Discovery of natural products from Curcuma longa that protect cells from beta-amyloid insult: a drug discovery effort against Alzheimer's disease

From Curcuma longa, two novel compounds, 4' '-(3' "-methoxy-4' "-hydroxyphenyl)-2' '-oxo-3' '-enebutanyl 3-(3'-methoxy-4'hydroxyphenyl)propenoate (calebin-A, 1) and 1,7-bis(4-hydroxy-3-methoxyphenyl)-1,4,6-heptatrien-3-one (2), and seven known compounds, 1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione (curcumin, 3), 1-(4-hydroxy-3-methoxyphenyl)-7-(4-hydroxyphenyl)-1,6-heptadiene-3,5-dione (demethoxycurcumin, 4), 1,7-bis(4-hydroxyphenyl)-1,6-heptadiene-3,5-dione (bisdemethoxycurcumin, 5), 1-hydroxy-1,7-bis(4-hydroxy-3-methoxyphenyl)-6-heptene-3,5-dione (6), 1,7-bis(4-hydroxyphenyl)-1-heptene-3,5-dione (7), 1,7-bis(4-hydroxyphenyl)-1,4,6-heptatrien-3-one (8), and 1,5-bis(4-hydroxy-3-methoxyphenyl)-1,4-pentadien-3-one (9), were isolated following a bioassay-guided fractionation scheme utilizing an assay to detect protection of PC12 cells from beta-amyloid insult. Compounds 1, 3-5, and 7 were found to more effectively protect PC12 cells from betaA insult (ED(50) = 0.5-10 microg/mL) than Congo red (10) (ED(50) = 37-39 microg/mL).     

Six new diarylheptanoids from the seeds of Alpinia blepharocalyx

Chromatographic separation of part of an EtOH extract of the seeds of Alpinia blepharocalyx resulted in the isolation of six new (1-6) and two known (7, 8) diarylheptanoids together with 12 known compounds. The structures of the new compounds, including their absolute stereochemistry, were elucidated by spectroscopic and chemical methods as (3S,5S)- (1) and (3S,5R)-3-hydroxy-5-methoxy-1-(4-hydroxyphenyl)-7-phenyl-6E-heptene (2), (3S,5S)- (3) and (3S,5R)-3-hydroxy-5-ethoxy-1-(4-hydroxyphenyl)-7-phenyl-6E-heptene (4), (3S)-methoxy-1,7-bis(4-hydroxyphenyl)-6E-hepten-5-one (5), and 1,7-bis(4-hydroxyphenyl)hepta-4E,6E-dien-3-one (6). Among the isolated compounds, 5, (3S,5S)-3,5-dihydroxy-1,7-bis(4-hydroxyphenyl)heptane (8), 4'-hydroxy-5,6-dehydrokawain (14), and/or phloroglucinol (20) showed significant antiproliferative activity against murine colon 26-L5 carcinoma (ED(50): 5, 5.2 microM; 8, 12.8 microM; 14, 20.7 microM; 20, 26.4 microM) and human HT-1080 fibrosarcoma (ED(50): 5, 10.1 microM; 14, 20.1 microM; 20, 20.9 microM) cells.     

Diarylheptanoids and a monoterpenoid from the rhizomes of Zingiber officinale: antioxidant and cytoprotective properties

Three new diarylheptanoids and one new monoterpenoid were isolated from the rhizomes of Zingiber officinale together with four known diarylheptanoids, 5-8. Their structures were elucidated mainly by spectroscopic methods, and they were deduced as 5-[4-hydroxy-6-(4-hydroxyphenethyl)tetrahydro-2 H-pyran-2-yl]-3-methoxybenzene-1,2-diol (1), sodium (E)-7-hydroxy-1,7-bis(4-hydroxyphenyl)hept-5-ene-3 S-sulfonate (2), sodium (E)-7-hydroxy-1,7-bis(4-hydroxyphenyl)hept-5-ene-3 R-sulfonate (3), and hydroxycineole-10-O-beta-D-glucopyranoside (4), respectively. Among the isolated compounds, compounds 1, 5, and 8 exhibited strong superoxide anion radical scavenging activities in a phenazine methosulfate-NADH system. In a more biological system, these compounds were demonstrated to exhibit potent protection against lipid peroxidation in mouse liver microsomes exposed to oxidative conditions. These compounds were subsequently tested on primary cultures of rat hepatocytes exposed to oxidative damage, and definitive cytoprotective actions were found.     

