一种整合了植物化学、计算机模拟和体内实验的方法,用于鉴定Caroxylon salicornicum对顺铂肝毒性的保护效应。
An integrated phytochemical, in silico and in vivo approach to identify the protective effect of Caroxylon salicornicum against cisplatin hepatotoxicity.
发表日期:2023 Oct
作者:
Shaymaa A Ramadan, Emadeldin M Kamel, Reem S Alruhaimi, Albandari Bin-Ammar, Madeha A Ewais, Akef A Khowailed, Emad H M Hassanein, Ayman M Mahmoud
来源:
ANTIOXIDANTS & REDOX SIGNALING
摘要:
顺铂(CIS)是治疗癌症的化疗药物。然而,肝毒性是限制其使用的不良反应之一。叉柄盐蓍草传统上用于治疗炎症性疾病。在这项研究中,检测到三种黄酮类化合物,四种香豆素类化合物和三种固醇类化合物存在于叉柄盐蓍草的石油醚部分(PEFCS)中。通过计算机模拟,发现这些分离出的植物化学物质具有与Keap1、NF-κB和SIRT1的结合亲和力。通过体内实验,研究了PEFCS(100、200和400 mg/kg)的肝保护作用。大鼠在连续14天接受PEFCS治疗,并在第15天接受CIS治疗。CIS增加了ALT、AST和ALP的水平,并导致组织损伤、ROS、MDA和NO的增加。在CIS处理的动物中,肝脏NF-κB p65水平、炎症介质、Bax和caspase-3均增加,而抗氧化剂和Bcl-2均降低。PEFCS能减轻肝细胞损伤,改善转氨酶、ALP、氧化应激和炎症标志物的情况。PEFCS下调了促凋亡标志物,并增加了Bcl-2和抗氧化剂的水平。此外,PEFCS在CIS处理的大鼠中上调了Nrf2、HO-1和SIRT1的表达水平。总之,PEFCS富含有益的植物化学成分,并通过减轻氧化应激和炎症以及上调Nrf2和SIRT1来对抗肝损伤。© 2023 The Author(s).
Cisplatin (CIS) is a chemotherapeutic medication for the treatment of cancer. However, hepatotoxicity is among the adverse effects limiting its use. Caroxylon salicornicum is traditionally used for treating inflammatory diseases. In this investigation, three flavonoids, four coumarins, and three sterols were detected in the petroleum ether fraction of C. salicornicum (PEFCS). The isolated phytochemicals exhibited binding affinity toward Keap1, NF-κB, and SIRT1 in silico. The hepatoprotective role of PEFCS (100, 200 and 400 mg/kg) was investigated in vivo. Rats received PEFCS for 14 days and CIS on day 15. CIS increased ALT, AST and ALP and caused tissue injury along with increased ROS, MDA, and NO. Hepatic NF-κB p65, pro-inflammatory mediators, Bax and caspase-3 were increased in CIS-treated animals while antioxidants and Bcl-2 were decreased. PEFCS mitigated hepatocyte injury, and ameliorated transaminases, ALP, oxidative stress (OS) and inflammatory markers. PEFCS downregulated pro-apoptosis markers and boosted Bcl-2 and antioxidants. In addition, PEFCS upregulated Nrf2, HO-1, and SIRT1 in CIS-administered rats. In conclusion, PEFCS is rich in beneficial phytoconstituents and conferred protection against liver injury by attenuating OS and inflammation and upregulating Nrf2 and SIRT1.© 2023 The Author(s).