Integrated network pharmacology and metabolomics to analyze the mechanism of Shaofu Zhuyu Decoction in treatment of dysmenorrhea of cold coagulation and blood stasis
Objective: To study the mechanism of Shaofu Zhuyu Decoction (SFZYD) in treating primary dysmenorrhea (PD) with cold coagulation and blood stasis based on metabonomics and network pharmacology. Methods: The disease model of primary dysmenorrhea in rats with cold coagulation and blood stasis was established according to the previous research methods. The model of cold coagulation and blood stasis was built with ice water bath, and the model of PD was built with estradiol and oxytocin injection.The success of modeling was judged according to the physiological condition of rats, the change of body weight, the number of twisting and the change of uterine blood flow. UPLC-Q/TOF MS technique was used to identify the components and their main components in plasma in the Wenjing group (WJ, means warming channel), Huoxue group (HX, means activating blood), and Quanfang group (QF, means complete prescription) group, and a ‘‘compound-target-pathway” network was constructed by network pharmacology. Untargeted metabolomics studies were applied to screen out endogenous differential metabolites and analyze their related metabolic pathways. The analgesic effect, pathological morphology and inflammatory mediators were evaluated, and the pathway targets were verified. Results: A total of 93 chemical components and 22 components in plasma were identified. A total of 52 potential targets of SFZYD for primary dysmenorrhea were identified by network pharmacological analysis, and 12 endogenous differential metabolites and four related metabolic pathways were screened out by metabonomics. The possible targets and pathways of action of the components of SFZYD into blood were analyzed by network pharmacology, and the results showed that it can widely act on the proteins and pathways related to thrombosis, new angiogenesis, vasodilation, inflammatory immune response and central sedation. Body torsion test showed that drug administration could reduce the frequency of body twisting in dysmorrhea rats, ELISAs showed that SFZYD could inhibit the release of inflammatory factors TNF-a and IL-6. Western blotting showed that SFZYD could reduced the protein expression of COX-2, p-ERK2 in uterine tissue, inhibiting inflammatory cell infiltration and inflammatory factor expression. By down-regulating the expression of p-MLC protein in uterine tissue, the strong contraction of smooth muscle was inhibited, thus relieving dysmenorrhea. Conclusion: Based on the research idea of ‘‘disease-syndrome-prescription-medicine”combination, this study discussed the internal relationship of SFZYD’s drug property, functional taste and efficacy. The substance basis of ‘‘warm property and pungent taste” in the WJ group reflects pungent taste is dispersive and propulsive, the warm property can dispel cold, to help Yang promoting circulation of qi and dispersing accumulation of pathogen, dredging connection tissue, dispersing fluid and promoting circulation of blood. Thus, it has the effect of WJ dispelling cold, regulating the circulation of qi and alleviating pain. The substance basis of ‘‘warm property, pungent and bitter taste” in HX group reflects that pungent taste is dispersive and propulsive, bitter taste can resolve stasis, warm property can dispel cold. All result in some effects of blood circulation, promoting qi, repelling congestion and improving dysmenorrhea. This study revealed the multi-component, multi-target and multi-pathway integration mechanism of SFZYD in the treatment of PD with cold coagulation and blood stasis, which preliminarily clarify scientific connotations about property theory of pungent, bitter taste and warm property,efficacy and material basis, laid a foundation for further research on the mechanism of action of SFZYD in the treatment of PD.
关键词:
寒凝血瘀;原发性痛经;少腹逐瘀汤;代谢组学;网络药理学;UPLC-Q / TOF MS
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This study was supported by the National Natural Science Foundation of China (No. 82174209). Thanks to Professor Changxiao Liu for his generous help in this study, his tireless work ethic and his iconoclastic approach to research have been a highlight for us. His passing this year leaves a huge hole in our collective life together.
Yilu Luo a,, Zengguang Wu b,, Ruifeng Ji a, Lingling Shen c, Xin He a, d,e. Integrated network pharmacology and metabolomics to analyze the mechanism of Shaofu Zhuyu Decoction in treatment of dysmenorrhea of cold coagulation and blood stasis[J]. Chinese Herbal Medicines (CHM),2026,18(2):420-438
