Ilexgenin A enhances the effects of simvastatin on non-alcoholic fatty liver disease without changes in simvastatin pharmacokinetics

Lu, Ya‐Wen; Zhu, Yuyan; Zhang, Li; Li, Ping; Yang, Jie; Wen, Xin

doi:10.1016/s1875-5364(18)30077-3

Cited by 5 publications

(3 citation statements)

References 24 publications

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“…SIM as a hypolipidemic drug has been widely employed for the treatment of lipid metabolism disorders, including hyperlipidemia, hypercholesterolemia (Miller et al, 2001;Krysiak et al, 2014). While most efforts to understand SIM have focused on genetic polymorphisms (Catry et al, 2015) and pharmacokinetics (Lu et al, 2018), recent study revealed that certain pharmacotherapies can improve metabolic diseases through modulation of the gut microbiota (Yoo et al, 2014). However, the composition of the gut microbiota in response to hypolipidemic effect of SIM has not yet been fully investigated.…”

Section: Discussionmentioning

confidence: 99%

The Effect of Simvastatin on Gut Microbiota and Lipid Metabolism in Hyperlipidemic Rats Induced by a High-Fat Diet

et al. 2020

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The objective of this study was to investigate the effects of simvastatin (SIM) on lipid metabolism disorders and gut microbiota in high-fat diet-induced hyperlipidemic rats. The obtained results revealed that feeding rats with SIM (20 mg/kg/day) significantly decreased serum lipid level and inhibited hepatic lipid accumulation and steatosis. Histological analysis further indicated that SIM reduced lipid deposition in adipocytes and hepatocytes in comparison with that of the HFD group. The underlying mechanisms of SIM administration against HFD-induced hyperlipidemia were also studied by UPLC-Q-TOF/MS-based liver metabonomics coupled with pathway analysis. Metabolic pathway enrichment analysis of liver metabolites with significant difference in abundance indicated that fatty acids metabolism and amino acid metabolism were the main metabolic pathways altered by SIM administration. Meanwhile, operational taxonomic units (OTUs) analysis revealed that oral administration of SIM altered the composition of gut microbiota, including Ruminococcaceae (OTU960) and Lactobacillus (OTU152), and so on. Furthermore, SIM treatment also regulated the mRNA levels of the genes involved in lipid and cholesterol metabolism. Immunohistochemistry (IHC) analysis of the liver-related proteins (CD36, CYP7A1 and SREBP-1C) showed that oral administration of SIM could regulate the levels of the protein expression related to hepatic lipid metabolism.

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Section: Discussionmentioning

confidence: 99%

The Effect of Simvastatin on Gut Microbiota and Lipid Metabolism in Hyperlipidemic Rats Induced by a High-Fat Diet

et al. 2020

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“…These advantages prompted us to further isolate the functional compounds from this herb. IA, one of the major components obtained from this herb, could improve nonalcoholic fatty liver disease in rats and ameliorate endothelial dysfunction (Lu et al, ). However, its mechanisms underlying its beneficial effects on endothelial injury are still unknown.…”

Section: Discussionmentioning

confidence: 99%

Ilexgenin A inhibits mitochondrial fission and promote Drp1 degradation by Nrf2‐induced PSMB5 in endothelial cells

Zhu

et al. 2019

Drug Development Research

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Atherosclerosis (AS) is one of important events involving in the pathological process of coronary artery disease. Many traditional Chinese medicines have been widely used for the treatment of AS. Previous studies have demonstrated that Ilexgenin A (IA) obtained from Ilex hainanensis Merr. could improve AS development. However, its underlying mechanism is still unknown. This study was conducted to explore the possible targets and mechanisms involving in the antiatheroclerosis effect of IA. The results showed IA significantly promoted NO production, reduced reactive oxygen species (ROS) generation, and inflammatory cytokine production induced by palmitate (PA) in endothelial cells, demonstrating IA could improve endothelial dysfunction. Meanwhile, IA dramatically inhibited dynamin-related protein 1 (Drp1) expression and mitochondrial fission induced by PA whereas proteasome inhibitor epoxomicin attenuated its effect on Drp1 expression, indicating IA decreased Drp1 expression with regulation of proteasome. Furthermore, IA also could increase the expression of proteasome subunit beta type5 (PSMB5) and activate nuclear factor-like 2 (Nrf2). Nrf2 knockdown eliminated the induction effect of IA on PSMB5 expression while abrogated its inhibition on ROS generation and mitochondrial fission stimulated by PA. These results demonstrated that IA could promote PSMB5 expression in an Nrf2-dependent manner, resulting in the suppression of mitochondrial fission, and thus improve endothelial dysfunction. These findings laid a foundation to the future development of IA as an agent to the prevention and treatment of AS. K E Y W O R D S endothelial dysfunction, Ilexgenin A, mitochondrial fission, Nrf2

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“…Specifically, atorvastatin has been shown to effectively ameliorate NAFLD-related hyperlipidemia in rats, reducing liver steatosis and modulating the expression of lipid metabolism-regulating genes [74]. Likewise, the treatment of NAFLD rats with simvastatin and fluvastatin reduced their liver weight, hepatic index, ALT, AST, and regulated abnormal lipid metabolism [75,76].…”

Section: Improvement Of Steatosismentioning

confidence: 99%

A Systematic Review of Statins for the Treatment of Nonalcoholic Steatohepatitis: Safety, Efficacy, and Mechanism of Action

Zhang,

Ren,

Zhang

et al. 2024

Molecules

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Nonalcoholic fatty liver disease (NAFLD) is the liver component of a cluster of conditions, while its subtype, nonalcoholic steatohepatitis (NASH), emerges as a potentially progressive liver disorder that harbors the risk of evolving into cirrhosis and culminating in hepatocellular carcinoma (HCC). NASH and cardiovascular disease (CVD) have common risk factors, but compared to liver-related causes, the most common cause of death in NASH patients is CVD. Within the pharmacological armamentarium, statins, celebrated for their lipid-modulating prowess, have now garnered attention for their expansive therapeutic potential in NASH. Evidence from a plethora of studies suggests that statins not only manifest anti-inflammatory and antifibrotic properties but also impart a multifaceted beneficial impact on hepatic health. In this review, we used “statin”, “NAFLD”, “NASH”, and “CVD” as the major keywords and conducted a literature search using the PubMed and Web of Science databases to determine the safety and efficacy of statins in patients and animals with NASH and NAFLD, and the mechanism of statin therapy for NASH. Simultaneously, we reviewed the important role of the intestinal microbiota in statin therapy for NASH, as it is hoped that statins will provide new insights into modulating the harmful inflammatory microbiota in the gut and reducing systemic inflammation in NASH patients.

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Ilexgenin A enhances the effects of simvastatin on non-alcoholic fatty liver disease without changes in simvastatin pharmacokinetics

Cited by 5 publications

References 24 publications

The Effect of Simvastatin on Gut Microbiota and Lipid Metabolism in Hyperlipidemic Rats Induced by a High-Fat Diet

The Effect of Simvastatin on Gut Microbiota and Lipid Metabolism in Hyperlipidemic Rats Induced by a High-Fat Diet

Ilexgenin A inhibits mitochondrial fission and promote Drp1 degradation by Nrf2‐induced PSMB5 in endothelial cells

A Systematic Review of Statins for the Treatment of Nonalcoholic Steatohepatitis: Safety, Efficacy, and Mechanism of Action

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