Cytotoxic and Melanogenesis‐Inhibitory Activities of Limonoids from the Leaves of Azadirachta indica (Neem)

Seventeen limonoids (tetranortriterpenoids), 1 – 17 , including three new compounds, i.e., 17‐defurano‐17‐(2,5‐dihydro‐2‐oxofuran‐3‐yl)‐28‐deoxonimbolide ( 14 ), 17‐defurano‐17‐(2ξ‐2,5‐dihydro‐2‐hydroxy‐5‐oxofuran‐3‐yl)‐28‐deoxonimbolide ( 15 ), and 17‐defurano‐17‐(5ξ‐2,5‐dihydro‐5‐hydroxy‐2‐oxofuran‐3‐yl)‐2′,3′‐dehydrosalannol ( 17 ), were isolated from an EtOH extract of the leaf of neem (Azadirachta indica). The structures of the new compounds were elucidated on the basis of extensive spectroscopic analyses and comparison with literature. Upon evaluation of the cytotoxic activities of these compounds against leukemia (HL60), lung (A549), stomach (AZ521), and breast (SK‐BR‐3) cancer cell lines, seven compounds, i.e., 1 – 3, 12, 13, 15 , and 16 , exhibited potent cytotoxicities with IC₅₀ values in the range of 0.1–9.9 μM against one or more cell lines. Among these compounds, cytotoxicity of nimonol ( 1 ; IC₅₀ 2.8 μM ) against HL60 cells was demonstrated to be mainly due to the induction of apoptosis by flow cytometry. Western blot analysis suggested that compound 1 induced apoptosis via both the mitochondrial and death receptor‐mediated pathways in HL60 cells. In addition, when compounds 1 – 17 were evaluated for their inhibitory activities against melanogenesis in B16 melanoma cells, induced with α‐melanocyte‐stimulating hormone (α‐MSH), seven compounds, 1, 2, 4 – 6, 15 , and 16 , exhibited inhibitory activities with 31–94% reduction of melanin content at 10 μM concentration with no or low toxicity to the cells (82–112% of cell viability at 10 μM ). All 17 compounds were further evaluated for their inhibitory effects against the Epstein? Barr virus early antigen (EBV‐EA) activation induced by 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA) in Raji cells.     

刺三加叶组成成分与质量分析

为评价刺三加这一药食两用植物,对刺三加叶中的粗灰分、粗纤维、粗蛋白、粗脂肪等部分营养成分与K、Ca、Mg、Fe、Mn、P、Zn、Na和Cu等部分矿质元素及活性成分(绿原酸和总黄酮)进行了测定分析。结果表明:刺三加叶中的粗灰分、粗纤维、粗蛋白及粗脂肪的含量分别为:2.75%、2.34%、4.63%和4.13%,与6种常见蔬菜相比较,是6种常见蔬菜的2~10倍;K、Ca、Mg、Fe、Mn、P、Zn、Na和Cu等矿质元素含量分别为:516.00、1061.00、86.58、8.13、4.18、156.12、9.61、8.27和0.044(mg/100 g);与6种常见蔬菜比较后发现除Na和Cu元素含量略低于6种常见蔬菜外,其它成分均相当或高于6种常见蔬菜,其中K、P、Ca、Fe、Mn、Zn是6种常见蔬菜的4~15倍;刺三加叶还含有丰富的药用活性成分黄酮和绿原酸,黄酮含量为4.06%,绿原酸含量为3.72%,证明刺三加是一种极具开发利用价值的药食两用植物。该研究为刺三加这一植物的开发利用提供一定的理论依据。     

三丫苦的化学成分研究

采用硅胶柱层析从三丫苦的乙酸乙酯萃取物中分离得到6种化合物,经波谱分析鉴定为4,7-二甲氧基呋喃喹啉生物碱(1)、顺式-3,4,5-三羟基-6-乙酰基-7-甲氧基-2,2-二甲基色烷(2)、3-羟基-4-乙氧基-5,7-二甲氧基-6-乙酰-2,2-二甲基色烷(3)、3,5-二羟基-4-乙氧基-6-乙酰基-7-甲氧基-2,2-二甲基色烷(4)、异吴茱萸酮酚(5)和异吴茱萸酮酚甲醚(6)。所有化合物均首次从该植物的根部分离得到。     