高良姜根茎中一个新的二芳基庚烷

目的：对高良姜（Alpinia officinarum Hance）根茎化学成分进行研究。方法：运用多种层析方法进行分离纯化,通过波谱解析进行结构鉴定。结果：分离鉴定了5个二芳基庚烷类化合物,分别为：5-乙氧基-7-（4-羟基-3-甲氧基苯基）-1-苯基-3-庚酮（1）,5-羟基-1,7-二苯基-3-庚酮（2）,5-羟基-7-（4-羟基-3-甲氧基苯基）-1-苯基-3-庚酮（3）,5-甲氧基-7-（4-羟基-3-甲氧基苯基）-1-苯基-3-庚酮（4）,（E）-7-（4-羟基-3-甲氧基苯基）-1-苯基-4-烯-3-庚酮（5）。结论：化合物1为新的二芳基庚烷类化合物。     

山药化学成分研究

目的研究山药Dioscorea opposita化学成分。方法采用硅胶、Sephadex LH-20、反相ODS等柱色谱方法对化合物进行分离纯化,运用核磁共振波谱等方法鉴定化合物的结构。结果从山药根茎95%乙醇提取物中分离纯化得到14个化合物,包括8个二苯基庚烷类化合物(1～8)和6个含氮化合物(9～14),分别鉴定为5-ethoxy-1,7-diphenylheptan-3-one(1)、5-hydroxy-1,7-bis(4-hydroxyphenyl)-heptan-3-one(2)、1,7-diphenyl-4-hepten-3-one(3)、1,7-bis(4-hydroxyphenyl)-4-hepten-3-one(4)、hannokinol(5)、1-(4-hydroxy-3-methoxyphenyl)-7-(4-hydroxyphen-yl)-3,5-heptanediol(6)、1,7-bis(4-hydroxy-3-methoxyphenyl)-3,5-heptanediol(7)、1,7-bis(4-hydroxyphenyl)-1,5-epoxy-3-hydroxyheptane(8)、trans-N-coumaroyltyramine(9)、trans-N-feruloyltyramine(10)、cis-N-coumaroyltyramine(11)、trans-N-cinnamoyltyramine(12)、pyrrolezanthine-6-ethyl ether(13)、divaricataester A(14)。结论化合物1是新的天然产物,命名为山药庚酮A,化合物3、4、10、12～14为首次从薯蓣科植物中分离得到,化合物2、6、8为首次从山药中分离得到。     

Antioxidative constituents of Etlingera elatior

Phytochemical studies on the rhizomes of Etlingera elatior have resulted in the isolation of 1,7-bis(4-hydroxyphenyl)-2,4,6-heptatrienone (1), demethoxycurcumin (2), 1,7-bis(4-hydroxyphenyl)-1,4,6-heptatrien-3-one (3), 16-hydroxylabda-8(17),11,13-trien-15,16-olide (4), stigmast-4-en-3-one, stigmast-4-ene-3,6-dione, stigmast-4-en-6beta-ol-3-one, and 5alpha,8alpha-epidioxyergosta-6,22-dien-3beta-ol. Compounds 1 and 4 are new, and their structures were elucidated by analysis of spectroscopic data. Diarylheptanoids 1-3 were found to inhibit lipid peroxidation in a more potent manner than alpha-tocopherol.     

Ardisinones A-E, novel diarylundecanones from Ardisia arborescens

A phytochemical study on an ethanol extract of Ardisia arborescens resulted in the isolation of five new diarylundecanones, named ardisinones A-E (1-5). The structures were established by HRESIMS and NMR ((1)H, (13)C, DEPT, HSQC, HMBC) as 11-(2-acetoxy-6-hydroxyphenyl)-1-(2,4,6-trihydroxyphenyl)undecan-1-one (1), 11-(2-acetoxy-6-hydroxyphenyl)-1-(2,6-dihydroxy-4-methoxyphenyl)undecan-1-one (2), 1-(2,6-dihydroxy-4-methoxyphenyl)-11-(2,6-dihydroxyphenyl)undecan-1-one (3), 1-(2,4,6-trihydroxyphenyl)-11-(2,6-dihydroxyphenyl)undecan-1-one (4), and 1-(2,4,6-trihydroxyphenyl)-11-(2-hydroxyphenyl)undecan-1-one (5). In our in vitro disk diffusion assay, compounds 1 and 4 showed some slight inhibition of three bacteria, while 2 and 3 did not show antimicrobial activity.     

