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Potential role of punicalagin against oxidative stress induced testicular damage.

ABSTRACT: Punicalagin is isolated from pomegranate and widely used for the treatment of different diseases in Chinese traditional medicine. This study aimed to evaluate the effect of Punicalagin (purity ?98%) on oxidative stress induced testicular damage and its effect on fertility. We detected the antioxidant potential of punicalagin in lipopolysaccharide (LPS) induced oxidative stress damage in testes, also tried to uncover the boosting fertility effect of Punicalagin (PU) against oxidative stress-induced infertility. Results demonstrated that 9 mg kg-1 for 7 days treatment significantly decreases LPS induced oxidative damage in testes and nitric oxide production. The administration of oxidative stress resulted in a significant reduction in testes antioxidants GSH, T-SOD, and CAT raised LPO, but treatment with punicalagin for 7 days increased antioxidant defense GSH, T-SOD, and CAT by the end of the experiment and reduced LPO level as well. PU also significantly activates Nrf2, which is involved in regulation of antioxidant defense systems. Hence, the present research categorically elucidates the protective effect of punicalagin against LPS induced oxidative stress induced perturbation in the process of spermatogenesis and significantly increased sperm health and number. Moreover, fertility success significantly decreased in LPS-injected mice compared to controls. Mice injected with LPS had fertility indices of 12.5%, while others treated with a combination of PU + LPS exhibited 75% indices. By promoting fertility and eliminating oxidative stress and inflammation, PU may be a useful nutrient for the treatment of infertility.

SUBMITTER: Rao F

PROVIDER: S-EPMC4955191 | biostudies-literature | 2016 Jul-Aug

REPOSITORIES: biostudies-literature

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Potential role of punicalagin against oxidative stress induced testicular damage.

Rao Faiza F Tian Hui H Li Wenqing W Hung Helong H Sun Fei F

Asian journal of andrology 20160701 4

Punicalagin is isolated from pomegranate and widely used for the treatment of different diseases in Chinese traditional medicine. This study aimed to evaluate the effect of Punicalagin (purity ≥98%) on oxidative stress induced testicular damage and its effect on fertility. We detected the antioxidant potential of punicalagin in lipopolysaccharide (LPS) induced oxidative stress damage in testes, also tried to uncover the boosting fertility effect of Punicalagin (PU) against oxidative stress-induc ...[more]

PMID: 26763544

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Project description: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.

Project description:Testes produce sperms, and gamete generation relies on a proper niche environment. The disruption of hierarchical regulatory homeostasis in Leydig or Sertoli cells may evoke a sterile phenotype in humans. In this study, we recapitulated type 2 diabetes mellitus by using a high-fat diet- (HFD-) fed mouse model to identify the phenotype and potential mechanism of diabetes-induced testicular impairment. At the end of the study, blood glucose levels, testosterone structure, testicular antioxidant capacity, and testosterone level and the expression of hypoxia-inducible factor- (HIF-) 1α, apoptosis-related protein cleaved-caspase3, and autophagy-related proteins such as LC3I/II, p62, and Beclin1 were evaluated. We found that long-term HFD treatment causes the development of diabetes mellitus, implicating increased serum glucose level, cell apoptosis, and testicular atrophy (P < 0.05 vs. Ctrl). Mechanistically, the results showed enhanced expression of HIF-1α in both Sertoli and Leydig cells (P < 0.05 vs. Ctrl). Advanced glycation end products (AGEs) were demonstrated to be a potential factor leading to HIF-1α upregulation in both cell types. In Sertoli cells, high glucose treatment had minor effects on Sertoli cell autophagy. However, AGE treatment stagnated the autophagy flux and escalated cell apoptosis (P < 0.05 vs. Ctrl+Ctrl). In Leydig cells, high glucose treatment was adequate to encumber autophagy induction and enhance oxidative stress. Similarly, AGE treatment facilitated HIF-1α expression and hampered testosterone production (P < 0.05 vs. Ctrl+Ctrl). Overall, these findings highlight the dual effects of diabetes on autophagy regulation in Sertoli and Leydig cells while imposing oxidative stress in both cell types. Furthermore, the upregulation of HIF-1α, which could be triggered by AGE treatment, may negatively affect both cell types. Together, these findings will help us further understand the molecular mechanism of diabetes-induced autophagy dysregulation and testicular impairment, enriching the content of male reproductive biology in diabetic patients.

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Potential role of punicalagin against oxidative stress induced testicular damage.

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Potential role of punicalagin against oxidative stress induced testicular damage.

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