The Affiliated Hospital of Hunan Academy of Traditional Chinese Medicine, Changsha, China.
Institute of Chinese Materia Medica, Hunan Academy of Chinese Medicine, Changsha, China; Hunan University of Chinese Medicine, Changsha, PR China.
J Ethnopharmacol. 2023 Mar 1;303:115997. doi: 10.1016/j.jep.2022.115997. Epub 2022 Dec 9.
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.
民族药理学相关性：西洋参是世界上最有价值的草药之一，具有广泛的健康益处，包括抗糖尿病。人参皂苷 Rb1 是西洋参的主要活性成分，可减轻胰岛素抵抗和代谢紊乱。肠道微生物群和粪便代谢物的功能障碍在 2 型糖尿病（T2DM）的发病机制中起着重要作用。然而，人参皂苷 Rb1 的降血糖作用是否与肠道微生物群有关仍不清楚。
研究目的：本研究旨在探讨人参皂苷 Rb1 的胰岛素增敏和抗糖尿病作用及其潜在机制。
材料和方法：采用高脂肪饮食（HFD）诱导的 Kkay 小鼠建立 T2DM 模型。通过随机血糖（RBG）、空腹血糖（FBG）、葡萄糖耐量试验（OGTT）、血清胰岛素水平、胰岛素抵抗指数（HOMA-IR）、胰腺组织学分析、肝指数、总甘油三酯（TG）和总胆固醇（TC）评估人参皂苷 Rb1（200mg/kg/天）的抗糖尿病作用。随后，应用 16S rRNA 测序和基于 LC-MS 的非靶向代谢组学分别对 HFD 诱导的 Kkay 小鼠的微生物组和代谢物谱进行了表征。最后，抗生素治疗用于通过调节肠道微生物群来验证人参皂苷 Rb1 的潜在机制。
结果：研究结果表明，人参皂苷 Rb1 降低了血糖、OGTT、血清胰岛素水平、HOMA-IR、肝指数和胰腺损伤。此外，人参皂苷 Rb1 逆转了糖尿病 Kkay 小鼠的肠道微生物群失调，表现为 Parasutterella 的丰度增加，Alistipes、f_Prevotellaceae_unclassified、Odoribacter、Anaeroplasma 的丰度降低。此外，人参皂苷 Rb1 改变了粪便代谢物中的游离脂肪酸（FFA）水平，如降低了α-亚麻酸、13-OxoODE、油酸、13-HODE、花生四烯酸、棕榈酸、硬脂酸的水平，同时增加了 PC（14:0/22:1(13Z)) 和 PC（16:0/16:0）的水平。值得注意的是，抗生素干预的 Kkay 小鼠中，人参皂苷 Rb1 未能改善 HFD 诱导的糖尿病。
结论：这些发现表明，人参皂苷 Rb1 可能作为一种潜在的益生元物质，通过调节特定的肠道微生物群和相关代谢物来发挥作用，这些物质在与糖尿病相关的代谢紊乱和胰岛素抵抗中起着重要作用。
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