Departamento de Bioquímica, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Apartado Postal 4-129, Admon. 4, México City 06401, Mexico.
J Enzyme Inhib Med Chem. 2009 Jun;24(3):903-9. doi: 10.1080/14756360802318902.
2,4,5-trimethoxycinnamic acid (TMC), the major and non toxic metabolite of alpha-asarone (2,4,5-trimethoxy-1-propenyl benzene), retains most of the pharmacological properties of alpha-asarone, since both substances, administered to hypercholesterolemic rats at 80 mg/kg body wt, decreased total serum cholesterol, lowered LDL-cholesterol levels and kept unaffected HDL-cholesterol levels. In addition, both substances increased bile flow, especially in hypercholesterolemic rats, by rising the secretion of bile salts, phospholipids and bile cholesterol. These drugs also reduced cholesterol levels of gallbladder bile, whereas phospholipids and bile salts concentrations were increased, decreasing the cholesterol saturation index (CSI). We also found that alpha-asarone was 20 times better inhibitor of HMG-CoA reductase than TMC. This effect on HMG-CoA reductase was the only property highly reduced in TMC in comparison with alpha-asarone, while the other pharmacological properties of alpha-asarone were retained by TMC. These experiments strongly suggest that TMC can be further studied as a possible hypocholesterolemic and cholelitholytic agent.
2,4,5-三甲氧基肉桂酸（TMC）是α-细辛脑（2,4,5-三甲氧基-1-丙烯基苯）的主要无毒代谢产物，保留了α-细辛脑的大部分药理特性，因为这两种物质在 80mg/kg 体重的高脂血症大鼠中给药时，均降低了总血清胆固醇，降低了 LDL-胆固醇水平，而 HDL-胆固醇水平不受影响。此外，这两种物质都增加了胆汁流量，特别是在高脂血症大鼠中，通过增加胆汁盐、磷脂和胆汁胆固醇的分泌。这些药物还降低了胆囊胆汁中的胆固醇水平，同时增加了磷脂和胆汁盐的浓度，降低了胆固醇饱和度指数（CSI）。我们还发现，α-细辛脑对 HMG-CoA 还原酶的抑制作用比 TMC 强 20 倍。与 α-细辛脑相比，这种对 HMG-CoA 还原酶的作用是 TMC 中唯一显著降低的性质，而 α-细辛脑的其他药理特性则被 TMC 保留。这些实验强烈表明，TMC 可以进一步作为一种潜在的降胆固醇和溶胆石药物进行研究。
