Hypocholesterolemic and choleretic effects of three dimethoxycinnamic acids in relation to 2,4,5-trimethoxycinnamic acid in rats fed with a high-cholesterol/cholate diet.

Autor: Serna M; Biochemistry Department, National School of Biological Sciences, National Polytechnic Institute, Mexico City, Mexico. Electronic address: qbpsern@hotmail.com., Wong-Baeza C; Biochemistry Department, National School of Biological Sciences, National Polytechnic Institute, Mexico City, Mexico. Electronic address: cwongb@ipn.mx., Santiago-Hernández JC; Biochemistry Department, National School of Biological Sciences, National Polytechnic Institute, Mexico City, Mexico. Electronic address: jsantia@hotmail.com., Baeza I; Biochemistry Department, National School of Biological Sciences, National Polytechnic Institute, Mexico City, Mexico. Electronic address: isabelbaeza@yahoo.com., Wong C; Biochemistry Department, National School of Biological Sciences, National Polytechnic Institute, Mexico City, Mexico. Electronic address: carloswongr@yahoo.com.
Jazyk: angličtina
Zdroj: Pharmacological reports : PR [Pharmacol Rep] 2015 Jun; Vol. 67 (3), pp. 553-9. Date of Electronic Publication: 2014 Dec 29.
DOI: 10.1016/j.pharep.2014.12.009
Abstrakt: Background: 2,4,5-Trimethoxycinnamic acid (2,4,5-TMC) is the major and non-toxic metabolite of α-asarone, which retains hypocholesterolemic and choleretic activities. We compared the activities of 2,4,5-TMC with those of 2,4-dimethoxycinnamic acid (2,4-DMC), 3,4-DMC and 3,5-DMC, to understand the role of the methoxyls on carbons 2, 4 and 5 on the pharmacologic properties of these compounds.
Methods: The methoxycinnamic acids were administered to high-cholesterol/cholate-fed rats. We measured bile flow, and quantified bile acids, phospholipids and cholesterol in bile, and cholesterol and cholesterol-lipoproteins in serum. The inhibition of HMG-CoA reductase by the methoxycinnamic acids was evaluated in vitro.
Results: The four methoxycinnamic acids decreased serum cholesterol, without affecting the concentration of HDL-cholesterol. 2,4,5-TMC produced the highest decrease in LDL-cholesterol, 73.5%, which exceeds the range of statins (20-40%), and produced the highest inhibition of the activity of HMG-CoA reductase. 3,4-DMC produced the highest increase in bile flow, bile acids and phospholipids concentrations, and reduction in bile cholesterol, which led to a decrease in the biliary cholesterol saturation index.
Conclusions: 2,4,5-TMC (which has three methoxyls) had the highest hypocholesterolemic activity, while 3,4-DMC, which lacks the methoxyl in carbon 2 but conserves the two other methoxyls in an adjacent position, had the highest choleretic activity and a probable cholelitholytic activity. In methoxycinnamic acids with two methoxyls in non-adjacent positions (2,4-DMC and 3,5-DMC), the hypocholesterolemic and choleretic activities were not as evident. 2,4,5-TMC and 3,4-DMC, which did not cause liver damage during the treatment period, should be further explored as a hypocholesterolemic and choleretic compounds in humans.
(Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.)
Databáze: MEDLINE
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