G.H. Patel Pharmacy Building, Centre for P.G. and Research in Pharmaceutical Sciences, Donor's Plaza, Fatehgunj, M.S. University of Baroda, Vadodara, Gujarat, India.
Pharm Biol. 2011 Apr;49(4):383-91. doi: 10.3109/13880209.2010.517759. Epub 2011 Mar 11.
Enicostemma hyssopifolium Verdoon (Gentianaceae) has been documented for various therapeutic effects in traditional systems of medicine; the hypoglycemic and hypolipidemic activities are also well reported.
Bioactivity guided fractionation of methanol extract of E. hyssopifolium to test the hypothesis that E. hyssopifolium and its constituents influence cells and systemic glucose homeostasis.
Derived fraction and isolated compounds were studied for (1) aldose reductase (AR) inhibition, (2) α-glucosidase inhibition, (3) effect on gluconeogenesis in rat hepatoma, (4) cytoprotection against streptozotocin (STZ)-induced toxicity on RINm5F cells, (5) normalization of glycemic control in acute hyperglycemic rat model, and (6) insulin-releasing effect both in vitro and in vivo.
The results indicated that E. hyssopifolium can modify the glucose homeostasis at the cellular level. Two bioactive constituents were identified. Swertisin was found to inhibit AR (IC(50) 1.23 μg/mL) and α-glucosidase (IC(50) 1.89 μg/mL). It also possessed a significant cytoprotective action of RINm5F cell line against toxicant STZ. Swertiamarin was found to have hepatic gluconeogenesis inhibiting and insulin-releasing effect on rat hepatoma and RINm5F cells, respectively. The results of the in vivo study showed that swertiamarin, unlike the in vitro effect, produced no significant raise of insulin secretion. Swertisin normalized the serum glucose 60 min after high dose of glucose (2 g/kg, i.p.) in rats.
These findings demonstrate that the fraction derived from the aerial part of E. hyssopifolium achieve normoglycemic status in hyperglycemic conditions via various mechanisms. The constituents swertiamarin and swertisin are responsible for bioactivity.
水苦荬（龙胆科）在传统医学体系中有多种治疗功效的记载，其降血糖和降血脂的作用也有很好的报道。
采用生物活性导向方法对水苦荬甲醇提取物进行分段，以验证水苦荬及其成分影响细胞和全身葡萄糖稳态的假说。
对衍生部分和分离的化合物进行以下研究：（1）醛糖还原酶（AR）抑制作用，（2）α-葡萄糖苷酶抑制作用，（3）对大鼠肝癌细胞糖异生的影响，（4）对链脲佐菌素（STZ）诱导的 RINm5F 细胞毒性的细胞保护作用，（5）在急性高血糖大鼠模型中对血糖控制的正常化作用，（6）体外和体内的胰岛素释放作用。
结果表明，水苦荬可以在细胞水平上调节葡萄糖稳态。鉴定出两种生物活性成分。当化合物 swertisin 的浓度为 1.23μg/mL 时，对 AR 有抑制作用；当浓度为 1.89μg/mL 时，对 α-葡萄糖苷酶有抑制作用。它还对 RINm5F 细胞系具有显著的细胞保护作用，可抵抗 STZ 这种毒性物质。swertiamarin 对大鼠肝癌和 RINm5F 细胞的肝糖异生有抑制作用和胰岛素释放作用。体内研究的结果表明，与体外作用不同，swertiamarin 不会显著提高胰岛素的分泌。当给大鼠腹腔注射 2g/kg 的高剂量葡萄糖 60 分钟后，swertisin 可使血清葡萄糖水平正常化。
这些发现表明，水苦荬地上部分的提取物通过多种机制在高血糖条件下达到正常血糖状态。化合物 swertiamarin 和 swertisin 是具有生物活性的成分。
