光叶决明中1个新的二聚苯丙素类化合物

目的对决明属植物光叶决明Cassia floribunda茎叶的化学成分进行研究。方法运用硅胶、MCI、RP-18、TLC、HPLC等多种色谱技术进行分离纯化,根据理化性质和波谱数据鉴定化合物的结构。结果从光叶决明90%乙醇提取物中分离得到18个化合物,分别鉴定为决明顺反二聚苯丙素(1)、反式对羟基肉桂酸乙酯(2)、shonanin(3)、邻苯二甲酸二丁酯(4)、1,6,8-三羟基-3-甲基蒽醌(5)、2,5-二甲基-7-羟基-色原酮(6)、2-(2′-羟丙基)-5-甲基-7-羟基色酮(7)、4′,7-二羟基-5-甲氧基黄酮(8)、柯伊利素(9)、山柰酚(10)、芹菜素(11)、3-甲氧基槲皮素(12)、6-demethoxycapillarisin(13)、7,4′-二羟基黄酮(14)、木犀草素(15)、butin(16)、甘草素(17)和圣草酚(18)。结论化合物1为新的苯丙素类化合物;化合物2～18均为首次从该植物中分离得到,其中,化合物2～4、8、9、11、13、14、16～18为首次从决明属植物中分离得到。     

古钩藤茎叶的化学成分研究

目的研究民族药用植物古钩藤Cryptolepis buchananii茎叶的化学成分。方法采用硅胶、Sephadex LH-20、ODS柱色谱以及制备HPLC等手段分离并纯化化合物,通过NMR、MS等波谱技术并结合文献数据鉴定化合物结构。结果从古钩藤茎叶甲醇提取物的醋酸乙酯部分共分离得到13个化合物,分别鉴定为异莨菪亭(1)、(+)-3-hydroxy-β-ionone(2)、(3R,6R,7E)-3-hydroxy-4,7-megastigmadien-9-one(3)、ficusic acid(4)、(+)-松脂素(5)、(+)-8-羟基松脂素(6)、(+)-丁香脂素(7)、异橙黄胡椒酰胺乙酸脂(8)、loliolide(9)、(–)-蛇菰宁(10)、金圣草素(11)、9-hydroxy-10E,12Z-octadecadienoic acid methyl ester(12)和ficusesquilignan A(13)。结论所有化合物均为首次从该属植物中分离得到。     

醉马草中黄酮类化学成分研究

目的研究禾本科芨芨草属植物醉马草Achnatheruminebrians中的化学成分。方法综合运用HP-20大孔树脂、ODS中压色谱、SephadexLH-20凝胶柱色谱以及制备型高效液相色谱等方法进行系统的分离纯化,根据化合物的理化性质及其波谱数据,并通过对比文献报道的波谱数据,鉴定化合物的化学结构。结果从醉马草乙醇提取物中分离得到15黄酮类化合物,分别鉴定为异红草素(1)、金丝桃苷(2)、槲皮素-3-O-β-D-吡喃葡萄糖基-(3′→O-3′′′)-槲皮素-3?-O-β-D-吡喃半乳糖苷(3)、3?-甲氧基槲皮素-3-O-α-L-吡喃鼠李糖基-(1→6)-β-D-吡喃葡萄糖苷(4)、异鼠李素-3-O-α-L-吡喃鼠李糖基-(1→2)-β-D-吡喃葡萄糖苷(5)、槲皮素-3-O-α-L-吡喃鼠李糖基-(1→2)-β-D-吡喃葡萄糖苷(6)、槲皮素-3-O-β-D-吡喃葡萄糖基-7-O-α-L-吡喃鼠李糖苷(7)、山柰酚-3-O-α-L-吡喃鼠李糖基-(1→2)-β-D-吡喃葡萄糖苷(8)、山柰酚-3-O-α-L-吡喃鼠李糖基-(1→4)-β-D-吡喃葡萄糖苷(9)、8-甲氧基槲皮素-3-O-β-吡喃葡萄糖苷(10)、槲皮素-3-O-α-L-吡喃鼠李糖基-(1→2)-β-D-吡喃半乳糖基-7-O-β-D-吡喃葡萄糖苷(11)、5,7,3?-三羟基-8,4?,5?-三甲氧基黄酮(12)、木犀草素-7-O-葡萄糖醛酸苷-6??-甲酯(13)、木犀草素-7-O-葡萄糖醛酸苷(14)和金圣草黄素(15)。结论所有化合物均为首次从醉马草中分离得到。     

Discovery of chrysoeriol,a PI3K-AKT-mTOR pathway inhibitor with potent antitumor activity against human multiple myeloma cells <Emphasis Type="Italic">in vitro</Emphasis>

