Mechanism of Mahuang Fuzi Gancao Tang and Its Pungent Single Herbs in Treating Primary Podocytopathies via TRPC5-RAC1 Feedforward Loop Based on Sweat Pore Theory
10.13422/j.cnki.syfjx.20250617
- VernacularTitle:基于玄府理论探究麻黄附子甘草汤及其辛味单药成分干预原发性足细胞病TRPC5-RAC1前馈循环的机制
- Author:
Meng JIA
1
;
Yi WANG
1
;
Shisheng HAN
1
Author Information
1. Shanghai Yueyang Integrated Traditional Chinese Medicine and Western Medicine Hospital Affiliated to Shanghai University of Traditional Chinese Medicine，Shanghai 200083，China
- Publication Type:Journal Article
- Keywords:
Xuanfu theory;
pungent herbs;
podocyte injury;
transient receptor potential canonical 5-recombinant Ras related C3 botulinum toxin substrate 1（TRPC5-RAC1） feed-forward loop
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2025;31(21):205-214
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the molecular mechanisms of Mahuang Fuzi Gancao Tang and its pungent single herbs， Ephedrae Herba and Aconiti Lateralis Radix Praeparaia， in repairing podocyte injury based on the sweat pore theory， with a focus on the podocyte cytoskeletal transient receptor potential canonical 5 （TRPC5）-Ras-related C3 botulinum toxin substrate 1 （RAC1） feedforward loop. MethodsAn animal model with puromycin aminonucleoside （PAN）-induced overexpression of TRPC5 was established. Interventions included Mahuang Fuzi Gancao Tang， Ephedrae Herba alone， and Aconiti Lateralis Radix Praeparaia alone. Biochemical parameters ， histopathological changes， and podocyte ultrastructure were analyzed. Western blotting was performed to determine the expression of cytoskeletal protein synaptopodin and mechanism-related proteins TRPC5， RAC1-GTP， and RAC1 in the kidney. Primary podocytes were isolated and cultured for three-dimensional imaging of foot processes， cytoskeletal fluorescence analysis， and TRPC5-RAC1 co-staining via immunofluorescence. ResultsCompared with the model group， Mahuang Fuzi Gancao Tang， Ephedrae Herba alone， and Aconiti Lateralis Radix Praeparaia alone increased serum albumin （ALB）， decreased UPCR， reduced podocyte foot process fusion rate， upregulated synaptopodin expression， and downregulated TRPC5， RAC1-GTP， and RAC1 expression （P<0.05）. Moreover， the interventions increased the phalloidin fluorescence area/field area ratio （P<0.01） and mean fluorescence intensity （P<0.05）， while decreasing the proportion of TRPC5-RAC1 co-stained double-positive cells/total cells per field （P<0.01） in primary podocytes. ConclusionMahuang Fuzi Gancao Tang and its pungent single herbs， Ephedrae Herba and Aconiti Lateralis Radix Praeparaia， ameliorated podocyte injury in the model with PAN-induced TRPC5 overexpression by reducing proteinuria and suppressing the TRPC5-RAC1 feedforward loop-mediated podocyte cytoskeletal damage.
