Anti-Alzheimer and Antioxidant Activities of Coptidis Rhizoma Alkaloids
Anti-Alzheimer and Antioxidant Activities of Coptidis Rhizoma Alkaloids
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DOI：
10.1248/bpb.32.1433
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发表时间：
2009-08-01
影响因子：
2
通讯作者：
Choi, Jae Sue
中科院分区：
文献类型：
--
作者：
Jung, Hyun Ah;Min, Byung-Sun;Choi, Jae Sue
甘草及其生物碱具有多种活性，包括神经保护和抗氧化作用。因此，六种原小檗碱生物碱的抗阿尔茨海默病和抗氧化作用（小檗碱、巴马汀、药根碱、表小檗碱、黄连碱和Groenlandicine）和一种阿朴啡生物碱通过β位点淀粉样前体蛋白（APP）裂解酶1（BACE 1）、乙酰胆碱酯酶（AChE）和丁酰胆碱酯酶（BChE）测定，沿着过氧亚硝酸盐（ONOO-）清除和总活性氧（ROS）抑制测定。6个原小檗碱生物碱表现出主要的胆碱酯酶（ChEs）抑制作用，IC 50值范围为0.44-1.07 μ M的AChE和3.32-6.84 μ M的BChE;只有表小檗碱（Ki =10.0）和groenlandicine（Ki =21.2）表现出良好的，非竞争性的BACE 1抑制活性，IC 50值分别为8.55和19.68 μ M。在两个抗氧化试验中，药根碱和groenlandicine表现出显着的ONOO-清除活性的IC 50值分别为0.78和0.84 μ M，黄连碱和groenlandicine表现出中等总活性氧抑制活性的IC 50值分别为48.93和51.78 μ M。这些结果表明，黄芪生物碱具有很强的抑制和预防阿尔茨海默病（AD）的潜力，主要是通过胆碱酯酶和β-淀粉样蛋白途径，并通过抗氧化能力。特别是，由于其对ChE和β-淀粉样蛋白形成的有效抑制活性以及显著的ONOO-清除和良好的ROS抑制能力，Groenlandicine可能是一种有前途的抗AD剂。因此，黄芪和其中所含的生物碱显然在开发AD和氧化应激相关疾病的治疗剂和预防剂中具有有益的用途。
Coptidis Rhizoma and its isolated alkaloids are reported to possess a variety of activities, including neuroprotective and antioxidant effects. Thus, the anti-Alzheimer and antioxidant effects of six protoberberine alkaloids (berberine, palmatine, jateorrhizine, epiberberine, coptisine, and groenlandicine) and one aporphine alkaloid (magnoflorine) from Coptidis Rhizoma were evaluated via beta-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1), acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) assays, along with peroxynitrite (ONOO-) scavenging and total reactive oxygen species (ROS) inhibitory assays. Six protoberberine alkaloids exhibited predominant cholinesterases (ChEs) inhibitory effects with IC50 values ranging between 0.44-1.07 mu M for AChE and 3.32-6.84 mu m for BChE; only epiberberine (K-i=10.0) and groenlandicine (K-i=21.2) exerted good, non-competitive BACE1 inhibitory activities with IC50 values of 8.55 and 19.68 mu M, respectively. In two antioxidant assays, jateorrhizine and groenlandicine exhibited significant ONOO- scavenging activities with IC50 values of 0.78 and 0.84 mu m, respectively; coptisine and groenlandicine exhibited moderate total ROS inhibitory activities with IC50 values of 48.93 and 51.78 mu M, respectively. These results indicate that Coptidis Rhizoma alkaloids have a strong potential of inhibition and prevention of Alzheimer's disease (AD) mainly through both ChEs and beta-amyloids pathways, and additionally through antioxidant capacities. In particular, groenlandicine may be a promising anti-AD agent due to its potent inhibitory activity of both ChEs and beta-amyloids formation, as well as marked ONOO- scavenging and good ROS inhibitory capacities. As a result, Coptidis Rhizoma and the alkaloids contained therein would clearly have beneficial uses in the development of therapeutic and preventive agents for AD and oxidative stress-related disease.