Abstract
Introduction and hypothesisWe investigated the effect of punicalagin (PUN; 2,3-hexahydroxydiphenoyl-gallagyl-D-glucose), on mechanical-trauma-induced stress urinary incontinence (SUI) in mouse and the mechanisms underlying any effects.MethodsNinety virgin female C57BL/6 mice were randomized into six groups: five groups underwent vaginal distention (VD) for 1 h and leak-point pressure (LPP) was measured on the 1st, 3rd, 7th, 14th, and 28th day following (VD groups 1 d, 3 d, 7 d, 14 d, and 28 d). The sixth group was a noninstrumented control (NC) group. Then, 75 virgin female C57BL/6 mice were randomized into five groups: a VD group (that just underwent VD) and an NC group were orally administered saline every day for 7 days; and three VD + PUN groups that underwent VD and were orally administered PUN respectively at 2.5, 5, and 10 mg/kg every day for 7 days. LPP was tested on the day 7, then all mice were sacrificed and their urethras and anterior vaginal walls harvested for Masson staining, immunohistochemistry study, Western blot analysis, and quantitative polymerase chain reaction (qPCR).ResultsLPPs after VD were significantly lower than the NC group, and the LPPs of mice on days 14 and 28 day after VD were significantly higher than on the days 1, 3, and 7. PUN significantly improved VD-induced drops in LPP and alleviated VD-induced decrease of collagen I, collagen III, α-smooth muscle actin (SMA), transforming growth factor (TGF)-β1, and p-Smad3, nuclear factor-erythroid 2 p45-related factor 2 (Nrf2), and glutathione peroxidase (GPx1) protein levels, and increase of 8-hydroxydeoxyguanosine (OHdG) in urethra and anterior vaginal wall. PUN also up-regulated the expression of manganese superoxide dismutase (MnSOD), whereas protein levels of Smad 2, p-Smad2, and Smad3 were not changed.ConclusionsPUN exerts certain therapeutic effect on mechanical-trauma-induced SUI in mice, which might be through the activation of TGF-β1/Smad3 and Nrf2/antioxidant response element (ARE) signaling activation.
Highlights
Introduction and hypothesisWe investigated the effect of punicalagin (PUN; 2,3-hexahydroxydiphenoyl-gallagyl-Dglucose), on mechanical-trauma-induced stress urinary incontinence (SUI) in mouse and the mechanisms underlying any effects
SUI is a common social and hygiene problem affecting the quality of life (QoL) of women worldwide and causing serious social economic load
We used PUN to reverse mechanical-trauma-induced SUI in a mouse model and found it has a therapeutic role against mechanicaltrauma-induced decreases in leak-point pressure (LPP) and metabolic disorders of the extracellular matrix (ECM)
Summary
We investigated the effect of punicalagin (PUN; 2,3-hexahydroxydiphenoyl-gallagyl-Dglucose), on mechanical-trauma-induced stress urinary incontinence (SUI) in mouse and the mechanisms underlying any effects. Stress urinary incontinence (SUI) is a common social and hygiene problem affecting the quality of life (QoL) of 25~57% adult women worldwide and causing serious social economic load [1,2,3,4,5]. Drug discovery and development for SUI is extremely urgent. Increasing research confirmed that mechanical-traumainduced oxidative damage and extracellular matrix (ECM) remodeling are probably involved in the pathogenesis of SUI, especially birth trauma and increased abdominalpressure-induced SUI or pelvic organ prolapase (POP) with SUI [7,8,9,10,11]. Nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) is an upstream transcription factor modulating
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