This study was designed to determine the impact of chrysoeriol on proliferation and cell cycle progression in the human multiple myeloma cell lines RPMI 8226 and KM3,and its related molecular mechanisms.Chryseoriol was identified by using the phosphorylated AKT-specific cytoblot high throughput assay.CCK-8 assay was employed to examine the growth inhibition rate and IC 50 (48 h) in peripheral blood mononuclear cells (PBMNCs),RPMI 8226 and KM3 cells treated with chrysoeriol at various concentrations.Cells were labeled with 5-6-carboxyfluorescein diacetate succinimidyl ester (CFSE),and the proliferation dynamics was detected by flow cytometry and analyzed with ModFit software.The cell cycles of RPMI 8226 and KM3 cells were measured by flow cytometry when the IC 50 concentration of chrysoeriol was adopted.The alterations in cell-cycle related proteins (Cyclin B1,Cyclin D1,p21) and proteins in PI3K-AKT-mTOR pathway were determined by Western blot analysis.The results showed the proliferation of multiple myeloma cells was significantly inhibited by chrysoeriol,resulting in cell cycle arrest in G 2 /M phase.Chrysoeriol could significantly reduce the expression of p-AKT (s473) and p-4eBP1 (t37/46) protein,meanwhile enhanced Cyclin B1 and p21 protein expression.Similar effects were not observed in PBMNCs from normal donors.It was concluded that chrysoeriol was a selective PI3K-AKT-mTOR pathway inhibitor.It restrained the proliferation of human multiple myeloma cells,but didn’t affect proliferation of PBMNCs from normal donors.It might exhibit the cell cycle regulatory effect via the inhibition of PI3K-AKT-mTOR signal pathway.     

Effects of Vernonia cinerea Compounds on Drug‐metabolizing Cytochrome P450s in Human Liver Microsomes

Vernonia cinerea has been widely used in traditional medicines for various diseases and shown to aid in smoking abstinence and has anticancer properties. V. cinerea bioactive compounds, including flavonoids and hirsutinolide‐type sesquiterpene lactones, have shown an inhibition effect on the nicotine‐metabolizing cytochrome P450 2A6 (CYP2A6) enzyme and hirsutinolides reported suppressing cancer growth. In this study, V. cinerea ethanol extract and its bioactive compounds, including four flavonoids and four hirsutinolides, were investigated for an inhibitory effect on human liver microsomal CYPs 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, and 3A4 using cocktail inhibition assays combined with LC‐MS/MS analysis. Among tested flavonoids, chrysoeriol was more potent in inhibition on CYP2A6 and CYP1A2 than other liver CYPs, with better binding efficiency toward CYP2A6 than CYP1A2 (K_i values in competitive mode of 1.93 ± 0.05 versus 3.39 ± 0.21 μM, respectively). Hirsutinolides were prominent inhibitors of CYP2A6 and CYP2D6, with IC₅₀ values of 12–23 and 15–41 μM, respectively. These hirsutinolides demonstrated time‐dependent inhibition, an indication of mechanism‐based inactivation, toward CYP2A6. Quantitative prediction of microsomal metabolism of these flavonoids and hirsutinolides, including half‐lives and hepatic clearance rate, was examined. These findings may have implications for further in vivo studies of V. cinerea. Copyright © 2017 John Wiley & Sons, Ltd.     

光叶铁仔根和茎化学成分研究

目的 对光叶铁仔Myrsine stolonifera根和茎化学成分进行研究。方法 运用D101型大孔吸附树脂、硅胶和凝胶Sephadex LH-20等柱色谱方法进行分离纯化,根据化合物的理化性质和波谱数据鉴定化合物结构。结果 从光叶铁仔95%乙醇提取物中分离得到11个化合物,分别鉴定为山柰酚(1)、二氢山柰酚(2)、槲皮素(3)、5,7,4′-三羟基异黄酮(4)、柯伊利素(5)、槲皮素-7-O-α-D-葡萄糖苷(6)、表儿茶素(7)、3,5-二甲氧基-苄醇-4-O-β-D-吡喃葡萄糖苷(8)、2,6-二甲氧基-4-羟基-苯酚-1-O-β-D-吡喃葡萄糖苷(9)、丁香苷(10)、(+)-lyoniresino 3α-O-β-D-glucopyranoside(11)。结论 化合物2、4~11首次从该属植物中分离得到,化合物1~11首次从该植物中分离得到。     

绵枣儿化学成分研究

目的 研究绵枣儿Scilla scilloides全草的化学成分。方法 利用硅胶柱色谱及制备液相等技术进行分离纯化,并利用波谱技术鉴定其结构。结果 从绵枣儿全草95%乙醇提取物中分离得到18个化合物,分别鉴定为绵枣儿素（1）、2-羟基- 7-O-甲基绵枣儿素（2）、4’-demethyleucomin（3）、5-羟基-7-甲氧基-3-(4-羟基苯亚甲基) 色原-4-酮（4）、4’-demethyl-3, 9-dihydroeucomin（5）、3’-hydroxy-3, 9-dihydroeucomin（6）、8-O-demethyl-7-O-methyl-3, 9-dihydropunctatin（7）、芹菜素（8）、木犀草素（9）、金圣草黄素（10）、3-脱氢-15-脱氧尤可甾醇（11）、15-脱氧尤可甾醇（12）、4-烯丙基儿茶酚（13）、norlichexanthone（14）、drimiopsin C（15）、6-阿魏酰梓醇（16）、梓苷（17）、黄金树苷（18）。结论 首次从绵枣儿属中分离得到环烯醚萜类化合物（16～18）;化合物4、7～10和化合物13～18为首次从该属植物中分离得到。     

