Qing-Re-Xiao-Zheng-Yi-Qi formula relieves kidney damage and activates mitophagy in diabetic kidney disease

Qiaoru Wu; Runze Yan; Hanwen Yang; Yixuan Wang; Chao Zhang; Jiale Zhang; Zhaoli Cui; Yaoxian Wang; Weiwei Sun

doi:10.3389/fphar.2022.992597

Qing-Re-Xiao-Zheng-Yi-Qi formula relieves kidney damage and activates mitophagy in diabetic kidney disease

Front Pharmacol. 2022 Dec 20:13:992597. doi: 10.3389/fphar.2022.992597. eCollection 2022.

Authors

Qiaoru Wu¹, Runze Yan², Hanwen Yang¹, Yixuan Wang¹, Chao Zhang³, Jiale Zhang¹, Zhaoli Cui¹, Yaoxian Wang⁴, Weiwei Sun¹

Affiliations

¹ Department of Nephrology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, BJ, China.
² Department of Nephrology, Beijing Dongcheng First People's Hospital, Beijing, BJ, China.
³ Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, BJ, China.
⁴ Beijing University of Chinese Medicine, Beijing, BJ, China.

Abstract

Introduction: Qing-Re-Xiao-Zheng-Yi-Qi Formula is an effective prescription in diabetic kidney disease treatment, we have confirmed the efficacy of Qing-Re-Xiao-Zheng therapy in diabetic kidney disease through clinical trials. In this study, we investigated the mechanisms of Qing-Re-Xiao-Zheng-Yi-Qi Formula in the treatment of diabetic kidney disease. Methods: We used Vanquish UHPLC^TM to analyze the chemical profiling of Qing-Re-Xiao-Zheng-Yi-Qi Formula freeze-dried powder. We constructed diabetic kidney disease rat models induced by unilateral nephrectomy and high-dose streptozocin injection. We examined blood urea nitrogen, serum creatinine, serum glucose, total cholesterol, triglyceride, serum total protein, albumin, alanine aminotransferase, aspartate aminotransferase and 24 h urinary total protein in diabetic kidney disease rats. The renal pathological changes were observed by HE, Masson, PAS stanning and transmission electron microscopy. The levels of fibrosis-related proteins and mitophagy-related proteins were detected by western blot analysis. We also conducted an immunofluorescence co-localization analysis on podocytes to further investigate the effect of Qing-Re-Xiao-Zheng-Yi-Qi Formula treatment on mitophagy. Results: A total of 27 constituents in Qing-Re-Xiao-Zheng-Yi-Qi Formula were tentatively identified. We found PINK1/Parkin-mediated mitophagy was inhibited in diabetic kidney disease. Qing-Re-Xiao-Zheng-Yi-Qi Formula treatment could raise body weight and reduce renal index, reduce proteinuria, improve glycolipid metabolic disorders, ameliorate renal fibrosis, and reduce the expression of Col Ⅳ and TGF-β1 in diabetic kidney disease rats. Qing-Re-Xiao-Zheng-Yi-Qi Formula treatment could also increase the expression of nephrin, activate mitophagy and protect podocytes in diabetic kidney disease rats and high glucose cultured podocytes. Conclusion: PINK1/Parkin-mediated mitophagy was inhibited in diabetic kidney disease, and Qing-Re-Xiao-Zheng-Yi-Qi Formula treatment could not only ameliorate pathological damage, but also promote mitophagy to protect podocytes in diabetic kidney disease.

Keywords: Qing-Re-Xiao-Zheng-Yi-Qi formula; diabetic kidney disease; mitophagy; podocyte damage; renal fibrosis.