紫金牛抗结核病有效成分的研究

抗痨中草药紫金牛全草的乙醇提取部分的水不溶物,用稀醇溶解后即得有效部分。经几个单位对201例病员进行临床治疗肺结核病试验,总有效率为81.5%。进而从有效部分中分离到两个抑制结核杆菌生长效力较强的新的酚性成分,称为紫金牛酚IC_(?)H_(?)O_2和紫金牛酚ⅡC_(19)H_(30)O_2。紫金牛酚Ⅰ抑菌效价为每ml12.5μg,紫金牛酚Ⅱ抑菌效价为25～50μg。另一酚性成分2-甲基腰果酚前人在紫金牛中没有报道过的。除此之外,我们还从全草中分离和鉴定了冬青醇(ilexol)、恩贝素(embelin)、矮地茶素(bergenin)和槲皮素(quercetin)等成分。

四川蜡瓣花、密花樫木、四川溲疏及云南豆腐柴的化学成分研究

本论文对四川蜡瓣花 (Corylopsis willmottiae Rehd. et Wils.)、密花樫木[Dysoxylum densiflorum (Blume) Miq.]、四川溲疏 (Deutzia setchuenensis Franch)及云南豆腐柴 (Premna yunnanensis W. W. Smith)的化学成分进行了研究。通过色谱分离得到44个化合物。主要基于波谱数据鉴定了它们的结构，其中1个为新化合物。 1．从四川蜡瓣花全株的95%乙醇提取物中共分离鉴定了13个化合物，它们是：1-O-(3-O-甲基没食子酸)-岩白菜素(1)、11-O-没食子酰基岩白菜素(2)、 11-O-紫丁香基岩白菜素(3) 、岩白菜素(4)、4-O-没食子酰基岩白菜素(5) 、4,11-O-二没食子酰基岩白菜素 (6)[14]、β-谷甾醇 (7)、acetyl aleuritolic acid (8)、(-)-表没食子儿茶素没食子酸酯(9)、对羟基苯甲酮 (10)、 11-香豆酸酰岩白菜素 (11)[19]、丁香酸 (12)和没食子酸 (13)。其中1为新化合物。 2．从密花樫木根的95%乙醇提取物中共分离纯化了13个化合物，它们是：β-白檀酮(14)、richenone (15)、β-谷甾醇 (7)、cabraleadiol (16)、β-香树脂醇 (17)、龙脑香醇酮 (18)、cabraleadiol monoacetate (19)、cabraleone (20)、3β-hydroxy-5 -pregnen-20-one (21)、3β-hydroxy-5α-pregnan-20-one (22)、cabraleahydroxylactone (23)、川楝子甾醇B (24)、表儿茶素 (25)。 3．从四川溲疏全株95%乙醇提取物中共分离11个化合物，鉴定了其中的9个化合物。它们是：β-谷甾醇 (7)、白桦酯醇(26)、齐墩果酸(27)、hydrangetin (28)、肉桂酸 (29)，齐墩果酸-3-O-β-D-吡喃葡萄糖醛酸苷(30)、β-胡萝卜苷 (31)、齐墩果酸-3-O-（β-D-吡喃葡萄糖醛酸-6-正丁酯）(32)、齐墩果酸-3-O-β-D-吡喃葡萄糖醛酸-28-O-β-D-吡喃葡萄糖苷 (33)。 4．从云南豆腐柴95%乙醇提取物中分离得到12个化合物，分别为白桦脂醇 (25)、7-羟基黄烷酮 (34)、松属素 (35)、2’,4’-羟基查儿酮 (36)、高良姜素-3-甲醚 (37) 、高良姜素-3,7-二甲醚 (38)、异甘草素-4-甲醚 (39)、豆蔻明 (40)、乔松酮 (41)、异甘草素 (42)、arjunolic acid (43)、槲皮素3-O-β-D-木糖苷(44)。 5．综述了1976年以来樫木属植物化学成分和活性研究的概况。 Phytochemical investigation on Corylopsis willmottiae, Dysoxylum densiflorum, Deutzia setchuenensis, and Premna yunnanensis, led to the isolation of 44 compounds, 1 of which was new one. 1. One new compound was isolated from 95% ehanolic extrat of the whole plants of C. willmottiae, identified as 11-O-(3-O-methylgalloyl)-bergenin (1). The twelve known compounds isolated were 11-O-galloylbergenin (2), 11-O-syringylbergenin (3), bergenin (4), 4-O-galloylbergenin (5), 4,11-di-O-galloylbergenin (6), β-sitosterol (7), acetyl aleuritolic acid (8), (-)-epigallocatechin 3-O-gallate (9), 1-(4-hydroxyphenyl) ethanone (10), 11-O-coumaroylbergenin (11), syringic acid (12), gallic acid (13). 2. Thirteen compounds were isolated from 95% ethanol extract from the roots of D. densiflorum and identified as β-amyrenone (14), richenone (15), β-sitosterol (7), cabraleadiol (16), β-amyrin (17), hydroxydammarenone-Ⅱ (18), cabraleadiol monoacetate (19), cabraleone (20), 3β-hydroxy-5-pregnen-20-one (21), 3β-hydroxy-5α-pregnan-20-one (22), cabraleahydroxylactone (23), toosendansterol B (24) and (-)-epicatechin (25). 3. Eleven compounds were isolated from ethanol extract of D. Setchuenensis. Nine were identified as β-sitosterol (7), betulin (26), oleanolic acid (27), hydrangetin (28), cinnamic acid (29), oleanolic acid 3-O-β-D-glucuronopyranoside (30), β-daucosterol (31), oleanolic acid 3-O-β-D-glucuronopyranoside-6-O-butyl ester）(32), oleanolic acid 3-O-β-D-glucuronopyranosyl-28-3-O-β-D-glucopyranoside (33). 4. Twelve compounds were isolated from ethanol extract of P. yunnanensis and identified as betulin (26), 7-hydroxyflavanone (34), pinocembrin (35), 2’,4’-dihydroxychalcone (36), galangin 3-methyl ether (37), galangin 3,7-dimethyl ether (38), isoliquiritigenin 4-methyl ether (39), cardamonin (40), pinostrobin (41), isoliquiritigenin (42), arjunolic acid (43), quercetin 3-O-β-D-lyxosopyranoside (44). 5. Chemical constituents and biological activities of the genus Dysoxylum (Meliaceae) were reviewed during 1976-2009.