Mono-, Bi-, and triphenanthrenes from the tubers of Cremastra appendiculata

Six newphenanthrene derivatives, including three monophenanthrenes (1-3), two biphenanthrenes (4 and 5), and a triphenanthrene (6), have been isolated from an ethanolic extract of the tubers of Cremastra appendiculata. Using spectroscopic methods, the structures of compounds 1-6 were determined as 1-hydroxy-4,7-dimethoxy-1-(2-oxopropyl)-1H-phenanthren-2-one (1), 1,7-dihydroxy-4-methoxy-1-(2-oxopropyl)-1H-phenanthren-2-one (2), 2-hydroxy-4,7-dimethoxyphenanthrene (3), 2,7,2'-trihydroxy-4,4',7'-trimethoxy-1,1'-biphenanthrene (4), 2,2'-dihydroxy-4,7,4',7'-tetramethoxy-1,1'-biphenanthrene (5), and 2,7,2',7',2' '-pentahydroxy-4,4',4' ',7' '-tetramethoxy-1,8,1',1' '-triphenanthrene (6), respectively. Compounds 1-6 and two known compounds, cirrhopetalanthin (7) and flavanthrinin (8), obtained previously from this plant, were evaluated against six human cancer cells and a normal cell line.     

草豆蔻的化学成分（英文）

目的：研究草豆蔻的化学成分。方法：采用硅胶和Sephadex LH-20柱色谱方法进行化合物的分离和纯化, 根据理化性质和光谱数据鉴定化合物结构。结果：从草豆蔻提取物中分离得到了10个化合物, 经鉴定分别为：1, 7-双苯-5-羟基-4, 6-庚烯-3-酮 （trans, trans-1, 7-diphenyl-5-hydroxy-4, 6-hepten-3-one, 1）, 乔松素 （pinocembrin, 2）, 山姜素 （alpinetin, 3）, 7, 4′-二羟基-5-甲氧基二氢黄酮 （4）, 蜡菊亭（helichrysetin, 5）, 2′, 4′-二羟基-6′-甲氧基二氢查尔酮 （uvangoletin, 6）, （1E, 4Z）-5-hydroxy-1-phenylhexa-1, 4-dien-3-one （7）, katsumadain B（8）, 羊踯躅素I（rhodomollein I, 9）和金色酰胺醇酯（aurantiamide acetate,10）。结论：化合物7为一个新天然产物, 化合物9和10为首次从该属中分离得到。     

Mixed lignan-neolignans from Tarenna attenuata

Six new mixed lignan-neolignans and 20 known compounds were isolated from the whole plant of Tarenna attenuata. By analysis of physical and spectroscopic data, the structures of the new compounds were elucidated as (1R,5R,6R)-6-{4-O-[2-(1-(4-hydroxy-3-methoxyphenyl))glycerol]-3,5-dimethoxyphenyl}-3,7-dioxabicyclo[3.3.0]octan-2-one (1), 5' '-methoxyhedyotisol A (2), 4' '-O-(8-guaiacylglycerol)buddlenol A (3), 5' '-methoxy-4' '-O-(8-guaiacylglycerol)buddlenol A (4), 4,6-dimethoxy-5-hydroxy-3-hydroxymethyl-2-(3,4,5-trimethoxyphenyl)-2,3-dihydrobenzofuran (5), and 7-O-ethylguaiacylglycerol (6). Compounds 1, 5, 6, and 8 showed potent antioxidant activities against H2O2-induced impairment in PC12 cells, and compounds 1, 2, 5, and 7 scavenged DPPH radical strongly with IC50 values of 72, 87, 45, and 55 microM, respectively.     

