Xiong Q, Fan W, Tezuka Y, Adnyana I K, Stampoulis P, Hattori M, Namba T, Kadota S
Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, Japan.
Planta Med. 2000 Mar;66(2):127-33. doi: 10.1055/s-2000-11135.
The leaves of Apocynum venetum L. are used as a tea material in north China and Japan. A water extract (500 mg/kg/day, one week administration) of the leaves of A. venetum showed protective effects against carbon tetrachloride (CCl4, 30 microliters/mouse) or D-galactosamine (D-GalN, 700 mg/kg)/lipopolysaccharide (LPS, 20 micrograms/kg)-induced liver injury in mice. Tumor necrosis factor-alpha (TNF-alpha) secreted from LPS-stimulated macrophages is the most crucial mediator in the D-GalN/LPS-induced liver injury model. The extract had no significant inhibition on the increase of serum TNF-alpha (1169 +/- 132 pg/ml vs. 1595 +/- 314 pg/ml of control), but exhibited a complete inhibition at the concentration of 100 micrograms/ml on TNF-alpha (100 ng/ml)-induced cell death in D-GalN (0.5 mM)-sensitized mouse hepatocytes. Further activity-guided fractionation resulted in the isolation of fifteen flavonoids viz. (-)-epicatechin (1), (-)-epigallocatechin (2), isoquercetin (3), hyperin (4), (+)-catechin (5), (+)-gallocatechin (6), kaempferol-6'-O-acetate (7), isoquercetin-6'-O-acetate (8), catechin-[8,7-e]-4 alpha-(3,4-dihydroxpyhenyl)-dihydro-2(3H)-pyranone (9), apocynin B (10), apocynin A (11), cinchonain Ia (12), apocynin C (13), apocynin D (14) and quercetin (15). All the compounds showed inhibitory effects on TNF-alpha-induced cell death with different intensities. The flavonol glycosides 3, 4, 7 and 8 and the phenylpropanoid-substituted flavan-3-ols 11 and 12 showed potent inhibitory effects on TNF-alpha-induced cell death with IC50 values of 37.5, 14.5, 31.2, 55.1, 71.9 and 41.2 microM, respectively. In contrast, the clinically used 5 and its analogues 1, 2 and 6 showed apparent activity only at 80 microM. These flavonoids appeared to be the hepatoprotective principles of the leaves of A. venetum. The hepatoprotective effects exhibited by the extract and its constituents suggest a validation of the leaves as a tea material.
罗布麻叶在中国北方和日本被用作茶饮原料。罗布麻叶水提取物（500毫克/千克/天，连续给药一周）对四氯化碳（CCl4，30微升/只小鼠）或D - 半乳糖胺（D - GalN，700毫克/千克）/脂多糖（LPS，20微克/千克）诱导的小鼠肝损伤具有保护作用。在D - GalN/LPS诱导的肝损伤模型中，LPS刺激的巨噬细胞分泌的肿瘤坏死因子 - α（TNF - α）是最关键的介质。该提取物对血清TNF - α的升高没有显著抑制作用（对照组为1169±132皮克/毫升，提取物组为1595±314皮克/毫升），但在100微克/毫升浓度时对TNF - α（100纳克/毫升）诱导的D - GalN（0.5毫摩尔）致敏小鼠肝细胞死亡表现出完全抑制作用。进一步的活性导向分离得到了15种黄酮类化合物，即（ - ） - 表儿茶素（1）、（ - ） - 表没食子儿茶素（2）、异槲皮苷（3）、金丝桃苷（4）、（ + ） - 儿茶素（5）、（ + ） - 没食子儿茶素（6）、山柰酚 - 6'-O - 乙酸酯（7）、异槲皮苷 - 6'-O - 乙酸酯（8）、儿茶素 - [8,7 - e] - 4α - （3,4 - 二羟基苯基） - 二氢 - 2（3H） - 吡喃酮（9）、罗布麻宁B（10）、罗布麻宁A（11）、金鸡纳宁Ia（12）、罗布麻宁C（13）、罗布麻宁D（14）和槲皮素（15）。所有化合物对TNF - α诱导的细胞死亡均表现出不同强度的抑制作用。黄酮醇苷3、4、7和8以及苯丙素取代的黄烷 - 3 - 醇11和12对TNF - α诱导的细胞死亡表现出强效抑制作用，IC50值分别为37.5、14.5、31.2、55.1、71.9和41.2微摩尔。相比之下，临床使用的5及其类似物1、2和6仅在80微摩尔时表现出明显活性。这些黄酮类化合物似乎是罗布麻叶的保肝成分。提取物及其成分所表现出的保肝作用表明罗布麻叶作为茶饮原料是有效的。
