Gypenosides Prevent and Dissolve Cholesterol Gallstones by Modulating the Homeostasis of Cholesterol and Bile Acids

Abstract

Gypenosides (GPs), obtained from Gynostemma pentaphyllum (Thunb.) Makino, have been traditionally prescribed to treat metabolic disorders in Asians. This study assessed whether GPs could prevent lithogenic diet (LD)-induced cholesterol gallstone (CG) formation and enhance CG dissolution in mice. Gallstone-susceptible C57BL/6J mice were fed an LD or normal chow, with or without GPs. Bile acids (BAs) in gallbladder bile were analyzed by liquid chromatography-tandem mass spectrometry. Differentially expressed hepatic genes were identified by RNA sequencing, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. GPs were found to prevent LD-induced CG formation and to dissolve pre-existing LD-induced CGs. GPs reduced total cholesterol levels and increased BA levels in bile, as well as reducing the BA Hydrophobicity Index, ratio of 12α-hydroxylated (12α-OH) to non-12α-OH BAs, and Cholesterol Saturation Index in gallbladder bile. GO and KEGG pathway enrichment analyses indicated that GPs-induced genes were involved in BA biosynthesis and cholesterol metabolism. GPs increased the hepatic expression of genes encoding the cytochrome P450 (Cyp) enzymes Cyp7a1, Cyp7b1, and Cyp8b1, while decreasing the hepatic expression of genes encoding the adenosine triphosphate-binding cassette (Abc) transporters Abcg5 and Abcg8. GPs may be a promising strategy for preventing and dissolving CGs.

Chaihu Shugan prevents cholesterol gallstone formation by ameliorating the microbiota dysbiosis and metabolic disturbance in mice

“…The intersection of the serum and liver metabolites revealed several potential therapeutic targets. Furthermore, KEGG functional analysis showed that ABC transporters and bile secretion were closely associated with CGS, previous microbiota and metabolism results, and other relevant studies ( Figueira-Mansur et al, 2020 ; Ye et al, 2021 ; Ye et al, 2022 ; Zhuang et al, 2022 ). In our study, obacunone was the most common active metabolite in the serum, liver, and gallbladder.…”

Natural Products Targeting PI3K/AKT in Myocardial Ischemic Reperfusion Injury: A Scoping Review

“…Gypenoside is the main component of Gynostemma pentaphyllum (Thunb.) Makino [ 33 , 34 ], and exist mainly as dammarane type-triterpene glycosides [ 35 ]. In an oxygen–glucose deprivation/reperfusion (OGD/R) cell and MIRI rat models, gypenoside treatment ameliorated impairments in cardiac morphology at a dose of 50 mg/kg, 100 mg/kg, and 200 mg/kg [ 29 ].…”

Integrative metabolomic and transcriptomic analyses reveals the accumulation patterns of key metabolites associated with flavonoids and terpenoids of Gynostemma pentaphyllum (Thunb.) Makino

“…Therefore, G. pentaphyllum is a plant with the same origin as medicine and food. G. pentaphyllum has many functions such as liver protection, anti-tumor, anti-inflammation, and balancing blood sugar and blood lipids 6 – 10 that is often made into G. pentaphyllum tea edible.…”