Abstract：
BACKGROUND: Myocardial infarction (MI) is the foremost cause of mortality in cardiovascular diseases. MI ultimately exacerbates cardiotoxicity due to the release of toxicity biomarkers and inflammatory infiltration.
OBJECTIVE: Vernodalin (VN) is a renowned cytotoxic sesquiterpene lactone that possesses antioxidant, anticancer, and anti-inflammatory properties. The cardioprotective mechanism of VN remains concealed. Hence, we explored the cardioprotective efficacy of VN on isoproterenol (ISO)- mediated MI and analyzed its underlying mechanism.
METHODS: Wistar albino rats were injected ISO (85 mg/kg bw) subcutaneously to induce MI to evaluate the cardioprotective potential of VN (10 mg/kg bw) by assessing heart weight/ body weight index, hemodynamic, toxicity enzymes, histopathology, inflammatory mediators, and signaling pathway. ISO enhanced heart weight/body weight index, cardiotoxicity enzymes, biomarkers, inflammation, and histopathological changes while reducing hemodynamic parameters and VEGF-B, AMPK, and eNOS signaling pathways.
RESULTS: Treatment with VN could significantly (p<0.05) mitigate the heart weight/body weight index, cardiotoxicity enzymes, biomarkers, inflammatory cytokines, and histopathological changes while enhancing hemodynamic parameters and VEGF-B, AMPK, and eNOS signaling pathways. Collectively, our findings revealed that the VN ameliorated defensive action against MI and averted myocardial injury by reducing the NF-κB-mediated inflammatory pathways in rats.
CONCLUSIONS: These findings established that VN expressively preserves the myocardium and employs anti-inflammatory actions by regulating NF-κB, VEGF-B, AMPK, and eNOS signaling pathways.
OBJECTIVE: Vernodalin (VN) is a renowned cytotoxic sesquiterpene lactone that possesses antioxidant, anticancer, and anti-inflammatory properties. The cardioprotective mechanism of VN remains concealed. Hence, we explored the cardioprotective efficacy of VN on isoproterenol (ISO)- mediated MI and analyzed its underlying mechanism.
METHODS: Wistar albino rats were injected ISO (85 mg/kg bw) subcutaneously to induce MI to evaluate the cardioprotective potential of VN (10 mg/kg bw) by assessing heart weight/ body weight index, hemodynamic, toxicity enzymes, histopathology, inflammatory mediators, and signaling pathway. ISO enhanced heart weight/body weight index, cardiotoxicity enzymes, biomarkers, inflammation, and histopathological changes while reducing hemodynamic parameters and VEGF-B, AMPK, and eNOS signaling pathways.
RESULTS: Treatment with VN could significantly (p<0.05) mitigate the heart weight/body weight index, cardiotoxicity enzymes, biomarkers, inflammatory cytokines, and histopathological changes while enhancing hemodynamic parameters and VEGF-B, AMPK, and eNOS signaling pathways. Collectively, our findings revealed that the VN ameliorated defensive action against MI and averted myocardial injury by reducing the NF-κB-mediated inflammatory pathways in rats.
CONCLUSIONS: These findings established that VN expressively preserves the myocardium and employs anti-inflammatory actions by regulating NF-κB, VEGF-B, AMPK, and eNOS signaling pathways.
摘要：
背景：心肌梗死（MI）是心血管疾病死亡的首要原因。由于毒性生物标志物的释放和炎症浸润,MI最终加剧心脏毒性。
目的：Vernodalin（VN）是一种著名的细胞毒性倍半萜内酯，具有抗氧化剂，抗癌，和抗炎特性。VN的心脏保护机制仍然隐藏。因此，我们探讨了VN对异丙肾上腺素（ISO）介导的MI的心脏保护作用，并分析了其潜在机制。
方法：Wistar白化病大鼠皮下注射ISO（85mg/kgbw）诱发MI，通过评估心脏重量/体重来评估VN（10mg/kgbw）的心脏保护潜力指数，血液动力学,毒性酶，组织病理学,炎症介质，和信号通路。ISO增强心脏重量/体重指数，心脏毒性酶，生物标志物，炎症,和组织病理学改变，同时降低血流动力学参数和VEGF-B，AMPK,和eNOS信号通路。
结果：用VN治疗可以显着（p<0.05）减轻心脏重量/体重指数，心脏毒性酶，生物标志物，炎性细胞因子，和组织病理学改变，同时增强血流动力学参数和VEGF-B，AMPK,和eNOS信号通路。总的来说，我们的研究结果表明,VN通过减少NF-κB介导的炎症通路,改善了大鼠对MI的防御作用,避免了心肌损伤.
结论：这些发现证实VN表达性保护心肌，并通过调节NF-κB发挥抗炎作用，VEGF-B,AMPK,和eNOS信号通路。
目的：Vernodalin（VN）是一种著名的细胞毒性倍半萜内酯，具有抗氧化剂，抗癌，和抗炎特性。VN的心脏保护机制仍然隐藏。因此，我们探讨了VN对异丙肾上腺素（ISO）介导的MI的心脏保护作用，并分析了其潜在机制。
方法：Wistar白化病大鼠皮下注射ISO（85mg/kgbw）诱发MI，通过评估心脏重量/体重来评估VN（10mg/kgbw）的心脏保护潜力指数，血液动力学,毒性酶，组织病理学,炎症介质，和信号通路。ISO增强心脏重量/体重指数，心脏毒性酶，生物标志物，炎症,和组织病理学改变，同时降低血流动力学参数和VEGF-B，AMPK,和eNOS信号通路。
结果：用VN治疗可以显着（p<0.05）减轻心脏重量/体重指数，心脏毒性酶，生物标志物，炎性细胞因子，和组织病理学改变，同时增强血流动力学参数和VEGF-B，AMPK,和eNOS信号通路。总的来说，我们的研究结果表明,VN通过减少NF-κB介导的炎症通路,改善了大鼠对MI的防御作用,避免了心肌损伤.
结论：这些发现证实VN表达性保护心肌，并通过调节NF-κB发挥抗炎作用，VEGF-B,AMPK,和eNOS信号通路。
