Korinek Michal, Tsai Yi-Hong, El-Shazly Mohamed, Lai Kuei-Hung, Backlund Anders, Wu Shou-Fang, Lai Wan-Chun, Wu Tung-Ying, Chen Shu-Li, Wu Yang-Chang, Cheng Yuan-Bin, Hwang Tsong-Long, Chen Bing-Hung, Chang Fang-Rong
Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical UniversityKaohsiung, Taiwan.
Department of Biotechnology, College of Life Science, Kaohsiung Medical UniversityKaohsiung, Taiwan.
Front Pharmacol. 2017 Jun 19;8:356. doi: 10.3389/fphar.2017.00356. eCollection 2017.
Increasing prevalence of allergic diseases with an inadequate variety of treatment drives forward search for new alternative drugs. Fatty acids, abundant in nature, are regarded as important bioactive compounds and powerful nutrients playing an important role in lipid homeostasis and inflammation. Phytochemical study on Nicolson and Sivadasan (Araceae), a folk anti-cancer and anti-inflammatory medicine, yielded four oxygenated fatty acids, 12-hydroxyoctadec-9,13-dienoic acid methyl ester () and 10-hydroxyoctadec-8,12-dienoic acid methyl ester (), 9-hydroxy-10-octadecenoic acid methyl ester (), and 12-hydroxy-10-octadecenoic acid methyl ester (). Isolated compounds were identified by spectroscopic methods along with GC-MS analysis. Isolated fatty acids together with a series of saturated, unsaturated and oxygenated fatty acids were evaluated for their anti-inflammatory and anti-allergic activities . Unsaturated (including docosahexaenoic and eicosapentaenoic acids) as well as hydroxylated unsaturated fatty acids exerted strong anti-inflammatory activity in superoxide anion generation (IC 2.14-3.73 μM) and elastase release (IC 1.26-4.57 μM) assays. On the other hand, in the anti-allergic assays, the unsaturated fatty acids were inactive, while hydroxylated fatty acids showed promising inhibitory activity in A23187- and antigen-induced degranulation assays (e.g., 9-hydroxy-10,12-octadecadienoic acid, IC 92.4 and 49.7 μM, respectively). According to our results, the presence of a hydroxy group in the long chain did not influence the potent anti-inflammatory activity of free unsaturated acids. Nevertheless, hydroxylation of fatty acids (or their methyl esters) seems to be a key factor for the anti-allergic activity observed in the current study. Moreover, ChemGPS-NP was explored to predict the structure-activity relationship of fatty acids. The anti-allergic fatty acids formed different cluster distant from clinically used drugs. The bioactivity of , which is historically utilized in folk medicine, might be related to the content of fatty acids and their metabolites.
过敏性疾病患病率不断上升，而治疗方法却种类不足，这推动了人们对新型替代药物的探索。自然界中丰富的脂肪酸被视为重要的生物活性化合物和强大的营养物质，在脂质稳态和炎症中发挥着重要作用。对民间用于抗癌和抗炎的药物尼科尔森天南星（天南星科）进行植物化学研究，得到了四种含氧脂肪酸，即12-羟基十八碳-9,13-二烯酸甲酯（）、10-羟基十八碳-8,12-二烯酸甲酯（）、9-羟基-10-十八碳烯酸甲酯（）和12-羟基-10-十八碳烯酸甲酯（）。通过光谱方法结合气相色谱-质谱分析对分离得到的化合物进行了鉴定。对分离得到的脂肪酸以及一系列饱和、不饱和和含氧脂肪酸的抗炎和抗过敏活性进行了评估。不饱和脂肪酸（包括二十二碳六烯酸和二十碳五烯酸）以及羟基化不饱和脂肪酸在超氧阴离子生成（IC 2.14 - 3.73 μM）和弹性蛋白酶释放（IC 1.26 - 4.57 μM）试验中表现出较强的抗炎活性。另一方面，在抗过敏试验中，不饱和脂肪酸无活性，而羟基化脂肪酸在A23187和抗原诱导的脱颗粒试验中显示出有前景的抑制活性（例如，9-羟基-10,12-十八碳二烯酸，IC分别为92.4和49.7 μM）。根据我们的结果，长链中羟基的存在并不影响游离不饱和酸的强效抗炎活性。然而，脂肪酸（或其甲酯）的羟基化似乎是本研究中观察到的抗过敏活性的关键因素。此外，利用ChemGPS-NP探索了脂肪酸的构效关系。抗过敏脂肪酸形成了与临床使用药物不同的簇。历史上在民间医学中使用的[具体物质]的生物活性可能与其脂肪酸及其代谢产物的含量有关。
