Jung Hyun Ah, Yoon Na Young, Bae Hyun Ju, Min Byung-Sun, Choi Jae Sue
Division of Food Science and Biotechnology, Pukyong National University, Busan 608-737, Korea.
Arch Pharm Res. 2008 Nov;31(11):1405-12. doi: 10.1007/s12272-001-2124-z. Epub 2008 Nov 21.
As part of our ongoing search of natural sources for therapeutic and preventive agents for diabetic complications, the rat lens aldose reductase (RLAR) inhibitory effect of Coptidis Rhizoma (the rhizome of Coptis chinensis Franch) was evaluated. Its extract and fractions exhibited broad and moderate RLAR inhibitory activities of 38.9 approximately 67.5 microg/mL. In an attempt to identify bioactive components, six quaternary protoberberine-type alkaloids (berberine, palmatine, jateorrhizine, epiberberine, coptisine, and groenlandicine) and one quaternary aporphine-type alkaloid (magnoflorine) were isolated from the most active n-BuOH fraction, and the chemical structures therein were elucidated on the basis of spectroscopic evidence and comparison with published data. The anti-diabetic complications capacities of seven C. chinensis-derived alkaloids were evaluated via RLAR and human recombinant AR (HRAR) inhibitory assays. Although berberine and palmatine were previously reported as prime contributors to AR inhibition, these two major components exhibited no AR inhibitory effects at a higher concentration of 50 microg/ml in the present study. Conversely, epiberberine, coptisine, and groenlandicine exhibited moderate inhibitory effects with IC(50) values of 100.1, 118.4, 140.1 microM for RLAR and 168.1, 187.3, 154.2 microM for HRAR. The results clearly indicated that the presence of the dioxymethylene group in the D ring and the oxidized form of the dioxymethylene group in the A ring were partly responsible for the AR inhibitory activities of protoberberine-type alkaloids. Therefore, Coptidis Rhizoma, and the alkaloids contained therein, would clearly have beneficial uses in the development of therapeutic and preventive agents for diabetic complications and diabetes mellitus.
作为我们持续探索用于糖尿病并发症治疗和预防药物天然来源工作的一部分，我们评估了黄连（黄连的根茎）对大鼠晶状体醛糖还原酶（RLAR）的抑制作用。其提取物和馏分表现出宽泛且中等程度的RLAR抑制活性，浓度为38.9至约67.5微克/毫升。为了鉴定生物活性成分，从活性最高的正丁醇馏分中分离出六种季铵型原小檗碱类生物碱（小檗碱、巴马汀、药根碱、表小檗碱、黄连碱和格陵兰黄连碱）和一种季铵型阿朴啡类生物碱（木兰碱），并根据光谱证据以及与已发表数据的比较阐明了其中的化学结构。通过RLAR和人重组AR（HRAR）抑制试验评估了七种源自黄连的生物碱的抗糖尿病并发症能力。尽管之前报道小檗碱和巴马汀是AR抑制的主要贡献者，但在本研究中，这两种主要成分在50微克/毫升的较高浓度下未表现出AR抑制作用。相反，表小檗碱、黄连碱和格陵兰黄连碱表现出中等抑制作用，RLAR的IC50值分别为100.1、118.4、140.1微摩尔，HRAR的IC50值分别为168.1、187.3、154.2微摩尔。结果清楚地表明，D环中二氧亚甲基基团的存在以及A环中二氧亚甲基基团的氧化形式部分负责原小檗碱类生物碱的AR抑制活性。因此，黄连及其所含生物碱在开发糖尿病并发症和糖尿病的治疗及预防药物方面显然具有有益用途。
