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©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
Shenzhuo formulation ameliorates diabetic nephropathy by regulating cytochrome P450-mediated arachidonic acid metabolism
Zhong-Yong Zhang, Yu-Ming Wang, Ning Wang, Yuan-Song Wang, Hui Zhang, Duo Wang, Li-Xin Wang, Huan-Tian Cui, Wei-Bo Wen, Shu-Quan Lv, Yong-Jun Cao
Zhong-Yong Zhang, Yuan-Song Wang, Hui Zhang, Li-Xin Wang, Shu-Quan Lv, Department of Endocrinology, Cangzhou Hospital of Integrated Traditional Chinese Medicine and Western Medicine of Hebei Province Affiliated to Hebei University of Chinese Medicine, Cangzhou 061012, Hebei Province, China
Yu-Ming Wang, College of Integrative Chinese and Western Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
Ning Wang, Huan-Tian Cui, Wei-Bo Wen, The First School of Clinical Medicine, Yunnan University of Chinese Medicine, Kunming 650500, Yunnan Province, China
Duo Wang, North China University of Science and Technology, Tangshan 063000, Hebei Province, China
Yong-Jun Cao, Department of Endocrinology, Nantong Affiliated Hospital, Nanjing University of Traditional Chinese Medicine, Nantong 226000, Jiangsu Province, China
Co-first authors: Zhong-Yong Zhang and Yu-Ming Wang.
Co-corresponding authors: Shu-Quan Lv and Yong-Jun Cao.
Author contributions: Zhang ZY and Wang YM contributed to writing-original draft, investigation; Cao YJ contributed to investigation; Wang YM and Wang N contributed to investigation, validation, data curation; Wang YS and Wang LX contributed to investigation, validation; Zhang H, Wang D contributed to investigation, formal analysis; Cui HT and Wen WB contributed to validation, conceptualization; Lv SQ contributed to writing - review & editing; All authors have read and approved the final manuscript. Lv SQ and Cao YJ contributed to conceptualization. Zhang ZY and Cao YJ contributed to funding acquisition. Lv SQ and Cao YJ have made crucial and indispensable contributions towards the completion of the project and thus qualified as the co-corresponding authors of the paper.
Supported by the Natural Science Foundation of Hebei Province Beijing-Tianjin-Hebei Basic Research Special Program, No. H2020110287; Key Laboratory for Diabetic Kidney Disease Syndrome and Treatment of the Traditional Chinese Medicine Administration of Hebei Province, No. 7 [2024]; Yuansong Wang National Famous Traditional Chinese Medicine Expert Heritage Studio, No. 3 [2024]; Hebei Key Laboratory of Integrated Traditional Chinese and Western Medicine for Diabetes and Its Complications, No. SZX2020015; and Jiangsu Province Chinese Medicine Science and Technology Development Program Project, No. YB2020065.
Institutional animal care and use committee statement: All experimental procedures followed the Guidelines for Animal Ethics and received approval from Cangzhou Hospital of Integrated Traditional Chinese Medicine and Western Medicine of Hebei Province (Approval Number: CZX2024-KY-129).
Conflict-of-interest statement: The authors report no relevant conflicts of interest for this article.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
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 at
czlvshuquan@163.com.
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, PhD, Chief Physician, Department of Endocrinology, Cangzhou Hospital of Integrated Traditional Chinese Medicine and Western Medicine of Hebei Province Affiliated to Hebei University of Chinese Medicine, No. 5 Xianghai Road, High-tech Zone, Cangzhou 061012, Hebei Province, China.
czlvshuquan@163.com
Received: November 28, 2024
Revised: December 31, 2024
Accepted: February 17, 2025
Published online: May 15, 2025
Processing time: 154 Days and 23.7 Hours
BACKGROUND
Diabetic nephropathy (DN) is a major complication of diabetes, marked by progressive renal damage and an inflammatory response. Although research has investigated the pathological mechanisms underlying DN, effective treatment options remain limited.
AIM
To evaluate the therapeutic impact of Shenzhuo formulation (SZF) on a DN mouse model and to examine its potential molecular mechanisms using transcriptomic and metabolomic approaches.
METHODS
We established a DN mouse model through a high-fat diet combined with streptozotocin (STZ) injection, followed by SZF treatment. We analyzed SZF’s effects on gene expression and metabolite profiles in renal tissues of DN mice using transcriptomics and metabolomics techniques. Additionally, based on transcriptomic and non-targeted metabolomic findings, we further assessed SZF’s influence on the expression of factors related to the cytochrome P450 (CYP450)-mediated arachidonic acid (AA) metabolism pathway, as well as its effects on inflammation and oxidative stress.
RESULTS
SZF intervention significantly decreased hyperglycemia and mitigated renal function impairment in DN mice. Pathological analysis revealed that SZF treatment improved renal tissue damage, reduced fibrosis, and diminished glycogen deposition. Transcriptomic analysis indicated that SZF influenced mRNA expression of CYP450-related genes, including Cyp2j13, Cyp2b9, Pla2 g2e/Cyp4a12a, Cyp4a32, Cyp2e1, and Cyp4a14. Non-targeted metabolomic results demonstrated that SZF altered the levels of metabolites associated with the AA metabolic pathway, including 5,6-EET, 14,15-EET, phosphatidylcholine, and 20-HETE. Further experiments showed that SZF upregulated the expression of CYP4A and CYP2E proteins in renal tissue, as well as CYP2J and CYP2B proteins. Additionally, SZF significantly reduced the expression of inflammatory factors in renal tissue, enhanced antioxidant enzyme activity, and alleviated oxidative stress.
CONCLUSION
SZF exerts anti-inflammatory and antioxidant effects by regulating CYP450-mediated AA metabolism, leading to improved renal function and improved pathological state in DN mice.
Core Tip: This study aimed to evaluate the therapeutic impact of Shenzhuo formulation (SZF) on a diabetic nephropathy (DN) mouse model and to examine its potential molecular mechanisms using transcriptomic and metabolomic approaches. The findings of this research substantiated the significant potential of SZF in ameliorating renal injury in DN mice. The primary pathway through which SZF mitigates renal injury appears to be the modulation of cytochrome P450-mediated AA metabolism, which contributes to its anti-inflammatory and antioxidant effects.
