Glvcyrrhizin attenuates MPTP neurotoxicity in mouse and MPP+-induced cell death in PC12 cells
Glvcyrrhizin attenuates MPTP neurotoxicity in mouse and MPP+-induced cell death in PC12 cells
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DOI：
10.4196/kjpp.2008.12.2.65
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发表时间：
2008-04-01
影响因子：
2
通讯作者：
Lee, Chung Soo
中科院分区：
文献类型：
--
作者：
Kim, Yun Jeong;Lee, Chung Soo
本研究考察了甘草化合物甘草酸及其代谢物18 β -甘草次酸对小鼠1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）神经毒性和1-甲基-4-苯基吡啶（MPP+）诱导的分化PC12细胞死亡的抑制作用。与对照小鼠相比，MPTP处理增加了大脑中总超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶的活性以及丙二醛和羰基的水平。同时给予甘草酸（16.8 mg/kg）可减弱MPTP对酶活性和组织过氧化产物形成的影响。在体外实验中，甘草化合物可减轻MPP+诱导的PC12细胞死亡和caspase-3的激活。甘草酸对MPP+的毒性可显著降低至100 PM。同时，18 -甘草次酸在10 μ M时抑制作用最大；超过这个浓度，抑制作用就减弱了。甘草酸和18 -甘草酸能减弱过氧化氢或氮诱导的细胞死亡。本研究结果表明，甘草酸可能通过抑制氧化性组织损伤来减轻MPTP小鼠的脑组织损伤。甘草酸和18 β -甘草酸可能通过抑制caspase-3的激活来降低PC12细胞的MPP+毒性。这种效果似乎归因于抗氧化作用。
The present study examined the inhibitory effect of licorice compounds glycyrrhizin and a metabolite 18 beta-glycyrrhetinic acid on the neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the mouse and on the 1-methyl-4-phenylpyridinium (MPP+)-induced cell death in differentiated PC12 cells. MPTP treatment increased the activities of total superoxide dismutase, catalase and glutathione peroxidase and the levels of malondialdehyde and carbonyls in the brain compared to control mouse brain. Co-administration of glycyrrhizin (16.8 mg/kg) attenuated the MPTP effect on the enzyme activities and formation of tissue peroxidation products. In vitro assay, licorice compounds attenuated the MPP+-induced cell death and caspase-3 activation in PC12 cells. Glycyrrhizin up to 100 PM significantly attenuated the toxicity of MPP+. Meanwhile, 18 beta-glycyrrhetinic acid showed a maximum inhibitory effect at 10 mu M; beyond this concentration the inhibitory effect declined. Glycyrrhizin and 18 beta-glycyrrhetinic acid attenuated the hydrogen peroxide- or nitrogen species-induced cell death. Results from this study indicate that glycyrrhizin may attenuate brain tissue damage in mice treated with MPTP through inhibitory effect on oxidative tissue damage. Glycyrrhizin and 18 beta -glycyrrhetinic acid may reduce the MPP+ toxicity in PC12 cells by suppressing caspase-3 activation. The effect seems to be ascribed to the antioxidant effect.