Phaleria macrocarpa Boerl. (Thymelaeaceae) leaves increase SR-BI expression and reduce cholesterol levels in rats fed a high cholesterol diet

Abstract

In vitro and in vivo studies of the activity of Phaleria macrocarpa Boerl (Thymelaeaceae) leaves against the therapeutic target for hypercholesterolemia were done using the HDL receptor (SR-BI) and hypercholesterolemia-induced Sprague Dawley rats. The in vitro study showed that the active fraction (CF6) obtained from the ethyl acetate extract (EMD) and its component 2',6',4-trihydroxy-4'-methoxybenzophenone increased the SR-BI expression by 95% and 60%, respectively. The in vivo study has proven the effect of EMD at 0.5 g/kgbw dosage in reducing the total cholesterol level by 224.9% and increasing the HDL cholesterol level by 157% compared to the cholesterol group. In the toxicity study, serum glutamate oxalate transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) activity were observed to be at normal levels. The liver histology also proved no toxicity and abnormalities in any of the treatment groups, so it can be categorized as non-toxic to the rat liver. The findings taken together show that P. macrocarpa leaves are safe and suitable as an alternative control and prevention treatment for hypercholesterolemia in Sprague Dawley rats.

Figure 1

Molecular structure of 2',6',4-trihydroxy-4'-methoxybenzophenone.

Figure 2

The effects of EMD (A), CF6 (B) and 2',6',4 trihydroxy-4' methoxybenzophenone (C) from P. macrocarpa leaves on the transcriptional activity of SR-BI promoter.

Figure 3

The changes of total cholesterol level during treatment on groups of non-cholesterol (A) (♦); cholesterol (B) (■); and EMD 0.5 g/kgbw(C) (▲).

Figure 4

The changes of HDL-cholesterol level during treatment on groups of non-cholesterol (A) (♦); cholesterol (B) (■); and EMD 0.5 g/kgbw (C) (▲).

Figure 5

The Effect of P. macrocarpa leaves on liver of hypercholesterolemia induced rat of group A, B, C and D at 28 and 42 days. A: control non cholesterol group; B: control cholesterol group; C: 0.5 g/kgbw of EMD treated rats; D: 0.25 g/kgbw of EMD treated rats. CV = Central Vein; H = Hepatocytes; S = Sinusoids. H&E staining, magnification = 200×.

Figure 6

Proposed mechanism for hypocholesterolemia activity of compounds C from P. macrocarpa leaves through the enhancement of SR-BI gene expression at the transcription level (modified from Leiva et al. [49] and Krieger [50]).