Effects of resveratrol, a grape polyphenol, on uterine contraction and Ca²⁺ mobilization in rats in vivo and in vitro

Dysmenorrhea is directly related to elevate prostaglandin F (PGF) _2α levels. In Western medicine, this condition is treated using nonsteroidal antiinflammatory drugs. Because nonsteroidal antiinflammatory drugs produce many side effects, Chinese medicinal therapy is considered as a feasible alternative for treating dysmenorrhea. Many special physiological components used in Chinese medicine, such as resveratrol, have been isolated and identified. Resveratrol has many physiological functions, such as antioxidation and anticarcinogenic effects. However, the relationship between uterine smooth muscle contraction and resveratrol remains unknown. Here, we studied the in vitro and in vivo effects of resveratrol on uterine smooth muscle contraction. The uterus was separated from a female Sprague Dawley rat, and uterine smooth muscle contraction activity was measured and recorded. The results demonstrated that 1) resveratrol treatment inhibited PGF_2α-, oxytocin-, acetylcholine-, and carbacholinduced uterine contractions in rats; 2) resveratrol inhibited uterine contractions stimulated by the Ca²⁺ channel activator (Bay K 8644) and depolarization in response to high K ⁺ (KCl); 3) resveratrol inhibited PGF_2α-induced increases in the [Ca²⁺]i in human uterine smooth muscle cells; 4) resveratrol could mimicCa²⁺ channel blockers to block Ca²⁺ influx through voltage-operated Ca²⁺ channels inthe plasma membrane; and 5) resveratrol inhibited PGF_2α-induced uterine contractions in rats in vivo. Resveratrol inhibited uterine contractions induced by PGF_2α and high K⁺ in a concentration-dependent manner in vitro; furthermore, it inhibited Ca²⁺-dependent uterine contractions. Thus, resveratrol consistently suppressed the increases in intracellular Ca²⁺ concentrations ([Ca²⁺]i) induced by PGF_2α and high K⁺ concentrations. It can be assumed that resveratrol probably inhibited uterine contraction by blocking external Ca²⁺ influx, leading to decreased [Ca²⁺]i. Therefore, resveratrol can be considered as a feasible alternative therapeutic agent for dysmenorrhea.