Giridharan Vijayasree Vayalanellore, Thandavarayan Rajarajan Amirthalingam, Konishi Tetsuya
J.K.K. Nattraja College of Pharmacy, Komarapalayam, Tamil Nadu 638 183, India ; Niigata University of Pharmacy & Applied Life Sciences, Niigata 956 8603, Japan.
Niigata University of Pharmacy & Applied Life Sciences, Niigata 956 8603, Japan ; Department of Cardiovascular Sciences, Houston Methodist Research Institute, Houston, TX 77030, USA.
Evid Based Complement Alternat Med. 2015;2015:584018. doi: 10.1155/2015/584018. Epub 2015 Nov 5.
The present study was designed to evaluate the preventive effect of antioxidative traditional oriental medicine formulae, Shengmai San (SMS) and LingGuiZhuGanTang (LGZGT), against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (i.p 30 mg·kg(-1) for 5 consecutive days) induced neurotoxicity. In in vitro antioxidant assays measured with Trolox and butyl hydroxyl toluene as reference antioxidant revealed that SMS has higher scavenging potential against hydroxyl radical than superoxide anion radical, but LGZGT was the reverse. The neuroprotective effect of SMS and LGZGT against MPTP was evaluated in mice by behavioral, biochemical, and immunohistochemical studies. In the behavioral study, both SMS and LGZGT significantly reversed the locomotive impairment induced by MPTP. Simultaneously, both formulae significantly prevented the MPTP induced dopaminergic neuron loss assessed by tyrosine hydroxylase in the midbrain. Both SMS and LGZGT significantly attenuated the elevated lipid peroxidation and protein carbonyls levels by MPTP. The DNA damage induced by MPTP was also prevented by both formulae. Although a little difference in the protective functions was observed between the two formulae, such as in DNA damage and behavioral studies, the results indicate that both SMS and LGZGT with antioxidant property act as a good candidate applicable for the antioxidant based complementary therapies of neurodegenerative diseases.
本研究旨在评估抗氧化传统东方医学配方生脉散(SMS)和苓桂术甘汤(LGZGT)对1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)(腹腔注射30mg·kg⁻¹,连续5天)诱导的神经毒性的预防作用。以Trolox和丁基羟基甲苯作为参考抗氧化剂进行的体外抗氧化测定表明,SMS对羟基自由基的清除潜力高于超氧阴离子自由基,但LGZGT则相反。通过行为学、生物化学和免疫组织化学研究评估了SMS和LGZGT对MPTP诱导的小鼠神经保护作用。在行为学研究中,SMS和LGZGT均显著逆转了MPTP诱导的运动功能障碍。同时,两种配方均显著预防了MPTP诱导的中脑酪氨酸羟化酶评估的多巴胺能神经元损失。SMS和LGZGT均显著减轻了MPTP诱导的脂质过氧化和蛋白质羰基水平升高。两种配方还预防了MPTP诱导的DNA损伤。尽管在两种配方之间观察到了保护功能上的一些差异,如在DNA损伤和行为学研究中,但结果表明,具有抗氧化特性的SMS和LGZGT均是适用于基于抗氧化剂的神经退行性疾病辅助治疗的良好候选药物。