Ginsenoside Rb1 protects against diabetes-associated metabolic disorders in Kkay mice by reshaping gut microbiota and fecal metabolic profiles. (1st March 2023)

• Record Type: Journal Article
• Authors: Zhou, Rongrong; He, Dan; Zhang, Haichao; Xie, Jing; Zhang, Shuihan; Tian, Xuefei; Zeng, Hongliang; Qin, Yuhui; Huang, Luqi
• Is Part Of: Journal of ethnopharmacology. Volume 303(2023)
• Publication Date: 2023-03-01
• Subjects: Ginsenoside Rb1 -- Gut microbiota -- Fecal metabolites -- Metabolic disorders -- Insulin resistance -- Antibiotics; Ethnopharmacology -- Periodicals; Pharmacognosy -- Periodicals; Herbs -- Periodicals; Herbs -- Periodicals; Pharmacognosy -- Periodicals; Pharmacognosie -- Périodiques; Herbes -- Périodiques; 615.1
• DOI: 10.1016/j.jep.2022.115997
• Languages: English
• ISSNs: 0378-8741

Abstract

Abstract: Ethnopharmacological relevance: Panax quinquefolius Linn. is one of the most valuable herbal medicine in the world for its broad health benefits, including anti-diabetes. Ginsenoside Rb1, the principal active constituent of Panax quinquefolius Linn., could attenuate insulin resistance and metabolic disorders. The dysfunction of gut microbiota and fecal metabolites plays an important role in the pathogenesis of Type 2 Diabetes mellitus (T2DM). However, whether ginsenoside Rb1's hypoglycemic effect is related to gut microbiota remains elusive. Aim of the study: Our study aimed to explore the insulin-sensitizing and anti-diabetic effects of ginsenoside Rb1 as well as the underlying mechanisms. Materials and methods: The T2DM model were established by high fat diet (HFD)-induced Kkay mice. The anti-diabetic effect of ginsenoside Rb1 (200 mg/kg/day) was evaluated by random blood glucose (RBG), fasting blood glucose (FBG), glucose tolerance test (OGTT), serum insulin level, insulin resistance index (HOMA-IR), pancreatic histology analysis, liver indexes, total triglyceride (TG) and total cholesterol (TC). Subsequently, 16S rRNA sequencing and LC-MS-based untargeted metabolomics were applied to characterize the microbiome and metabolites profile in HFD-induced Kkay mice, respectively. Finally, antibiotic treatment was used to validate the potential mechanism of ginsenoside Rb1 by modulating gut microbiota. Results: Our results showed that ginsenoside Rb1 reduced blood glucose, OGTT, serum insulin level, HOMA-IR, liver indexes as well as pancreatic injury. In addition, the ginsenoside Rb1 reversed the gut microbiota dysbiosis in diabetic Kkay mice, as indicated by the elevated abundance of Parasutterella, decreased population of Alistipes, f_Prevotellaceae_unclassified, Odoribacter, Anaeroplasma . Moreover, ginsenoside Rb1 altered free fatty acid (FFA) levels in fecal metabolites, such as decreased the level of α-linolenic acid, 13-OxoODE, oleic acid, 13-HODE, arachidonic acid, palmitic acid, stearic acid, while increased the level of PC (14:0/22:1(13Z)) and PC (16:0/16:0). Notably, ginsenoside Rb1 failed to improve HFD-induced diabetes in Kkay mice with antibiotics intervention. Conclusion: These findings suggested that ginsenoside Rb1 may serve as a potential prebiotic agent to modulate specific gut microbes and related metabolites, which play essential roles in diabetes-associated metabolic disorders and insulin resistance. Graphical abstract: Image 1 Highlights: Ginsenoside Rb1 exerted anti-diabetic effects in HFD-induced Kkay mice. Ginsenoside Rb1 modulated the diabetes-associated bacterial taxa. Ginsenoside Rb1 attenuated the free fatty acids metabolism disorders. Ginsenoside Rb1 from ginseng may serve as a potential prebiotic agent against metabolic disorders in diabetic patients.