刘寄奴化学成分研究

目的 研究刘寄奴Artemisia anomala的化学成分.方法 采用溶剂法和多种柱色谱法进行分离纯化,并经波谱分析鉴定化合物的结构.结果 从刘寄奴95％乙醇提取物的醋酸乙酯部位分离得到7个化合物,分别鉴定为(4aS,7S,7aR)-7-羟基-7-甲基-1,4a,5,6,7,7a-六氢环戊二烯[c]吡喃-4-羧酸甲酯(1)、rehmaglutin D(2)、(E)-6-羟基-2,6-二甲基辛-2,7-二烯酸(3)、金圣草酚(4)、木犀草素(5)、芹菜素(6)、对羟基苯丙烯酸(7).结论 其中化合物1为新的环烯醚萜,命名为刘寄奴醚萜;化合物2为首次从该属植物中分离得到,化合物3、4和7为首次从该植物中分离得到.     

基于网络药理学的淫羊藿抗疲劳作用机制研究

目的利用网络药理学的方法研究淫羊藿抗疲劳的作用机制。方法利用中药系统药理数据库和分析平台(TCMSP)获取淫羊藿的活性成分及活性成分的作用靶点;在GeneCards数据库中检索与疲劳相关的靶点;由Cytoscape 3.6.1构建活性成分-疾病-靶点网络;String数据库构建靶点蛋白互作网络;DAVID数据库对靶点基因进行基因本体(GO)富集分析及京都基因和基因组百科全书(KEGG)通路富集分析。结果从淫羊藿中筛选得到9种具有抗疲劳作用的活性成分:金圣草(黄)素、山柰酚、脱水淫羊藿素、C-homoerythrinan,1,6-didehydro-3,15,16-trimethoxy-,(3.beta.)-、8-(3-methylbut-2-enyl)-2-phenylchromone、木犀草素、广玉兰内酯、槲皮素、8-isopentenyl-kaempferol,作用于PPARG、GABRA1、CASP3、ICAM1等31个疲劳靶点,生物功能与通路富集分析表明,淫羊藿主要涉及细胞的缺氧反应、凋亡过程的调控、一氧化氮生物合成过程的正向调节、细胞对过氧化氢的反应、血糖稳态、细胞对高氧的反应、脂质贮存负调节等生物过程,通过调节PI3K-Akt、P53、HIF-1、TNF、Fox O、ErbB、MAPK等信号通路来发挥抗疲劳作用。结论研究结果体现了淫羊藿抗疲劳多成分、多靶点、多途径的作用特点,为淫羊藿抗疲劳的进一步研究提供参考。     

Protective effect of chrysoeriol against doxorubicin-induced cardiotoxicity in vitro

Background The use of doxorubicin （DOX） is limited by its dose-dependent cardiotoxicity. Reactive oxygen species （ROSs） play an important role in the pathological process of DOX-induced cardiotoxicity. The aim of this study was to evaluate the protective effect of chrysoeriol, a flavone compound, against DOX-induced apoptosis and death in H9c2 cells and to find out its preliminary mechanism. Methods We used 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyl-2H-tetrazolium bromide （MTT） assay, Hoechst33258 staining and measurement of lactate dehydrogenase （LDH） release to evaluate the protective effect of chrysoeriol against DOX-induced apoptosis and death in H9c2 cells. To find out the mechanism of this protective effect, we observed the immunofluorescence of intracellular ROS and measured the activities of malondialdehyde （MDA）, superoxide dismutase （SOD） and glutathione peroxidase （GPx）. Furthermore, we evaluated the effect of chrysoeriol on the antitumor activity of DOX in HeLa cells with MTT assay. Results The results of MTT assay, Hoechst 33258 staining and measurement of LDH release showed that chrysoeriol significantly reduced doxorubicin-induced apoptosis and cell death. Chrysoeriol at a dose of 20 μg/ml notably reduced intracellular ROS, decreased the concentration of MDA in the supernatant of DOX-treated H9c2 cells and increased SOD and GPx activities to their normal levels. Further study showed that the addition of chrysoeriol did not affect the antitumor activity of DOX. Conclusion Chrysoeriol could potentially serve as a novel cardioprotective agent against DOX-induced cardiotoxicity without affecting the antitumor activity of DOX.