Myrtenal attenuates diethylnitrosamine-induced hepatocellular carcinoma in rats by stabilizing intrinsic antioxidants and modulating apoptotic and anti-apoptotic cascades
Myrtenal attenuates diethylnitrosamine-induced hepatocellular carcinoma in rats by stabilizing intrinsic antioxidants and modulating apoptotic and anti-apoptotic cascades
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DOI：
10.1007/s13402-012-0086-4
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发表时间：
2012-08-01
影响因子：
6.6
通讯作者：
Balasubramanian, Maruthaiveeran Periyasamy
中科院分区：
文献类型：
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作者：
Babu, Lingaiah Hari;Perumal, Srinivasan;Balasubramanian, Maruthaiveeran Periyasamy
背景：肉豆蔻醛是一种天然单萜，存在于孜然、胡椒、薄荷和桉树中。单萜烯是由两个异戊二烯单元组成的天然植物碳氢化合物，广泛存在于植物区系中，最为人所知的是存在于精油中。单萜类化合物在不同的癌症模型中具有显著的生物活性，如抗氧化、化学治疗和化学预防作用。本研究旨在探讨桃金娘烯醛对致癌物诱发的大鼠肝细胞癌的抗氧化和抗癌作用。方法采用不同的体外抗氧化剂测定桃金娘醛对羟基、超氧阴离子、一氧化氮、1，1-二苯基-2-苦基肼、2，2-azino-bis-3-ethylbenzothiazoline-6-sulphonic酸自由基阳离子的清除作用。通过抗氧化酶活性、凋亡和抗凋亡蛋白Bcl2、Bax和caspase 3的表达以及对二乙基亚硝胺诱发的Wistar大鼠肝细胞癌的组织病理学分析，评价了桃金娘烯醛的体内抗氧化和抗癌活性。结果在所有体外实验中，桃金娘烯醛都具有很强的抗氧化活性，体内实验结果表明，荷瘤动物体内的抗氧化状态明显降低。在荷瘤动物中，抗凋亡蛋白表达上调，而凋亡蛋白表达下调。肉豆蔻醛对荷瘤动物的治疗可使体内的抗氧化剂显着增加，并对凋亡和抗凋亡级联反应的蛋白质有很好的调节作用。结论肉豆蔻醛通过对Wistar大鼠肝细胞癌的抑制作用，具有良好的清除自由基活性和抗癌活性。从而为将该化合物作为一种有效的肝癌治疗剂提供了积极的见解。
Background Myrtenal, a natural monoterpene occurred in cumin, pepper, mint and eucalyptus. Monoterpenes are naturally occurring plant hydrocarbons composed of two isoprene units and are widely distributed in plant flora and are best known for occurrence in essential oils. Monoterpenes have been shown to have remarkable biological activities such as antioxidant, chemotherapeutic and chemopreventive effects in different models of cancer. The aim of the study was to investigate the antioxidant and anticancer activity of myrtenal against carcinogen induced hepatocellular caricinoma in rats.Methods The antioxidant properties of myrtenal were evaluated by using different in vitro antioxidant assays such as by determining its scavenging effect against hydroxyl (OHaEuro cent), superoxide anion (O2(aEuro cent a')), nitric oxide, 1,1-diphenyl-2-picrylhydrazyl (DPPHaEuro cent) and 2,2-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid radical cation (ABTS(aEuro cent+)). In vivo antioxidant and anticancer activity of myrtenal were evaluated by determining the antioxidant enzymes, apoptotic and anti-apoptotic proteins such as Bcl-2, Bax and caspase-3 expression and histopathological analysis against the diethylnitrosamine induced hepatocellular carcinoma in wistar albino rats.Results Our results demonstrated that myrtenal exhibits strong antioxidant property in all the in vitro assays and the in vivo results revealed that the antioxidant status was significantly decreased in hepatoma bearing animals. The expression of anti-apoptotic proteins was up regulated and in contrast the apoptotic protein was down regulated in hepatoma bearing animals. Treatment with myrtenal to cancer bearing animals resulted in remarkable increase in the inherent antioxidants and excellent modulation in the proteins of apoptotic and anti-apoptotic cascade. Further, the RT-PCR analysis of protein expressions and histological analysis of liver tissues inevitably confirms the anticancer property of myrtenal.Conclusions It is concluded that myrtenal exhibits excellent free radical scavenging activity and anticancer activity through the suppression of hepatocellular carcinoma in wistar rats. Thereby giving a positive insight to take this compound as an effective therapeutic agent against hepatoma.