Protective Effects of Astragaloside IV on Uric Acid-Induced Pancreatic β-Cell Injury through PI3K/AKT Pathway Activation. (10th January 2022)

• Record Type: Journal Article
• Authors: Jiang, Zhenhuan; Wang, Gang; Meng, Lingling; Tang, Yunzhao; Yang, Min; Ni, Changlin
• Other Names: Zaid Hilal Academic Editor.
• Is Part Of: Evidence-based complementary and alternative medicine. Volume 2022(2022)
• Publication Date: 2022-01-10
• Subjects: Alternative medicine -- Periodicals; 615.505
• DOI: 10.1155/2022/2429162
• Languages: English
• ISSNs: 1741-427X

Abstract

Abstract : Background . Elevated uric acid (UA) has been found to damage pancreatic β -cell, promote oxidative stress, and cause insulin resistance in type 2 diabetes (T2D). Astragaloside IV (AS-IV), a major active monomer extracted from Astragalus membranaceus (Fisch.) Bunge. which belongs to TRIB. Galegeae (Br.) Torrey et Gray, Papilionaceae, exhibits various activities in a pathophysiological environment and has been widely employed to treat diseases. However, the effects of AS-IV on UA-induced pancreatic β -cell damage need to be investigated and the associating mechanism needs to be elucidated. This study was designed to determine the protective effects and underlying mechanism of AS-IV on UA-induced pancreatic β -cell dysfunction in T2D. Methods . UA-treated Min6 cells were exposed to AS-IV or wortmannin. Thereafter, the 3-(45)-dimethylthiahiazo(-z-y1)-35-di-phenytetrazoliumromide (MTT) assay and flow cytometry were employed to determine the effect of AS-IV on cell proliferation and apoptosis, respectively. Insulin secretion was evaluated using the glucose-stimulated insulin secretion (GSIS) assay. Finally, western blot and quantitative real-time polymerase chain reaction (qRT-PCR) were performed to determine the effect of AS-IV on the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway in UA-treated cells. Results . AS-IV had no cytotoxic effects on Min6 cells. UA significantly suppressed Min6 cell growth, promoted cell apoptosis, and enhanced caspase-3 activity; however, AS-IV abolished these effects in a dose-dependent manner. Further, decreased insulin secretion was found in UA-treated Min6 cells compared to control cells, and the production of insulin was enhanced by AS-IV in a dose-dependent manner. AS-IV significantly increased phosphorylated (p)-AKT expression and the ratio of p-AKT/AKT in Min6 cells exposed to UA. No evident change in AKT mRNA level was found in the different groups. However, the effects of AS-IV on UA-stimulated Min6 cells were reversed by 100 nM wortmannin. Conclusion . Collectively, our data suggest that AS-IV protected pancreatic β -cells from UA-treated dysfunction by activating the PI3K/AKT pathway. Such findings suggest that AS-IV may be an efficient natural agent against T2D.