常春藤皂苷元的抗抑郁药效学研究

Pharmacodynamical evaluation of hederagenin as an antidepressant

目的探讨常春藤皂苷元(HG)的抗抑郁效果,为开发新型抗抑郁药提供科学的理论依据。方法采用皮质酮诱导PC12细胞损伤模型和经典的行为绝望动物模型(即小鼠悬尾实验和强迫游泳实验)对HG的抗抑郁活性进行初步研究,检测海马超氧化物歧化酶(SOD)活性和丙二醛(MDA)含量,进一步确定其药效学。结果 HG能提高皮质酮损伤PC12细胞存活率。小鼠实验结果显示,急性单次给药后,与对照组相比,HG低剂量(10 mg/kg)明显缩短小鼠悬尾不动时间。连续灌胃给药2周后,在悬尾实验和强迫游泳实验中,与对照组相比,HG在不影响小鼠自主活动能力的前提下降低小鼠不动时间,其中低剂量具有显著性差异。同时,HG能提高SOD活性,显著降低MDA含量。结论初步证实HG具有一定的抗抑郁作用,其机制可能与保护细胞及抗氧化有关。

Objective To preliminarily evaluate the antidepressant-like activity of hederagenin（HG） for the development of a novel antidepressant drug.Methods The antidepressant-like effects of HG in vitro were explored by MTT assay in corticosterone-induced cytotoxicity on PC12 cells.Classical behavior tests（including tail-suspension test（TST） and forced swimming test（FST）） were used to confirm the antidepressant-like effect of HG in vivo.Furthermore,the activity of SOD and content of MDA in hippocampus were detected by colorimetric assay kit.Results Corticosterone-induced cytotoxicity on PC12 cells was reversed by HG.Compared with vehicle（Veh） treatment,immobility time was significantly reduced by HG（10 mg/kg） in TST after single administration,so was immobility time in TST and FST at low dosage without any effect on locomotor activity after two consecutive weeks of administration.Moreover,the increase in SOD activity and significant decrease in MDA content were also observed after HG treatment.Conclusion HG produces antidepressant-like effects that may be associated with cell protection and antioxidation.