防己诺林碱作为双作用治疗剂：癌症与感染性疾病研究的最新进展

文献信息

中文摘要

防己诺林碱（FC）是一种从防己科药用植物中分离得到的天然双苄基异喹啉生物碱，因其多样的药理特性和治疗潜力而受到广泛关注。近期研究强调了其强效的抗癌和抗感染活性，这些活性通过调控多个细胞和分子靶点介导。FC对多种癌症表现出显著的抗癌疗效，包括结肠腺癌、非小细胞肺癌、肺癌、食管鳞状细胞癌、结膜黑色素瘤、胆囊癌、鼻咽癌、肾细胞癌、肝细胞癌、骨肉瘤、卵巢癌、多形性胶质母细胞瘤、胆管癌、乳腺癌和胃癌。其抗癌作用主要归因于对关键信号通路的调控，包括PI3K/Akt/mTOR、MAPK、NF-κB和AMPK，以及诱导ROS介导的凋亡、细胞周期阻滞和自噬。除抗癌活性外，FC还对病毒、细菌和真菌病原体表现出广谱抗感染活性。值得注意的是，它对甲型流感病毒、SARS-CoV、MERS-CoV、SARS-CoV-2及多种SARS-CoV-2变异株表现出强效抗病毒作用。此外，FC与瑞德西韦或氯法齐明联用时表现出增强的抗病毒疗效。本综述全面概述了FC的化学、药理活性、分子机制和治疗应用，特别强调其抗癌和抗感染潜力。总体而言，FC是一种结构多样、多功能的先导化合物，具有进一步治疗开发的巨大前景。

英文摘要

Fangchinoline (FC) is a naturally occurring bisbenzylisoquinoline alkaloid isolated from medicinal plants of the Menispermaceae family that has attracted considerable attention owing to its diverse pharmacological properties and therapeutic potential. Recent studies have highlighted its potent anti-cancer and anti-infective activities, which are mediated through the regulation of multiple cellular and molecular targets. FC has demonstrated significant anticancer efficacy against a wide range of cancers, including colon adenocarcinoma, non-small cell lung cancer, lung cancer, esophageal squamous cell carcinoma, conjunctival melanoma, gallbladder cancer, nasopharyngeal carcinoma, renal cell carcinoma, hepatocellular carcinoma, osteosarcoma, ovarian cancer, glioblastoma multiforme, cholangiocarcinoma, breast cancer, and gastric cancer. Its anticancer effects are primarily attributed to the modulation of key signaling pathways, including PI3K/Akt/mTOR, MAPK, NF-κB, and AMPK, as well as to the induction of ROS-mediated apoptosis, cell-cycle arrest, and autophagy. Beyond anticancer activity, FC exhibits broad-spectrum anti-infective activity against viral, bacterial, and fungal pathogens. Notably, it has demonstrated potent antiviral effects against influenza A viruses, SARS-CoV, MERS-CoV, SARS-CoV-2, and several SARS-CoV-2 variants. Moreover, FC exhibited enhanced antiviral efficacy when used in combination with remdesivir or clofazimine. This review provides a comprehensive overview of the chemistry, pharmacological activities, molecular mechanisms, and therapeutic applications of FC, with special emphasis on its anti-cancer and anti-infective potential. Overall, FC represents a structurally versatile and multifunctional lead compound with considerable promise for further therapeutic development.