Lin Yi-Ruu, Chen Hwei-Hsien, Ko Chien-Hsin, Chan Ming-Huan
Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan.
Eur J Pharmacol. 2006 May 10;537(1-3):64-9. doi: 10.1016/j.ejphar.2006.03.035. Epub 2006 Mar 24.
The aim of the present study was to investigate the neuroprotective effects of honokiol and magnolol, two major bioactive constituents of the bark of Magnolia officinalis, against neuron toxicity induced by glucose deprivation, excitatory amino acids and hydrogen peroxide (H(2)O(2)) in cultured rat cerebellar granule cells. Cell membrane damage was measured with a lactate dehydrogenase (LDH) release assay and 3-(4,5-dimethyl-2 thiazoyl)-2,5-diphenyl-tetrazolium bromide (MTT) assay was used to assess mitochondrial activity, reflecting cell survival. Results showed that honokiol and magnolol alone did not affect mitochondrial function and cell damage, but significantly reversed glucose deprivation-induced mitochondrial dysfunction and cell damage. The glutamate receptor blocker MK-801 and antioxidant vitamin E also provided protection against this damage. Furthermore, honokiol was more potent than magnolol in protecting against glutamate-, N-methyl-D-aspartate (NMDA)- and H(2)O(2)-induced mitochondrial dysfunction. These results demonstrated that the neuroprotective effects of honokiol and magnolol may be related to their anti-oxidative actions and antagonism of excitotoxicity induced by excitatory amino acids, suggesting that both compounds may be potential therapeutic agents for neurodegenerative diseases.
本研究的目的是探讨厚朴树皮中的两种主要生物活性成分和厚朴酚对培养的大鼠小脑颗粒细胞中由葡萄糖剥夺、兴奋性氨基酸和过氧化氢（H₂O₂）诱导的神经元毒性的神经保护作用。用乳酸脱氢酶（LDH）释放试验测定细胞膜损伤，并用3-（4,5-二甲基-2-噻唑基）-2,5-二苯基溴化四氮唑（MTT）试验评估线粒体活性，反映细胞存活情况。结果表明，和厚朴酚单独使用不影响线粒体功能和细胞损伤，但能显著逆转葡萄糖剥夺诱导的线粒体功能障碍和细胞损伤。谷氨酸受体阻滞剂MK-801和抗氧化剂维生素E也能提供针对这种损伤的保护作用。此外，在预防谷氨酸、N-甲基-D-天冬氨酸（NMDA）和H₂O₂诱导的线粒体功能障碍方面，和厚朴酚比厚朴酚更有效。这些结果表明，和厚朴酚和厚朴酚的神经保护作用可能与其抗氧化作用以及对兴奋性氨基酸诱导的兴奋性毒性的拮抗作用有关，提示这两种化合物可能是神经退行性疾病的潜在治疗药物。
