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黄蜀葵花中黄酮类化合物抗抑郁活性及其上调大鼠海马组织中BDNF的作用机制研究 被引量:8

Antidepressant activity of flavonoid ethanol extract of Abelmoschus manihot corolla with BDNF up-regulation in the hippocampus
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摘要 黄蜀葵花为中国民间草药,是锦葵科秋葵属黄蜀葵[Abelmoschus manihot(L.)Medic.]的干燥花冠,已报道其具有抗抑郁活性。本文从黄蜀葵花中分离纯化得到主要黄酮类化合物,并探索其中5种化合物抗抑郁活性及其作用机制。采用D101大孔树脂柱、聚酰胺柱和Sephadex LH-20柱对黄酮类成分进行分离与纯化,经UHPLC与NMR等技术鉴定,得到8个黄酮类化合物,为杨梅素-3-O-β-D-葡糖苷(1)、棉皮素-8-O-β-D-葡糖苷酸(2,G-8-G)、棉皮素-3'-O-β-D-葡糖苷(3)、槲皮素-3'-葡糖苷(4,Q-3-G)、异槲皮苷(5,IQT)、金丝桃苷(6,HY)、杨梅黄酮(7)和槲皮素(8,QT)。采用小鼠分别灌胃化合物2、4、5、6和8(15、30、60 mg·kg^(-1))24 h后,观察悬尾实验(tail suspension test,TST)和强迫游泳实验(forced swimming test,FST),并采用Western blot技术检测小鼠海马组织中脑源性神经营养因子(BDNF)、酪氨酸受体激酶B(Trk B)和磷酸化的真核延伸因子2(p-e EF2)的表达。结果表明,化合物2和4能够显著缩短小鼠在FST和TST中的不动时间,显著增加BDNF和Trk B的表达,减少p-e EF2的表达。可见,化合物2和4可上调BDNF表达而发挥其抗抑郁活性。 Abelmoschus manihot(L.) Medic.,a folk herbal medicine in China,is a flowering plant belonging to Abelmoschus L. genus and Malvaceae family,which has been reported with an antidepressant activity. The study was designed to isolate flavonoids from Abelmoschus manihot corolla and explore the action mechanism of antidepressant activities. The flavonoids were isolated and purified by D101 macroporous resin column,polyamide column and Sephadex LH-20 sequentially and identified as myricetin-3-O-β-D-glucoside(1),gossypetin-8-O-β-D-glucuronide(2,G-8-G),gossypetin-3'-O-β-D-glucoside(3),quercetin-3'-glucoside(4,Q-3-G),isoquercitrin(5,IQT),hyperoside(6,HY),myricetin(7),quercetin(8,QT). Compounds 2,4,5,6 and 8(15,30 and 60 mg·kg^(-1)) were orally administered to mice and the reaction was observed in tail suspension test(TST) and forced swimming test(FST). Western blot analysis was used in determination of the protein expressions of brain-derived neurotrophic factor(BDNF),tyrosine receptor kinase B(Trk B) and phosphorylation eukaryotic elongation factor 2(p-e EF2). The results revealed that only Q-3-G and G-8-G(15,30,60 mg·kg-1) significantly reduced the immobility time in FST and TST. Furthermore,Q-3-G and G-8-G remarkably increased the expression of BDNF and Trk B,and decreased the expression of p-e EF2. These results suggest that Q-3-G and G-8-G had an obvious antidepressant activity via up-regulation of BDNF expression. The new observation will provide a new direction in the development of antidepressant in the treatment of major depressive disorder(MDD).
出处 《药学学报》 CAS CSCD 北大核心 2017年第2期222-228,共7页 Acta Pharmaceutica Sinica
基金 国家自然科学基金资助项目(81473408) 江苏省方剂高技术研究重点实验室建设项目(BM2010578) 江苏省中药学优势学科II期建设项目(ysxk-2014) 2013年国家教育部"新世纪优秀人才"计划项目(NCET-13-0873) 江苏省"333高层次人才培养工程"资助项目(BRA2015391)
关键词 锦葵科 秋葵属 抗抑郁 黄酮类化合物 脑源性神经营养因子 酪氨酸受体激酶B Malvaceae Abelmoschus antidepressant activity flavonoid brain derived neurotrophic factor tyrosine receptor kinase B
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