Journal
JOURNAL OF ETHNOPHARMACOLOGY
Volume 281, Issue -, Pages -Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.jep.2021.114558
Keywords
Astragaloside IV; T2DM; Insulin resistance; AMPK; SIRT1 and PI3K; AKT signaling; pathways; Gut microbiota
Categories
Funding
- Natural Science Foundation of China [21407104, 81803698, 31760016]
- Fundamental Research Funds for the Central Universities [3102019CXY002]
- General Plan of Shaanxi Province [2021NY-161, 2019GY-138, 2020GY-236]
- Key industrial chain projects of Shaanxi Province-Agricultural Field [2021ZDLNY04-01]
- Project from Yulin Science and Technology Bureau [2019-169]
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Astragaloside IV (AS-IV) significantly reversed abnormalities in diabetic mice, protected cellular architecture, and regulated intestinal flora. Its anti-diabetic effects are mediated through modulating the AMPK/SIRT1 and PI3K/AKT signaling pathways.
Ethnopharmacological relevance: Radix Astragali, the dried root of Astragalus mongholicus Bunge, has long been used in traditional Chinese Medicine to treat diabetes. Astragaloside IV (AS-IV), one of the most active ingredients in the root, has been shown to have anti-diabetes ability; however, its underlying mechanism is still unclear. Materials and methods: In this study, we evaluated the hypoglycemic effect and possible mechanisms of AS-IV in diabetic mice and insulin resistance-HepG2 cells. The components of the intestinal microflora in mice with type 2 diabetes mellitus (T2DM) were determined using high-throughput 16S rRNA gene sequencing. Moreover, the molecular mechanisms of specific members of insulin signaling pathways were analyzed. Results: AS-IV significantly reversed the abnormalities in blood lipids, glucose, insulin resistance, as well as oxidative stress levels in T2DM mice. Histological finding showed that AS-IV could protect the cellular architecture of the liver and pancreas. AS-IV also regulated the abundance and diversity of intestinal flora of T2DM mice in a positive direction and increased butyric acid levels. The active role of AS-IV as an anti-diabetic compound by regulating the AMPK/SIRT1 and PI3K/AKT signaling pathways was revealed using a T2DM model and verified through the intervention of inhibitors using insulin-resistance HepG2 cells. Conclusion: Our results suggested that AS-IV may be used as an anti-diabetic drug candidate owing to its effects of regulating gut microbiota and AMPK/SIRT1 and PI3K/AKT signaling pathways.
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