HuangE Capsules Improve Bladder Function in BOO-induced Overactive Bladder Rats: Network Pharmacology and Experimental Validation.

AIMS: Our objective is to assess the therapeutic impact of HEC on OAB rats and investigate potential mechanisms.

BACKGROUND

Overactive bladder (OAB) is a syndrome of urinary storage symptoms characterized by "urinary urgency with or without urinary acute incontinence, usually accompanied by increased daytime and nocturnal urination", which impacts patients' quality of life. We found the potential therapeutic impact of HuangE capsules (HEC) on OAB patients through clinical practice. However, the exact effect and mechanism of action remain unclear.

METHODS

We developed a "drugs- active ingredients- targets- diseases" network and employed the pathway enrichment analysis to identify the potential mechanisms of HEC on OAB. Bladder outlet obstruction (BOO) models and sham-operated ones were established in healthy male Wistar rats through surgical procedures. Following 28 days of continuous gavage administration of HEC, saturated copper sulfate test paper was utilized to quantify the frequency of urination over a 24-hour period. Subsequently, cystostomy was conducted to perform cystometry, and Masson staining was applied to a portion of the bladder tissue. Finally, we investigated the Rho/Rho-kinase pathway's expression and assessed the oxidative stress and inflammatory factor levels in the rat bladder through western blotting and ELISA techniques.

RESULTS

Through network pharmacological analysis, we identified RhoA/Rho-kinase pathway and cytokine including TNF-α, IL-6, SOD and MDA as potential mechanisms of HEC on OAB. The rats in the 2× HuangE group exhibited significantly enhanced urodynamic outcomes and decreased 24-hour urination frequency compared to the model group. Masson staining indicated a decrease in the proportion of collagenous tissue and an improvement in histomorphology. We observed a decrease expression of RhoA, ROCK1, and ROCK2 protein in the bladder tissue of 2× HuangE group rats, along with elevated SOD levels and decreased levels of TNF-α, IL-6, and MDA.

DISCUSSION: Mechanistically, HEC suppressed the Rho/Rho-kinase pathway in bladder tissue, reducing the expression of RhoA, ROCK1, and ROCK2, while decreasing inflammatory cytokines and oxidative stress, thereby alleviating fibrosis and improving urodynamics. Given that HEC also inhibits prostatic proliferation, a synergistic benefit for OAB patients with BPH is plausible. Gender differences and efficacy in neurogenic OAB warrant further investigation. Overall, HEC is a promising multi-target TCM option for OAB, though clinical validation remains necessary.

CONCLUSION

HEC could improve bladder function and morphology in BOO-induced OAB rats by reducing the expression of RhoA, ROCK1, and ROCK2 and lowering levels of oxidative stress and inflammation.