A Network Pharmacology-Based Approach for Exploring Key Active Compounds and Pharmacological Mechanisms of Tangshen Formula for Treatment of Diabetic Nephropathy

Diabetic nephropathy (DN) is one of the common and severe microvascular complications of diabetes mellitus (DM). The occurrence and development of DN are related to multiple factors in the human body, which makes DN a complex disease, and the pathogeneses of DN have not yet been fully illustrated. F...

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Main Authors: Weie Zhou, Xuefeng Zhou, Yuan Zhang, Yuyang Wang, Wenjie Wu, Haojun Zhang, Tingting Zhao, Liang Peng, Hailing Zhao, Ping Li
Format: Article
Language:English
Published: Wiley 2021-01-01
Series:Journal of Diabetes Research
Online Access:http://dx.doi.org/10.1155/2021/8833688
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author Weie Zhou
Xuefeng Zhou
Yuan Zhang
Yuyang Wang
Wenjie Wu
Haojun Zhang
Tingting Zhao
Liang Peng
Hailing Zhao
Ping Li
author_facet Weie Zhou
Xuefeng Zhou
Yuan Zhang
Yuyang Wang
Wenjie Wu
Haojun Zhang
Tingting Zhao
Liang Peng
Hailing Zhao
Ping Li
author_sort Weie Zhou
collection DOAJ
description Diabetic nephropathy (DN) is one of the common and severe microvascular complications of diabetes mellitus (DM). The occurrence and development of DN are related to multiple factors in the human body, which makes DN a complex disease, and the pathogeneses of DN have not yet been fully illustrated. Furthermore, DN lacks effective drugs for treatment nowadays. Chinese herbal medicine (CHM) often shows the feature of multicomponents, multitargets, multipathways, and synergistic effects and shows a promising source of new therapeutic drugs for DN. As a CHM, Tangshen Formula (TSF) was used to treat DN patients in China. However, its bioactive compounds and holistic pharmacological mechanisms on DN are both unclear. A network pharmacology approach was firstly applied to explore multiple active compounds and multiple key pharmacological mechanisms for TSF treating DN by drug-targeted interaction databases, herb-compound-target network, protein-protein interaction network, compound-target-pathway network, and analysis methods. And the results showed that TSF have the characteristic of multicomponents, multitargets, multipathways, and synergistic effects for treating DN. The quercetin, naringenin, kaempferol, and isorhamnetin as key active compounds and the PI3K-Akt signaling pathway, TNF signaling pathway, nonalcoholic fatty liver disease (NAFLD), focal adhesion, rap1 signaling pathway, T cell receptor signaling pathway, MAPK signaling pathway, and insulin resistance as the key molecular mechanisms play important roles in TSF treating DN. Moreover, quercetin, naringenin, kaempferol, and isorhamnetin were successfully detected in TSF by the UHPLC-MS/MS analysis method. And their concentrations were 0.224, 8.295, 0.0564, and 0.0879 mg·kg-1, respectively. The present findings not only provide new insights for a deeper understanding of the constituent basis and pharmacology of TSF but also provide guidance for further pharmacological studies on TSF.
