二十八烷醇的研究进展

本文介绍了二十八烷醇的来源、理化性质、提取工艺以及二十八烷醇的生理功能,概括了二十八烷醇在医药、食品、化妆品和饲料等多个领域中的应用进展。     

高纯度二十八烷醇的制备与应用

以虫白蜡为原料,采用醇相皂化法制备长碳链脂肪醇.经重结晶制得高纯度二十八烷醇,采用毛细管气相色谱测定产物中二十八烷醇含量,结果表明:长链脂肪醇的平均得率为23.30%,二十八烷醇含量为39.08%.纯化产物中二十八烷醇含量为82.45%,并试制以二十八烷醇为主要功效物质的微胶囊冲剂.     

二十八烷醇缓解小鼠体力疲劳的作用

目的探讨二十八烷醇对小鼠体力疲劳的缓解作用。方法将小鼠分成对照组、二十八烷醇低剂量组和二十八烷醇高剂量组,用乳化的二十八烷醇分别以10和20 mg/(kg·d)的剂量饲育低剂量组和高剂量组小鼠,对照组供给自来水,实验期为4周。检测二十八烷醇对小鼠运动耐力、血乳酸(lactic acid,LAC)、尿素氮(blood urea nitrogen,BUN)、糖原含量及血乳酸脱氢酶(lactate dehydrogenase,LDH)活力的影响。结果二十八烷醇能提高小鼠的运动耐力;明显降低运动一段时间后的LAC和BUN含量(P0.05),提高LDH的活力(P0.05),显著增加肌糖原和肝糖原的储备量(P0.05);雌雄小鼠各项指标差异无统计学意义(P0.05)。结论二十八烷醇具有明显的缓解实验小鼠体力疲劳的作用,为富含二十八烷醇抗疲劳功能性运动员食品的开发利用提供了实验依据。     

从甘蔗渣中超临界CO2萃取二十八烷醇的研究

用超临界CO2萃取技术从甘蔗渣中萃取二十八烷醇,用正交实验的方法得到了优化工艺条件：萃取压力30MPa,萃取温度50℃,萃取时间为4h.并对萃出物作气相色谱分析,得萃出物中二十八烷醇的含量为24.80%.     

从甘蔗渣中超临界CO_2萃取二十八烷醇的研究

用超临界CO2萃取技术从甘蔗渣中萃取二十八烷醇,用正交实验的方法得到了优化工艺条件:萃取压力30MPa,萃取温度50℃,萃取时间为4h。并对萃出物作气相色谱分析,得萃出物中二十八烷醇的含量为24.80%。     

从蜂蜡分离粗三十烷醇-1的研究

本文研究了从天然蜂蜡出发,经工艺简单的结晶纯化方法,得到二十八烷醇含量低于3.3％的粗三十烷醇。由于采用丁醇-盐酸为重结晶溶剂,且省去了分离步骤,该法经济可行。     

几种高级烷醇的研究概述

概述了国内外有关二十六烷醇、二十八烷醇和三十烷醇的来源、性质、用途及重要生理活性方面的研究情况和成果。     

从峰蜡分离粗三十烷醇—1的研究

本文研究了从天然蜂蜡出发，经工艺简单的结晶纯化方法，得到二十八烷醇含量低于3．3％的粗三十烷醇。由于采用丁醇－盐酸为重结晶溶剂，且省去了分离步聚，该法经济可行。     

几种高级烷醇的研究概述

概述了国内外有关二十六烷醇、二十八烷醇和三十烷醇的来源、性质、用途及重要生理活性方面的研究情况和成果。     

二十八烷醇的合成

采用廉价易得的(Z)-13-二十二烯酸(芥酸)为起始原料,经酰基化、Dieckmann开环、催化氢化、黄鸣龙改良的Wolff-Kishner还原反应,最后经氢化铝锂还原得到GC纯度大于99.9%的1-二十八烷醇。反应共经历6步线性反应,总收率为65.4%。在公斤级中试生产中,二十八烷醇的总收率达到65%以上,产品GC纯度大于99%。     

Antinociceptive and Anti-Inflammatory Effects of Octacosanol from the Leaves of Sabicea grisea var. grisea in Mice

