Epigallocatechin-3-gallate alleviates bladder overactivity in a rat model with metabolic syndrome and ovarian hormone deficiency through mitochondria apoptosis pathways.

Metabolic syndrome (MetS) and ovarian hormone deficiency could affect bladder storage dysfunction. Epigallocatechin-3-gallate (EGCG), a polyphenolic compound in green tea, has been shown to protect against ovarian hormone deficiency induced overactive bladder (OAB). The present study investigated oxidative stress induced by MetS and bilateral ovariectomy (OVX), and elucidated the mechanism underlying the protective effect of EGCG (10 umol/kg/day) on bladder overactivity. Rats were fed with high fat high sugar (HFHS) diet to induce MetS and received ovariectomy surgery to deprive ovarian hormone. By dieting with HFHS for 6 months, rats developed MetS and OAB. MetS + OVX deteriorated bladder storage dysfunction more profound than MetS alone. MetS and MetS + OVX rats showed over-expression of inflammatory and fibrosis markers (1.7~3.8-fold of control). EGCG pretreatment alleviated storage dysfunction, and protected the bladders from MetS and OVX - induced interstitial fibrosis changes. Moreover, OVX exacerbated MetS related bladder apoptosis (2.3~4.5-fold of control; 1.8~2.6-fold of Mets group), enhances oxidative stress markers (3.6~4.3-fold of control; 1.8~2.2-fold of Mets group) and mitochondrial enzyme complexes subunits (1.8~3.7-fold of control; 1.5~3.4-fold of Mets group). EGCG pretreatment alleviated bladder apoptosis, attenuated oxidative stress, and reduced the mitochondrial and endoplasmic reticulum apoptotic signals. In conclusions, HFHS feeding and ovarian hormone deficiency enhances the generation of oxidative stress mediated through mitochondrial pathway. EGCG reduced the generation of oxidative stress and lessened bladder overactivity.

Tea contains potent inhibitors of tyrosine phosphatase PTP1B.

Tea is widely consumed all over the world. Studies have demonstrated the role of tea in prevention and treatment of various chronic diseases including diabetes and obesity, but the underlying mechanism is unclear. PTP1B is a widely expressed tyrosine phosphatase which has been defined as a target for therapeutic drug development to treat diabetes and obesity. In screening for inhibitors of PTP1B, we found that aqueous extracts of teas exhibited potent PTP1B inhibitory effects with an IC50 value of 0.4-4 g dry tea leaves per liter of water. Black tea shows the strongest inhibition activities, followed by oolong and then by green tea. Biochemical fractionations demonstrated that the major effective components in tea corresponded to oxidized polyphenolic compounds. This was further verified by the fact that tea catechins became potent inhibitors of PTP1B upon oxidation catalyzed by tyrosinases. When applied to cultured cells, tea extracts induced tyrosine phosphorylation of cellular proteins. Our study suggests that some beneficial effects of tea may be attributed to the inhibition of PTP1B.