五枫藤、小驳骨和川西茶藨的化学成分研究

八月瓜属植物五枫藤(Holboellia latifolia Wall.)和驳骨草属植物小驳骨(Gendarussa vulgaris Nees)均为药用植物, 前者化学成分研究不深入, 后者的化学成分未见报道。川西茶藨(Ribes takare D. Don)为茶藨子属植物, 没有化学成分的报道。本论文对三个植物的化学成分和活性成分进行了研究, 主要通过色谱方法分离得到了48 个化合物, 采用波谱分析或与已知标准品对照等手段鉴定了它们的结构, 其中有1 个新的原小檗碱类化合物和3 个新的联苯类化合物,发现了具有细胞毒活性和α-葡萄糖苷酶抑制活性的化合物。1、从五枫藤地上部分的95%乙醇提取物中分离得到了12 个化合物: 五加苷K (1)、hederagenin 3-O- α-L-rhamnopyranosyl-(1→2)- α-L-arabinopyranoside (2)、β-萘乙酸(3) 、3-O-α-L-rhamnopyranosyl-(1→2)-[β-D-glucopyranosyl-(1→3)]-α-L-arabinopyranosyl oleanolic acid 28-O-α-L-rhamnopyranosyl-(1→4)-β-D-glucopyranosyl-(1→6)-β-D-glucopyranosyl ester (4) 、3-O- α-L-rhamnopyranosyl-(1→2)-O- β- D-glucopyranosyl-(1→2)- α-L-arabinopyranosyl oleanolic acid (5) 、3-O-( β-D-glucopyranosiduronic acid)-oleanolic acid 28-O- β-D-glucopyranoside (6)、lup-20(29)-en-3-one (7)、lupeol (8)、β-谷甾醇(9)、齐墩果酸(10)、乌苏酸(11)、β-胡萝卜苷(12)。化合物1 对Lu-06、N-04 和Bre-04 癌细胞株的GI50 分别是0.77µg/mL、1.26 µg/mL 和1.55 µg/mL, 化合物2 对N-04 癌细胞株的GI50 为2.44 µg/mL。2、从小驳骨地上部分的95%乙醇提取物中分离得到了1 个原小檗碱类新化合物13-hydroxyl gusanlung A (25), β-谷甾醇(9)、齐敦果酸(10)、β-胡萝卜苷(12)、棕榈酸(1-)甘油酯(13)、棕榈酸(14)、阿苯哒唑(15)、阿苯哒唑砜(16)、阿苯哒唑亚砜(17)、aurantiamide acetate (18)、华良姜素(19)、芫花素(20)、(-)-丁香树酯醇(21)、gusanlung B (22) 、eupteleasaponinsⅤ acetate (23)、gusanlungA (24)、刺五加苷E (26)、岩白菜素(27)、咖啡酸(28)。化合物25 对肝癌细胞株(HepG2) 的GI50 为2.08 µg/mL。3、从川西茶藨地上部分的95%乙醇提取物中分离鉴定了22 个化合物: β-谷甾醇(9) 、β- 胡萝卜苷(12) 、O-acetyloleanolic aldehyde (29),4,7,8-trimethoxy-2,3-methylenedioxydibenzofuran (30) 、3', 5-dimethoxy-3, 4-methylenedioxybiphenyl (31) 、桦木醇(32) 、6,7-dimethoxy-1-methyl-3,4-dihydroquinolin-2-one (33)、3'-hydroxy-5-methoxy-3,4-methylenedioxybiphenyl (34) 、7-hydroxy-4,8-dimethoxy-2,3-methylenedioxydibenzofuran (35)、桦木醛(36)、没食子酸(37) 、6β- 羟基-4- 烯-3- 酮- 豆甾醇(38) 、5α, 8α-epidioxy-(22E,24R)-ergosta-6, 22-dien-3β-ol (39)、verrucofortine (40)、6-methoxycalpogoniumisoflavone A (41)、2-羟基二苯甲酮(42)、桦木酸(43), 3, 5-二甲氧基苯甲酸-4-O-β-D-吡喃葡萄糖苷(44)、洋芹素(45)、刺槐素(46)、水杨酸(47)、洋芹素-5-O- β-D-葡萄糖苷(48), 化合物30、31 和35 为新的联苯化合物。化合物30的α-葡萄糖苷酶抑制率为10.2% (1.00 mg/mL); 化合物35 的抑制率为17.2% (1.00mg/mL)。4、综述了1960 年以来原小檗碱类化合物药理活性研究进展。 Plants Holboellia latifolia Wall and Gendarussa vulgaris Nees, are used as folkmedicine. Ribes takare D. Don belongs to the genus Ribes. The three plants have notbeen chemically studied in detail. Chemical and bioactive study of three plants led tothe isolation of 48 compounds by chromatography. Their structures were elucidatedon the basis of spectroscopic evidence or comparison with authentic samples. Amongthe 48 componds isolated one protoberberine alkaloid and three biphenyls are newones. Cytotoxic and α-glucosidase inhibitory compounds had been