Modified Suoquan Wan ameliorate bladder overactivity via Piezo1/MAPK/MLC axis in partial bladder outlet obstruction rats.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE: Modified Suoquan Wan (MSQW) is a well-know traditional Chinese prescription, has shown efficacy in alleviating Overactive bladder (OAB) syndrome. MSQW has been widely utilized in the management of OAB, significantly improving the quality of life for affected patients, however, the molecular mechanism remains unclear. AIM OF THE STUDY: This study aimed to systematically investigate the therapeutic efficacy of Modified SQW (MSQW) on OAB in partial bladder outlet obstruction (PBOO) rats and delineate its underlying molecular mechanisms. METHODS: Partial Bladder Outlet Obstruction (PBOO) operation was used to construct a model of Overactive Bladder. Mechanistic insights were generated through snRNA-seq analysis of the OAB model. Disease targets were screened using a combined approach of network pharmacology and molecular docking. MSQW effects on bladder structure and function were assessed via urodynamics, organ bath tests, and H&E/Masson staining. Sequencing data validation was performed using qPCR, Western blot, and immunofluorescence assays. RESULTS: Urodynamics and tension revealed a significant overactive bladder symptoms in PBOO model. After MSQW treatment, significantly reduces both non-micturition contraction frequency and residual urine volume, in addition to markedly enhancing urinary efficiency. Furthermore, it alleviates detrusor hyperactivity in OAB rats against external stimuli, including electrical-field stimulation (EFS), carbachol (CCh), and KCl. Additionally, MSQW improved bladder wall thickening and bladder collagen ratio in OAB animals. SnRNA-seq data and network pharmacology indicate that MSQW modulates bladder Piezo1 and MAPK/MLC pathway. Sequencing data validation was performed using qPCR, Western blot, and immunofluorescence assays. CONCLUSION: This study elucidated the crucial role of Piezo1 in OAB. MSQW alleviated OAB by specifically modulating the Piezo1/MAPK/MLC pathway.