Diabetes, Metabolic Syndrome and Obesity (Jan 2022)
Astragaloside IV Ameliorates Streptozotocin Induced Pancreatic β-Cell Apoptosis and Dysfunction Through SIRT1/P53 and Akt/GSK3β/Nrf2 Signaling Pathways
Abstract
Yuqiong Lin,1 Ying Xu,1 Xin Zheng,1 Jingwen Zhang,1 Junfeng Liu,1 Guotu Wu2 1Department of Basic Medical Science, Fujian Health College, Fuzhou, 350101, Fujian Province, People’s Republic of China; 2Department of Basic Medical Science, Fujian Medical University, Fuzhou, 350101, Fujian Province, People’s Republic of ChinaCorrespondence: Yuqiong LinDepartment of Basic Medical Science, Fujian Health College, No. 366 Jingxi Town, Fuzhou, 350101, Fujian Province, People’s Republic of ChinaEmail [email protected]: Absolute or relative lack of insulin secretion caused by pancreatic β-cell dysfunction can lead to diabetes. Astragaloside IV (AS-IV), the main components of the traditional Chinese medicine Astragalus, has anti-oxidant, anti-inflammatory and anti-apoptotic properties, and exerts anti-diabetic pharmacological effects.Purpose: To explore whether AS-IV can protect the apoptosis and dysfunction of pancreatic β-cells induced by streptozotocin (STZ) and its underlying molecular mechanism.Methods: STZ-induced pancreatic β-cell line INS-1 was treated with different concentrations of AS-IV, then cell viability, apoptosis, oxidative stress and insulin secretion was assessed by CCK-8, TUNEL staining, Western blot, commercial kits and qRT-PCR, respectively. The expression of proteins involved in Sirtuin 1 (SIRT1)/p53 and Akt/glycogen synthase kinase-3 β (GSK3β)/nuclear factor E2-related factor 2 (Nrf2) signaling was measured by Western blot assay. Besides, Akt inhibitor MK-2206 and SIRT1 inhibitor EX-527 were used to co-treat STZ-induced INS-1 cells in the presence of AS-IV, and the above experiments were repeated.Results: AS-IV increased the cell viability of INS-1 cells induced by STZ. AS-IV also reduced the increase in apoptosis rate and reversed STZ-induced down-regulation of Bcl-2 and up-regulation of Bax and Cleaved caspase 3. In addition, AS-IV significantly reduced STZ-induced malondialdehyde upregulation and reduced superoxide dismutase and glutathione peroxidase levels. Furthermore, the use of AS-IV was found to increase the insulin secretion capacity of INS-1 cells with impaired function, along with the increase of the mRNA levels of insulin 1 and insulin 2. Mechanism studies further showed that MK-2206 and EX-527 reversed the protective effect of AS-IV against STZ-induced injury on INS-1 cells.Conclusion: AS-IV exerted cytoprotective effect on STZ-induced INS-1 cells through regulating SIRT1/p53 and Akt/GSK3β/Nrf2 signaling pathways. These findings are expected to provide new supplements to the molecular mechanism of AS-IV in the treatment of diabetes.Keywords: astragaloside IV, pancreatic β-cell, apoptosis, dysfunction, SIRT1/p53, Akt/GSK3β/Nrf2
