Shenlian extract protects against ultrafine particulate matter-aggravated myocardial ischemic injury by inhibiting inflammation response via the activation of NLRP3 inflammasomes.

Air pollution is a growing public health burden associated with several negative health effects, especially cardiovascular disease. Shenlian extract (SL), a traditional Chinese medicine, has the effects of clearing heat-toxin and promoting blood circulation for removing blood stasis, and it has long been used to treat cardiovascular diseases and atherosclerosis. This study explored the underlying action mechanism of SL against ultrafine particle-induced myocardial ischemic injury (UFP-MI) through network pharmacology prediction and experimental verification. Male Sprague-Dawley rats with UFP-MI were pre-treated with SL intragastrically for 7 days. All the rats were then euthanized. Inflammatory cytokine detection and histopathological analysis were performed to assess the protective effects of SL. For the mechanism study, differentially expressed genes (DEGs) were identified in UFP-MI rats treated with SL through transcriptomic analysis. Subsequently, in combination with network pharmacology, potential pathways involved in the effects of SL treatment were identified using the Internet-based Computation Platform (www.tcmip.cn) and Cytoscape 3.6.0. Further validation experiments were performed to reveal the mechanism of the therapeutic effects of SL on UFP-MI. The results show that SL significantly suppressed inflammatory cell infiltration into myocardial tissue and exhibited significant anti-inflammatory activity. Transcriptomic analysis revealed that the DEGs after SL treatment had significant anti-inflammatory, immunomodulatory, and anti-viral activities. Network pharmacology analysis illustrated that the targets of SL were mainly involved in regulation of the inflammatory response, apoptotic process, innate immune response, platelet activation, and coagulation process. By combining transcriptomic and network pharmacology data, we found that SL may exert anti-inflammatory effects by acting on the NOD-like signaling pathway to regulate immune response activation and inhibit systemic inflammation. Verification experiments revealed that SL can suppress the secretion of the inflammatory cytokines Interleukin-1 (IL-1), Interleukin-18(IL-18) and Interleukin-33(IL-33) and suppress NLRP3 inflammasome activity. The results suggested that SL can directly inhibit the activation of NLRP3 inflammasomes and reduce the release of cytokines to protect against ultrafine particulate matter-aggravated myocardial ischemic injury.