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

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...

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Main Authors: Qiaoru Wu, Runze Yan, Hanwen Yang, Yixuan Wang, Chao Zhang, Jiale Zhang, Zhaoli Cui, Yaoxian Wang, Weiwei Sun
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-12-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2022.992597/full
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author Qiaoru Wu
Runze Yan
Hanwen Yang
Yixuan Wang
Chao Zhang
Jiale Zhang
Zhaoli Cui
Yaoxian Wang
Weiwei Sun
author_facet Qiaoru Wu
Runze Yan
Hanwen Yang
Yixuan Wang
Chao Zhang
Jiale Zhang
Zhaoli Cui
Yaoxian Wang
Weiwei Sun
author_sort Qiaoru Wu
collection DOAJ
description 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 UHPLCTM 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.
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spelling doaj.art-5d7dbf32399047cfacc49d5f9c4b232f2022-12-22T04:42:07ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-12-011310.3389/fphar.2022.992597992597Qing-Re-Xiao-Zheng-Yi-Qi formula relieves kidney damage and activates mitophagy in diabetic kidney diseaseQiaoru Wu0Runze Yan1Hanwen Yang2Yixuan Wang3Chao Zhang4Jiale Zhang5Zhaoli Cui6Yaoxian Wang7Weiwei Sun8Department of Nephrology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, BJ, ChinaDepartment of Nephrology, Beijing Dongcheng First People’s Hospital, Beijing, BJ, ChinaDepartment of Nephrology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, BJ, ChinaDepartment of Nephrology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, BJ, ChinaKey Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, BJ, ChinaDepartment of Nephrology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, BJ, ChinaDepartment of Nephrology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, BJ, ChinaBeijing University of Chinese Medicine, Beijing, BJ, ChinaDepartment of Nephrology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, BJ, ChinaIntroduction: 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 UHPLCTM 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.https://www.frontiersin.org/articles/10.3389/fphar.2022.992597/fulldiabetic kidney diseaserenal fibrosispodocyte damagemitophagyQing-Re-Xiao-Zheng-Yi-Qi formula
spellingShingle Qiaoru Wu
Runze Yan
Hanwen Yang
Yixuan Wang
Chao Zhang
Jiale Zhang
Zhaoli Cui
Yaoxian Wang
Weiwei Sun
Qing-Re-Xiao-Zheng-Yi-Qi formula relieves kidney damage and activates mitophagy in diabetic kidney disease
Frontiers in Pharmacology
diabetic kidney disease
renal fibrosis
podocyte damage
mitophagy
Qing-Re-Xiao-Zheng-Yi-Qi formula
title Qing-Re-Xiao-Zheng-Yi-Qi formula relieves kidney damage and activates mitophagy in diabetic kidney disease
title_full Qing-Re-Xiao-Zheng-Yi-Qi formula relieves kidney damage and activates mitophagy in diabetic kidney disease
title_fullStr Qing-Re-Xiao-Zheng-Yi-Qi formula relieves kidney damage and activates mitophagy in diabetic kidney disease
title_full_unstemmed Qing-Re-Xiao-Zheng-Yi-Qi formula relieves kidney damage and activates mitophagy in diabetic kidney disease
title_short Qing-Re-Xiao-Zheng-Yi-Qi formula relieves kidney damage and activates mitophagy in diabetic kidney disease
title_sort qing re xiao zheng yi qi formula relieves kidney damage and activates mitophagy in diabetic kidney disease
topic diabetic kidney disease
renal fibrosis
podocyte damage
mitophagy
Qing-Re-Xiao-Zheng-Yi-Qi formula
url https://www.frontiersin.org/articles/10.3389/fphar.2022.992597/full
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