Zili Kong, Min Xiao, Bin Wang, Wenjie Zhang, Kui Che, Wenshan Lv, Yahao Wang, Yajing Huang, Han Zhao, Yanyun Zhao, Mengmeng Qi, Jingwei Chi, Yangang Wang
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Renoprotective Effect of Isoorientin in Diabetic Nephropathy via Activating Autophagy and Inhibiting the PI3K-AKT-TSC2-mTOR Pathway.
Diabetic nephropathy (DN) is one of the most serious complications of diabetes and the most common cause of death. The autophagy of podocytes plays an important role in the pathogenesis of DN. Here, through screening the constituent compounds of practical and useful Chinese herbal formulas, we identified that isoorientin (ISO) strongly promoted the autophagy of podocytes and could effectively protect podocytes from high glucose (HG)-induced injury. ISO significantly improved autophagic clearance of damaged mitochondria under HG conditions. Through a proteomics-based approach, we identified that ISO could reverse the excessive phosphorylation of TSC2 S939 under HG conditions and stimulate autophagy through inhibition of the PI3K-AKT-TSC2-mTOR pathway. Furthermore, ISO was predicted to bind to the SH2 domain of PI3Kp85[Formula: see text], which is crucial for the recruitment and activation of PI3K. The protective effect of ISO and its effects on autophagy and particularly on mitophagy were further proved using a DN mice model. To summarize, our study identified the protective effects of ISO against DN and demonstrated that ISO was a strong activator of autophagy, which could provide a basis for drug development.
期刊介绍:
The American Journal of Chinese Medicine, which is defined in its broadest sense possible, publishes original articles and essays relating to traditional or ethnomedicine of all cultures. Areas of particular interest include:
Basic scientific and clinical research in indigenous medical techniques, therapeutic procedures, medicinal plants, and traditional medical theories and concepts;
Multidisciplinary study of medical practice and health care, especially from historical, cultural, public health, and socioeconomic perspectives;
International policy implications of comparative studies of medicine in all cultures, including such issues as health in developing countries, affordability and transferability of health-care techniques and concepts;
Translating scholarly ancient texts or modern publications on ethnomedicine.
The American Journal of Chinese Medicine will consider for publication a broad range of scholarly contributions, including original scientific research papers, review articles, editorial comments, social policy statements, brief news items, bibliographies, research guides, letters to the editors, book reviews, and selected reprints.