Liu Dengke, Ding Xiaoyan, Yang Yafeng
Department of Cardiology and Endodontics, Stomatological Hospital, General Hospital of Ningxia Medical University, No.769 Shengli Road, Xingqing District, Ningxia Hui Autonomous Region, Ningxia, 750003, China.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Apr 12. doi: 10.1007/s00210-025-04010-4.
The most prevalent malignant tumor in the oral cavity, accounting for more than 90% of all oral malignancies, is oral squamous cell carcinoma (OSCC). Therefore, detection or prevention of malignant transformation remains a viable target for the future. Carnosol is a compound derived from rosemary that contains both antioxidant and anti-carcinogens. This study examined the defensive properties of carnosol in DMBA-induced oral carcinogenesis. We have developed the computational based docking analysis to predict the binding affinity and interaction of carnosol with inflammatory and pro-apoptotic proteins. Carnosol was the most potential bioactive compound shows strong binding affinity to low binding energy to bind above the proteins. Following this, we created a hamster model to study buccal pouch carcinogenesis induced by DMBA and assessed buccal tissues using histopathological, biochemical, and western blotting. Carnosol treatment effectively reduced DMBA-induced pathological changes in buccal tissues: Altered detoxification, increased antioxidant levels, and reduced lipid peroxidation enzymes levels. We then examined the impact of carnosol intervention on the modulation of the levels of inflammatory factors and pro-apoptotic markers in oral carcinogenesis. Binding energy was studied between the carnosol between the inflammatory (NF-κB and COX-2) and apoptotic (Bax, caspase-3, and caspase-9) proteins using molecular docking. Our findings suggest that carnosol enhances antioxidant and detoxification levels, potentially prevents oral carcinogenesis by modifying the inflammatory and pro-apoptotic signaling pathways, and acts as an anti-cancer agent.
口腔中最常见的恶性肿瘤是口腔鳞状细胞癌（OSCC），占所有口腔恶性肿瘤的90%以上。因此，检测或预防恶性转化仍然是未来可行的目标。鼠尾草酸是一种从迷迭香中提取的化合物，兼具抗氧化剂和抗癌剂的特性。本研究检测了鼠尾草酸在二甲基苯并蒽（DMBA）诱导的口腔癌发生过程中的防御特性。我们开展了基于计算的对接分析，以预测鼠尾草酸与炎症和促凋亡蛋白的结合亲和力及相互作用。鼠尾草酸是最具潜力的生物活性化合物，对蛋白质具有较强的结合亲和力和较低的结合能。在此基础上，我们建立了仓鼠模型来研究DMBA诱导的颊囊癌变，并使用组织病理学、生化和蛋白质印迹法对颊组织进行评估。鼠尾草酸治疗有效减轻了DMBA诱导的颊组织病理变化：解毒功能改变、抗氧化水平升高以及脂质过氧化酶水平降低。然后，我们研究了鼠尾草酸干预对口腔癌发生过程中炎症因子和促凋亡标志物水平调节的影响。使用分子对接技术研究了鼠尾草酸与炎症蛋白（核因子κB和环氧合酶-2）和凋亡蛋白（ Bax、半胱天冬酶-3和半胱天冬酶-9）之间的结合能。我们的研究结果表明，鼠尾草酸可提高抗氧化和解毒水平，可能通过改变炎症和促凋亡信号通路来预防口腔癌发生，并具有抗癌作用。
