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©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
Jianpi Gushen Huayu decoction ameliorated diabetic nephropathy through modulating metabolites in kidney, and inhibiting TLR4/NF-κB/NLRP3 and JNK/P38 pathways
Zi-Ang Ma, Li-Xin Wang, Hui Zhang, Han-Zhou Li, Li Dong, Qing-Hai Wang, Yuan-Song Wang, Bao-Chao Pan, Shu-Fang Zhang, Huan-Tian Cui, Shu-Quan Lv
Zi-Ang Ma, Graduate School, Hebei University of Chinese Medicine, Shijiazhuang 050000, Hebei Province, China
Li-Xin Wang, Hui Zhang, Li Dong, Qing-Hai Wang, Yuan-Song Wang, Bao-Chao Pan, Shu-Fang Zhang, Department of Endocrinology, Cangzhou Hospital of Integrated Traditional Chinese Medicine and Western Medicine of Hebei Province Affiliated to Hebei University of Chinese Medicine, Cangzhou 061000, Hebei Province, China
Han-Zhou Li, School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300000, China
Huan-Tian Cui, The First School of Clinical Medicine, Yunnan University of Traditional Chinese Medicine, Kunming 065000, Yunnan Province, China
Shu-Quan Lv, Department of Endocrinology, Hebei Cangzhou Hospital of Integrative Medicine, Cangzhou 061000, Hebei Province, China
Author contributions: Cui HT and Lv SQ conceived and designed the study; Ma ZA, Wang LX, Zhang H, and Li HZ conducted the experiments and obtained the data; Li HZ, Dong L, and Wang QH analyzed and collated the data; Ma ZA, Wang YS, and Pan BC drafted and written the final version of the manuscript; Zhang SF, Cui HT, and Lv SQ contributed equally to this work; and all authors approved the final version of the manuscript.
Supported by the Scientific Foundation of Administration of Traditional Chinese Medicine of Hebei Province, China, No. 2023257.
Institutional animal care and use committee statement: The animal study was reviewed and approved by Ethics Committee of Hebei University of Chinese Medicine (Approval No. CZX2021-KY-026).
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding authors.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Shu-Quan Lv, Doctor, Chief Physician, Department of Endocrinology, Hebei Cangzhou Hospital of Integrative Medicine, No. 31 Huanghe Road, Cangzhou 061000, Hebei Province, China. czlvshuquan@163.com
Received: September 24, 2023
Peer-review started: September 24, 2023
First decision: November 30, 2023
Revised: December 21, 2023
Accepted: January 30, 2024
Article in press: January 30, 2024
Published online: March 15, 2024
ARTICLE HIGHLIGHTS
Research background
As a frequent complication of type 2 diabetes mellitus, diabetic nephropathy (DN) is insidious and highly prevalent. The dysfunction of metabolism is closely related to the progression of diabetes and diabetic complications. Regulating metabolism to ameliorate DN has recently become a well explored research area.
Research motivation
Jianpi Gushen Huayu Decoction (JPGS) is highly efficacious clinically on DN, nevertheless, its renoprotective mechanism of action on DN has not yet been intensively investigated.
Research objectives
To evaluate the therapeutic effects and the possible mechanism of JPGS on DN based on untargeted metabolomics.
Research methods
The therapeutic potentials of JPGS was first evaluated on a DN mouse model. Then, the effect of JPGS on the kidney metabolite levels in DN mice was tested using non-targeted metabolomics. Furthermore, the effects of JPGS on c-Jun N-terminal kinase (JNK)/P38-mediated apoptosis and inflammatory responses mediated by toll-like receptor 4 (TLR4)/nuclear factor-kappaB (NF-κB)/NOD-like receptor family pyrin domain containing 3 (NLRP3) were examined.
Research results
JPGS administration improved body weight loss, hyperglycemia, kidney injury, and factors of oxidative stress and inflammation in DN mice. In addition, JPGS altered 51 differential metabolites of kidney in DN mice. Pathways related to cysteine and methionine metabolism, alanine, tryptophan metabolism, aspartate and glutamate metabolism, and riboflavin metabolism were identified as the key pathway of JPGS on DN. Further experimental validation showed that JPGS treatment reduced the expression of expression of TLR4/NF-κB/NLRP3 pathway and JNK/P38 pathway-mediated apoptosis related factors.
Research conclusions
JPGS could improve kidney inflammatory responses and kidney injury in DN mice via the TLR4/NF-κB/NLRP3 pathway and inhibit kidney cell apoptosis in DN mice via the JNK/P38 pathway. It is possibly related to regulate cysteine and methionine metabolism, alanine, aspartate, and glutamate metabolism, tryptophan metabolism and riboflavin metabolism in kidney.
Research perspectives
This study can provide scientific evidence for the clinal used of JPGS. Moreover, our study can be a useful for researchers in studying the relationship between metabolites and pathways in drug intervention.