Melanogenesis‐Inhibitory and Cytotoxic Activities of Diarylheptanoids from Acer nikoense Bark and Their Derivatives

Nine cyclic diarylheptanoids, 1 – 9 , including two new compounds, i.e., 9‐oxoacerogenin A ( 8 ) and 9‐O‐β‐D ‐glucopyranosylacerogenin K ( 9 ), along with three acyclic diarylheptanoids, 10 – 12 , and four phenolic compounds, 13 – 16 , were isolated from a MeOH extract of the bark of Acer nikoense (Aceraceae). Acid hydrolysis of 9 yielded acerogenin K ( 17 ) and D ‐glucose. Two of the cyclic diarylheptanoids, acerogenin A ( 1 ) and (R)‐acerogenin B ( 5 ), were converted to their ether and ester derivatives, 18 – 24 and 27 – 33 , respectively, and to the dehydrated derivatives, 25, 26, 34 , and 35 . Upon evaluation of compounds 1 – 16 and 18 – 35 for their inhibitory activities against melanogenesis in B16 melanoma cells, induced with α‐melanocyte‐stimulating hormone (α‐MSH), eight natural glycosides, i.e., six diarylheptanoid glycosides, 2 – 4, 6, 9 , and 12 , and two phenolic glycosides, 15 and 16 , exhibited inhibitory activities with 24–61% reduction of melanin content at 100 μM concentration with no or almost no toxicity to the cells (88–106% of cell viability at 100 μM ). In addition, when compounds 1 – 16 and 18 – 35 were evaluated for cytotoxic activity against human cancer cell lines, two natural acyclic diarylheptanoids, 10 and 11 , ten ether and ester derivatives, 18 – 22 and 27 – 31 , and two dehydrated derivatives, 34 and 35 , exhibited potent cytotoxicities against HL60 human leukemia cell line (IC₅₀ 8.1–19.3 μM ), and five compounds, 10, 11, 20, 29 , and 30 , against CRL1579 human melanoma cell line (IC₅₀ 10.1–18.4 μM ).     

鸦胆子化学成分及肿瘤细胞毒活性研究(英文)

从鸦胆子(Brucea javanica)种子的甲醇提取物中分离和鉴别得到11个化合物,经波谱数据分析分别鉴定为鸦胆子内酯A(1),鸦胆子素D(2),鸦胆子苷A(3),C(4),F(5),G(6),L(7),3β-羟基-孕甾-5-烯-20-酮(8),3β-羟基-5α-孕甾-20-酮(9),3-O-β-D-吡喃葡萄糖基-(1→2)-α-L-吡喃阿拉伯糖基-(20R)-孕甾-5-烯-3β,20-二醇(10)和6,22-二烯-3β-羟基5,8-过氧麦角甾(11)。其中化合物8、9和11为首次从该植物中分离得到。鸦胆子内酯A(1)和鸦胆子素D(2)对人类癌细胞株BGC-823,Huh-7,KE-97和Jurkat具有很好的细胞毒作用。     

野生植物苦豆子的化学成分和主要药理作用

豆科槐属植物苦豆子是一种分布量大的野生荒漠植物,不仅具有耐盐碱、干旱等环境保护性质,其体内作为主要次生代谢产物的生物碱和黄酮两大类化合物也显示出多方面的重要药理作用。就其在抗病毒,抗肿瘤和免疫等药理活性的近期研究做一综述。     

Chemical Constituents of the Seed Cake of Camellia oleifera and Their Antioxidant and Antimelanogenic Activities

