adipose and Liver Tissues

2021 ◽  
Vol 27 ◽  
Author(s):  
Sepideh Shekari ◽  
Fatemeh Khonsha ◽  
Mohammad Rahmati-Yamchi ◽  
Hamid Reza Nejabati ◽  
Ali Mota
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Vanillic Acid ◽  
Fatty Liver Disease ◽  
Wide Spectrum ◽  
Special Focus ◽  
Protective Effects ◽  
Mice Model ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

: Non-alcoholic fatty liver disease (NAFLD), a growing health issue around the world, is defined as the presence of steatosis in the liver without any other detectable byproducts such as alcohol consumption which includes a wide spectrum of pathologies, such as steatohepatitis, cirrhosis, and hepatocellular carcinoma. A growing body of evidence indicates that the reduction in the 5' adenosine monophosphate-activated protein kinase (AMPK) activity, which could be activated by the consumption of the drugs, hormones, cytokines, and dietary restriction, is related to some metabolic disorders such as obesity, diabetes, PCOS, and NAFLD. Vanillic acid (VA), as an anti-inflammatory, anti-oxidative, anti-angiogenic and anti-metastatic factor, has protective effects on the liver as in two animal models of liver damage. It reduces serum levels of transaminases, inflammatory cytokines, and the accumulation of collagen in the liver and prevents liver fibrosis. Besides, it decreases body and adipose tissue weight in a mice model of obesity and, similar to the liver tissue, diminishes adipogenesis through the activation of AMPK. It has been reported that VA can target almost all of the metabolic abnormalities of NAFLD, such as hepatic steatosis, inflammation, and hepatic injury, at least partially through the activation of AMPK. Therefore, in this review, we will discuss the possible and hypothetical roles of VA in NAFLD, with a special focus on AMPK.

scholarly journals Fermented Korean Red Ginseng Extract Enriched in Rd and Rg3 Protects against Non-Alcoholic Fatty Liver Disease through Regulation of mTORC1

Nutrients ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 2963 ◽  
Author(s):  
Su-Yeon Choi ◽  
Jeong-Su Park ◽  
Chang-Ho Shon ◽  
Chae-Young Lee ◽  
Jae-Myun Ryu ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fast Food ◽  
Fatty Liver Disease ◽  
Protective Effects ◽  
Red Ginseng ◽  
Korean Red Ginseng ◽  
Ginseng Extract ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

The fermentation of Korean red ginseng (RG) increases the bioavailability and efficacy of RG, which has a protective role in various diseases. However, the ginsenoside-specific molecular mechanism of the fermented RG with Cordyceps militaris (CRG) has not been elucidated in non-alcoholic fatty liver disease (NAFLD). A mouse model of NAFLD was induced by a fast-food diet (FFD) and treated with CRG (100 or 300 mg/kg) for the last 8 weeks. CRG-mediated signaling was assessed in the liver cells isolated from mice. CRG administration significantly reduced the FFD-induced steatosis, liver injury, and inflammation, indicating that CRG confers protective effects against NAFLD. Of note, an extract of CRG contains a significantly increased amount of ginsenosides (Rd and Rg3) after bioconversion compared with that of conventional RG. Moreover, in vitro treatment with Rd or Rg3 produced anti-steatotic effects in primary hepatocytes. Mechanistically, CRG protected palmitate-induced activation of mTORC1 and subsequent inhibition of mitophagy and PPARα signaling. Similar to that noted in hepatocytes, CRG exerted anti-inflammatory activity through mTORC1 inhibition-mediated M2 polarization. In conclusion, CRG inhibits lipid-mediated pathologic activation of mTORC1 in hepatocytes and macrophages, which in turn prevents NAFLD development. Thus, the administration of CRG may be an alternative for the prevention of NAFLD.

scholarly journals β-Cryptoxanthin Prevents Non-alcoholic Fatty Liver Disease Through Different Mechanisms Depending on the Presence or Absence of Carotenoid Cleavage Enzymes (FS06-03-192)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Ji Ye Lim ◽  
Chun Liu ◽  
Kang-Quan Hu ◽  
Donald E Smith ◽  
Dayong Wu ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Molecular Mechanisms ◽  
Protective Effects ◽  
Alcoholic Fatty Liver ◽  
Mesenteric Adipose Tissue ◽  
Alcoholic Fatty Liver Disease ◽  
Β Carotene

Abstract Objectives β-Cryptoxanthin (BCX), a provitamin A carotenoid, is cleaved by carotenoid cleavage enzymes including β-carotene-15, 15′-oxygenase (BCO1) to generate vitamin A, and β-carotene-9′, 10′-oxygenase (BCO2) which yields bioactive apo-carotenoids. Dietary supplementation of BCX can prevent non-alcoholic fatty liver disease (NAFLD), which is the most common chronic liver disease worldwide. This study aimed to investigate whether BCX-mediated protection against NAFLD proceeds through the liver-mesenteric adipose tissue axis depending on the presence or absence of BCO1/BCO2. Methods Six-week-old male wild type (WT) mice (n = 30) and congenic BCO1−/−/BCO2−/− double KO (DKO) mice (n = 30) were randomly fed either a high-refined carbohydrate diet (HRCD, 66.5% CHO) or HRCD with BCX (10 mg/kg diet) for 24 weeks. Results Hepatic levels of BCX, but not retinol and retinyl palmitate, were significantly (P < 0.001) higher (33-fold) in the DKO mice than in the WT mice. BCX significantly reduced hepatic steatosis and total cholesterol levels in both WT and DKO mice in comparison with their HRCD counterparts (P < 0.01 and P < 0.001, respectively), albeit through different mechanisms. In the liver, BCX significantly (P < 0.05) down-regulated mRNA for cholesterol synthesis genes Hmgcr and Hmgs1 and nuclear bile acid receptor Fxr, and up-regulated cholesterol catabolism gene Cyp7a1 in DKO mice in comparison with their HRCD counterparts. Furthermore, BCX significantly (P < 0.05) up-regulated antioxidant enzymes Sod1 and Cat in DKO mice in comparison with HRCD littermates. In WT mice, BCX significantly (P < 0.05) up-regulated hepatic mRNA for cholesterol efflux gene Abcg5 and nuclear receptor Shp in comparison with their HRCD counterparts. In mesenteric adipose tissue, BCX significantly down-regulated (P < 0.05) the inflammatory cytokine Il6 and up-regulated fatty acid β-oxidation marker Acox1 and Sirt1 in DKO mice but significantly (P < 0.05) suppressed lipogenesis marker Acc1 in WT mice. Conclusions The protective effects of dietary BCX against HRCD-induced NAFLD are achieved through different molecular mechanisms in the liver-mesenteric adipose tissue axis and depend on the carotenoid cleavage enzymes. Funding Sources NIFA/AFRI (2017-67017-26363) and USDA/ARS (58-1950-0074).

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