Sabicea species are used in the Amazon for treatment of fever and malaria, which suggests that its chemical constituents may have some effect on pain and inflammation. Phytochemical analysis of the hexane fraction obtained from the crude ethanol extract from Sabicea grisea var. grisea Cham. & Schltdl (Rubiaceae), an endemic plant in Brazil, resulted in the isolation of octacosanol. This study investigated the antinociceptive and anti-inflammatory effects of the octacosanol in different experimental models. The crude ethanolic extract and hexane fraction obtained from the leaves of S. grisea produced an inhibition of acetic acid-induced pain. Moreover, octacosanol isolated from the hexane fraction produced a significant inhibition of pain response elicited by acetic acid. Pre-treatment with yohimbine, an alpha 2-adrenergic receptor antagonist, notably reversed the antinociceptive activity induced by octacosanol in the abdominal constriction test. Furthermore, mice treated with octacosanol did not exhibit any behavioral alteration during the hot plate and rota-rod tests, indicating non-participation of the supraspinal components in the modulation of pain by octacosanol with no motor abnormality. In the formalin test, octacosanol did not inhibit the licking time in first phase (neurogenic pain), but significantly inhibited the licking time in second phase (inflammatory pain) of mice. The anti-inflammatory effect of octacosanol was evaluated using carrageenan-induced pleurisy. The octacosanol significantly reduced the total leukocyte count and neutrophils influx, as well as TNF-α levels in the carrageenan-induced pleurisy. This study revealed that the mechanism responsible for the antinociceptive and anti-inflammatory effects of the octacosanol appears to be partly associated with an inhibition of alpha 2-adrenergic transmission and an inhibition of pathways dependent on pro-inflammatory cytokines. Finally, these results demonstrated that the octacosanol from the leaves of S. grisea possesses antinociceptive and anti-inflammatory activities, which could be of relevance for the pharmacological control of pain and inflammatory processes.     

二十八烷醇的合成新工艺

本文报道了一种高效的合成1-二十八烷醇的工艺。该工艺利用价格相对更加低廉的化工原料（Z）-13-二十二烯酸（芥酸）,经由酰基化,Dieckmann开环,催化氢化,黄鸣龙改良的Wolff-Kishner还原反应还原,最后经由氢化铝锂还原得到纯度大于99.9%的1-二十八烷醇。反应共经历6步线性反应,总收率为65.4%,目前已经实现公斤级别中试生产。本合成工艺具有原料廉价易得,合成操作安全简单,收率稳定,关键中间体及终产物易于分离纯化的优点。     

Octacosanol Enhances the Proliferation and Migration of Human Umbilical Vein Endothelial Cells via Activation of the PI3K/Akt and MAPK/Erk Pathways

Atherosclerosis is characterized by endothelial dysfunction, lipid deposition, fibro‐proliferative reactions and inflammation. Octacosanol is a high‐molecular‐weight primary aliphatic alcohol. As the main component of a cholesterol‐lowering drug, octacosanol could inhibit lipids accumulation and cholesterol metabolism. To explore the indication of octacosanol on endothelial protection, we evaluated its effects on the proliferation and migration of human umbilical vein endothelial cells (HUVEC). Cell viability assay using methyl thiazolyl tetrazolium and 5‐ethynyl‐2′‐deoxyuridine revealed that 3.125 μg/ml octacosanol promoted the proliferation of HUVEC. A cell migration assay indicated that 0.781 and 3.125 μg/ml octacosanol increased the migration of HUVEC. Moreover, the phosphorylation levels of Akt and Erk1/2 were significantly elevated under exposure to octacosanol. Blocking the activation of Akt and Erk with their potent inhibitors LY294002 and PD98059, respectively, markedly attenuated the octacosanol‐induced proliferation and migration of HUVEC. These findings demonstrated for the first time that octacosanol enhanced the proliferation and migration of HUVEC and mediated these effects through activation of the PI3K/Akt and MAPK/Erk1/2 signaling pathways.     

Efficient Synthesis of Octacosanol Linoleate Catalyzed by Ionic Liquid and Its Structure Characterization

Octacosanol, as the major active policosanol, has attracted much attention due to the potential beneficial effects for human health. However, free octacosanol has a high melting point, poor oil solubility and low bioavailability, which greatly restricts its practical application. In this study, we report a highly efficient method for an ionic liquids (IL)‐catalyzed synthesis of octacosanol ester by direct esterification with linoleic acid. The synthesized product was purified, subsequently characterized by FT‐IR, MS and NMR and finally confirmed to be octacosanol linoleate. The reaction parameters were investigated and the conversion reached 91.3 ± 4.8 % under the optimum conditions: IL 1‐butylsulfonate‐3‐methylimidazolium hydrogen sulfate ([BSO₃HMim][HSO₄]) as catalyst, IL dose 1.5 % (related to the mass of both reactants), 1:1 molar ratio of octacosanol to linoleic acid, 80 °C, and 1 h. The melting point and oil solubility of octacosanol were greatly improved by esterification with linoleic acid, facilitating the incorporation into a variety of oil‐based systems.     

