Hypolipidemic and Anti-Atherogenic Effects of Sesamol and Possible Mechanisms of Action: A Comprehensive Review

Abstract

Sesamol is a phenolic lignan isolated from Sesamum indicum seeds and sesame oil. Numerous studies have reported that sesamol exhibits lipid-lowering and anti-atherogenic properties. The lipid-lowering effects of sesamol are evidenced by its effects on serum lipid levels, which have been attributed to its potential for significantly influencing molecular processes involved in fatty acid synthesis and oxidation as well as cholesterol metabolism. In this review, we present a comprehensive summary of the reported hypolipidemic effects of sesamol, observed in several in vivo and in vitro studies. The effects of sesamol on serum lipid profiles are thoroughly addressed and evaluated. Studies highlighting the ability of sesamol to inhibit fatty acid synthesis, stimulate fatty acid oxidation, enhance cholesterol metabolism, and modulate macrophage cholesterol efflux are outlined. Additionally, the possible molecular pathways underlying the cholesterol-lowering effects of sesamol are presented. Findings reveal that the anti-hyperlipidemic effects of sesamol are achieved, at least in part, by targeting liver X receptor α (LXRα), sterol regulatory element binding protein-1 (SREBP-1), and fatty acid synthase (FAS) expression, as well as peroxisome proliferator-activated receptor α (PPARα) and AMP activated protein kinase (AMPK) signaling pathways. A detailed understanding of the molecular mechanisms underlying the anti-hyperlipidemic potential of sesamol is necessary to assess the possibility of utilizing sesamol as an alternative natural therapeutic agent with potent hypolipidemic and anti-atherogenic properties. Research into the optimal sesamol dosage that may bring about such favorable hypolipidemic effects should be further investigated, most importantly in humans, to ensure maximal therapeutic benefit.

Keywords: Sesamum indicum; atherosclerosis; cholesterol; lipids; macrophages; sesamol.

Figure 1

A summary of the regulatory effects of sesamol on serum lipid profile and signaling factors and proteins involved in fatty acid synthesis, fatty acid oxidation, cholesterol metabolism, and macrophage cholesterol homeostasis. The major signaling pathways targeted by sesamol are denoted as well. (* with the addition of sesame oil). TC: total cholesterol; TG: triglyceride; LDL-C: low-density lipoprotein cholesterol; HDL: high-density lipoprotein cholesterol; VLDL: very low-density lipoprotein; PPARα: peroxisome proliferator-activated receptor α; SREBP-1: sterol regulatory element binding protein-1; NADPH: nicotinamide adenine dinucleotide phosphate; DGLA: dihomo-γ-linolenic acid; AA: arachidonic acid; PUFA: polyunsaturated fatty acid; TFA: total fatty acids; CPT1A: carnitine palmitoyltransferase-1A; PGC1A: peroxisome proliferator-activated receptor-gamma coactivator-1A; β-HB: β-hydroxybutyric acid; HSL: hormone-sensitive lipase; pHSL: phosphorylated hormone-sensitive lipase; LPL: lipoprotein lipase; HMGCR: 3-hydroxy-3-methylglutaryl-CoA reductase; ACAT2: acetyl-CoA acetyltransferase 2; LXRα: liver X receptor α; LXRβ: liver X receptor α; ABCG5: ATP-binding cassette sub-family G member 5; ABCG8: ATP-binding cassette sub-family G member 8; ABCA1: ATP-binding cassette sub-family A member 1; CYP7A1: cytochrome P450 family 7 subfamily A member 1; PPARγ1: peroxisome proliferator-activated receptor γ 1; ApoAI: apolipoprotein AI; FAS: fatty acid synthase; AMPK: AMP-activated protein kinase; MAPK: mitogen-activated protein kinase.