Studies on the octacosanols-lowering effect of eicosanoids

Octacosanol are a natural mixture of aliphatic primary alcohols with carbon chains ranging from 22 to 34 (C-22-C-34) that are extracted primarily from the waxes of sugarcane, rice, and grains. The three most common cotton-cotyl alcohols in dietary programs are eicosanoids (C-28, 60%), triacontanols (C-30, 12-14%), and hexacontanols (C-26, 6-12%), with fewer other components. It is a promising therapeutic target for obesity and obesity-related metabolic disorders such as type 2 diabetes, atherosclerosis, hyperlipidemia, and NAFLD. It has been reported to lower cholesterol through several mechanisms. It binds to the ß subunit of AMP-activated protein kinase (AMPK) and activates the AMPK pathway, which inhibits HMG-CoA reductase activity and increases hepatic receptor-mediated LDL uptake by increasing the number of hepatic LDL receptors.AMPK activation inhibits the binding of cholesteryl ester transfer proteins, HDL cholesterol, and LDL cholesterol and increases the catabolism of LDL cholesterol while decreasing total cholesterol metabolism. In clinical studies, oxacillinol (C-28) has also been shown to be effective in lowering cholesterol levels with comparable efficacy to statins at the same dose. Compared to lovastatin, oxacinonol can affect the lipid profile through lipid peroxidation, lowering low-density lipoprotein cholesterol (LDL-C), T-CHO and TG levels in patients.

 

 

Rice bran oil (RBO) has cholesterol-lowering health benefits. These benefits are attributed to the fatty acid composition of RBO: oleic (18:1ω9) and linoleic (18:2ω6) acids, which make up about 70%; palmitic (C16:0) acid, which makes up about 22%; and the bioactive constituents of RBO that are biologically active for cholesterol-lowering, including oryzanol, phytosterols, tocotrienols and tocopherols, squalene, and eicosapentadecanol. Coconut oil (CCO) has likewise been found to have cholesterol-lowering health benefits. Saturated fatty acids are the main components of CCO, with lauric acid (C12:0) (52%) being the major component, followed by myristic acid (19%), caprylic acid (9%) and capric acid (10%). Lauric acid and CCO enhance their cardioprotective effects by lowering T-CHO, TG, phospholipids, and LDL cholesterol levels while increasing HDL cholesterol levels. In addition, lauric acid inhibits protein targets associated with hyperlipidemia, which suggests reduced HMG-CoA activity and enhanced cholesterol metabolism, resulting in additional benefits.

 

 

Natural eicosanoids in plants have been found to exist in esterified form, but their extraction releases fatty acids and free fatty alcohols. Previous studies have reported results showing that eicosanoids esterified with oleic acid (an unsaturated fatty acid) have better cholesterol-lowering activity, higher bioavailability compared to non-esterified eicosanoids, and enhanced bile acid secretion due to upregulation of 7-alpha-hydroxylase and increased LDL receptors, resulting in improved clearance of LDL cholesterol. However, the underlying mechanism of its cholesterol-lowering action has not been clarified, and there are no studies on the role of saturated fatty acid esterified eicosanoids in cholesterol-lowering activity. Therefore, the aim of the present study was to evaluate the cholesterol modulating effects of lauric acid esterified eicosanoids (LEO) and oleic acid esterified eicosanoids (OEO) compared to their unmodified counterparts and to investigate the underlying mechanisms by partially replacing the body fat content in high-fat diet (HFD)-induced obese C57BL/6J mice. The results showed that all supplement groups significantly inhibited high-fat diet-induced weight gain, but the effect was more pronounced in the group treated with esterified eicosanoids. Esterified eicosanoids significantly inhibited weight gain by decreasing fatty acid synthase (FASN) (0.78-fold ± 0.09, p < 0.05) transcripts and affecting the phosphoacetyl-CoA carboxylase/acetyl-CoA carboxylase (p-ACC/ACC) (1.42-fold ± 0.18, p < 0.05) ratio, as well as by decreasing the sterol regulatory element-binding protein 2 (SREBP-2) (1.42-fold ± 0.18, p < 0.05), which is responsible for cholesterol uptake, and by decreasing the sterol-regulatory element-binding protein 2 ( SREBP-2) (0.75-fold ± 0.08, p < 0.05) and low-density lipoprotein receptor (LDL-R) (1.24-fold ± 0.1, p < 0.05) to inhibit cholesterol synthesis. Effects of OEO on fatty acid and cholesterol synthesis compared to other drugs.

 

 

China's "General Standard for Health (Functional) Foods", clearly listed eicosanoids as an efficacy component of health food, and in the "2008 Consensus of Cardiovascular Disease Prevention and Treatment Guidelines" as well as the "2010 China Type 2 Diabetes Disease Prevention and Treatment Guidelines" to the patients with high blood lipids and diabetes mellitus recommended, known as the sixth largest lipid-lowering nutrients, with anti-thrombosis, regulating blood lipids, anti-arteriosclerosis, regulation of blood pressure, prevention of cerebral stroke, and anti-fatigue and other effects. With the deepening of research, eicosanoids will gradually be widely used in functional foods, nutritional preparations, pharmaceuticals, cosmetics, high-grade feeds, often made into tablets, pills, capsules, but also candies, chocolates, pastries and beverages.

 

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Source of technical content:《Fatty Acid Esterification of Octacosanol Attenuates Triglyceride and Cholesterol Synthesis in Mice》Sudthida Kamchonemenukool, Yen-Chun Koh, Pin-Yu Ho, Min-Hsiung Pan, Monthana Weerawatanakorn.