Gut Microbiota Modulates the Protective Role of Ginsenoside Compound K Against Sodium Valproate-Induced Hepatotoxicity in Rat

Abstract

This study aimed to investigate the potential role of gut microbiota in the hepatotoxicity of sodium valproate (SVP) and the protective effect of ginsenoside compound K (G-CK) administration against SVP-induced hepatotoxicity in rats. Measurements of 16S rRNA showed that SVP supplementation led to a 140.749- and 248.900-fold increase in the relative abundance of Akkermansia muciniphila (A. muciniphila) and Bifidobacterium pseudolongum (B. pseudolongum), respectively (p < 0.05). The increase in A. muciniphila was almost completely reversed by G-CK treatment. The relative abundance of A. muciniphila was strongly positively correlated with aspartate transaminase (AST) and alanine aminotransferase (ALT) levels (r > 0.78, p < 0.05). The PICRUSt analysis showed that G-CK could inhibit the changes of seven pathways caused by SVP, of which four pathways, including the fatty acid biosynthesis, lipid biosynthesis, glycolysis/gluconeogenesis, and pyruvate metabolism, were found to be negatively correlated with AST and ALT levels (r ≥ 0.70, p < 0.01 or < 0.05). In addition, the glycolysis/gluconeogenesis and pyruvate metabolism were negatively correlated with the relative abundance of A. muciniphila (r > 0.65, p < 0.01 or < 0.05). This alteration of the gut microbiota composition that resulted in observed changes to the glycolysis/gluconeogenesis and pyruvate metabolism may be involved in both the hepatotoxicity of SVP and the protective effect of G-CK administration against SVP-induced hepatotoxicity. Our study provides new evidence linking the gut microbiota with SVP-induced hepatotoxicity.

Biological Activity and Sterilization Mechanism of Marine Fungi‐derived Aromatic Butenolide Asperbutenolide A Against Staphylococcus aureus

“…KEGG could provide molecular biological function of the DEGs at the molecular, cellular and organism levels. [27] The biological pathways are important for understanding the sterilization mechanism of asperbutenolide A against with MRSA and, in the current study, the DEGs were mainly involved in the metabolic pathways of amino acid metabolism, carbon metabolism, membrane transport, etc (Figure 3B). The top five downregulated and up-regulated genes of the amino acid metabolism pathways were argF, arcC1, tdcB, ald, argH and ureB, trpC, ureC, trpD, ureA, respectively (Figure 4).…”

Akkermansia muciniphilaMucT attenuates sodium valproate‐induced hepatotoxicity and upregulation of Akkermansia muciniphila in rats

“…muciniphila increased after the oral administration of SVP, and there was a strong positive correlation between the relative abundance of A. muciniphila and liver function indicators ALT and AST activities (correlation coefficient >0.78). 15 Because the opposite effects of A. muciniphila under different conditions have been reported, it Oxidative stress is one of the common features of SVP-induced liver injury, 38 and anti-oxidative stress is one of the important mechanisms by which A. muciniphila exerts hepatoprotective effect. 18,20 Oxidative stress results from an imbalance between oxidative and antioxidant effects, and is manifested by elevated levels of total oxidants and oxidation products, as well as reduced levels of endogenous antioxidants.…”

“…The study of the ‘drug‐microbe‐gut‐liver’ model and the interactions of its components is of great significance, and it is becoming a new direction for the exploration of the mechanism of drug‐induced liver injury. Our previous study demonstrated that SVP resulted in a disruption of the gut microbiota's structure with a 140‐fold increase in the relative abundance of faecal Akkermansia muciniphila ( A. muciniphila ) in rats, which was partially ameliorated by ginsenoside compound K, a liver‐protective compound 15 …”

The changes of gut microbiota and metabolites in different drug-induced liver injuries

“…VPA is a commonly used antiepileptic agent whose induced hepatotoxicity has been identified as the third most common cause of drug-induced liver death by the World Health Organization [88,89]. Zhou et al [90]found that sodium valproate-induced hepatotoxicity was related to gut microbiota dysbiosis.…”