Mafu Yishen Formula ameliorates membranous nephropathy by promotion of regulatory T cell differentiation - a multi-omics study

Sep 29, 2026

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Primary membranous nephropathy (PMN) is a leading cause of adult nephrotic syndrome, with edema as a key symptom. This study evaluates the Mafu Yishen Formula (MFYS), developed from classical prescriptions for edema-related conditions, to determine its therapeutic effects and molecular mechanisms. Using a passive Heymann nephritis rat model and comparative treatments, MFYS is assessed for impacts on proteinuria, renal pathology, podocyte injury, immune cell responses, cytokine profiles, and Treg differentiation.

LanguageEnglish

CategoryResearch & Report

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Pages22

Reading Time55 min

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Abstract

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Zhao et al. Chinese Medicine (2026) 21:5 Chinese Medicine [https://doi.org/10.1186/s13020-025-01272-1](https://doi.org/10.1186/s13020-025-01272-1) RESEARCH Open Access Mafu Yishen Formula ameliorates membranous nephropathy by promotion of regulatory T cell differentiation: a multi-omics study Qihan Zhao1†, Haoran Dai1†, Naiqian Zhang1†, Shuxian Huang2, Xiaoyu Cui1, Yanyu Cui1, Hanxue Jiang1, Wu Liu1, Yangzi Chen1, Yalin Zheng3,4, Qian Ding5, Yuehong Hu1, Gen Li2, Xinyue Tang1, Yang Zheng1*, Hongliang Rui 1,6* and Baoli Liu 1,3* Abstract Background Primary membranous nephropathy (PMN) is one of the main causes of nephrotic syndrome in adults, with edema as the primary symptom. The Mafu Yishen Formula (MFYS) is derived from a combination of classical prescriptions for treating edema diseases recorded in the Treatise on Cold Damage and Miscellaneous Diseases. While clinical efficacy of MFYS in treating PMN has been supported by evidence-based studies, its specific mechanisms remain unclear. This study aims to investigate the therapeutic effects and molecular mechanisms of MFYS in the treatment of membranous nephropathy, with a focus on whether MFYS promotes regulatory T cells (Treg) differentiation and modulates immune responses. Methods The passive Heymann nephritis (PHN) rat model was employed to simulate human PMN. Rats were treated with either low-or high-dose Mafu Yishen Formula (MFYS) or cyclosporine A (CsA) as a positive control. Urinary protein levels, serum biochemical parameters, renal pathological changes, and podocyte injury were evaluated. Immunofluorescence and flow cytometry were used to assess renal IgG deposition, B cell proliferation, and the proportion ofTreg. Serum cytokine levels were measured using appropriate assays. The absorbed components of MFYS were identified via metabolomic analysis. Integrated strategies including network pharmacology, spleen transcriptomics, and proteomics were applied to identify key targets and signaling pathways. In vitro Treg polarization assays, supplemented with pathway inhibitors, were conducted to validate mechanistic findings. Molecular docking simulations were performed to explore interactions between active components of MFYS and potential target proteins. Results MFYS significantly reduced urinary protein levels in PHN rats, improved biochemical indicators such as serum albumin and blood lipids. Pathological examination revealed that MFYS alleviated glomerular and podocyte †Qihan Zhao, Haoran Dai, and Naiqian Zhang have contributed equally to this work and share first authorship. *Correspondence: Yang Zheng [bjzykyc@163.com](bjzykyc@163.com)[ ](bjzykyc@163.com)Hongliang Rui [ruihl@ccmu.edu.cn](ruihl@ccmu.edu.cn)[ ](ruihl@ccmu.edu.cn)Baoli Liu [liubaoli@bjzhongyi.com](liubaoli@bjzhongyi.com) Full list of author information is available at the end of the article © The Author(s) 2026. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creativecommons.org/licenses/by/4.0/](http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ()[. The Creative Commons Public Domain Dedication waiver (](http://creativecommons.org/licenses/by/4.0/. The Creative Commons Publ

FAQs

What is the main therapeutic goal of the study regarding membranous nephropathy?

The study aims to evaluate MFYS therapeutic effects and molecular mechanisms in membranous nephropathy, especially whether it promotes regulatory T cell (Treg) differentiation and modulates immune responses.

How were the effects of MFYS assessed in the passive Heymann nephritis rat model?

Rats received low- or high-dose MFYS or cyclosporine A as a positive control, and outcomes included urinary protein levels, serum biochemical indices, renal pathology and podocyte injury, IgG deposition, B cell activation, Treg proportions, cytokines, and metabolomic characterization of MFYS components.

Which signaling pathways and molecular targets did MFYS influence according to the results?

Integrated analyses and experiments indicated MFYS upregulates the PI3K/AKT signaling pathway, enhances mitochondrial oxidative phosphorylation, increases PGC-1α, and downregulates pSTAT3 expression; blocking PI3K/AKT counteracted MFYS-induced Treg differentiation.

Sep 29, 2026

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