松柏醇的化学合成及抗炎镇痛活性研究

Chemical synthesis and anti-inflammatory and analgesic activities studies of coniferyl alcohol

目的采用化学方法合成天然产物松柏醇(CA)并评价其抗炎镇痛活性。方法以阿魏酸为原料,与亚砜生成酰氯、再酯化,最后还原得到CA,其结构经红外、质谱和核磁确证。采用脂多糖(LPS)致RAW264.7细胞损伤模型评价CA的体外抗炎活性;构建小鼠足肿胀炎症模型和醋酸致小鼠扭体模型分别评价CA的抗炎镇痛活性。结果本研究共合成1.1 g CA,其化学结构与已报到的结果相符合。MTT测定结果表明松柏醇(1~32μmol/L)本身对RAW264.7细胞生长无明显影响。LPS干预RAW264.7细胞后,细胞生长受到明显抑制。与LPS组相比,CA在4,8和16μmol/L时对LPS致RAW264.7细胞损伤具有保护作用。CA可剂量依赖性地降低细胞上清液中一氧化氮(NO)、前列腺素E_(2)(PGE_(2))、肿瘤坏死因子-α(TNF-α)、白介素6(IL-6)和白介素1-β(IL-1β)水平,显示出较好的抗炎作用。动物实验结果表明腹腔注射给予CA(20、40 mg/kg)能明显改善角叉菜胶致小鼠足肿胀程度,也能明显减少醋酸致小鼠扭体次数。结论CA具有良好的抗炎镇痛活性,在炎症疾病领域具有开发价值。

Objective To synthesize coniferol alcohol(CA)and observe its anti-inflammatory and analgesic effects.Methods Ferulic acid was used as a precursor via ethyl ferulate to produce CA.The structures were identified by IR,NMR,and MS data.The in vitro anti-inflammatory activity of CA was evaluated through using LPS induced RAW264.7 cell model,and the in vivo anti-inflammatory and analgesic effects of CA were evaluated through using carrageenan induced paw edema and acetic acid writhing tests in mice.Results In this study,about 1.1 g of CA was obtained by chemical synthesis method,and its chemical structure is consistent with that reported in the previous literature.CA demonstrated no cytotoxicity on RAW264.7 cells at concentration range from 1 to 32μmol/L.Compared with the model group,CA at concentration of 4,8 and 16μmol/L showed significantly protective effects on LPS-mediated injury in RAW264.7 cells.In addition,in vitro results showed CA dose-dependently decreased the levels of NO,PGE_(2),TNF-α,IL-6 and IL-1βin varying degrees.The in vivo results showed that the intraperitoneal injection of 20 mg/kg and 40 mg/kg of CA significantly reduced carrageenan induced paw swelling as well as significantly decreased acetic acid-induced writhing times in mice,respectively.Conclusion CA shows significant anti-inflammatory and analgesic activities,which has good development value in the field of inflammatory diseases prevention and treatment.