San-Huang-Yi-Shen Capsule Ameliorates Diabetic Kidney Disease through Inducing PINK1/Parkin-Mediated Mitophagy and Inhibiting the Activation of NLRP3 Signaling Pathway

San-Huang-Yi-Shen capsule (SHYS) has been used in the treatment of diabetic kidney disease (DKD) in clinics. However, the mechanism of SHYS on DKD remains unclear. In this study, we used a high-fat diet combined with streptozocin (STZ) injection to establish a rat model of DKD, and different doses o...

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Main Authors: Hanzhou Li, Yuansong Wang, Xiuhai Su, Qinghai Wang, Shufang Zhang, Wenjuan Sun, Tianyu Zhang, Mengxue Dong, Zhaiyi Zhang, Shuquan Lv
Format: Article
Language:English
Published: Wiley 2022-01-01
Series:Journal of Diabetes Research
Online Access:http://dx.doi.org/10.1155/2022/2640209
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author Hanzhou Li
Yuansong Wang
Xiuhai Su
Qinghai Wang
Shufang Zhang
Wenjuan Sun
Tianyu Zhang
Mengxue Dong
Zhaiyi Zhang
Shuquan Lv
author_facet Hanzhou Li
Yuansong Wang
Xiuhai Su
Qinghai Wang
Shufang Zhang
Wenjuan Sun
Tianyu Zhang
Mengxue Dong
Zhaiyi Zhang
Shuquan Lv
author_sort Hanzhou Li
collection DOAJ
description San-Huang-Yi-Shen capsule (SHYS) has been used in the treatment of diabetic kidney disease (DKD) in clinics. However, the mechanism of SHYS on DKD remains unclear. In this study, we used a high-fat diet combined with streptozocin (STZ) injection to establish a rat model of DKD, and different doses of SHYS were given by oral gavage to determine the therapeutic effects of SHYS on DKD. Then, we studied the effects of SHYS on PINK1/Parkin-mediated mitophagy and the activation of NLRP3 inflammasome to study the possible mechanisms of SHYS on DKD. Our result showed that SHYS could alleviate DKD through reducing the body weight loss, decreasing the levels of fasting blood glucose (FBG), and improving the renal function, insulin resistance (IR), and inhibiting inflammatory response and oxidative stress in the kidney. Moreover, transmission electron microscopy showed SHYS treatment improved the morphology of mitochondria in the kidney. In addition, western blot and immunoflourescence staining showed that SHYS treatment induced the PINK1/Parkin-mediated mitophagy and inhibited the activation of NLRP3 signaling pathway. In conclusion, our study demonstrated the therapeutic effects of SHYS on DKD. Additionally, our results indicated that SHYS promoted PINK1/Parkin-mediated mitophagy and inhibited NLRP3 inflammasome activation to improve mitochondrial injury and inflammatory responses.
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issn 2314-6753
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record_format Article
series Journal of Diabetes Research
spelling doaj-art-03e7df7d07714a359f824b1651deb6742025-02-03T05:57:54ZengWileyJournal of Diabetes Research2314-67532022-01-01202210.1155/2022/2640209San-Huang-Yi-Shen Capsule Ameliorates Diabetic Kidney Disease through Inducing PINK1/Parkin-Mediated Mitophagy and Inhibiting the Activation of NLRP3 Signaling PathwayHanzhou Li0Yuansong Wang1Xiuhai Su2Qinghai Wang3Shufang Zhang4Wenjuan Sun5Tianyu Zhang6Mengxue Dong7Zhaiyi Zhang8Shuquan Lv9Chengde Medical UniversityCangzhou Hospital of Integrated Traditional Chinese Medicine and Western Medicine of Hebei ProvinceCangzhou Hospital of Integrated Traditional Chinese Medicine and Western Medicine of Hebei ProvinceCangzhou Hospital of Integrated Traditional Chinese Medicine and Western Medicine of Hebei ProvinceCangzhou Hospital of Integrated Traditional Chinese Medicine and Western Medicine of Hebei ProvinceCangzhou Hospital of Integrated Traditional Chinese Medicine and Western Medicine of Hebei ProvinceCangzhou Hospital of Integrated Traditional Chinese Medicine and Western Medicine of Hebei ProvinceTianjin University of Traditional Chinese MedicineTianjin University of Traditional Chinese MedicineCangzhou Hospital of Integrated Traditional Chinese Medicine and Western Medicine of Hebei ProvinceSan-Huang-Yi-Shen capsule (SHYS) has been used in the treatment of diabetic kidney disease (DKD) in clinics. However, the mechanism of SHYS on DKD remains unclear. In this study, we used a high-fat diet combined with streptozocin (STZ) injection to establish a rat model of DKD, and different doses of SHYS were given by oral gavage to determine the therapeutic effects of SHYS on DKD. Then, we studied the effects of SHYS on PINK1/Parkin-mediated mitophagy and the activation of NLRP3 inflammasome to study the possible mechanisms of SHYS on DKD. Our result showed that SHYS could alleviate DKD through reducing the body weight loss, decreasing the levels of fasting blood glucose (FBG), and improving the renal function, insulin resistance (IR), and inhibiting inflammatory response and oxidative stress in the kidney. Moreover, transmission electron microscopy showed SHYS treatment improved the morphology of mitochondria in the kidney. In addition, western blot and immunoflourescence staining showed that SHYS treatment induced the PINK1/Parkin-mediated mitophagy and inhibited the activation of NLRP3 signaling pathway. In conclusion, our study demonstrated the therapeutic effects of SHYS on DKD. Additionally, our results indicated that SHYS promoted PINK1/Parkin-mediated mitophagy and inhibited NLRP3 inflammasome activation to improve mitochondrial injury and inflammatory responses.http://dx.doi.org/10.1155/2022/2640209
spellingShingle Hanzhou Li
Yuansong Wang
Xiuhai Su
Qinghai Wang
Shufang Zhang
Wenjuan Sun
Tianyu Zhang
Mengxue Dong
Zhaiyi Zhang
Shuquan Lv
San-Huang-Yi-Shen Capsule Ameliorates Diabetic Kidney Disease through Inducing PINK1/Parkin-Mediated Mitophagy and Inhibiting the Activation of NLRP3 Signaling Pathway
Journal of Diabetes Research
title San-Huang-Yi-Shen Capsule Ameliorates Diabetic Kidney Disease through Inducing PINK1/Parkin-Mediated Mitophagy and Inhibiting the Activation of NLRP3 Signaling Pathway
title_full San-Huang-Yi-Shen Capsule Ameliorates Diabetic Kidney Disease through Inducing PINK1/Parkin-Mediated Mitophagy and Inhibiting the Activation of NLRP3 Signaling Pathway
title_fullStr San-Huang-Yi-Shen Capsule Ameliorates Diabetic Kidney Disease through Inducing PINK1/Parkin-Mediated Mitophagy and Inhibiting the Activation of NLRP3 Signaling Pathway
title_full_unstemmed San-Huang-Yi-Shen Capsule Ameliorates Diabetic Kidney Disease through Inducing PINK1/Parkin-Mediated Mitophagy and Inhibiting the Activation of NLRP3 Signaling Pathway
title_short San-Huang-Yi-Shen Capsule Ameliorates Diabetic Kidney Disease through Inducing PINK1/Parkin-Mediated Mitophagy and Inhibiting the Activation of NLRP3 Signaling Pathway
title_sort san huang yi shen capsule ameliorates diabetic kidney disease through inducing pink1 parkin mediated mitophagy and inhibiting the activation of nlrp3 signaling pathway
url http://dx.doi.org/10.1155/2022/2640209
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