短花蛙提取物对钙诱导的大鼠肝脏线粒体通透性过渡孔打开的调节作用

T. Oyedeji, Chibuzor I. Akobi, Daniel O. Onireti, O. Olorunsogo
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引用次数: 1

摘要

线粒体功能障碍(MD)和凋亡通路受损导致线粒体通透性转换(MPT)孔的不可逆打开,导致癌症、衰老和神经退行性疾病等多种病理状况。许多来自植物的生物活性化合物已被确定为MPT孔的调节剂,这使它们成为治疗MD相关疾病的可能药物。短花腺草(a. breviflorus)是一种热带药用植物,在民间医学中用作堕胎药和治疗淋病。本研究考察了短花甲乙酸乙酯和甲醇组分对大鼠肝脏MPT孔和线粒体atp酶(mATPase)的影响。用水提取短花莲果实得到水提取物(AEAB),水提取物经真空液相色谱(VLC)分馏得到短花莲的乙酸乙酯和甲醇组分(EFAB和MFAB)。用EFAB和MFAB分光光度法测定MPT的开孔程度和mATPase。结果表明,在Ca2+不存在的情况下,EFAB和MFAB对MPT孔没有明显的诱导作用。然而,在Ca2+存在下,EFAB以非浓度依赖的方式抑制钙诱导的MPT孔打开。在50 μg/ml浓度下,MPT对气孔的最大抑制率为57.1%。有趣的是,MFAB通过进一步打开孔隙来增强钙离子的作用。在50、150、250和350 μg/ml浓度下,MFAB对MPT孔的打开率分别为11%、10%、17%和9%。EFAB和MFAB在62.5、187.5、312.5和437.5 μg/ml浓度下对大鼠肝脏线粒体mATPase活性的抑制作用分别为2.6、18.8、37.3、52.6%和41.8、6.8、24.3、8.4%。短花腺的乙酸乙酯和甲醇组分具有调节大鼠肝脏线粒体通透性过渡孔开放和抑制线粒体atp酶活性的潜在植物化学物质。这些馏分可能用于针对发生过度细胞凋亡的疾病的药物开发。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Fractions of Adenopus breviflorus Extract Modulate Calcium-induced Mitochondrial Permeability Transition Pore Opening in Rat Liver
Abstract Mitochondrial dysfunction (MD) and impaired apoptotic pathways cause irreversible opening of the Mitochondrial Permeability Transition (MPT) pore, resulting in several pathological conditions e.g. cancer, ageing and neurodegenerative diseases. Many bioactive compounds from plants have been identified as modulators of the MPT pore which makes them possible drugs for the management of MD associated diseases. Adenopus breviflorus (A.breviflorus) is a tropical medicinal plant used in folkore medicine as an abortifacient and in treating gonorrhoea. In this study, the effects of ethylacetate and methanol fractions of A.breviflorus were assessed on rat liver MPT pore and Mitochondrial ATPase (mATPase). The fruit of A.breviflorus was extracted with water to obtain the aqueous Extract (AEAB), which was fractionated using vacuum liquid chromatography (VLC) to obtain ethylacetate and methanol fractions of A.breviflorus (EFAB, and MFAB). The extent of MPT pore opening and mATPase by EFAB and MFAB were assayed spectrophotometrically. The results obtained showed that EFAB and MFAB have no significant inductive effect on the MPT pore in the absence of Ca2+. However, in the presence of Ca2+, EFAB inhibited calcium-induced MPT pore opening in a non-concentration dependent manner. Maximum inhibition of MPT pore opening was 57.1% at 50 μg/ml. Interestingly, MFAB potentiated calcium ion effect by opening the pore further. Specifically, MFAB opened the MPT pore by 11, 10, 17 and 9% at 50, 150, 250 and 350 μg/ml, respectively. Furthermore, EFAB and MFAB inhibited mATPase activity in rat liver mitochondria at 62.5, 187.5, 312.5 and 437.5 μg/ml by 2.6, 18.8, 37.3, 52.6% and 41.8, 6.8, 24.3, 8.4%, respectively. The ethylacetate and methanol fractions of Adenopus breviflorus possess potential phytochemicals that can modulate opening of the mitochondrial permeability transition pore and inhibit mitochondrial ATPase activity in rat liver. These fractions may find use in drug development against diseases where excessive apoptosis takes place.
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