Astragalus polysaccharides and astragaloside IV ameliorates cyclophosphamide-induced mouse model of overactive bladder

Abstract

Objective: Previous studies have shown that Astragalus polysaccharides (APS) and Astragaloside IV (AS-IV) protect against inflammation-related cell damage and exhibit immune enhancement. Since urothelial injury may result in an overactive bladder (OAB), the aim of this study was to investigate the efficacy of APS and AS-IV on urothelial injury in an experimental animal model. Materials and methods: The effects of APS and AS-IV on the proliferation and migration of primary human urothelial cells (HUCs) or primary human fibroblast cells (HFCs) were assessed using an in vitro wounding model and colorimetric thiazolyl blue assays. Sixty virgin female mice were randomized into five groups: group 1–saline-injected plus treatment with H2O, group 2–cyclophosphamide (CYP) plus treatment with H2O, group 3–CYP plus treatment with solifenacin succinate (SS; 10 mg/kg), group 4–CYP plus treatment with AS-IV (100 mg/kg), and group 5–CYP plus treatment with APS (100 mg/kg). Cystometry assessment was conducted and cell junction-associated protein zonula occludens-2 (ZO-2) expression was measured. Voiding interval values (time between voids) were assessed in mice under anesthesia. Lastly, immunohistochemistry analysis was used to confirm the location and level, respectively, of ZO-2 expression. Results: APS and AS-IV did not influence the cell viability but increased migration in HFCs compared with the controls. The OAB mice showed significantly lower voiding interval values. Voiding interval values were significantly higher in the CYP plus treatment with APS (100 mg/kg) and AS-IV (100 mg/kg) groups than in the CYP-induced OAB group. Additionally, the expression of ZO-2, a tight junction protein, was increased in the CYP plus treatment APS (100 mg/kg) and AS-IV (100 mg/kg) groups compared with the CYP-induced OAB group. Conclusion: These findings suggest that APS and AS-IV modulate urothelial wound healing, which ameliorates urinary frequency of mice treated with CYP. APS or AS-IV may have the potential benefit of acting as urothelial wound healing modulators. Keywords: Astragalus polysaccharides, Astragaloside IV, Overactive bladder, Urothelial injury, Cyclophosphamide, Cell junction-associated protein zonula occludens-2