Integerrimides A and B, cyclic heptapeptides from the latex of Jatropha integerrima

Two new cyclic heptapeptides, integerrimides A and B, have been isolated from the latex of Jatropha integerrima. Their structures were elucidated by using extensive 1D and 2D NMR, MS, and chemical degradation. At 50 microM both peptides 1 and 2 significantly inhibited neurite outgrowth in neuronal cell culture. They also partially inhibited proliferation of human IPC-298 melanoma cells as well as migration of human Capan II pancreatic carcinoma cells, but were inactive in HSV-1, antifungal, and antimalarial assays.     

Characterization of a fucoarabinogalactan,the main polysaccharide from the gum exudate of Croton urucurana

A fucoarabinogalactan (CU-1), the main component of the gum exudate of the medicinal plant Croton urucurana, has been isolated by precipitation and subsequent dialysis and finally purified by ion-exchange chromatography. The estimated average molecular weight of CU-1 by gel permeation chromatography was approximately 2.48 x 10(6) Da. CU-1 was found to contain 1.0% proteins and 93.7% total sugars, mainly fucose, arabinose, and galactose (molar ratio: 7.8, 8.1, 19.0), and minor quantities of mannose, xylose, glucose, and uronic acids (molar ratio: 2.2, 1.0, 0.3, 3.0). Among the uronic acids, glucuronic acid was identified and the presence of mannuronic acid could be also presumed. Methylation analysis of this polysaccharide revealed high proportions of 1,3-linked, 1,2,3-linked, and 1,2,3,6-linked galactose, 1-linked fucose, and 1-linked arabinose. This suggests that CU-1 is constituted by a principal skeleton of (1-->3)-linked galactopyranose units, with some of these galactose units branched at the 2-position or at both the 2- and 6-positions, and with mainly terminal fucopyranosyl and arabinofuranosyl residues in the side chains. This is the first report on the polysaccharide constitution of a gum exudate from a Croton species.     

Cembranolides from the leaves of Croton gratissimus

Ten new cembranolides, (-)-(1R*,4R*,10R*)-4-methoxycembra-2E,7E,11Z-trien-20,10-olide (1), (-)-(1S*,4R*,10R*)-1-hydroxy-4-methoxycembra-2E,7E,11Z-trien-20,10-olide (2), (-)-(1S*,4S*,10R*)-1,4-dihydroxycembra-2E,7E,11Z-trien-20,10-olide (3), (-)-(1S*,4S*,10R*)-1,4-dihydroxycembra-2E,7E,11Z-trien-20,10-olide (4), (+)-(10R*)-cembra-1E,3E,7E,11Z,16-pentaen-20,10-olide (5), (+)-(10R*)-cembra-1Z,3Z,7E,11Z,15-pentaen-20,10-olide (6), (+)-(5R*,10R*)-5-methoxycembra-1E,3E,7E,11Z,15-pentaen-20,10-olide (7), (+)-(1S*,4S*,7R*,10R*)-1,4,7-trihydroxycembra-2E,8(19),11Z-trien-20,10-olide (8), (-)-(1S*,4S*,7S*,10R*)-1,4,7-trihydroxycembra-2E,8(19),11Z-trien-20,10-olide (9), and (+)-(1S*,4R*,8S*,10R*)-1,4,8-trihydroxycembra-2E,6E,11Z-trien-20,10-olide (10), together with six known compounds, lupeol, 4(15)-eudesmene-1β,6α-diol, α-glutinol, 24-ethylcholesta-4,22-dien-3-one, (+)-(1R*,10R*)-cembra-2E,4E,7E,11Z-tetraen-20,10-olide, and (+)-(1R*,4S*,10R*)-4-hydroxycembra-2E,7E,11Z-trien-20,10-olide (4a), have been isolated from the leaves of Croton gratissimus. The acetyl derivatives of 8 and 4a were evaluated against a chloroquine-sensitive strain of Plasmodium falciparum (D10).     

New diterpenes from Croton insularis

Two new diterpenes (1 and 2) have been isolated from the aerial parts of Croton insularis. Their structures have been established by NMR and mass spectral data, and the absolute configuration of 1 and related trachylobane diterpenes was determined through a series of chemical correlations.     

