In vitro neuroprotective activities of compounds from Angelica shikokiana Makino.
In vitro neuroprotective activities of compounds from Angelica shikokiana Makino.
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DOI：
10.3390/molecules20034813
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发表时间：
2015-03-16
期刊：
影响因子：
--
通讯作者：
Shimizu K
中科院分区：
文献类型：
--
作者：
Mira A;Yamashita S;Katakura Y;Shimizu K
当归在日本作为膳食补充剂广泛销售。重点关注神经退行性疾病，如阿尔茨海默病，提取地上部分，并通过生物导向分级分离，得到15种化合物[α-藜芦醇，β-香树脂醇，山奈酚，木犀草素，槲皮素，山奈酚-3-O-葡萄糖苷，山奈酚-3-O-芸香糖苷，绿原酸甲酯，绿原酸，Hyuganin E，5-（羟甲基）-2-糠醛、β-谷甾醇-3-O-葡萄糖苷、腺苷（首次从A. shikokiana）、isoepoxypteryxin和isopteryxin]。使用乙酰胆碱酯酶抑制剂、对过氧化氢和淀粉样β肽（Aβ25-35）诱导的神经毒性的保护作用、羟自由基和细胞内活性氧的清除作用以及硫磺素T测定，评价了分离的化合物的体外神经保护作用。槲皮素通过分别与乙酰胆碱酯酶催化位点和阴离子位点的His-440和Tyr-70残基结合，显示出最强的AChE抑制作用（IC 50值= 35.5 µM）。绿原酸及其甲酯、槲皮素和木犀草素对H_2O_2诱导的神经细胞毒性、羟自由基和细胞内活性氧有明显的保护作用。山奈酚-3-O-芸香苷、异环氧鸟苷和异环氧鸟苷能显著降低Aβ25-35诱导的神经毒性和Th-T荧光。据我们所知，这是第一个关于Hyuganin E和isoepoxypteryxin对Aβ25-35诱导的神经毒性的神经保护作用的报道。
Angelica shikokiana is widely marketed in Japan as a dietary food supplement. With a focus on neurodegenerative conditions such as Alzheimer’s disease, the aerial part was extracted and through bio-guided fractionation, fifteen compounds [α-glutinol, β-amyrin, kaempferol, luteolin, quercetin, kaempferol-3-O-glucoside, kaempferol-3-O-rutinoside, methyl chlorogenate, chlorogenic acid, hyuganin E, 5-(hydroxymethyl)-2-furaldehyde, β-sitosterol-3-O-glucoside, adenosine (isolated for the first time from A. shikokiana), isoepoxypteryxin and isopteryxin] were isolated. Isolated compounds were evaluated for in vitro neuroprotection using acetylcholine esterase inhibitory, protection against hydrogen peroxide and amyloid β peptide (Aβ25-35)-induced neurotoxicity in neuro-2A cells, scavenging of hydroxyl radicals and intracellular reactive oxygen species and thioflavin T assays. Quercetin showed the strongest AChE inhibition (IC50 value = 35.5 µM) through binding to His-440 and Tyr-70 residues at the catalytic and anionic sites of acetylcholine esterase, respectively. Chlorogenic acid, its methyl ester, quercetin and luteolin could significantly protect neuro-2A cells against H2O2-induced neurotoxicity and scavenge hydroxyl radical and intracellular reactive oxygen species. Kaempferol-3-O-rutinoiside, hyuganin E and isoepoxypteryxin significantly decreased Aβ25-35-induced neurotoxicity and Th-T fluorescence. To the best of our knowledge, this is the first report about neuroprotection of hyuganin E and isoepoxypteryxin against Aβ25-35-induced neurotoxicity.
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