半夏乙酸乙酯部位化学成分及抗炎活性研究

Chemical constituents from EtOAc extract of Pinelliae Rhizoma and their anti-inflammatory activity

研究半夏(Pinelliae Rhizoma)的化学成分及其抗炎活性。采用硅胶、MCI、ODS、Toyopearl HW-40C柱色谱及半制备液相等方法对半夏乙酸乙酯萃取部位进行分离纯化,根据理化性质结合现代波谱技术鉴定化合物结构。从中共分离鉴定了26个化合物,分别为环-(L-脯-8-羟基-D-异亮)二肽(1)、环-(L-脯-L-亮)二肽(2)、环-(L-脯-L-苯丙)二肽(3)、环-(L-脯-L-缬)二肽(4)、腺苷(5)、5′-硫甲基-5′-硫代腺(6)、2′-O-甲基腺苷(7)、腺嘌呤(8)、1,8,15-三氮杂环二十一烷-2,9,16-三酮(9)、1,8,15,22-四氮杂环二十八烷-2,9,16,23-四酮(10)、1,8,15,22,29-五氮杂环三十五烷-2,9,16,23,30-五酮(11)、壬二酸二甘油酯(12)、棕榈酸单甘油酯(13)、亚油酸甘油酯(14)、9,12-十八烷二烯基N-羟乙基(15)、亚麻酸2-丁氧基乙酯(16)、(2 S)-1-O-(9 Z,12 Z-十八烷二烯基)-3-O-β-半乳糖基甘油(17)、胡萝卜苷-6′-O-棕榈酸酯(18)、邻苯二甲酸二-(2-乙基)-己酯(19)、落叶松脂素(20)、落叶松脂醇-9-O-β-吡喃葡萄糖苷(21)、(+)-表松脂素-4′-O-β-吡喃葡萄糖苷(22)、(+)-异落叶松脂素-9′-O-β-吡喃葡萄糖苷(23)、(+)-异落叶松脂素-9-O-β-吡喃葡萄糖苷(24)、香草酸(25)、对羟基肉桂醇(26)。其中,化合物1、3、4、8~12、15、16、19、22和23为首次从半夏中分离得到。采用脂多糖(LPS)诱导小鼠巨噬细胞(RAW 264.7)模型对部分单体化合物进行抗炎活性筛选。结果显示,化合物2、3、11、16和21具有抑制NO释放作用,其中化合物16的NO抑制作用较强,其IC 50值为10.47±0.89μmol/L。

This study aims to invstigate the chemical constituents from Pinelliae Rhizoma and their anti-inflammatory activity.Twenty-six compounds were isolated and purified from the ethyl acetate extract of Pinelliae Rhizoma silica gel,MCI,ODS and Toyopearl HW-40C column chromatography and semi-preparative HPLC methods.Their chemical structures were elucidated by physiochemical properties and spectral data as cyclo-(L-Pro-8-hydroxy-D-Ile)(1),cyclo-(L-Pro-L-Leu)(2),cyclo-(L-Pro-L-Phe)(3),cyclo-(L-Pro-L-Val)(4),adenosine(5),5′-S-methyl-5′-thioadenosine(6),2′-methoxyadenosine(7),adenine(8),1,8,15-triazecycloterpine-2,9,16-trione(9),1,8,15,22-tetraazacyclooctacosane-2,9,16,23-tetraketone(10),1,8,15,22,29-pentaaza-pentadecane-2,9,16,23,30-pentanone(11),diethylene glycol azelate(12),glycerol monopalmitate(13),glycerin monolinoleate(14),9,12-octadecadienoic acid N-(2-hydroxyethyl)(15),2-butoxyethyl linolenate(16),(2 S)-1-O-(9 Z,12 Z-octadecandienyl)-3-O-β-galactosyl glycerol(17),β-sitosteryl-3β-glucopyranoside-6′-O-palmitate(18),bis(2-ethylhexyl)phthalate(19),lariciresinol(20),lariciresinol-9-O-β-glucopyranoside(21),(+)-epipinoresinol-4′-O-β-glucopyranoside(22),(+)-isolariciresinol-9′-O-β-glucopyranoside(23),(+)-isolariciresinol-9-O-β-glucopyranoside(24),vanillic acid(25),and(E)-p-coumaroyl alcohol(26).Compounds 1,3,4,8-12,15,16,19 and 23 were isolated from Pinelliae Rhizoma for the first time.Some of isolated compounds were further evaluated for their anti-inflammatory activity in lipopolysaccharide(LPS)-induced mouse macrophage(RAW 264.7)cells.The results showed that compounds 2,3,11,16 and 21 had inhibitory effects on NO release,and compound 16 had stronger NO inhibition with IC 50 values of 10.47±0.89μmol/L.