Manikandan P, Letchoumy P Vidjaya, Gopalakrishnan M, Nagini S
Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar 608 002, Tamil Nadu, India.
Food Chem Toxicol. 2008 Jul;46(7):2332-43. doi: 10.1016/j.fct.2008.03.013. Epub 2008 Mar 18.
We evaluated the chemopreventive potential of Azadirachta indica (neem) leaf fractions based on in vitro antioxidant assays, and in vivo inhibitory effects on 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis. In addition we also identified the major constituents in neem leaf fractions by HPLC. Analysis of the free radical scavenging activities and reducing potential of crude ethanolic extract (CEE), ethyl acetate fraction (EAF) and methanolic fraction (MF) of neem leaf revealed a concentration-dependent increase in antioxidant potential that was in the order EAF>MF>CEE. Administration of neem leaf fractions reduced the incidence of DMBA-induced HBP carcinomas at a lower concentration compared to the crude extract. Chemoprevention by neem leaf fractions was associated with modulation of phase I and phase II xenobiotic-metabolising enzymes, lipid and protein oxidation, upregulation of antioxidant defences, inhibition of cell proliferation and angiogenesis, and induction of apoptosis. However, EAF was more effective than MF in terms of antiproliferative and antiangiogenic effects, and expression of CYP isoforms. The greater efficacy of EAF may be due to higher content of constituent phytochemicals as revealed by HPLC analysis. The results of the present study suggest that the antioxidant properties of neem leaf fractions may be responsible for modulating key hallmark capabilities of cancer cells such as cell proliferation, angiogenesis and apoptosis in the HBP carcinogenesis model.
我们基于体外抗氧化试验以及对7,12-二甲基苯并[a]蒽（DMBA）诱导的仓鼠颊囊（HBP）癌变的体内抑制作用，评估了印楝叶提取物的化学预防潜力。此外，我们还通过高效液相色谱法（HPLC）鉴定了印楝叶提取物中的主要成分。对印楝叶的粗乙醇提取物（CEE）、乙酸乙酯提取物（EAF）和甲醇提取物（MF）的自由基清除活性和还原能力分析表明，抗氧化潜力呈浓度依赖性增加，顺序为EAF>MF>CEE。与粗提取物相比，印楝叶提取物在较低浓度下可降低DMBA诱导的HBP癌的发生率。印楝叶提取物的化学预防作用与I相和II相外源性代谢酶的调节、脂质和蛋白质氧化、抗氧化防御的上调、细胞增殖和血管生成的抑制以及细胞凋亡的诱导有关。然而，在抗增殖和抗血管生成作用以及CYP同工型的表达方面，EAF比MF更有效。HPLC分析显示，EAF的更高疗效可能归因于其所含植物化学物质的含量更高。本研究结果表明，印楝叶提取物的抗氧化特性可能负责调节HBP癌变模型中癌细胞的关键特征能力，如细胞增殖、血管生成和细胞凋亡。