There is a growing interest in the exploitation of agricultural byproducts. This study explored the potential beneficial health effects from the main biowaste, tea seed pomace of Camellia oleifera Abel (Theaceae), produced when tea seed is processed. Eighteen compounds were isolated from the 70% EtOH extract of the seed cake of C. oleifera. Their structures were determined by ESI‐MS, ¹H‐ and ¹³C‐NMR together with literature data. All fractions and compounds were evaluated for the antioxidant and melanogenesis inhibitory activities. As the result, AcOEt fraction has the best in vitro antioxidant and antimelanogenesis activities, compounds 7 – 12 and 15 showed remarkable antioxidant activity, compounds 4 , 6 , 8 , and 15 – 17 exhibited superior inhibitory activities against melanogenesis. Furthermore, tyrosinase inhibitory activity assay suggested that compound 8 could suppress melanogenesis by inhibiting the expression of tyrosinase.     

Limonoids and Flavonoids from the Flowers of Azadirachta indica var. siamensis,and Their Melanogenesis‐Inhibitory and Cytotoxic Activities

A new limonoid, 7‐O‐acetyl‐7‐O‐debenzoyl‐22‐hydroxy‐21‐methoxylimocinin ( 2 ), and two new flavonoids, 3′‐(3‐hydroxy‐3‐methylbutyl)naringenin ( 7 ) and 4′‐O‐methyllespedezaflavanone C ( 9 ), along with nine known compounds, including two limonoids, 1 and 3 , and seven flavonoids, 4 – 6, 8 , and 10 – 12 , were isolated from a MeOH extract of the flowers of Azadirachta indica A.Juss. var. siamensis Valeton (Siamese neem tree; Meliaceae). The structures of new compounds were elucidated on the basis of extensive spectroscopic analysis and comparison with literature data. All of these compounds were evaluated for their melanogenesis‐inhibitory activities in B16 melanoma cells induced with α‐melanocyte‐stimulating hormone (α‐MSH). Compound 2 (16.9% melanin content at 30 μM ), 6‐deacetylnimbin ( 3 ; 49.6% melanin content at 100 μM ), and kaempferide ( 10 ; 41.7% melanin content at 10 μM ) exhibited inhibitory effects with no, or almost no, toxicity to the cells (81.0–111.7% cell viability). In addition, evaluation of their cytotoxic activities against HL60, A549, AZ521, and SK‐BR‐3 human cancer cell lines, isoazadironolide ( 1 ), 4′‐O‐methyl‐8‐prenylnaringenin ( 5 ), euchrestaflavanone A ( 8 ), 9 , and 3‐methoxy‐3′‐prenylnaringenin ( 12 ) revealed potent cytotoxicities against one or more cell lines with IC₅₀ values in the range of 4.5–9.9 μM .     

Vibsane‐Type Diterpenoids from Viburnum odoratissimum and Their Cytotoxic and HSP90 Inhibitory Activities

Four new vibsane‐type diterpenoids, vibsanol I ( 1 ), 15‐hydroperoxyvibsanol A ( 2 ), 14‐hydroperoxyvibsanol B ( 3 ), 15‐O‐methylvibsanin U ( 4 ), and a new natural product, 5,6‐dihydrovibsanin B ( 5 ), as well as six known analogues, were isolated from the twigs and leaves of Viburnum odoratissimum. Their structures were elucidated by spectroscopic analyses and chemical derivatization method. All compounds showed different levels of cytotoxicity against five cell lines (HL‐60, A‐549, SMMC‐7721, MCF‐7, and SW480). Remarkably, 14,18‐O‐diacetyl‐15‐O‐methylvibsanin U ( 4a ) showed significant cytotoxicity against HL‐60, A‐549, SMMC‐7721, MCF‐7, and SW480, with IC₅₀ values of 0.15 ± 0.01, 0.69 ± 0.01, 0.41 ± 0.02, 0.75 ± 0.03, and 0.48 ± 0.03 μm , respectively. In addition, vibsanin K ( 10 ) was identified as a HSP90 inhibitor with an IC₅₀ value of 19.16 μm .     