Neoclerodane diterpenoids from Croton eluteria

Five new neoclerodane diterpenoids, rel-(3R,4S,5R,7R,8S,9R,10S,12R,20S)-7-acetoxy-15,16,12,20-diepoxy-3,4-dihydroxy-20-methoxyneocleroda-13(16),14-diene (1), rel-(3R,4S,5R,7R,8S,9R,10S,12R,20S)-7-acetoxy-15,16,12,20-diepoxy-3,4,20-trihydroxyneocleroda-13(16),14-diene (2), rel-(3R,4S,5S,6R,7S,8S, 9R,10S,12R,20S)-6,7-diacetoxy-3,4,15,16,12,20-triepoxy-20-hydroxyneocleroda-13(16),14-diene (3), rel-(3R,4S,5R,7R,8S,9R,10S,12R,20S)-7-acetoxy-3,4,15,16,12,20-triepoxy-20-hydroxyneocleroda-13(16),14-diene (4), and rel-(3R,4S,5R,7R,8S,9R,10S,12R,20R)-7,20-diacetoxy-3,4,15,16,12,20-triepoxyneocleroda-13(16),14-diene (5), have been isolated from the bark of Croton eluteria. The structures of the compounds 1-5 (cascarillins E-I) were determined by spectroscopic data interpretation.     

Neocrotocembranal from Croton oblongifolius.

A new cembranoid diterpene, neocrotocembranal (3), was isolated from the stem bark of Croton oblongifolius. Its structure was established on the basis of spectroscopic analysis. This compound inhibited platelet aggregation induced by thrombin, with an IC50 value of 47.21 microg/mL, and exhibited cytotoxicity against P-388 cells in vitro, with an IC(50) value of 6.48 microg/mL.     

Furanocembranoids from the stem bark of Croton oblongifolius

Four novel furanocembranoids (1-4) were isolated from the stem bark of Croton oblongifolius. Their structures were elucidated on the basis of spectroscopic analysis, mainly NMR and MS. Compounds 1, 3, and 4 exhibited good cytotoxicity against several human tumor cell lines.     

Musidunin and musiduol, insect antifeedants from Croton jatrophoides

Two novel limonoids, musidunin (1) and musiduol (2), were isolated from a methanol extract of Croton jatrophoides by bioassay-guided fractionation. Their structures were established by extensive NMR experiments. Interestingly, A,B-seco limonoid 1 contains a unique acetal annulation of A, A', and B' rings. Both limonoids exhibited antifeedant activities against two pests, Pectinophora gossypiella and Spodoptera frugiperda.     

A novel extract SB-300 from the stem bark latex of Croton lechleri inhibits CFTR-mediated chloride secretion in human colonic epithelial cells

An oligomeric proanthocyanidin (SP-303) extracted from the bark latex of the tree Croton lechleri (family Euphorbiaceae) is a potent inhibitor of cholera toxin-induced fluid accumulation and chloride secretion. The manufacturing process for SP-303 was optimized and simplified to produce an increased yield of the herbal extract. The novel extract (named SB-300) contained on average 70.6+/-7.2% SP-303 by weight (mean +/- S.D.; n=56 lots). Here, we describe the effectiveness of SB-300 on cAMP-regulated chloride secretion, which is mediated by the cystic fibrosis transmembrane conductance regulator Cl- channel (CFTR) in human colonic T84 cells. Exposure of the apical surface to SB-300 blocked forskolin-stimulated Cl- secretion by 92.2+/-3.0% with a half-maximal inhibition constant (KB) of 4.8+/-0.8 microM. For SP-303, stimulated Cl- currents were decreased by 98.0+/-7.2 % and KB averaged 4.1+/-1.3 microM. There was no significant difference between the blocking kinetics of SP-303 and SB-300. Forskolin-stimulated whole cell Cl- currents were effectively blocked by extracellular addition of SB-300 (63+/-8.5%; n=3) and to a similar extent by SP-303 (83 +/- 0.6%; n=2; at 50 microM each). Both extracts inhibited a time- and voltage-independent Cl- conductance, which indicated the involvement of CFTR Cl- channels. We conclude that both SP-303 (used in Provir) and SB-300 (used in NSF Normal Stool Formula) are novel natural products that target the CFTR Cl- channel. SB-300 is a low cost herbal extract and may present a complementary and alternative medicine approach for the treatment of fluid loss in watery diarrhea.     

