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

Area of Science:

• Urology
• Pharmacology
• Molecular Biology

Background:

• Modified Suoquan Wan (MSQW) is a traditional Chinese medicine shown to alleviate overactive bladder (OAB) symptoms.
• The precise molecular mechanisms underlying MSQW's efficacy in OAB management remain unclear.

Purpose of the Study:

• To investigate the therapeutic effects of MSQW on OAB in a rat model of partial bladder outlet obstruction (PBOO).
• To elucidate the molecular pathways targeted by MSQW in OAB treatment.

Main Methods:

• Constructed an OAB rat model using partial bladder outlet obstruction (PBOO).
• Employed snRNA-seq, network pharmacology, and molecular docking to identify therapeutic targets.
• Assessed bladder function via urodynamics, organ bath tests, and histological analysis (H&E/Masson staining).
• Validated molecular targets using qPCR, Western blot, and immunofluorescence.

Main Results:

• PBOO rats exhibited significant OAB symptoms, including detrusor hyperactivity and increased bladder wall thickening.
• MSQW treatment significantly reduced non-micturition contractions, residual urine volume, and improved urinary efficiency.
• MSQW alleviated detrusor hyperactivity and improved bladder structure in OAB rats.
• snRNA-seq and network pharmacology identified Piezo1 and the MAPK/MLC pathway as key targets modulated by MSQW.

Conclusions:

• Piezo1 plays a critical role in the pathophysiology of OAB.
• MSQW effectively alleviates OAB symptoms by modulating the Piezo1/MAPK/MLC signaling pathway.