假烟叶树叶挥发油化学成分分析

采用水蒸汽蒸馏法、两相溶剂萃取法提取,运用毛细管气相色谱-质谱联用法结合计算机检索对茄科植物假烟叶树(Solanum verbascifoliumL.)叶挥发油的化学成分进行分析和鉴定。其新鲜叶片提取10 h的挥发油得率为0.0611%。经毛细管色谱分离出18个峰,共鉴定出17种化合物,占挥发油总量的99.73%;用气相色谱面积归一化法计算各组分的相对含量,其主要化学成分为:大牻牛儿烯D(37.07%),咕巴烯(26.29%),1β-(1-甲基乙基)-4,7-二甲基-1α,2,4a()β,5,8,8a()α-六氢萘(13.63%),石竹烯(8.03%),1-β乙烯基-1-α甲基-2,β4-β双(1-甲基乙烯基)-环己烷(5.81%),-γ榄香烯(2.16%),α-筚澄茄油烯(2.06%),异喇叭烯(0.98%)。以上8种化合物占总挥发油含量的90.22%。     

芒果叶化学成分研究 II

为探讨芒果(Mangifera indica L.)的化学成分,从芒果叶的70%乙醇提取物中分离鉴定了13个化合物,经波谱分析,分别鉴定为:(–)-secoisolariciresinol-9′-O-D-glucopyranoside(1)、7S,8R-erythro-4,7,9-trihydroxy-3,3′-dimethoxy-8-O-4′-neolignan-9′-O-β-D-glucopyranoside(2)、7R,8R-threo-4,7,9-trihydroxy-3,3′-dimethoxy-8-O-4′-neolignan-9′-O-β-D-glucopyranoside(3)、(7R/S,8R)-7,8-dihydro-9′-hydroxyl-3′-methoxyl-8-hydroxymethyl-7-(4-hydroxy-3-methoxyphenyl)-1′-benzofuranpropanol 9′-O-β-D-glucopyranoside(4)、citrusin D(5)、丁香苷(6)、2,6-二甲氧基-4-羟基苯基-1-O-β-D-葡萄糖苷(7)、原儿茶酸(8)、没食子酸(9)、没食子酸甲酯(10)、没食子酸乙酯(11)、4,5-二羟基-3-甲氧基苯甲酸(12)、β-胡萝卜苷(13)。其中化合物1～7和12为首次从芒果属植物中分离得到。     

Daturanolide A–C,Three New Withanolides from Datura metel L. and Their Cytotoxic Activities

Three new withanolides ( 1 – 3 ), named as daturanolide A–C, along with six known withanolides ( 4 – 9 ) were isolated from the flowers of Datura metel L. Their structures with absolute configurations were elucidated by a series of spectroscopic methods, electronic circular dichroism (ECD) analyses, and X‐ray crystallography. All the isolates were evaluated for cytotoxicity against five human cancer cell lines (HCT116, U87‐MG, NCI‐H460, BGC823, and HepG2), and 6 exhibited marked cytotoxicity.     

Chemical Constituents of the Vietnamese Marine Sponge Gelliodes sp. and Their Cytotoxic Activities

A new decenoic acid derivative, gelliodesinic acid, and a naturally new alkaloid, together with three known furanoterpenoids and two known indole alkaloids, were isolated from the MeOH extract of the marine sponge Gelliodes sp. collected in Vietnam. The chemical structures of the isolated compounds were determined by analyses of 1D‐ and 2D‐NMR and MS data and by comparisons of the data with those reported in the literature. The cytotoxicity assay against HeLa, MCF‐7, and A549 cancer cell lines revealed that the three known furanoterpenes exhibited cytotoxic activities with IC₅₀ values ranging from 23.6 to 75.5 μM against the three cell lines, and that 1H‐indole‐3‐carboxylic acid showed cytotoxicity with an IC₅₀ value of 89.2 μM against A549 cancer cell lines.     