血党化学成分的研究

目的:研究血党Ardisia punctata的化学成分。方法:采用反复硅胶柱色谱和制备高效液相色谱进行分离纯化,根据理化性质和光谱数据进行结构鉴定。结果:得到12个化合物,鉴定为3-羟基-5-十三烷基-苯甲醚(1),5-十五烷基-1,3-间苯二酚(2),2-甲氧基-6-十三烷基-1,4-苯醌(3),2-甲氧基-6-十五烷基-1,4-苯醌(4),glutinol(5),ar-disicrenoside A(6),ardisiacrispin B(7),24-乙基-Δ7,22-胆甾二烯-3-酮(8),24-乙基-Δ7,22-胆甾二烯-3-醇(9),胡萝卜苷(10),香草酸(11),正三十四烷酸(12)。结论:所有化合物均为首次从该植物中获得。     

刺异叶花椒根中香豆素类成分

目的:对刺异叶花椒Zanthoxylum dimorphophyllum var. spinifolum根的化学成分进行研究.方法:采用现代色谱分离技术进行化学成分的分离,运用波谱方法确定结构.结果:从中分离得到5个化合物,分别鉴定为5-甲氧基-7-羟基-6-(3'-甲基-2',3'-二羟基丁基)-香豆素(Ⅰ),6-(3'-甲基-2',3'-二羟基丁基)-7-甲氧基-8-(3″-甲基-丁-2″-烯基)-香豆素(Ⅱ),6-(3'-甲基-2',3'-二羟基丁基)-7-羟基-8-(3″-甲基-丁-2″-烯基)-香豆素(Ⅲ),6-(3'-甲基-2',3'-环氧丁基)-7-甲氧基-8-(3″-甲基-丁-2″-烯基)-香豆素(Ⅳ),7-甲氧基-8-(3'-甲基-丁-2'-烯基)-香豆素(Ⅴ).结论:以上化合物均为首次从该植物中分得.     

Anti-inflammatory isoflavonoids from the rhizomes of Iris germanica

The anti-inflammatory activity of nine isoflavonoids 5,7-dihydroxy-3-(3'-hydroxy-4',5'dimethoxy)-8-methoxy-4H-1-benzopyran-4-one 1, 5,7-dihydroxy-3-(3'-hydroxyl-4', 5'-dimethoxy)-6-methoxy-4H-1-benzopyran-4-one 2, 5, 7-dihydroxy-3-(4'-hydroxy)-6-methoxy-4H-1-benzopyrane-4-one 3, 5-hydroxy-3-(4'-hydroxy)-6,7-methylenedioxy-4H-1-benzopyran-4-one 4, 5-hydroxy-3-(4'-methoxy)-6,7-methylenedioxy-4H-1-benzopyran-4-one 5, 5-methoxy-3-(4'-hydroxy)-6,7-methyenedioxy-4H-1-benzopyran-4-one 6, 5,7-dihydroxy-3-(3'-hydroxy-4'-methoxy)-6-methoxy-4H-1-benzopyran-4-one 7, 5,7-dihydroxy-3-(3'-methoxy-4'-hydroxy)-6-methoxy-4H-1-benzopyran-4-one 8, and isopeonol 9 determined by a spectrophotometric assay using the activated human neutrophils. These isoflavonoids were isolated from an important folkloric medicinal plant Irsa (Iris germanica L.), a member of the family Iridaceae. Structures of these compounds were identified by spectral comparison with the reported data and active members of this group adds into the growing number of non-steroidal anti-inflammatory agents.     

Aromatase inhibitors from Broussonetia papyrifera.

