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

Sun, Xue; Duan, Xingping; Wang, Changyuan; Liu, Zhihao; Sun, Pengyuan; Huo, Xiaokui; Ma, Xiaodong; Sun, Huijun; Liu, Kexin; Meng, Qiang

doi:10.1016/j.ejphar.2017.04.021

Cited by 66 publications

(52 citation statements)

References 20 publications

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“…Glycyrrhhizic acid (18α- and 18β-, GA) is a triterpenoid derived from Glycyrrhiza glabra L. (licorice) root. Previous investigations of the active components in licorice mainly focused on glycyrrhhizic acid and its derivatives, as they were normally thought to be responsible for the hepatoprotective, antioxidant, anticancer, and anti-inflammatory effects of licorice [ 13 , 14 , 15 ]. We therefore hypothesize that GA may help to protect against ALD.…”

Section: Introductionmentioning

confidence: 99%

RETRACTED: Protective Effect of Glycyrrhizic Acid on Alcoholic Liver Injury in Rats by Modulating Lipid Metabolism

et al. 2018

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Glycyrrhhizic acid (GA), including 18α-glycyrrhizic acid (18α-GA) and 18β-glycyrrhizic acid (18β-GA), is the main active ingredient of licorice. GA is generally considered an effective pharmacological strategy protecting against hepatic disease; however, the optimal compatibility proportion of 18α-GA and 18β-GA against alcoholic liver disease (ALD) and the underlying mechanism are not well established. Hence, this study was designed to explore the optimal compatibility proportion of 18α-GA and 18β-GA against ALD, followed by investigating the underlying mechanisms. SD rats were administered 40% ethanol once a day, accompanied by treatment with different proportions of 18α-GA and 18β-GA for four weeks. Then all rats were anesthetized with chloral hydrate and blood samples were taken from the abdominal aorta for biochemical assay. Livers were also collected and the liver function, lipid profile, ROS production, and mRNA and protein levels of related genes involved in lipid metabolism were assessed. The results showed that 18α-GA and 18β-GA, particularly at a proportion of 4:6, significantly reduced liver damage, lipid accumulation, and oxidative stress in ethanol-induced rats, as indicated by the decreased levels of alanine aminotransferase (ALT) and aminotransferase (AST) in serum, improvement of liver histopathological changes, regulation of total cholesterol (TC), total triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), and modulation of superoxide dismutase (SOD), glutathione (GSH), and malonaldehyde (MDA). Moreover, the combination treatment with 18α-GA and 18β-GA substantially reduced the mRNA and protein levels of sterol regulatory element-binding protein-1c (SREBP-1c) and acetyl-coal carboxylase (ACC); meanwhile, increased levels of peroxisome proliferators activated receptor-α (PPAR-α) and carnitine palmitoy transferase-1 (CTP-1) in the liver tissues of ethanol-induced rats. In conclusion, our results indicated that the optimal compatibility proportion of 18α-GA and 18β-GA protecting against ALD was 4:6, and the mechanism was associated with the regulation of oxidative stress and lipid metabolism.

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Section: Introductionmentioning

confidence: 99%

RETRACTED: Protective Effect of Glycyrrhizic Acid on Alcoholic Liver Injury in Rats by Modulating Lipid Metabolism

et al. 2018

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“…Shenling Baizhu San (SLBZS) is a famous traditional Chinese medicine formula that has been used for hundreds of years for the treatment of digestive and metabolic disorders. More recently, accumulating evidence reveals that several bioactive ingredients of SLBZS, such as Ginsenoside Rb2, Ginsenoside Rg3, and glycyrrhizic acid, exert positive effects in protecting against NAFLD [16][17][18]. Our previous studies have demonstrated that SLBZS can protect against NAFLD by improving hepatic inflammation, inhibiting hepatic lipid accumulation, and thereby reducing hepatic steatosis [19,20].…”

Section: Introductionmentioning

confidence: 97%

Chinese Herbal Medicine Formula Shenling Baizhu San Ameliorates High-Fat Diet-Induced NAFLD in Rats by Modulating Hepatic MicroRNA Expression Profiles

