Astragaloside II Ameliorated Podocyte Injury and Mitochondrial Dysfunction in Streptozotocin-Induced Diabetic Rats

Jun Su; Chongting Gao; Ling Xie; Ying Fan; Yilan Shen; Qunwei Huang; Niansong Wang; Youhua Xu; Nizhi Yang; Dingkun Gui

doi:10.3389/fphar.2021.638422

Astragaloside II Ameliorated Podocyte Injury and Mitochondrial Dysfunction in Streptozotocin-Induced Diabetic Rats

Front Pharmacol. 2021 Mar 16:12:638422. doi: 10.3389/fphar.2021.638422. eCollection 2021.

Authors

Jun Su¹, Chongting Gao¹, Ling Xie², Ying Fan¹, Yilan Shen¹, Qunwei Huang¹, Niansong Wang¹, Youhua Xu³, Nizhi Yang⁴, Dingkun Gui¹

Affiliations

¹ Department of Nephrology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
² Shanghai Ocean University, Shanghai, China.
³ Faculty of Chinese Medicine, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macao, China.
⁴ Department of Nephrology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China.

Abstract

Astragaloside II (AS II), a novel saponin purified from Astragalus membranes, has been reported to modulate the immune response, repair tissue injury, and prevent inflammatory response. However, the protective effects of AS II on podocyte injury in diabetic nephropathy (DN) have not been investigated yet. In this study, we aimed to investigate the beneficial effects of AS II on podocyte injury and mitochondrial dysfunction in DN. Diabetes was induced with streptozotocin (STZ) by intraperitoneal injection at 55 mg/kg in rats. Diabetic rats were randomly divided into four groups, namely, diabetic rats and diabetic rats treated with losartan (10 mg·kg^-1·d^-1) or AS II (3.2 and 6.4 mg·kg^-1·d^-1) for 9 weeks. Normal Sprague-Dawley rats were chosen as nondiabetic control group. Urinary albumin/creatinine ratio (ACR), biochemical parameters, renal histopathology and podocyte apoptosis, and morphological changes were evaluated. Expressions of mitochondrial dynamics-related and autophagy-related proteins, such as Mfn2, Fis1, P62, and LC3, as well as Nrf2, Keap1, PINK1, and Parkin, were examined by immunohistochemistry, western blot, and real-time PCR, respectively. Our results indicated that AS II ameliorated albuminuria, renal histopathology, and podocyte foot process effacement and podocyte apoptosis in diabetic rats. AS II also partially restored the renal expression of mitochondrial dynamics-related and autophagy-related proteins, including Mfn2, Fis1, P62, and LC3. AS II also increased the expression of PINK1 and Parkin associated with mitophagy in diabetic rats. Moreover, AS II facilitated antioxidative stress ability via increasing Nrf2 expression and decreasing Keap1 protein level. These results suggested that AS II ameliorated podocyte injury and mitochondrial dysfunction in diabetic rats partly through regulation of Nrf2 and PINK1 pathway. These important findings might provide an innovative therapeutic strategy for the treatment of DN.

Keywords: astragaloside II; diabetic nephrology; mitochondrial dynamics; mitophagy; podocyte injury.