Bioassay-guided fractionation of an ethyl acetate-soluble extract from the whole plants of Broussonetia papyrifera, using an in vitro aromatase inhibition assay, led to the isolation of five new active compounds, 5,7,2',4'-tetrahydroxy-3-geranylflavone (1), isogemichalcone C (8), 3'-[gamma-hydroxymethyl-(E)-gamma-methylallyl]-2,4,2',4'-tetrahydroxychalcone 11'-O-coumarate (9), demethylmoracin I (10), and (2S)-2',4'-dihydroxy-2' '-(1-hydroxy-1-methylethyl)dihydrofuro[2,3-h]flavanone (11), and 10 known (12-21) compounds which were also found to be active. Of these compounds, the most potent were 9 (IC(50) 0.5 microM), 11 (IC(50) 0.1 microM), isolicoflavonol (12, IC(50) 0.1 microM), and (2S)-abyssinone II (13, IC(50) 0.4 microM). Additionally, six new compounds, 5,7,3',4'-tetrahydroxy-6-geranylflavonol (2), 5,7,3',4'-tetrahydroxy-3-methoxy-6-geranylflavone (3), (2S)-7,4'-dihydroxy-3'-prenylflavan (4), 1-(2,4-dihydroxyphenyl)-3-(4-hydroxyphenyl)propane (5), 1-(2,4-dihydroxy-3-prenylphenyl)-3-(4-hydroxyphenyl)propane (6), and 1-(4-hydroxy-2-methoxyphenyl)-3-(4-hydroxy-3-prenylphenyl)propane (7), were isolated and characterized, but proved to be inactive as aromatase inhibitors, as were an additional 21 known compounds. The structures of the new compounds (1-11) were elucidated by spectroscopic methods. Structure-activity relationships in the aromatase assay were determined for the benzofurans, biphenylpropanoids, coumarins, and various types of flavonoids (chalcones, flavans, flavanones, and flavones) obtained among a total of 42 constituents of B. papyrifera.     

Terpenoids and a diarylheptanoid from Zingiber ottensii

Four new terpenoids and a diarylheptanoid were isolated together with 16 known compounds from rhizomes of Zingiber ottensii. The structures of the new compounds were determined to be 1,10,10-trimethylbicyclo[7,4,0]tridecane-3,6-dione (1), (E)-14-hydroxy-15-norlabda-8(17),12-dien-16-al (2), (E)-labda-8(17),12,14-trien-15(16)-olide (3), (E)-14,15,16-trinorlabda-8(17),11-dien-13-oic acid (4), and rel-(3R,5S)-3,5-dihydroxy-1-(4-hydroxy-3-methoxyphenyl)-7-(3, 4-dihydroxyphenyl)heptane (5) by spectroscopic evidence.     

蓬莪术姜黄素类化学成分研究

目的研究蓬莪术Curcuma phaeocaulis根茎的姜黄素类化学成分及其细胞毒活性。方法将蓬莪术根茎的95%乙醇提取物经石油醚、醋酸乙酯、正丁醇依次萃取,对醋酸乙酯萃取部位采用硅胶和葡聚糖凝胶Sephadex LH-20柱色谱、反相中压液相色谱、制备薄层色谱及半制备高效液相色谱等分离技术进行分离纯化,利用现代波谱学手段对分离的化学成分进行结构鉴定;采用MTT法对分离得到的化合物进行细胞毒活性筛选。结果从蓬莪术根茎的醋酸乙酯萃取部位分离得到4个姜黄素类化合物,分别鉴定为1,7-双(4-羟基苯基)-1E,6E-庚二烯-3-酮(1)、1,7-双(4-羟基苯基)-1,4,6-庚三烯-3-酮(2)、1,7-双(4-羟基苯基)-4E,6E-庚二烯-3-酮(3)和(1R,5S,6S)-1,5-环氧-6-羟基-1,7-双(3-甲氧基-4-羟基苯基)-庚烷(4)。MTT实验显示化合物1～3均可抑制人胃癌HGC-27细胞的增殖,仅化合物2对人乳腺癌MDA-MB-231细胞有抑制作用;化合物2和3还对人正常肝细胞L-02表现出强烈的毒性作用。结论从蓬莪术中分离得到4个姜黄素类成分,其中化合物1为新化合物,命名为姜黄素P。化合物1～3均具有一定的抑制HGC-27细胞增殖作用,其中化合物1可选择性抑制HGC-27细胞的增殖并对人正常肝L-02细胞无明显毒性作用。     

Antiemetic principles of Alpinia officinarum

Bioasay-guided fractionation of the antiemetic constituents of Alpinia officinarum was performed, and eight compounds (1-8) including a new compound were isolated. Among the seven known compounds, two flavonoids (1, 2), four diarylheptanoids (3, 5, 6, 8), and one sterol (4) were obtained, with five (2-6) of those compounds showing antiemetic activity in a copper sulfate induced emesis assay in young chicks. The structure of the new compound 7, which also showed antiemetic activity, was determined as 5-hydroxy-7-(4-hydroxy-3-methoxyphenyl)-1-(4-hydroxyphenyl)-3-heptanone. The structure of 7 was established on the basis of spectroscopic data interpretation.     

