Sedik Ahmed A, Hassan Soha A, Gouida Mona S O, Khalifa Eman
Pharmacology Department, Medical Research and Clinical Studies Institute, National Research Centre, Cairo, 12622, Egypt.
Department of Biotechnology, Faculty of Applied Health Sciences Technology, October 6 University, October 6 City, Egypt.
Sci Rep. 2025 Jul 2;15(1):23599. doi: 10.1038/s41598-025-08525-x.
Acrylamide (ACR) is a hazardous and possibly carcinogenic chemical compound that humans are constantly exposed to in their daily life. ACR passively affect many organ systems, including the cardiovascular system. Cordycepin (Cor) is a bioactive molecule derived from various species in the fungal kingdom, especially the genera Cordyceps and Ophiocordyceps. Cordycepin is known for its large-scale pharmacological activities. This study was conducted to evaluate the potential therapeutic effect of Cor on ACR-induced cardiotoxicity. Thirty-two Sprague‒Dawley rats were randomly divided into four groups (8 rats/group). Group I represented the control group, Group II received ACR (20 mg/kg/day) orally for 27 days, and Groups III and IV represented the control group. Rats received ACR (20 mg/kg) orally concurrently with Cor (10 and 20 mg/kg, b.w.), respectively, for 27 days. Serum cardiac biomarkers, such as cardiac troponin I (cTnI), creatine kinase (CK)-MB and lactate dehydrogenase (LDH), were evaluated. In addition, the antioxidant status and inflammatory response to ACR were evaluated. Moreover, detailed histopathological and ultrastructural observations were conducted. Our findings revealed that rats subjected to ACR presented increased levels of serum cardiac biomarkers, tumor necrosis factor-alpha (TNF-α), interleukin-6 (Il-6), malondialdehyde (MDA), annexin V, and Bax values, and programmed death ligand-1 (PD-L1) and decreased activities of nuclear factor erythroid 2-related factor 2 (Nrf-2) and heme oxygenase-1 (HO-1) and reduced glutathione (GSH), superoxide dismutase (SOD) and Bcl-2 expression. Conversely, the administration of Cor to rats treated with ACR in a dose-dependent manner succeeded in restoring serum cardiac biomarkers, modulated redox homeostasis and reduced inflammatory and apoptotic biomarkers. Consequently, a marked improvement was observed in the histopathological and ultrastructural images of the heart. In conclusion, Cor provides cardiac protection by inhibiting ACR-induced Nrf2/HO-1 and Bax/Bcl2 signaling failure, hence maintaining heart function. These findings suggest that Cor could be a promising treatment candidate for reducing ACR-induced cardiac damage.
丙烯酰胺（ACR）是一种具有危险性且可能致癌的化合物，人类在日常生活中会持续接触到它。ACR会对包括心血管系统在内的许多器官系统产生消极影响。虫草素（Cor）是一种源自真菌界多种物种，特别是虫草属和线虫草属的生物活性分子。虫草素以其广泛的药理活性而闻名。本研究旨在评估虫草素对ACR诱导的心脏毒性的潜在治疗效果。将32只Sprague-Dawley大鼠随机分为四组（每组8只）。第一组为对照组，第二组口服ACR（20毫克/千克/天），持续27天，第三组和第四组为对照组。大鼠分别同时口服ACR（20毫克/千克）和虫草素（10毫克/千克和20毫克/千克，体重），持续27天。评估了血清心脏生物标志物，如心肌肌钙蛋白I（cTnI）、肌酸激酶（CK）-MB和乳酸脱氢酶（LDH）。此外，还评估了对ACR的抗氧化状态和炎症反应。而且，进行了详细的组织病理学和超微结构观察。我们的研究结果显示，接受ACR处理的大鼠血清心脏生物标志物、肿瘤坏死因子-α（TNF-α）、白细胞介素-6（Il-6）、丙二醛（MDA）、膜联蛋白V和Bax值升高，程序性死亡配体-1（PD-L1）升高，而核因子红细胞2相关因子2（Nrf-2）、血红素加氧酶-1（HO-1）和还原型谷胱甘肽（GSH）、超氧化物歧化酶（SOD）的活性以及Bcl-2表达降低。相反，以剂量依赖方式给接受ACR处理的大鼠施用虫草素成功恢复了血清心脏生物标志物，调节了氧化还原稳态，并降低了炎症和凋亡生物标志物。因此，在心脏的组织病理学和超微结构图像中观察到明显改善。总之，虫草素通过抑制ACR诱导的Nrf2/HO-1和Bax/Bcl2信号传导失败来提供心脏保护，从而维持心脏功能。这些研究结果表明，虫草素可能是减轻ACR诱导的心脏损伤的一种有前景的治疗候选物。
