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.

中文翻译：

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神莲提取物通过激活 NLRP3 炎症小体抑制炎症反应，防止超细颗粒物加重心肌缺血损伤

空气污染是一种日益严重的公共卫生负担，与多种负面健康影响有关，尤其是心血管疾病。神莲提取物（SL）是一种中药，具有清热解毒、活血化瘀的功效，长期以来被用于治疗心血管疾病和动脉粥样硬化。本研究通过网络药理学预测和实验验证，探讨了SL抗超细颗粒心肌缺血损伤（UFP-MI）的潜在作用机制。患有 UFP-MI 的雄性 Sprague-Dawley 大鼠用 SL 胃内预处理 7 天。然后将所有大鼠安乐死。进行炎性细胞因子检测和组织病理学分析以评估 SL 的保护作用。对于机理研究，通过转录组学分析，在用 SL 治疗的 UFP-MI 大鼠中鉴定出差异表达基因 (DEG)。随后，结合网络药理学，使用基于互联网的计算平台（www.tcmip.cn）和Cytoscape 3.6.0确定了涉及SL治疗作用的潜在途径。进行了进一步的验证实验以揭示SL对UFP-MI的治疗作用机制。结果表明，SL显着抑制炎症细胞向心肌组织的浸润并表现出显着的抗炎活性。转录组学分析表明，SL 处理后的 DEGs 具有显着的抗炎、免疫调节和抗病毒活性。网络药理学分析表明，SL的靶点主要参与炎症反应、凋亡过程、先天免疫反应、血小板活化和凝血过程的调节。通过结合转录组学和网络药理学数据，我们发现 SL 可能通过作用于 NOD 样信号通路来调节免疫反应激活和抑制全身炎症，从而发挥抗炎作用。验证实验表明，SL可以抑制炎症细胞因子白细胞介素1（IL-1）、白细胞介素18（IL-18）和白细胞介素33（IL-33）的分泌，抑制NLRP3炎症小体的活性。