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

Weiran Zheng,Baoxin Li,Baojie Lv,Wei Xiao,Lilan Chen,Zhenzhong Wang,Meng Li,Yongxiang Wang,Xinzhuang Zhang,Kejin Zhu

doi:10.1155/2020/8607931

Abstract

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.

Highlights

Guizhi Fuling (GZFL) decoction is a classical formula first described in the Essential Prescriptions from the Golden Cabinet (Jingui Yaolue) by Zhang Zhongjing of the Han Dynasty
We and others have shown that Guizhi Fuling capsule (GZFLc) or similar formulae were able to reduce pains and ameliorate symptoms associated with dysmenorrhea
To delineate the major ingredients responsible for GZFLc effect, the contents of GZFLc were resuspended in PBS and tested in a mouse dysmenorrhea model developed by Yang et al [16]

Summary

Introduction

Guizhi Fuling (GZFL) decoction is a classical formula first described in the Essential Prescriptions from the Golden Cabinet (Jingui Yaolue) by Zhang Zhongjing of the Han Dynasty E drug is collected in spring and summer, removed from leaf, and dried in the sun after being sliced. E drug is collected in summer or autumn, washed clean, removed from two ends and rootlet, either peeled after boiling in water or boiled after peeling, and dried in the sun. E root is collected in autumn and removed from rootlets and soil, and the root bark is stripped off and dried in the sun. GZFL formula and several similar Wenjing decoctions have demonstrated equal or superior activities against symptoms of primary dysmenorrhea [3]. In addition to being effective against induced dysmenorrhea, GZFLc inhibited COX2 activity directly, indicating COX2 enzymatic assay could be used as a bioefficacy assay for GZFLc quality controls

Materials and Methods

Results

Discussions

Conflicts of Interest