羊肚菌的生物活性提取物通过调节 KEAP1/NRF2 和促炎基因表达来改善环磷酰胺诱导的线粒体功能障碍和心脏毒性。
Bioactive extract of Morchella esculenta ameliorates cyclophosphamide-induced mitochondrial dysfunction and cardiotoxicity by modulating KEAP1/NRF2 and pro-inflammatory genes expression.
发表日期:2024 Jul 02
作者:
Sneha Das, Thekkuttuparambil A Ajith, Kainoor Krishnankutty Janardhanan, B S Harikumaran Thampi
来源:
ANTIOXIDANTS & REDOX SIGNALING
摘要:
预防抗癌药物引起的心脏毒性仍然是肿瘤学研究的一个重要领域,因为它仍然是癌症化疗的主要挑战。本研究旨在探讨羊肚菌(ME)甲醇提取物对环磷酰胺(CP)引起的心脏毒性的保护作用。通过生化和组织病理学方法评估心肌损伤。通过RT-PCR分析测定促炎细胞因子基因表达。为了评估线粒体功能障碍,测定了 TCA 循环和电子传递链复合物酶活性。 ME 的化学指纹图谱由 HPTLC 完成。 CP (200 mg/kg) 治疗的动物显示出心脏损伤标记物的升高,而 ME 减弱了这种标记物 (p<0.05)。 ME 可以恢复 CP 诱导的抗氧化状态下降和核因子红细胞 2 相关因子 2 表达的下降。 ME (500 mg/kg) 减弱了 CP 诱导的 NF-κB、IL1-β、IL-6、TNF-α、COX-2 和 iNOS 表达 (p<0.05)。提取物中存在的生物活性化合物,即 5-二十碳五烯酸 (C20H30O2)、8-羟基十八二烯酸 (C18H32O3)、4,4-二聚-zetacarotene (C30H44)、CynarosideA (C21H32O10) 可能具有心脏保护作用。研究结果揭示了 ME 对 CP 诱发的心肌病的保护作用。版权所有 © 2024。由 Elsevier Ltd 出版。
Prevention of anticancer drugs-induced cardiotoxicity remains an imperative area of oncology research as it continues to be a major challenge in cancer chemotherapy. This study was undertaken to investigate the protective effect of methanol extract of Morchella esculenta (ME) against cyclophosphamide (CP)-induced cardiotoxicity. Myocardial damage was assessed by biochemical and histopathological methods. Proinflammatory cytokines gene expression was determined by RT-PCR analysis. To assess the mitochondrial dysfunction, TCA cycle and electron transport chain complexes enzymes activities were determined. Chemical finger print of ME was accomplished by HPTLC. CP (200 mg/kg) treated animals showed elevation in cardiac injury markers which was attenuated by ME (p<0.05). CP-induced decline of antioxidant status and expression of nuclear factor erythroid 2-related factor 2 were restored by ME. CP-induced expression of NF-ĸB, IL1-β, IL-6, TNF-α, COX-2 and iNOS (p<0.05) was attenuated by ME (500 mg/kg). Bioactive compounds namely, 5-eicosapentaenoicacid (C20H30O2), 8-hydroxyoctadecadienoic acid (C18H32O3), 4,4-dipo-zetacarotene (C30H44), CynarosideA ( C21H32O10) present in the extract might be responsible for cardioprotection. The findings reveal the protective effect of ME against CP-induced cardiomyopathy.Copyright © 2024. Published by Elsevier Ltd.