Programmed Cell Death: A Key Mechanism of Traditional Chinese Medicine in the Treatment of Membranous Nephropathy.

Authors

Xixi Han, Jingwen Kong, Baike Liu, Chao Wei

Published in

Drug design, development and therapy. Volume 20. Pages 623323. Epub Jul 31, 2026.

Abstract

Membranous nephropathy (MN) is the leading cause of adult nephrotic syndrome with rising global incidence. A substantial proportion of patients progress to end-stage renal disease. Multiple programmed cell death (PCD) pathways-including apoptosis, pyroptosis, ferroptosis, and autophagy-are activated by complement-dependent and -independent pathogenic factors, collectively driving podocyte injury and MN progression. Current immunosuppressive therapies are limited by adverse reactions and variable responses. Traditional Chinese medicine (TCM), characterized by multi-component, multi-target, and multi-pathway regulation, shows therapeutic advantages in MN.
To systematically review the regulatory mechanisms of PCD in MN, summarize the molecular basis of TCM interventions targeting PCD, and identify current research limitations and future directions.
This narrative review systematically elaborates the regulatory association between PCD and podocyte injury in MN. Literatures were systematically retrieved from PubMed, Embase and China National Knowledge Infrastructure (CNKI) from the establishment of each database to May 2026, and 41 preclinical studies exploring TCM modulation of PCD in MN were included after strict screening.
Complement-dependent and complement-independent pathways in MN can synergistically initiate podocyte apoptosis, pyroptosis, ferroptosis, and autophagy dysfunction. TCM can regulate PCD through core signaling pathways such as phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR), nuclear factor erythroid 2-related factor 2/heme oxygenase 1 (Nrf2/HO-1), mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase/forkhead box O1 (JNK/FoxO1), and PTEN-induced kinase 1/Parkin (PINK1/Parkin), while simultaneously intervening in non-PCD pathological processes including inflammation, oxidative stress, and renal fibrosis. Clinical evidence further indicates that TCM or combined with conventional therapy can elevate MN remission rates and decrease adverse reactions.
PCD represents a core mechanism mediating podocyte injury and MN progression. TCM effectively modulates PCD imbalance through multi-target regulation, demonstrating prominent clinical efficacy and safety. These findings provide a theoretical basis and translational direction for developing high-efficacy, low-toxicity therapeutic strategies for MN.

PMID:
42553762
Bibliographic data and abstract were imported from PubMed on 05 Aug 2026.

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