Guizhi Fuling Capsule Exhibits Antidysmenorrhea Activity by Inhibition of Cyclooxygenase Activity.

Guizhi Fuling capsule (GZFLc) is a modern preparation from traditional Chinese Medicine. Guizhi Fuling was first prescribed by Zhang Zhongjing almost two thousand years ago for the treatment of primary dysmenorrhea. It has also been used to treat uterine fibroids, dysfunctional uterine bleeding, and endometriosis. Although effective against dysmenorrhea clinically, there are limited information on the mechanism of its action. The major components responsible for the activity are not well defined. The aim of this study has been to elucidate a mechanism that may facilitate the development of a bioactivity-based assay for quality control during drug formulation and manufacturing. Using an oxytocin-induced mouse dysmenorrhea model, we showed that oral administration of GZFLc at 150 and 300 mg/kg, dosages relevant to clinic usages, significantly suppressed oxytocin-induced writhing response. The antidysmenorrhea effect was also demonstrated by a rotarod assay. We showed that GZFLc treatment significantly prolonged the hanging time of mice on the rotating rod. Histological studies showed that GZFLc treatment reduced lamina propria edema, while no effect on COX2 expression was detected. GZFLc instead exhibited direct inhibitory effect against COX2, a critical enzyme that catalyzes arachidonic acid conversion to prostaglandins. By HPLC profiling, we showed that paeoniflorin, paeonol, and cinnamaldehyde are the major components from the corresponding plants. At 5 and 10 mg/kg, both paeoniflorin and paeonol were active against induced dysmenorrhea. The study not only links GZFLc antidysmenorrhea activity to COX2 inhibition but also uncovers a mechanism of action by which an assay can be developed for bioefficacy evaluation of GZFLc.