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胡椒碱、姜黄素和苦味叶下珠对小鼠镉免疫毒性的比较疗效

Comparative efficacy of piperine, curcumin and picroliv against Cd immunotoxicity in mice.

作者信息

Pathak Neelima, Khandelwal Shashi

机构信息

Indian Institute of Toxicology Research, Mahatma Gandhi Marg, P.O. Box 80, Lucknow, 226001, India.

出版信息

Biometals. 2008 Dec;21(6):649-61. doi: 10.1007/s10534-008-9150-y. Epub 2008 Jun 20.

Abstract

Cadmium (Cd), a well known environmental carcinogen, is a potent immunotoxicant. In rodents, it is primarily characterized by marked thymic atrophy and splenomegaly. Cadmium induces apoptosis in murine lymphocytes and alters the immune functions. Thus, for the amelioration of its effect, three structurally different bioactive herbal extracts such as piperine-alkaloid, picroliv-glycosides and curcumin-polyphenols were evaluated and their efficacy compared. For ascertaining their immunomodulatory role, various biochemical indices of cell damage such as cytotoxicity, oxidative stress (ROS, GSH), apoptosis (mitochondrial membrane potential, caspase-3 activity, phosphatidylserine externalization, apoptotic DNA) along with lymphocyte phenotyping, blastogenesis and cytokine secretion were assessed in thymic and splenic cell suspensions. Of the three herbals examined, piperine displayed maximum efficacy. All the three doses of piperine (1, 10 and 50 microg/ml) increased cell viability in a dose dependent manner, whereas curcumin and picroliv were also effective, but to a lesser degree. Only the two higher doses exhibited cell viability efficacy. The median doses ie 10 microg/ml, were therefore selected, for comparison of their antioxidant, anti-apoptotic and immune function modulation. Restoration of ROS and GSH was most prominent with piperine. The anti-apoptotic potential was directly proportional to their antioxidant nature. In addition, Cd altered blastogenesis, T and B cell phenotypes and cytokine release were also mitigated best with piperine. The ameliorative potential was in order of piperine > curcumin > picroliv and former could be considered the drug of choice under immunocompromised conditions.

摘要

镉(Cd)是一种广为人知的环境致癌物,也是一种强效免疫毒性物质。在啮齿动物中,其主要特征是明显的胸腺萎缩和脾肿大。镉可诱导小鼠淋巴细胞凋亡并改变免疫功能。因此,为了减轻其影响,评估了三种结构不同的生物活性草药提取物,即胡椒碱 - 生物碱、苦味叶下珠苷和姜黄素 - 多酚,并比较了它们的功效。为了确定它们的免疫调节作用,在胸腺和脾细胞悬液中评估了各种细胞损伤的生化指标,如细胞毒性、氧化应激(活性氧、谷胱甘肽)、凋亡(线粒体膜电位、半胱天冬酶 - 3活性、磷脂酰丝氨酸外化、凋亡DNA)以及淋巴细胞表型分析、细胞增殖和细胞因子分泌。在所研究的三种草药中,胡椒碱显示出最大的功效。所有三种剂量的胡椒碱(1、10和50微克/毫升)均以剂量依赖性方式提高细胞活力,而姜黄素和苦味叶下珠苷也有效,但程度较小。只有两个较高剂量表现出细胞活力功效。因此,选择中位数剂量即10微克/毫升,用于比较它们的抗氧化、抗凋亡和免疫功能调节作用。胡椒碱对活性氧和谷胱甘肽的恢复最为显著。抗凋亡潜力与其抗氧化性质成正比。此外,镉改变的细胞增殖、T和B细胞表型以及细胞因子释放也用胡椒碱缓解得最好。改善潜力的顺序为胡椒碱>姜黄素>苦味叶下珠苷,在免疫功能低下的情况下,前者可被视为首选药物。

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