薄荷属植物挥发性成分及药理作用研究进展

薄荷属(Mentha L.)植物广泛分布于世界各地,有着悠久的药食两用史。目前,薄荷属植物挥发性物质主要应用于医药、食品、化妆品、香料、烟草等工业。现代研究表明其挥发性成分主要含有多种单萜类化合物,药理学研究显示其具有抗氧化、抗菌、抗辐射、抗癌、降血压等生物活性。本文主要对该属植物挥发性化学成分及药理作用的研究现状进行综述,以期为进一步开发和利用该属植物提供科学依据。     

Melanogenesis‐Inhibitory and Cytotoxic Activities of Limonoids,Alkaloids, and Phenolic Compounds from Phellodendron amurense Bark

Four limonoids, 1  –  4 , five alkaloids, 5  –  9 , and four phenolic compounds, 10  –  13 , were isolated from a MeOH extract of the bark of Phellodendron amurense (Rutaceae). Among these, compound 13 was new, and its structure was established as rel‐(1R,2R,3R)‐5‐hydroxy‐3‐(4‐hydroxy‐3‐methoxyphenyl)‐6‐methoxy‐1‐(methoxycarbonylmethyl)indane‐2‐carboxylic acid methyl ester (γ‐di(methyl ferulate)) based on the spectrometric analysis. Upon evaluation of compounds 1  –  13 against the melanogenesis in the B16 melanoma cells induced with α‐melanocyte‐stimulating hormone (α‐MSH), four compounds, limonin ( 1 ), noroxyhydrastinine ( 6 ), haplopine ( 7 ), and 4‐methoxy‐1‐methylquinolin‐2(1H)‐one ( 8 ), exhibited potent melanogenesis‐inhibitory activities with almost no toxicity to the cells. Western blot analysis revealed that compound 6 inhibited melanogenesis, at least in part, by inhibiting the expression of protein levels of tyrosinase, TRP‐1, and TRP‐2 in α‐MSH‐stimulated B16 melanoma cells. In addition, when compounds 1  –  13 were evaluated for their cytotoxic activities against leukemia (HL60), lung (A549), duodenum (AZ521), and breast (SK‐BR‐3) cancer cell lines, five compounds, berberine ( 5 ), 8 , canthin‐6‐one ( 9 ), α‐di‐(methyl ferulate) ( 12 ), and 13 , exhibited cytotoxicities against one or more cancer cell lines with IC₅₀ values in the range of 2.6 – 90.0 μm . In particular, compound 5 exhibited strong cytotoxicity against AZ521 (IC₅₀ 2.6 μm ) which was superior to that of the reference cisplatin (IC₅₀ 9.5 μm ).     

洋紫荆(Bauhinia variegata L.)花的化学成分研究

民间用药洋紫荆(Bauhinia variegata L.)为豆科羊蹄甲属植物,广泛分布于我国南部省份。基于前人的研究,并未发现对洋紫荆花化学成分研究的相关报道,本文以采自云南德宏地区的洋紫荆(B.variegata)花为研究对象,运用各种柱色谱分离手段,从其乙酸乙酯部分中分离得到了8个化合物,经核磁共振波谱及质谱解析,分别鉴定为Isoliquiritigenin(1)、Naringenin(2)、Kaempferol(3)、Kaempferol-7-O-β-D-glucopyranoside(4)、Kaempferol-3-O-β-D-glucopyranoside(5)、Caffeic acid(6)、(-)-Catechin(7)及Kaempferol-3-O-L-rhamnopyranoside(8)。化合物1和4为首次从该种植物中分离得到。     

黄酮对刺五加嫩叶采后保鲜的研究

将 0、 0 .1、 1 .0、 1 0、 5 0 mg/ L浓度的黄酮溶液对剌五加进行叶面喷施 ,2 4 h后采嫩梢装塑料袋置于4°C冰箱中保存。分别取样分析保存 0 d和 6 d后叶片中的维生素 C的含量 ,以及保存 0 d和 1 2 d后叶片的水、可溶性糖、叶绿素和粗蛋白的含量 ,比较不同浓度的黄酮溶液处理对剌五加嫩叶中上述几种营养成分的分解情况。通过统计分析得出 :0 .1 mg/ L的黄酮溶液对延缓叶片中上述几种营养成分分解的效果最好 ,说明其对剌五加嫩叶采后保鲜有一定的作用