found.1. Twelve compounds were isolated from the 95% ethanol extract of the aerial partof H. latifolia Wall. They were characterized as fellow: eleutheroside K (1),hederagenin-3-O- α-L-rhamnopyranosyl-(1→2)- α-L-arabinopyranoside (2),2-naphthyl acetic acid (3),3-O-α-L-rhamnopyranosyl-(1→2)-[β-D-glucopyranosyl-(1→3)]-α-L-arabinopyranosyl oleanolic acid 28-O-α-L-rhamnopyranosyl-(1→4)-β-D-glucopyranosyl-(1→6)-β-D-glucopyranosyl ester (4), 3-O- α-L-rhamnopyranosyl-(1→2)-O- β- D-glucopyranosyl-(1→2)- α-L-arabinopyranosyl oleanolic acid (5),3-O-( β-D-glucopyranosiduronic acid)-oleanolic acid-28-O- β-D-glucopyranoside (6),lup-20(29)-en-3-one (7), lupeol (8), β-sitosterol (9), oleanolic acid (10), ursolicacid (11), and β-daucosterol (12). Compound 1 showed moderate cytotoxicity againstLu-06 (GI50, 0.77 µg/mL), N-04 (GI50, 1.26 µg/mL) and Bre0-4 (GI50=1.55 µg/mL)and compound 2 showed moderate cytotoxicity against N-04 (GI50=2.44 µg/mL).2. A new protoberberine alkaloid, 13-hydroxyl gusanlung A (25), was isolated fromthe aerial part of Gendarussa vulgaris Nees, together with β-sitosterol (9), oleanolicacid (10), β-daucosterol (12), glycerol monopalmitate (13), palmific acid (14),albendazole (15), albendazole sulphone (16), albendazole sufloxide (17), aurantiamideacetate (18), kumatakenin (19), genkwanin (20), (-)-syringaresinol (21), gusanlung B(22), eupteleasaponinsⅤ acetate (23), gusanlung A (24), eleutheroside E (26),bergenin (27) and caffeic acid (28). Compound 25 showed cytotoxicity against HepG2 cells (GI50, 2.08 µg/mL).3. Phytochemical study of the Ribes takare D. Don led to the isolation of three newbiphenyls, 4,7,8-trimethoxy-2,3-methylenedioxydibenzofuran (30), 3', 5-dimethoxy-3,4-methylenedioxybiphenyl (31) and 7-hydroxy-4,8-dimethoxy-2,3-methylenedioxydibenzofuran (35), along with nineteenknown compounds, β-sitosterol (9), β-daucosterol (12), O-acetyloleanolic aldehyde(29), betulin (32), 6,7-dimethoxy-1-methyl-3,4-dihydroquinolin-2-one (33),3'-hydroxy-5-methoxy-3, 4-methylenedioxybiphenyl (34), betulinic aldehyde (36),gallic acid (37), stigmast-4-en-6β-ol-3-one (38), 5α, 8α-epidioxy-(22E, 24R)-ergosta-6,22-dien-3β-ol (39), verrucofortine (40), 6-methoxycalpogonium isoflavone A (41),2-hydroxybenzophenone (42), betulinic acid (43), 3,5-dimethoxygallic acid-4-O- β-D-glucopryranoside (44), apigenin (45), acacetin (46), salicylic acid (47) andapigenin-5-O- β-D-glucopryranoside (48). α-Glucosidase inhibitory rates ofcompound 30 and 35 were respectively 10.2% and 17.2% at a concentration of 1.00 mg/mL).4. Pharmacological activities of protoberberines were summarized.

