Study on the therapeutic mechanism of Guizhi Fuling Capsules and its main components for treatment of primary dysmenorrhea syndrome by serum metabolomics

Objective: To study the mechanism of Guizhi Fuling Capsules and its principal components (paeoniflorin,paeonol and amygdalin) for treating primary dysmenorrhea syndrome from the aspect of endogenous metabolites by metabolomics. Methods: Thirty-six SD rats were randomly divided into six groups,including blank group,model group,Guizhi Fuling group,paeoniflorin group,paeonol group and amygdalin group (n = 6). Rats were injected with estradiol benzoate (for 10 d) and oxytocin (on the 10th day) to set the model of primary dysmenorrhea except those in the blank group. The efficacy of the drug was evaluated by twisting reaction of rats and the MDA & NO contents in rat uterus tissues. Meanwhile,UPLC-Q-TOF-MS/MS combined with multivariate analysis and database search was used to analyzed the endogenous metabolites in rat serum from different groups and discover differential metabolites. Besides,metabolites were analyzed by Metabo Analyst software for possible metabolic pathways. Results: Guizhi Fuling Capsules,paeoniflorin and paeonol were able to well inhibit the writhing reaction and reduce NO and MDA levels in the uterus of rats. Distinct change of metabolites between the blank group and the model group could be seen by PCA and PLS-DA. What’s more,12 potential differential metabolites of primary dysmenorrhea were identified. Involved potential metabolic pathways included linoleic acid metabolism,phenylalanine,tyrosine and tryptophan biosynthesis,phenylalanine metabolism,arachidonic acid metabolism,and tryptophan metabolism. Guizhi Fuling Capsules,paeoniflorin and paeonol had a certain callback effect on the five metabolic pathways in primary dysmenorrhea rats,while amygdalin had no effect on linoleic acid metabolism.Conclusion: Guizhi Fuling Capsules and its principal components (paeoniflorin,paeonol and amygdalin) have a certain callback effect on the metabolic disorder of the primary dysmenorrhea rats. Paeoniflorin and paeonol play a major role,which is consistent with the pharmacodynamics results. Their therapeutic mechanism is mainly related to lipid metabolism and amino acid metabolism.