Free primary alcohols in oils and waxes from germs,kernels and other components of nuts,seeds, fruits and cereals

The composition of free primary alcohols in oils and waxes obtained from the germ, kernel, seed coat, shell and skin (peel) of various nuts, seeds, fruits and cereals and from the chrysalis of silkworm was examined. These alcohols are usually present in small amounts, along with large quantities of hydrocarbons, esters and glycerides in oils and waxes. Thus, it is necessary to remove hydrocarbons, esters and glycerides to analyze the alcohols. We found that preparative reverse-phase thin-layer chromatography (TLC) was the best way to isolate alcohols from oils and waxes. Gas liquid chromatography (GLC) then detected hexacosanol, octacosanol and triacontanol in the oils and waxes. Octacosanol usually was the predominant alcohol. Relationships between the organs from nuts, seeds, fruits and cereals and the contents of octacosanol are suggested. For example, degermed kernels contained two times more octacosanol than the germ, and the skin coat and shell contained one-half and one-fortieth the octacosanol of the germ, respectively.     

Changes in nutraceutical lipid components of rice at different degrees of milling

The concentrations of several nutraceutical lipid components [tocol (i.e. tocopherol + tocotrienol) phytosterol, γ‐oryzanol, octacosanol, and squalene] in milled rice and brown rice were determined. The lipid content decreased significantly (p <0.05) as the degree of milling increased, as did the total tocol content. Significant differences (p <0.05) were observed in the relative percentages of α‐tocopherol, α‐tocotrienol, and γ‐tocotrienol in brown rice and milled rice. β‐Sitosterol was the most abundant sterol, representing 50–56% of the total sterol content of all samples analyzed. There were no significant differences in the relative percentages of the sterol isomers as the degree of milling increased. The concentrations of γ‐oryzanol, squalene, and octacosanol in rice decreased significantly (p <0.05) as the degree of milling increased.     

A study of the alcohols of carnauba wax

Summary and Conclusions 1. Fractional crystallization alone is not an adequate method for isolating pure alcohols from carnauba wax. 2. More than 50 per cent of the alcohols of carnauba wax can be distilled at 0.5 mm. pressure without serious decomposition. 3. Fractional distillation of the free wax alcohols at 0.5 mm. is a useful method of separating these compounds, but recrystallization of the resulting fractions is necessary. 4. There are substances in the unsaponifiable portion of carnauba wax which are of an unknown nature but which are probably not n-aliphatic alcohols. 5. For the first time, three alcohols, octacosanol (C₂₈), triacontanol (C₃₀), and dotriacontanol (C₃₂) have been isolated from carnauba wax in states of purity of 95 per cent or better. 6. Dotriacontanol is even more abundant in the wax than is triacontanol. Submitted in partial fulfillment of the degree of Doctor of Philosophy, the Graduate School.     

Octacosanol Administration to Humans Decreases Neutral Sterol and Bile Acid Concentration in Feces

To investigate octacosanol (OC) metabolism in humans and its influence on cholesterol metabolism, two studies were conducted. In the first study ten healthy women received daily 30 mg OC for a period of 4 weeks. Blood and feces samples were collected at baseline and after the intervention. Serum concentrations of total cholesterol, LDL cholesterol, and HDL cholesterol were not altered following OC administration. Concentrations of excreted cholesterol end products decreased with the intervention (neutral sterols: 24.6 ± 9.7 mg/g vs. 20.3 ± 7.5 mg/g dry matter, P < 0.05; bile acids: 6.47 ± 3.89 mg/g vs. 4.03 ± 2.26 mg/g dry matter, P < 0.05). OC was not detected in serum samples, but the fecal OC concentration increased after the intervention period (11 ± 7 μg/g vs. 817 ± 179 μg/g dry matter, P < 0.05). In the second kinetic study on three participants, OC was identified in serums after oral application of 50 mg OC within 8 h. The decrease in the concentration of fecal cholesterol end products may underline a systemic effect of OC on cholesterol metabolism, even though the serum cholesterol levels were not influenced. Dual first authorship. S. Keller and F. Gimmler having contributed equally to the basic science presented.