Acetilbergenina: obtenção e avaliação das atividades antinociceptiva e anti-inflamatória

Endopleura uchi (Huber) Cuatrec. (Humiriaceae), uma planta da Amazônia brasileira, comumente conhecida como “uxi” é utilizada na medicina popular para o tratamento de diversas patologias, como artrite. Bergenina, um dos constituintes químicos das cascas do caule de E. uchi, tem várias atividades biológicas, incluindo antiinflamatória e antinociceptiva. Visando a obtenção de um derivado mais potente que a bergenina decidiu-se acetilar esta substância. Acetilbergenina foi testada em modelos de nocicepção e de inflamação. Bergenina foi isolada a partir do fracionamento por cromatografia por via úmida do extrato aquoso das cascas do caule de E. uchi e acetilbergenina a partir da acetilação da bergenina. As substâncias foram identificadas com base na análise espectral de RMN ¹H, RMN ¹³C, DEPT e COSY, e comparação com dados da literatura. Nos modelos de nocicepção foram realizados os testes de contorção abdominal, placa quente e formalina. Enquanto que nos modelos de inflamação foram realizados os testesdermatite induzida pelo óleo de cróton, edema de pata induzido por carragenina e dextrana e peritonite induzida por carragenina. Além disso, para avaliar o potencialulcerogênico de acetilbergenina foi utilizado o modelo de úlcera gástrica induzida por estresse. No teste de contorção abdominal induzida por ácido acético 0,6%, acetilbergenina nas doses de 1, 5, 10, 15 e 25 mg/kg bloqueou o número de contorções abdominais em 28,2%, 52,7%, 61,1%, 68,3% e 95,0%, respectivamente, e de maneira dose-dependente quando comparada ao grupo controle. DE50 calculada foi de 6,8 mg/kg. No teste da placa quente (55 ºC), acetilbergenina (6,8 mg/kg) não induziu alterações no tempo de latência quando comparada ao grupo controle. No teste da formalina, acetilbergenina (6,8 mg/kg) inibiu em 88,3% o estímulo álgico na 2ª fase (inflamatória) quando comparada ao grupo controle. Além disso, a naloxona reverteu o efeito de acetilbergenina nessa 2ª fase do teste. Na dermatite induzida por óleo de cróton, acetilbergenina (6,8 mg/kg) provocou efeito inibitório de 75,60% em relação ao grupo controle. No edema de pata induzido por carragenina, acetilbergenina (6,8 mg/kg) foi capaz de reduzir o desenvolvimento do edema da 2ª à 5ª hora em comparação ao grupo controle. No edema de pata induzido por dextrana, acetilbergenina (6,8 mg/kg) reduziu o edema em todos os tempos. Na peritonite induzida por carragenina, acetilbergenina (6,8 mg/kg) bloqueou em 70% o número de neutrófilos quando comparada ao grupo controle. No ensaio de úlcera gástrica, acetilbergenina bloqueou em 78,55% a geração de lesões gástricas por estresse quando comparada ao grupo indometacina. Os resultados sugerem que acetilbergenina apresenta atividade antinociceptiva e atividade antiinflamatória, provavelmente, de origem periférica.