怀菊花茎叶化学成分的研究

目的研究怀菊花Chrysanthemum morifolium Ramat.茎叶的化学成分。方法怀菊花茎叶50%丙酮提取物采用Toyopearl HW-40、Diaion HP-20、Sephadex LH-20、ODS、半制备HPLC进行分离纯化,根据理化性质及波谱数据鉴定所得化合物的结构。结果从中分离得到22个化合物,分别鉴定为1H-吲唑(1)、6,7-二羟基香豆素(2)、8E-decaene-4,6-diyn-l-O-β-D-glucopyranoside (3)、2′-脱氧胸腺嘧啶核苷(4)、2′-脱氧尿嘧啶核苷(5)、尿嘧啶(6)、litchiol B (7)、8E-decacnc-4,6-diyn-l-O-β-D-glucopyranosyl-(1″→2′)-β-D-glucopyranoside (8)、lippianoside E (9)、1-核糖醇基-2,3-二酮-1,2,3,4-四氢-6,7-二甲基-喹喔啉(10)、黑麦草内酯(11)、异嗪皮啶(12)、(+)-去氢催吐萝芙木醇(13)、cytidine (14)、paeoveitols B (15)、4β,6β-dihydroxy-10α-methoxy-1α,5β,7α(H)-guaiane (16)、scopoletin (17)、(2E,9Z)-pentodeca-2,9-dien-12,14-diynoic acid piperidide (18)、tetradeca-2E,4E,10E-trien-8-ynoic acid pyrrolidide (19)、7-羟基香豆素(20)、6-羟基-7,8-二氧亚甲基香豆素(21)、3-吲哚甲酸(22)。结论化合物1、7、9~22为首次从该植物中分离得到。     

大高良姜的化学成分研究

目的：对大高良姜的根茎部位化学成分进行系统研究。方法：采用硅胶和Sephadex LH-20柱色谱等手段进行分离纯化，运用UV、IR、^1H—NMR13C—NMR、MS等谱学方法进行结构鉴定。结果：共分离鉴定了11个化合物，分别为4-[（E）-3-hydroxyprop-1-enyl]phenylacetate（1），反式对羟基桂皮醛乙酯（2），5-hydroxy-7-（4″-hydroxy-3″-methoxyphenyl）-1-phenyl-3-heptanone（3），7-（4″-hydroxy-3″-methoxy—phenyl）-1-phenylhep-4-en-3-one（4），[1′S]-1′-乙酰氧丁香酚乙酯（5），反式对羟基桂皮醛（6），对羟基苯甲醛（7），1-（4-hydroxyphenyl）propan．1-one（8），高良姜素（9），trans—P—coumaryl diacetate（10），β-谷甾醇（11）。结论：化合物1是首次从自然界分离得到的天然产物，化合物2为首次从该属植物中分离得到的苯丙素类化合物，化合物3和4是首次从该种植物中分离得到的双苯庚烷类化合物。     

Mycophenolic derivatives from Eupenicillium parvum

A new compound, euparvic acid (1, C(14)H(16)O(6)), and the known compounds 5,7-dihydroxy-4-methylphthalide (2), 6-(3-carboxybutyl)-7-hydroxy-5-methoxy-4-methylphthalan-1-one (3), 6-(5-carboxy-3-methylpent-2-enyl)-7-hydroxy-5-methoxy-4-methylphthalan-1-one (4), and 6-(5-carboxy-4-hydroxy-3-methylpent-2-enyl)-7-hydroxy-5-methoxy-4-methylphthalan-1-one (5) were isolated from the EtOAc extract of Eupenicillium parvum. The structure of 1 was determined by interpretation of MS and homo- and heteronuclear 2D NMR spectroscopic data and confirmed by X-ray crystallography. The absolute configuration of 5 was determined via MPA ester derivatization.