Department of Biochemistry & Biotechnology, Faculty of Science, Annamalai University, Annamalainagar, Tamil Nadu, India.
Department of Pathology, Microbiology, and Immunology, University of South Carolina School of Medicine, Columbia, South Carolina, USA.
Med Res Rev. 2024 Mar;44(2):457-496. doi: 10.1002/med.21988. Epub 2023 Aug 17.
Neem (Azadirachta indica A. Juss.), a versatile evergreen tree recognized for its ethnopharmacological value, is a rich source of limonoids of the triterpenoid class, endowed with potent medicinal properties. Extracts of neem have been documented to display anticancer effects in diverse malignant cell lines as well as in preclinical animal models that has largely been attributed to the constituent limonoids. Of late, neem limonoids have become the cynosure of research attention as potential candidate agents for cancer prevention and therapy. Among the various limonoids found in neem, azadirachtin, epoxyazadiradione, gedunin, and nimbolide, have been extensively investigated for anticancer activity. Azadirachtin, a potent biodegradable pesticide, exhibits profound antiproliferative effects by preventing mitotic spindle formation and cell division. The antiproliferative activity of gedunin has been demonstrated to be mediated primarily via inhibition of heat shock protein90 and its client proteins. Epoxyazadiradione inhibits pro-inflammatory and kinase-driven signaling pathways to block tumorigenesis. Nimbolide, the most potent cytotoxic neem limonoid, inhibits the growth of cancer cells by regulating the phosphorylation of keystone kinases that drive oncogenic signaling besides modulating the epigenome. There is overwhelming evidence to indicate that neem limonoids exert anticancer effects by preventing the acquisition of hallmark traits of cancer, such as cell proliferation, apoptosis evasion, inflammation, invasion, angiogenesis, and drug resistance. Neem limonoids are value additions to the armamentarium of natural compounds that target aberrant oncogenic signaling to inhibit cancer development and progression.
印楝（Azadirachta indica A. Juss.）是一种用途广泛的常绿乔木，因其具有民族药理学价值而受到认可，是三萜类植物中丰富的柠檬素来源，具有强大的药用特性。研究记录表明，印楝提取物在多种恶性细胞系和临床前动物模型中均具有抗癌作用，这在很大程度上归因于其成分柠檬素。最近，印楝柠檬素已成为研究关注的焦点，因为它们可能成为癌症预防和治疗的候选药物。在印楝中发现的各种柠檬素中，azadirachtin、epoxyazadiradione、gedunin 和 nimbolide 已被广泛研究用于抗癌活性。azadirachtin 是一种有效的生物可降解农药，通过阻止有丝分裂纺锤体的形成和细胞分裂，表现出强烈的抗增殖作用。gedunin 的抗增殖活性主要通过抑制热休克蛋白 90 及其客户蛋白来介导。环氧azadiradione 通过抑制促炎和激酶驱动的信号通路来阻止肿瘤发生。Nimbolide 是最有效的细胞毒性印楝柠檬素，通过调节驱动致癌信号的关键激酶的磷酸化来抑制癌细胞的生长，此外还调节表观基因组。有大量证据表明，印楝柠檬素通过防止获得癌症的标志性特征，如细胞增殖、凋亡逃逸、炎症、侵袭、血管生成和耐药性，发挥抗癌作用。印楝柠檬素是针对异常致癌信号抑制癌症发展和进展的天然化合物武器库的附加值。
