Potential therapeutic role of punicalagin against mechanical-trauma-induced stress urinary incontinence via upregulation of Nrf2 and TGF-β1 signaling : Effect of punicalagin on mechanical trauma induced SUI.
OBJECTIVE
We 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.


METHODS
Ninety 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).


RESULTS
LPPs 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.


CONCLUSIONS
PUN 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.
Department of Gynecology and Obstetrics, Renmin Hospital of Wuhan University, #238 Liberation Road, Wuhan, 430060, Hubei Province, People's Republic of China.
Jianming
J
Tang
Department of Gynecology and Obstetrics, Renmin Hospital of Wuhan University, #238 Liberation Road, Wuhan, 430060, Hubei Province, People's Republic of China.
Cheng
C
Liu
Department of Gynecology and Obstetrics, Renmin Hospital of Wuhan University, #238 Liberation Road, Wuhan, 430060, Hubei Province, People's Republic of China.
Jie
J
Min
Department of Gynecology and Obstetrics, Renmin Hospital of Wuhan University, #238 Liberation Road, Wuhan, 430060, Hubei Province, People's Republic of China.
Ming
M
Hu
Department of Gynecology and Obstetrics, Renmin Hospital of Wuhan University, #238 Liberation Road, Wuhan, 430060, Hubei Province, People's Republic of China.
Yang
Y
Li
Department of Gynecology and Obstetrics, Renmin Hospital of Wuhan University, #238 Liberation Road, Wuhan, 430060, Hubei Province, People's Republic of China. drhongli7777@gmail.com.
Li
L
Hong
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000199:Actins / Q000378:metabolism; D000818:Animals; D003094:Collagen / Q000378:metabolism; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005979:Glutathione Peroxidase / Q000378:metabolism; D047348:Hydrolyzable Tannins / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D051900:Smad3 Protein / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects*; D014521:Urethra / Q000378:metabolism; D014550:Urinary Incontinence, Stress / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D014621:Vagina / Q000378:metabolism; D000094765:Glutathione Peroxidase GPX1
D000199:Actins; D047348:Hydrolyzable Tannins; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D051900:Smad3 Protein; D053773:Transforming Growth Factor beta1; C544013:alpha-smooth muscle actin, mouse; C115642:punicalagin; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003094:Collagen; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D003849:Deoxyguanosine; D000094765:Glutathione Peroxidase GPX1; C000722068:Gpx1 protein, mouse
Extracellular matrix; Mechanical trauma; Oxidative damage; Punicalagin; Stress urinary incontinence; Vaginal distension