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Integrated transcriptomics and network pharmacology analyses reveal potential effective components and mechanism of
1State Key Laboratory of Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture (Jiangsu Kanion Pharmaceutical Co., Ltd.), Nanjing, Jiangsu, 211112, China.
Ethnopharmacological Relevance:
Blood stasis syndrome (BSS) is a pathological state associated with blood circulation disorders and vascular injury, which predisposes to cardiovascular diseases. Tianshu capsule (TS) is a Chinese patent medicine with properties of activating blood circulation and dredging meridians. However, its potential effective components and mechanism in BSS were incompletely understood.
Aim Of The Study:
To investigate the pharmacological effect, molecular mechanism and potential effective components of TS in zebrafish blood stasis model.
Materials And Methods:
Phenylhydrazine-induced blood stasis model was established in transgenic zebrafish to evaluate the anti-blood stasis effect of TS using the high-content imaging system. Transcriptome profiling was employed to dissect the potential mechanism of TS. Network pharmacology and molecular docking were applied to predict BSS-associated targets and component-target interactions for TS.
Results:
TS treatment significantly increased blood flow velocity, reduced blood cell aggregation, and restored platelet circulation, while also markedly downregulating the expression of coagulation factors. Transcriptomic analysis identified mmp13a, hmox1a, mmp9 and complement-related factors (c3a.2, c3a.3) as candidate targets that may mediate the pharmacological effect of TS. A total of 11 components exhibited the anti-blood stasis activity, and network pharmacology combined with molecular docking further predicted that parishin B, parishin C, parishin E, and senkyunolide I may interact with MMP13, HMOX1 and MMP9.
Conclusions:
Our study provides new insights into the anti-blood stasis effect of TS, which is possibly mediated by regulating mmp13a, hmox1a, mmp9 and complement-related factors expression. A total of 11 components were identified as potential effective components responsible for the anti-blood stasis effect, thereby providing a scientific basis for the future selection of potential quality markers for TS.
