2,4,5-trimethoxycinnamic acid: the major metabolite of alpha-asarone, retains most of the pharmacological properties of alpha-asarone.
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.
Antunez-Solis
Javier
J
Departamento de Bioquímica, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Apartado Postal 4-129, Admon. 4, México City 06401, Mexico.
Hernández-Derramadero
Fernando
F
Aquino-Vega
Mayda
M
Ibarra-Ramírez
Selene
S
Rodríguez-Páez
Lorena
L
Baeza
Isabel
I
Wong
Carlos
C
D000081248:Allylbenzene Derivatives; D000818:Animals; D000840:Anisoles / Q000378:metabolism* / Q000494:pharmacology*; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D001646:Bile / Q000187:drug effects / Q000378:metabolism; D001647:Bile Acids and Salts / Q000097:blood / Q000378:metabolism; D002784:Cholesterol / Q000097:blood / Q000378:metabolism; D002934:Cinnamates / Q000494:pharmacology*; D006903:Hydroxymethylglutaryl CoA Reductases / Q000097:blood / Q000378:metabolism; D006937:Hypercholesterolemia / Q000378:metabolism; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D008074:Lipoproteins / Q000097:blood / Q000378:metabolism; D008297:Male; D010743:Phospholipids / Q000097:blood / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
C552680:2,4,5-trimethoxycinnamic acid; D000081248:Allylbenzene Derivatives; D000840:Anisoles; D000924:Anticholesteremic Agents; D001647:Bile Acids and Salts; D002934:Cinnamates; D000960:Hypolipidemic Agents; D008074:Lipoproteins; D010743:Phospholipids; C012195:asarone; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases