Treatment of Stress Urinary Incontinence by Ginsenoside Rh2

The molecular mechanisms underlying stress urinary incontinence (SUI) are unclear. We aimed to evaluate the molecular alterations in mice urethras following vaginal trauma and ovariectomy (OVX). Twenty-four virgin female mice were equally distributed into four groups: noninstrumented control; vaginal distension (VD) group; OVX group; and VD + OVX group. Changes in leak point pressures (LPPs), genital tract morphology, body weight gain, plasma 17β-estradiol level and expressions of neuronal nitric oxide synthase (nNOS), induced nitric oxide synthase (iNOS), and estrogen receptors (ERs—ERα and ERβ) were analyzed. Three weeks after VD, the four groups differed significantly in genital size and body weight gain. Compared with the control group, the plasma estradiol levels were significantly decreased in the OVX and VD + OVX groups, and LPPs were significantly decreased in all three groups. nNOS, iNOS, and ERα expressions in the urethra were significantly increased in the VD and VD + OVX groups, whereas ERβ expression was significantly increased only in the VD + OVX group. These results show that SUI following vaginal trauma and OVX involves urethral upregulations of nNOS, iNOS, and ERs, suggesting that NO- and ER-mediated signaling might play a role in the synergistic effect of birth trauma and OVX-related SUI pathogenesis.

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“…The peak bladder pressure was taken as the LPP. At least 3 LPPs were obtained for each animal, and the mean LPP was calculated [24, 25]. …”

Section: Methodsmentioning

confidence: 99%

Synergistic Effect of Vaginal Trauma and Ovariectomy in a Murine Model of Stress Urinary Incontinence: Upregulation of Urethral Nitric Oxide Synthases and Estrogen Receptors

Chen

Lin

et al. 2014

Mediators of Inflammation

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“…VD is used to induce SUI in mice and rats, as evidenced by LPP and/or maximal urethral closing pressure (MUCP) on urodynamic testing [1, 8, 21, 22]. An SUI mouse model revealed that a 0.3-ml intravaginal balloon (diameter ∼8 mm, equal to brain-case diameter of newborn mice) produced greater LPP than 0.1- and 0.2-ml balloons [23].…”

Section: Discussionmentioning

confidence: 99%

Potential therapeutic role of punicalagin against mechanical-trauma-induced stress urinary incontinence via upregulation of Nrf2 and TGF-β1 signaling

et al. 2017

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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.

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“…The peak bladder pressure was taken as the LPP. At least three LPPs were obtained for each animal, and the mean LPP was calculated [43] , [44] .…”

Section: Methodsmentioning

confidence: 99%

Urethral Dysfunction in Female Mice with Estrogen Receptor β Deficiency

Chen

Yeh

et al. 2014

PLoS ONE

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Estrogen has various regulatory functions in the growth, development, and differentiation of the female urogenital system. This study investigated the roles of ERβ in stress urinary incontinence (SUI). Wild-type (ERβ+/+) and knockout (ERβ−/−) female mice were generated (aged 6–8 weeks, n = 6) and urethral function and protein expression were measured. Leak point pressures (LPP) and maximum urethral closure pressure (MUCP) were assessed in mice under urethane anesthesia. After the measurements, the urethras were removed for proteomic analysis using label-free quantitative proteomics by nano-liquid chromatography–mass spectrometry (LC-MS/MS) analysis. The interaction between these proteins was further analysed using MetaCore. Lastly, Western blot was used to confirm the candidate proteins. Compared with the ERβ+/+ group, the LPP and MUCP values of the ERβ−/− group were significantly decreased. Additionally, we identified 85 differentially expressed proteins in the urethra of ERβ−/− female mice; 57 proteins were up-regulated and 28 were down-regulated. The majority of the ERβ knockout-modified proteins were involved in cell-matrix adhesion, metabolism, immune response, signal transduction, nuclear receptor translational regelation, and muscle contraction and development. Western blot confirmed the up-regulation of myosin and collagen in urethra. By contrast, elastin was down-regulated in the ERβ−/− mice. This study is the first study to estimate protein expression changes in urethras from ERβ−/− female mice. These changes could be related to the molecular mechanism of ERβ in SUI.

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Treatment of Stress Urinary Incontinence by Ginsenoside Rh2

Cited by 20 publications

References 44 publications

Synergistic Effect of Vaginal Trauma and Ovariectomy in a Murine Model of Stress Urinary Incontinence: Upregulation of Urethral Nitric Oxide Synthases and Estrogen Receptors

Synergistic Effect of Vaginal Trauma and Ovariectomy in a Murine Model of Stress Urinary Incontinence: Upregulation of Urethral Nitric Oxide Synthases and Estrogen Receptors

Potential therapeutic role of punicalagin against mechanical-trauma-induced stress urinary incontinence via upregulation of Nrf2 and TGF-β1 signaling

Urethral Dysfunction in Female Mice with Estrogen Receptor β Deficiency

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