Pan

Deng

Zheng

et al. 2019

Evidence-Based Complementary and Alternative Medicine

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Objective. The purpose of present study was to investigate the potential mechanism underlying the protective effect of Shenling Baizhu San (SLBZS) on nonalcoholic fatty liver disease (NAFLD) by microRNA (miRNA) sequencing. Methods. Thirty male Wistar rats were randomly divided into a normal control (NC) group, a high-fat diet (HFD) group, and an SLBZS group. After 12 weeks, the biochemical parameters and liver histologies of the rats were assessed. The Illumina HiSeq 2500 sequencing platform was used to analyse the hepatic miRNA expression profiles. Representative differentially expressed miRNAs were further validated by qRT-PCR. The functions of the differentially expressed miRNAs were analysed by bioinformatics. Results. Our results identified 102 miRNAs that were differentially expressed in the HFD group compared with the NC group. Among those differentially expressed miRNAs, the expression levels of 28 miRNAs were reversed by SLBZS administration, suggesting the modulation effect of SLBZS on hepatic miRNA expression profiles. The qRT-PCR results confirmed that the expression levels of miR-155-5p, miR-146b-5p, miR-132-3p, and miR-34a-5p were consistent with those detected by sequencing. Bioinformatics analyses indicated that the target genes of the differentially expressed miRNAs reversed by SLBZS were mainly related to metabolic pathways. Conclusion. This study provides novel insights into the mechanism of SLBZS in protecting against NAFLD; this mechanism may be partly related to the modulation of hepatic miRNA expression and their target pathways.

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“…20,21 Abundant studies provide strong evidence that PEPCK, G6Pase, SREBP-1c and FAS are implicated in regulating glucose and lipid homeostasis. 22 For instance, a recent study demonstrated that Yangonin, a kavalactone isolated from Kava, not only modulated blood glucose homeostasis through regulation of gluconeogenesis-related genes such as PEPCK and G6Pase, but attenuated lipid accumulation in the liver via inhibition of hepatic lipogenesis-related proteins including SREBP-1c and FAS. 4 In addition, alterations of glucose and lipid metabolism can lead to an increased accumulation of TG in liver cells and formation of the fatty liver.…”

Section: Discussionmentioning

confidence: 99%

Knockdown of long non‐coding RNA Gm10804 suppresses disorders of hepatic glucose and lipid metabolism in diabetes with non‐alcoholic fatty liver disease

Huang

Zhi

et al. 2020

Cell Biochemistry & Function

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Deregulated glucose and lipid metabolism are the primary underlying manifestations associated with diabetes mellitus (DM) and non-alcoholic fatty liver disease (NAFLD). This study aims to investigate the role of Gm10804, a novel long noncoding RNA (lncRNA), in regulating hepatic glucose and lipid metabolism in DM complicated with NAFLD (DM-NAFLD). Mouse primary hepatocytes exposed to high glucose (HG) were used as a cell model. A mouse DM-NAFLD model was established by high-energy feeding combined with intraperitoneal injection of streptozotocin. The results showed that Gm10804 expression was upregulated in HG-treated hepatocytes and livers from DM-NAFLD mice. Results in hepatocytes in vitro demonstrated that Gm10804 overexpression aggravated, whereas Gm10804 silencing abrogated HG-induced increase in intracellular triglyceride (TG) content, lipid accumulation and expression of hepatic lipogenic proteins (sterol regulatory element-binding proteins 1-c [SREBP-1c] and fatty acid synthase [FAS]) and enzymes for gluconeogenesis (phosphoenolpyruvate carboxykinase [PEPCK] and glucose-6-phosphatase [G6Pase]). Further in vivo assays showed that lentivirus-mediated hepatic knockdown of Gm10804 alleviated hepatic steatosis and lipid accumulation, and decreased expression of hepatic PEPCK, G6Pase, SREBP-1c and FAS in DM-NAFLD mice. In summary, Gm10804 knockdown attenuates hepatic lipid accumulation by ameliorating disorders of hepatic glucose and lipid metabolism in DM-NAFLD. Significance of the study: We first discovered that Gm10804 knockdown attenuated hepatic lipid accumulation by ameliorating disorders of hepatic glucose and lipid metabolism in DM-NAFLD. These results help to understand the pathogenesis and development of DM-NAFLD and provide some clues for further understanding the regulation of lncRNAs in glucose and lipid metabolism.

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

Cited by 66 publications

References 20 publications

RETRACTED: Protective Effect of Glycyrrhizic Acid on Alcoholic Liver Injury in Rats by Modulating Lipid Metabolism

RETRACTED: Protective Effect of Glycyrrhizic Acid on Alcoholic Liver Injury in Rats by Modulating Lipid Metabolism

Chinese Herbal Medicine Formula Shenling Baizhu San Ameliorates High-Fat Diet-Induced NAFLD in Rats by Modulating Hepatic MicroRNA Expression Profiles

Knockdown of long non‐coding RNA Gm10804 suppresses disorders of hepatic glucose and lipid metabolism in diabetes with non‐alcoholic fatty liver disease

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