Systems Pharmacology Study On The Mechanism Of Action Of Chuanxiong-Shengdi Herb Pair

Primary dysmenorrhea(PD)without any evident pathology,is a common,and frequently asthenic,gynecological condition.Its incidence is high,which seriously affects women's health and work efficiency.Traditional Chinese medicine(TCM)has a great prospect in preventing this disease in an integrated and holistic way.And in clinical practice,formulae display good efficacy in the treatment of PD.However,it is very difficult to study the mechanism of Chinese herbal medicines because of its hundreds of thousands of components and corresponding a large number of targets.According to records,Chuanxiong-Shengdi herb pair is clinically used for the treatment of qi stagnation and blood stasis type diseases,especially PD.However,its mechanism of action is still unclear.This study explored and explained the mechanism of action of Chuanxiong-Shengdi herb pair on the treatment of PD by a systems pharmacology method.Through data mining,we have established the most complete database of ingredients for Chuanxiong-Shengdi herb pair.Furthermore,through oral bioavailability screening and drug-like evaluation,13 ingredients of the herbs were identified as active compounds,targeting 37 proteins.Then,through network pharmacological analysis,the mechanism of action of Chuanxiong-Shengdi herb pair on the treatment of PD was elucidated.We found that,it is through quadruple function modules,i.e.,the promotion of blood circulation,the inhibition of inflammation response,the relief of pain,as well as the enhancement of immune system that Chuanxiong-Shengdi herb pair exerts its therapeutic effects on PD treatment.Furthermore,the implement of these modules relies on a complex pathway network including especially neuroactive ligand-receptor interaction pathway,calcium signaling pathway,PI3K-Akt signaling pathway,vascular smooth muscle contraction and NF-?B signaling pathway.To sum it up,our work not only deciphers the underlying mechanism of Chuanxiong-Shengdi herb pair in treatment of PD,but also provides an novel approach for drug development and applications.