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publishDate 2021-01-01
publisher Wiley
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series Journal of Diabetes Research
spelling doaj-art-0406195428364251ac16d6510270cb332025-02-03T06:05:27ZengWileyJournal of Diabetes Research2314-67452314-67532021-01-01202110.1155/2021/88336888833688A Network Pharmacology-Based Approach for Exploring Key Active Compounds and Pharmacological Mechanisms of Tangshen Formula for Treatment of Diabetic NephropathyWeie Zhou0Xuefeng Zhou1Yuan Zhang2Yuyang Wang3Wenjie Wu4Haojun Zhang5Tingting Zhao6Liang Peng7Hailing Zhao8Ping Li9Beijing Key Laboratory for Immune-Mediated Inflammatory Diseases, Department of Nephrology, China-Japan Friendship Hospital, Beijing 100029, ChinaBeijing Key Laboratory for Immune-Mediated Inflammatory Diseases, Department of Nephrology, China-Japan Friendship Hospital, Beijing 100029, ChinaInstitute of Food Safety, Chinese Academy of Inspection & Quarantine, 100176 Beijing, ChinaBeijing Key Laboratory for Immune-Mediated Inflammatory Diseases, Department of Nephrology, China-Japan Friendship Hospital, Beijing 100029, ChinaInstitute of Food Safety, Chinese Academy of Inspection & Quarantine, 100176 Beijing, ChinaBeijing Key Laboratory for Immune-Mediated Inflammatory Diseases, Department of Nephrology, China-Japan Friendship Hospital, Beijing 100029, ChinaBeijing Key Laboratory for Immune-Mediated Inflammatory Diseases, Department of Nephrology, China-Japan Friendship Hospital, Beijing 100029, ChinaBeijing Key Laboratory for Immune-Mediated Inflammatory Diseases, Department of Nephrology, China-Japan Friendship Hospital, Beijing 100029, ChinaBeijing Key Laboratory for Immune-Mediated Inflammatory Diseases, Department of Nephrology, China-Japan Friendship Hospital, Beijing 100029, ChinaBeijing Key Laboratory for Immune-Mediated Inflammatory Diseases, Department of Nephrology, China-Japan Friendship Hospital, Beijing 100029, ChinaDiabetic nephropathy (DN) is one of the common and severe microvascular complications of diabetes mellitus (DM). The occurrence and development of DN are related to multiple factors in the human body, which makes DN a complex disease, and the pathogeneses of DN have not yet been fully illustrated. Furthermore, DN lacks effective drugs for treatment nowadays. Chinese herbal medicine (CHM) often shows the feature of multicomponents, multitargets, multipathways, and synergistic effects and shows a promising source of new therapeutic drugs for DN. As a CHM, Tangshen Formula (TSF) was used to treat DN patients in China. However, its bioactive compounds and holistic pharmacological mechanisms on DN are both unclear. A network pharmacology approach was firstly applied to explore multiple active compounds and multiple key pharmacological mechanisms for TSF treating DN by drug-targeted interaction databases, herb-compound-target network, protein-protein interaction network, compound-target-pathway network, and analysis methods. And the results showed that TSF have the characteristic of multicomponents, multitargets, multipathways, and synergistic effects for treating DN. The quercetin, naringenin, kaempferol, and isorhamnetin as key active compounds and the PI3K-Akt signaling pathway, TNF signaling pathway, nonalcoholic fatty liver disease (NAFLD), focal adhesion, rap1 signaling pathway, T cell receptor signaling pathway, MAPK signaling pathway, and insulin resistance as the key molecular mechanisms play important roles in TSF treating DN. Moreover, quercetin, naringenin, kaempferol, and isorhamnetin were successfully detected in TSF by the UHPLC-MS/MS analysis method. And their concentrations were 0.224, 8.295, 0.0564, and 0.0879 mg·kg-1, respectively. The present findings not only provide new insights for a deeper understanding of the constituent basis and pharmacology of TSF but also provide guidance for further pharmacological studies on TSF.http://dx.doi.org/10.1155/2021/8833688
spellingShingle Weie Zhou
Xuefeng Zhou
Yuan Zhang
Yuyang Wang
Wenjie Wu
Haojun Zhang
Tingting Zhao
Liang Peng
Hailing Zhao
Ping Li
A Network Pharmacology-Based Approach for Exploring Key Active Compounds and Pharmacological Mechanisms of Tangshen Formula for Treatment of Diabetic Nephropathy
Journal of Diabetes Research
title A Network Pharmacology-Based Approach for Exploring Key Active Compounds and Pharmacological Mechanisms of Tangshen Formula for Treatment of Diabetic Nephropathy
title_full A Network Pharmacology-Based Approach for Exploring Key Active Compounds and Pharmacological Mechanisms of Tangshen Formula for Treatment of Diabetic Nephropathy
title_fullStr A Network Pharmacology-Based Approach for Exploring Key Active Compounds and Pharmacological Mechanisms of Tangshen Formula for Treatment of Diabetic Nephropathy
title_full_unstemmed A Network Pharmacology-Based Approach for Exploring Key Active Compounds and Pharmacological Mechanisms of Tangshen Formula for Treatment of Diabetic Nephropathy
title_short A Network Pharmacology-Based Approach for Exploring Key Active Compounds and Pharmacological Mechanisms of Tangshen Formula for Treatment of Diabetic Nephropathy
title_sort network pharmacology based approach for exploring key active compounds and pharmacological mechanisms of tangshen formula for treatment of diabetic nephropathy
url http://dx.doi.org/10.1155/2021/8833688
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