Du Xiao-Ming, Irino Nobuto, Furusho Norihiro, Hayashi Jun, Shoyama Yukihiro
Seiwa Pharmaceuticals Ltd., 1-12-15 Shiba-Daimon, Minato-ku, Tokyo, 105-8585, Japan.
J Nat Med. 2008 Apr;62(2):132-48. doi: 10.1007/s11418-007-0169-0. Epub 2008 Jan 18.
The extract of Anoectochilus formosanus showed significant activity in decreasing the levels of the cytosolic enzymes LDH, GOT, and GPT, and the result demonstrated that A. formosanus possessed prominent hepatoprotective activity against CCl(4)-induced hepatotoxicity. Moreover, in the results of the test using aurothioglucose-induced obese mice, the extract showed a significant antihyperliposis effect. A. formosanus grown in the wild and propagated by tissue culture contain ten compounds, including a major known component, (3R)-3-(beta-D-glucopyranosyloxy)butanolide (kinsenoside; 1), and two new components, (3R)-3-(beta-D-glucopyranosyloxy)-4-hydroxybutanoic acid (2) and 2-[(beta-D-glucopyranosyloxy)methyl]-5-hydroxymethylfuran (3), along with the known compounds, isopropyl-beta-D-glucopyranoside (4), (R)-3,4-dihydroxybutanoic acid gamma-lactone (5), 4-(beta-D-glucopyranosyloxy) benzyl alcohol (6), (6R,9S)-9-(beta-D-glucopyranosyloxy)megastigma-4,7-dien-3-one (7), and (3R)-3-(beta-D-glucopyranosyloxy)-4-hydroxybutanolide (8). Since a higher concentration of kinsenoside (1) was detected in the crude drugs A. formosanus and A. koshunensis by high-performance liquid chromatography (HPLC) analysis, we proved a simple purification system for kinsenoside (1), giving 180 mg of kinsenoside (1) from 1 g of dried samples for further pharmacological experiments. In an anti-hyperliposis assay using high-fat-diet rats, 1 significantly reduced the weights of the body and the liver, and also decreased the triglyceride level in the liver compared to those of control rats. On the other hand, the epimer of 1, (3S)-3-(beta-D-glucopyranosyloxy)butanolide, goodyeroside A (9), which was isolated from the Goodyera species, had no effect for anti-hyperliposis. In aurothioglucose-induced obese mice, 1 suppressed the body and liver weight increase, significantly ameliorated the triglyceride level in the liver, and also reduced the deposition of uterine fat pads. The anti-hepatoxic activities of 9 and goodyerosides B (10) were studied on injury induced by CCl(4) in primary cultured rat hepatocytes by measuring the levels of LDH, GOT, and GPT. In the CCl(4)-treated control group, there were marked increases in LDH, GOT, and GPT activities compared with the normal group. In contrast, these levels were suppressed in 9- and 10-treated groups. Goodyerin (11), a new typical flavone glycoside, exhibited a significant and dose-dependent sedative and anticonvulsant effect.
台湾金线莲提取物在降低胞质酶乳酸脱氢酶（LDH）、谷草转氨酶（GOT）和谷丙转氨酶（GPT）水平方面表现出显著活性，结果表明台湾金线莲对四氯化碳诱导的肝毒性具有显著的肝保护活性。此外，在使用金硫葡萄糖诱导的肥胖小鼠的试验结果中，该提取物显示出显著的抗高血脂作用。野生生长并通过组织培养繁殖的台湾金线莲含有十种化合物，包括一种主要的已知成分，（3R）-3-（β-D-吡喃葡萄糖氧基）丁内酯（金线莲苷；1），以及两种新成分，（3R）-3-（β-D-吡喃葡萄糖氧基）-4-羟基丁酸（2）和2-[(β-D-吡喃葡萄糖氧基)甲基]-5-羟甲基呋喃（3），以及已知化合物异丙基-β-D-吡喃葡萄糖苷（4）、（R）-3,4-二羟基丁酸γ-内酯（5）、4-（β-D-吡喃葡萄糖氧基）苄醇（6）、（6R,9S）-9-（β-D-吡喃葡萄糖氧基）大柱头草-4,7-二烯-3-酮（7）和（3R）-3-（β-D-吡喃葡萄糖氧基）-4-羟基丁内酯（8）。通过高效液相色谱（HPLC）分析在台湾金线莲和高雄金线莲的粗药物中检测到较高浓度的金线莲苷（1），我们证明了一种金线莲苷（1）的简单纯化系统，从1克干燥样品中得到180毫克金线莲苷（1）用于进一步的药理实验。在使用高脂饮食大鼠的抗高血脂试验中，1显著降低了体重和肝脏重量，与对照大鼠相比，还降低了肝脏中的甘油三酯水平。另一方面，从斑叶兰属植物中分离出的1的差向异构体，（3S）-3-（β-D-吡喃葡萄糖氧基）丁内酯，高枝金线莲苷A（9），对抗高血脂没有作用。在金硫葡萄糖诱导的肥胖小鼠中，1抑制了体重和肝脏重量的增加，显著改善了肝脏中的甘油三酯水平，还减少了子宫脂肪垫的沉积。通过测量LDH、GOT和GPT水平，研究了9和高枝金线莲苷B（10）对原代培养大鼠肝细胞中四氯化碳诱导损伤的抗肝毒性活性。在四氯化碳处理的对照组中，与正常组相比，LDH、GOT和GPT活性显著增加。相比之下，在9和10处理组中这些水平受到抑制。新的典型黄酮苷类化合物高枝金线莲素（11）表现出显著的剂量依赖性镇静和抗惊厥作用。
