School of Biomedical Sciences, Faculty of Sciences, Charles Sturt University, Wagga Wagga, NSW 2678, Australia; Graham Centre for Agricultural Innovation, Charles Sturt University, Wagga Wagga, NSW 2678, Australia.
School of Biomedical Sciences, Faculty of Sciences, Charles Sturt University, Wagga Wagga, NSW 2678, Australia; Graham Centre for Agricultural Innovation, Charles Sturt University, Wagga Wagga, NSW 2678, Australia.
Fitoterapia. 2018 Jul;128:118-129. doi: 10.1016/j.fitote.2018.05.011. Epub 2018 May 24.
The focus of this study was on inhibition of enzymes involved in the pathogenesis Alzheimer's disease (AD) including prime amyloid beta (Aβ) producing enzyme (β-secretase: BACE-1) and disease progression enzymes including acetylcholinesterase (AChE), butyrylcholinesterase (BChE), histone deacetylase (HDAC), and tyrosinase along with the catecholamine L-DOPA, by using olive biophenols. Here we report the strongest inhibition of BACE-1 from rutin (IC: 3.8 nM) followed by verbascoside (IC: 6.3 nM) and olive fruit extract (IC: 18 ng), respectively. Olive biophenol, quercetin exhibited strongest enzyme inhibitory activity against tyrosinase (IC: 10.73 μM), BChE (IC: 19.08 μM), AChE (IC: 55.44 μM), and HDAC (IC: 105.1 μM) enzymes. Furthermore, olive biophenol verbascoside (IC: 188.6 μM), and hydroxytyrosol extreme extract (IC: 66.22 μg) were showed the highest levels of inhibition against the HDAC enzyme. Neuroprotective capacity against levodopa-induced toxicity in neuroblastoma (SH-SY5Y) cells of olive biophenols were assessed, where rutin indicated the highest neuroprotection (74%), followed by caffeic acid (73%), and extract hydroxytyrosol extreme (97%), respectively. To the best of our knowledge, this is the first in vitro report on the enzymes inhibitory activity of olive biophenols. Taken together, our in vitro results data suggest that olive biophenols could be a promising natural inhibitor, which may reduce the enzyme-induced toxicity associated with the oxidative stress involved in the progression of AD.
Acetylthiocholine iodide (PubChem CID: 74629); S-Butyrylthiocholine chloride (PubChem CID: 3015121); Caffeic acid (PubChem CID: 689043); Dimethyl sulfoxide (DMSO) (PubChem: 679); L-3,4-Dihydroxyphenylalanine (L-DOPA) (PubChem CID: 6047); 5,5'-Dithiobis (2-nitrobenzoic acid) (DTNB) (PubChem CID: 6254); Epigallocatechin gallate (EGCG) (PubChem CID: 65064); Ethylenediamine tetraacetic acid (EDTA) (PubChem CID: 6049); Galantamine hydrobromide (PubChem CID: 121587); l-Glutamine (PubChem CID: 5961); Hydroxytyrosol (PubChem CID: 82755); Kojic acid (PubChem CID: 3840); Luteolin (PubChem CID: 5280445); Oleuropein (PubChem CID: 5281544); Penicillin-streptomycin (PubChem CID: 131715954); Quercetin (PubChem CID: 5280343); Rutin (PubChem CID: 5280805); Tris-HCl buffer (PubChem: 93573); Trypan blue (PubChem: 9562061).
本研究的重点是抑制阿尔茨海默病（AD）发病机制中涉及的酶，包括主要淀粉样蛋白β（Aβ）产生酶（β-分泌酶：BACE-1）和疾病进展酶，包括乙酰胆碱酯酶（AChE）、丁酰胆碱酯酶（BChE）、组蛋白去乙酰化酶（HDAC）和酪氨酸酶以及儿茶酚胺 L-多巴，使用橄榄生物酚。在这里，我们报告了芦丁（IC：3.8 nM）对 BACE-1 的最强抑制作用，其次是 Verbascoside（IC：6.3 nM）和橄榄果实提取物（IC：18 ng）。橄榄生物酚，槲皮素对酪氨酸酶（IC：10.73 μM）、BChE（IC：19.08 μM）、AChE（IC：55.44 μM）和 HDAC（IC：105.1 μM）表现出最强的酶抑制活性。此外，橄榄生物酚 Verbascoside（IC：188.6 μM）和羟基酪醇极提取物（IC：66.22 μg）对 HDAC 酶的抑制作用最高。评估了橄榄生物酚对神经母细胞瘤（SH-SY5Y）细胞中左旋多巴诱导毒性的神经保护能力，其中芦丁显示出最高的神经保护作用（74%），其次是咖啡酸（73%）和提取物羟基酪醇极（97%）。据我们所知，这是第一个关于橄榄生物酚对酶抑制活性的体外报告。综上所述，我们的体外结果数据表明，橄榄生物酚可能是一种有前途的天然抑制剂，它可以减少与 AD 进展相关的氧化应激相关的酶诱导毒性。
乙酰硫代胆碱碘化物（PubChem CID：74629）；丁酰硫代胆碱氯化物（PubChem CID：3015121）；咖啡酸（PubChem CID：689043）；二甲基亚砜（DMSO）（PubChem：679）；L-3,4-二羟基苯丙氨酸（L-DOPA）（PubChem CID：6047）；5,5'-二硫代双（2-硝基苯甲酸）（DTNB）（PubChem CID：6254）；表没食子儿茶素没食子酸酯（EGCG）（PubChem CID：65064）；乙二胺四乙酸（EDTA）（PubChem CID：6049）；加兰他敏氢溴酸盐（PubChem CID：121587）；l-谷氨酰胺（PubChem CID：5961）；羟基酪醇（PubChem CID：82755）；曲酸（PubChem CID：3840）；木犀草素（PubChem CID：5280445）；橄榄苦苷（PubChem CID：5281544）；青霉素-链霉素（PubChem CID：131715954）；槲皮素（PubChem CID：5280343）；芦丁（PubChem CID：5280805）；Tris-HCl 缓冲液（PubChem：93573）；台盼蓝（PubChem：9562061）。
