Astragaloside IV reversed the autophagy and oxidative stress induced by the intestinal microbiota of AIS in mice

• Published in: The journal of microbiology Vol. 56; no. 11; pp. 838 - 846
• Main Authors: Xu, Nan, Kan, Pengcheng, Yao, Xiuhua, Yang, Ping, Wang, Jiwei, Xiang, Lei, Zhu, Yu
• Format: Journal Article
• Language: English
• Published: Seoul The Microbiological Society of Korea 01.11.2018; Springer Nature B.V; 한국미생물학회
• Subjects: Animals; Antioxidants; Antioxidants - metabolism; Autophagy; Autophagy - drug effects; Autophagy-Related Protein 12 - metabolism; Bacteria - classification; Bacteria - drug effects; Beclin-1 - metabolism; Biomedical and Life Sciences; Brain; Brain - pathology; CYBB protein; Disease Models, Animal; Fatty acids; Fatty Acids - blood; Feces - microbiology; Gastrointestinal Microbiome - drug effects; Gastrointestinal Microbiome - physiology; Gene expression; Genetic Vectors; Germfree; Glutathione; Homocysteine; Homocysteine - blood; Intestinal microflora; Intestine; Ischemic Attack, Transient - drug therapy; Ischemic Attack, Transient - microbiology; Life Sciences; Male; Malondialdehyde; Malondialdehyde - metabolism; Mice; Mice, Inbred C57BL; Microbial Pathogenesis and Host-Microbe Interaction; Microbiology; Microbiota; Microtubule-Associated Proteins - metabolism; NAD(P)H oxidase; NADPH Oxidase 2 - metabolism; NADPH Oxidase 4 - metabolism; Oxidative stress; Oxidative Stress - drug effects; Patients; Phagocytosis; Quality of life; Reactive oxygen species; Reactive Oxygen Species - metabolism; Saponins - genetics; Saponins - pharmacology; Saponins - therapeutic use; Serum; Stroke; Stroke - drug therapy; Stroke - microbiology; Superoxide dismutase; Superoxide Dismutase - metabolism; Tissue; Transient ischemic attack; Triterpenes - pharmacology; Triterpenes - therapeutic use; 생물학; transient ischaemic attack; intestinal microecology; autophagy; Astragaloside IV; acute ischaemic stroke; oxidative stress
• ISSN: 1225-8873; 1976-3794
• DOI: 10.1007/s12275-018-8327-5

Acute ischaemic stroke (AIS) seriously affects patient quality of life. We explored the role of the intestinal microbiota on oxidative stress and autophagy in stroke, and Astragaloside IV (AS-IV) reversed the changes induced by intestinal microbiota. We determined the characteristics of the intestinal microbiota of AIS and transient ischaemic attack (TIA) patients by 16S sequencing and found that the structure and diversity of the intestinal microbiota in patients with AIS and TIA were significantly different from those in healthy subjects. Specifically, the abundance of genus Bifidobacterium , Megamonas , Blautia , Holdemanella , and Clostridium , content of homocysteine and triglyceride was increased significantly, thus it may be as a potential mechanism of AIS and TIA. Furthermore, germ-free mice were infused intracolonically with fecal supernatants of TIA and AIS with/without feed AS-IV for 12 weeks, and we found that the feces of AIS up-regulated the autophagy markers Beclin-1, light chain 3 (LC3)-II and autophagy-related gene (Atg)12, and the expression of reactive oxygen species (ROS) and NADPH oxidase 2/4 (NOX2/4), malondialdehyde (MDA), however, the expression of total antioxidant capacity (T-AOC) and activity of superoxide dismutase (SOD) and glutathione (GSH) was down-regulated in brain tissue, the content of homocysteine and free fatty acids (FFA) in serum of the mice. Meanwhile, AS-IV could reverse the above phenomenon, however, it does not affect the motor function of mice. AS-IV reversed these changes and it may be a potential drug for AIS therapeutics.