Pharmacological effects of Artocarpus lakoocha methanol extract on inhibition of squalene synthase and other downstream enzymes of the cholesterol synthesis pathway

Abstract

Context: Artocarpus lakoocha Roxb. (Moraceae) is reported to possess antioxidant, anti-inflammatory, and anti-skin ageing agents.

Objective: This study evaluates the pharmacological effects of A. lakoocha leaves methanol extract on enzymes involved in the cholesterol synthesis pathway in high-fat diet-induced hyperlipidemic rats.

Materials and methods: Twenty-four male Wistar rats, weighing approximately 180-220 g, were divided into four groups: control, diseased (hyperlipidemic), A. lakoocha leaves extract treated, and simvastatin treated. The rats were fed with high-fat diet for 2 months to induce hyperlipidaemia, afterward, experimental groups received A. lakoocha leaves methanol extract (250 mg/kg) and simvastatin (10 mg/kg) orally until the 89^th day of the experiment, while the diseased group continued to receive high-fat diet along with normal saline.

Results: It was found that A. lakoocha extract significantly lowered the serum total cholesterol, triglycerides, and low-density lipoprotein (LDL) levels, while effectively increasing serum high-density lipoprotein (HDL) levels as compared to the diseased group (p ≤ 0.05). The mRNA expression levels of squalene synthase and HMG-CoA reductase were found to be effectively down-regulated after the treatment with A. lakoocha leaves extract (17.45 ± 2.48 vs. 31.91 ± 5.292 and 5.85 ± 3.164 vs. 37.37 ± 6.492) and simvastatin (7.148 ± 0.76 vs. 31.91 ± 5.292, and 3.098 ± 2.09 vs. 37.37 ± 6.492) as compared to the diseased group.

Discussion and conclusions: The results suggested that A. lakoocha leaves extract have observable beneficial effects on inhibition of enzymes involved in cholesterol synthesis pathway and improve lipid profile analogous to simvastatin.

Keywords: Antioxidant; atherosclerosis; simvastatin.

Figure 1.

Graphical representation of mean ± SD relative total cholesterol levels in all groups (n = 6). *** = p ≤ 0.001 and ** = p ≤ 0.01 indicate significant difference in comparison to the diseased group while ### = p ≤ 0.001 indicates significant difference in comparison to the control group.

Figure 2.

Graphical representation of mean ± SD relative HDL levels in all groups (n = 6). ** = p ≤ 0.01 and * p ≤ 0.05 indicate significant difference in comparison to the diseased group while # = p ≤ 0.05 indicates significant difference in comparison to the control group.

Figure 3.

Graphical representation of mean ± SD relative LDL levels in all groups (n = 6). *** = p ≤ 0.001 and ** = p ≤ 0.01 indicate significant difference when compared to the diseased group while ##= p ≤ 0.01 indicates significant difference in comparison to the control group.

Figure 4.

Graphical representation of mean ± SD of triglycerides levels in all groups (n = 6). *** = p ≤ 0.001 indicates significant difference when compared to the diseased group while ### = p ≤ 0.001 indicates significant difference in comparison to the control group.

Figure 5.

Graphical representation of mean ± SD relative mRNA expression levels of squalene synthase in all groups (n = 6). *** = p ≤ 0.001 and ** = p ≤ 0.01 indicate significant difference when compared to the diseased group while ### = p ≤ 0.001 indicates significant difference when compared to the control group.

Figure 6.

Graphical representation of mean ± SD relative mRNA expression levels of HMG-CoA reductase in all groups (n = 6). *** = p ≤ 0.001 indicates significant difference when compared to the diseased group while ## = p ≤ 0.01 indicates significant difference when compared to the control group.