河朔荛花枝叶中激活潜伏HIV的活性成分研究  

Active components of latent HIV activation in leaves and branches of Wikstroemia chamaedaphne

作　　者：魏云霞 王修艺 王雯皓 张立伟[1] 李石飞[1] WEI Yun-xia;WANG Xiu-yi;WANG Wen-hao;ZHANG Li-wei;LI Shi-fei(Key Laboratory of Chemical Biology and Molecular Engineering Ministry of Education,Institute of Molecular Science,Shanxi University,Taiyuan 030006,China;Shanxi Key Laboratory of Active Constituents Research and Utilization of TCM,Modern Research Center for Traditional Chinese Medicine,Shanxi University,Taiyuan 030006,China)

机构地区：[1]山西大学分子科学研究所,化学生物学与分子工程教育部重点实验室,山西太原030006 [2]山西大学中医药现代研究中心,地产中药功效物质研究与利用山西省重点实验室,山西太原030006

出　　处：《中草药》2023年第2期465-472,共8页Chinese Traditional and Herbal Drugs

基　　金：国家自然科学基金资助项目(31800293);山西科技攻关项目(201603D3113008,2016ZD0504,202203021211290)。

摘　　要：目的 研究河朔荛花Wikstroamia chamaedaphne枝叶中具有激活潜伏人类免疫缺陷病毒(human immunodeficiency virus,HIV)的活性成分。方法 运用硅胶柱色谱、Sephadex LH-20凝胶柱色谱和制备型HPLC等方法进行分离纯化;通过高分辨质谱、核磁、圆二色谱等光谱技术进行化合物结构鉴定;采用萤火虫荧光素酶报告基因试剂盒评价化合物对人宫颈癌HeLa-NH2细胞激活潜伏HIV-1病毒的活性。结果 从河朔荛花枝叶甲醇提取部位分离鉴定出13个化合物,包括2个甾类化合物:2,20-dihydroxyspregna-1,4-diene-3-one(1)、2-hydroxypregna-1,4-diene-3,20-dione(2);7个木脂素类化合物:松脂素(3)、连翘脂素(4)、acutissimalignan B(5)、罗汉松脂素(6)、3,4-二香草基四氢呋喃(7)、2,6,2′,6′-tetramethoxy-4,4′-bis (2,3-epoxy-1-hydroxypropyl) biphenyl(8)、薄荷醇(9)和4个其他类型化合物:邻苯二甲酸二辛酯(10)、1-linolenoylglycerol(11)、2-linolenoylglycerol(12)、4′-carbomethoxy-2′-hydroxyphenyl ferulate(13)。对HeLa-NH2细胞激活潜伏HIV-1病毒的活性结果表明,化合物6、10~12在10.0μmol/L的激活倍数为28.2~38.9倍,阳性对照药prostratin激活倍数为40.0倍。结论 化合物1为新化合物,命名为河朔荛花孕甾酮A,化合物2为新天然产物,化合物4、5、7~13首次从荛花属中分离得到。13个化合物均为首次从河朔荛花中分离得到。化合物6、10~12表现出较好的激活潜伏HIV活性。Objective To study the active ingredients in the branches and leaves of Heshuoraohua(Wikstroemia chamaedaphne) that have activated latent human immunodeficiency virus(HIV). Methods A combination of silica gel column chromatography, Sephadex LH-20 column chromatography and preparative HPLC were used for the separation and purification;The compounds were structurally characterized by high-resolution mass spectrometry, nuclear magnetic and circular dichroism spectroscopy;And a firefly luciferase reporter gene kit was used to evaluate the activity of the compounds in activating latent HIV-1 virus in human cervical cancer HeLaNH2 cells. Results A total of 13 compounds were isolated and identified, including two steroids, seven lignans and four other compounds and were identified as: 2,20-dihydroxyspregna-1,4-diene-3-one(1), 2-hydroxypregna-1,4-diene-3-dione(2),( +)-pinoresinol(3), phillygenin(4), acutissimalignan B(5),(-)-matairesinol(6), 3,4-divanillyltetrahydrofuran(7), 2,6,2′,6′-tetramethoxy-4,4′-bis(2,3-epoxy-1-hydroxypropyl) biphenyl(8),(+)-piperitol(9), bis(2-ethylhexyl) phthalate(10), 1-linolenoylglycerol(11), 2-linolenoylglycerol(12), 4′-carbomethoxy-2′-hydroxyphenyl ferulate(13). Compared with the control group, the fold change of these compounds in activating latent HIV at 10.0 μmol/L concentration was 28.2—38.9, and the fold change of positive control prostratin was 40.0. Conclusion Compound 1 is a new compound and compound 2 is a new natural product. Compounds 4, 5, 7—13 are obtained from the genus Wikstroemia for the first time. All compounds are isolated for the first time from W. chamaedaphne. In addition,all compounds were tested to activate latent HIV in HeLa-NH2 cell model. The results showed that compounds 6, 10—12 showed significant activation of latent HIV.

关 键 词：河朔荛花 人类免疫缺陷病毒 潜伏激活剂 河朔荛花孕甾酮A 连翘脂素 罗汉松脂素 bis(2-ethylhexyl)phthalate 1-linolenoylglycerol 2-linolenoylglycerol 

分 类 号：R284.1[医药卫生—中药学]