A combination of tetramethylpyrazine and berberine prevents coronary microembolization in rats by regulating miR-34a-5p in platelet-derived exosomes.

Ethnopharmacological Relevance: Both chuanxiong rhizome and Coptis chinensis were first recorded in the Shennong's Classic of Materia Medica. Chuanxiong rhizome and Coptis chinensis are a classic herbal pair in Traditional Chinese Medicine (TCM), renowned for their effects in activating blood circulation and resolving toxicity. They are widely used to treat chest impediment and heart pain.Tetramethylpyrazine (TMP) and berberine (BBR) are the main active components isolated from Chuanxiong Rhizome and Coptis chinensis, respectively. Both components have been applied to the treatment of various cardiovascular diseases owing to their anti-platelet, anti-inflammatory, and endothelial-protective effects. It has been demonstrated that the combination of TMP with BBR produces more effective anti-thrombotic effects compared with the monotherapy based on either agent.

Aim Of The Study: This study was designed to explore the potential role and mechanisms of TMP combined with BBR in reducing the formation of coronary microembolization (CME) in rats.

Materials And Methods: CME was induced by the injection of sodium laurate into the left ventricular of rats. CME formation and myocardial damage were examined using histopathology, while echocardiography was used to assess cardiac functions. Additionally, a series of in vitro experiments was performed to examine how platelet-derived exosomes (PLT-exo) enriched with miR-34a-5p influence human umbilical vein endothelial cells (HUVECs) subjected to ox-LDL and macrophages stimulated with LPS.Moreover, TMP and BBR were added to observe their effects.

Results: The combination of TMP and BBR significantly mitigated CME formation, myocardial injury, and left ventricular ejection fraction (LVEF) in rats. Besides, the pretreatment with TMP and BBR inhibited platelet activation, alleviated endothelial cell damage, and reduced the number of M1 macrophages. Additionally, the levels of miR-34a-5p in PLT-exo of CME rats were suppressed after the pretreatment with TMP and BBR. However, these effects of TMP and BBR were attenuated after the injection of agomiR-34a-5p in CME rats. Furthermore, TMP combined with BBR ameliorated in vitro HUVEC damage and M1-type macrophage polarization induced by an increase in miR-34a-5p in PLT-exo.

Conclusions: Our study concluded that the combination of TMP and BBR prevented CME and improved cardiac functions in rats by suppressing miR-34a-5p in PLT-exo.