2,4,5-trimethoxycinnamic acid: the major metabolite of α-asarone, retains most of the pharmacological properties of α-asarone

Figures & data

Table I.  Serum total cholesterol and lipoproteins-cholesterol distribution in rats.

		Serum cholesterol (mg/dL)
Rats (10/group)	Treatment (80 mg/kg body wt/day)	Total	LDL cholesterol	HDL cholesterol
Normolipemic	No-treatment	104.5 ± 5.42	13.6 ± 2.45	50.2 ± 4.37
Normolipemic	TMC	103.6 ± 5.12	12.1 ± 2.21	51.6 ± 4.22
Normolipemic	α-asarone	102.7 ± 5.24	12.1 ± 2.21	51.9 ± 4.11
Hypercholesterolemic	No-treatment	176.7 ± 7.52*	19.59 ± 0.86	83.5 ± 3.64
Hypercholesterolemic	TMC	131.6 ± 4.14**	5.23 ± 0.32**	83.3 ± 3.25
Hypercholesterolemic	α-asarone	123.7 ± 7.30**	4.96 ± 0.32**	74.4 ± 5.99

Results are expressed as means ± S.E. p showed the difference between the TMC and the α-asarone-treated and the non-treated groups. Number of rats per group = 10. *p < 0.005 versus normolipemic no-treatment. ** p < 0.05 versus hypercholesterolemic no-treatment.

Figure 1.  Comparative effect of α-asarone and 2,4,5-trimethoxycinnamic acid on several biochemical and physiological parameters related to cholesterol metabolism in hypercholesterolemic rats. Total serum cholesterol (T-CHOL), LDL, HDL, cholesterol (CHOL), bile acids (BA), phospholipids (PL), bile flow (FLOW), bile cholesterol saturation index (CSI).

Table II.  Effect of TMC and α-asarone on biliary lipids concentration and CSI.

			Biliary lipids concentration (mM)
Rats (10/group)	Treatment (80 mg/kg body wt/day)	Bile flow (μL/min/g)	Cholesterol	Bile acids	Phospholipids	CSI
Normolipemic	No-treatment	0.55 ± 0.04	0.42 ± 0.04	5.58 ± 0.98	2.21 ± 0.22	0.81 ± 0.03
Normolipemic	TMC	0.65 ± 0.05*	0.51 ± 0.03	6.85 ± 0.97	2.98 ± 0.16	0.77 ± 0.03
Normolipemic	α-asarone	0.66 ± 0.05*	0.52 ± 0.03	7.13 ± 0.99	3.02 ± 0.20	0.78 ± 0.03
Hypercholesterolemic	No-treatment	1.00 ± 0.05	0.82 ± 0.18	11.90 ± 0.75	2.90 ± 0.38	1.07 ± 0.02
Hypercholesterolemic	TMC	1.50 ± 0.06**	0.60 ± 0.09**	14.70 ± 0.81**	3.70 ± 0.36**	0.75 ± 0.03**
Hypercholesterolemic	α-asarone	1.79 ± 0.07**	0.60 ± 0.10**	13.60 ± 0.80**	3.60 ± 0.50**	0.73 ± 0.04**

Results are expressed as means ± S.E. p, showed the difference between the TMC and the α-asarone-treated and the non-treated groups. Number of rats per group = 10. *p < 0.005 versus normolipemic no-treatment. ** p < 0.05 versus hypercholesterolemic no-treatment. CSI: Bile cholesterol saturation index.

Figure 2.  Inhibition of HMG-CoA reductase by TMC (A) and α-asarone (B). Experiments were carried out as described in materials and methods. The results are expressed as percentage of mevalonolactone of the control HMG-CoA reductase activity without inhibitor; control value was 0.122 nmol/min/mg protein.