Three new sesquiterpenes from Croton arboreous

Three new sesquiterpenes, 5alpha,7alpha,10betaH-3-patchoulen-2-one (1), 5alpha,7alpha10betaH-4(14)-patchoulen-2alpha-ol (2), and 9alpha,10beta-dihydroxy-2beta,4beta-peroxy-1alpha,5beta,7alphaH-guaiane (3), were isolated from the aerial parts of Croton arboreous along with 14 known compounds. The structures of these compounds were determined on the bases of their spectroscopic data (IR, UV, OR, 1D and 2D NMR, and MS). The anti-inflammatory activity against ear edema in mice produced by 12-O-tetradecanoylphorbol-13-acetate (TPA) was evaluated for all the pure compounds and showed that compounds 4-7 are active.     

Antioestrogenic effect of trans-dehydrocrotonin, a nor-clerodane diterpene from Croton cajucara Benth. in rats

This study examined trans-dehydrocrotonin (t-DCTN), a nor-clerodane diterpene isolated from the Brazilian medicinal plant Croton cajucara Benth., for a possible antioestrogenic activity using immature rats as a model system for bioassay of oestrogen, and for an antiimplantation effect in regularly cycling rats of proven fertility. In the antioestrogen test, t-DCTN (25 and 50 mg/kg) effectively prevented oestrogen-induced increases of uterine wet weights. In addition, the vaginal openings provoked by oestrogen were completely prevented by t-DCTN. However, blastocyst-implantation was only insignificantly affected in t-DCTN pretreated animals. These results suggest that t-DCTN may be an antioestrogen and warrants further studies with regard to its mechanism of action.     

056 芦荟叶干汁，乳液

活性成分与药理作用芦荟药用部位为干的叶汁或乳液，其成分蒽衍生物在结肠中可分解成芦荟-大黄素蒽酮，蒽酮可刺激肠黏膜，引起黏液分泌和肠蠕动增加。芦荟可增加结肠的运动，因此能推进并缩短食物转运时间，还可引起液体和电解质在腔内分泌。芦荟可引起胀感。摄入一定量后的10h内发生导泻作用，抑制水和电解液的再吸收。芦荟汁和乳液还可使钾丢失，引起肠肌麻痹。连续使用，剂量必须增加到维持轻泻的作用。蒽类轻泻用途与发生结肠直肠腺瘤或癌无关。     

芦荟叶干汁,乳液

又名 Aloe Juice, Aloe Latex, Burn Plant, Elephant's Gall, Hsiang-Dan, Lily of the Desert, Lu-Hui, Miracle Plant, Plant of Immortality.     

Insect antifeedants from Croton jatrophoides: structures of zumketol, zumsenin, and zumsenol

Three new A-seco limonoids, zumketol (1), zumsenin (2), and zumsenol (3), were isolated from a methanol extract of Croton jatrophoides by bioassay-guided fractionation, and their structures were determined by NMR analysis. The alpha-ketol 1 may be biosynthesized via the intramolecular acyloin condensation of a dicarboxylate intermediate.     

Microcyclamide, a cytotoxic cyclic hexapeptide from the cyanobacterium Microcystis aeruginosa

Microcyclamide (1), a cytotoxic cyclic hexapeptide, was isolated from the cultured cyanobacterium Microcystis aeruginosa (NIES-298). Its structure was elucidated to be 1 on the basis of two-dimensional (1)H-(1)H, (1)H-(13)C, and (1)H-(15)N NMR correlation experiments and the HRFABMS measurement. The absolute stereochemistry of the asymmetric centers was determined by the Marfey's method. This peptide showed a moderate cytotoxicity against P388 murine leukemia cells.     

Cimipronidine, a cyclic guanidine alkaloid from Cimicifuga racemosa

A new cyclic guanidine alkaloid, cimipronidine (1), together with the known compound fukinolic acid (2), was isolated from the n-BuOH-soluble fraction of Cimicifuga racemosa roots that showed 5-HT7 receptor binding activity. Structure elucidation of 1, a minor constituent, presented unique challenges based on its polarity, but was accomplished with the use of a combination of one- and two-dimensional NMR as well as MS analyses. The relative configuration was established by analyzing the H,H-coupling constants and the results of the 2-D gradient NOESY spectrum. The previously reported serotonergic (5-HT7), highly polar, n-BuOH-soluble fraction was characterized by HPLC-ELSD and was shown to be a mixture containing the following compounds: cimicifugic acids A, B, and F, fukinolic acid, ferulic acid, isoferulic acid, and compound 1, potentially significant as a marker compound of C. racemosa.     

Cyclonellin, a new cyclic octapeptide from the marine sponge Axinella carteri

Cyclonellin (1), a new cyclic octapeptide, was isolated from an aqueous extract of the marine sponge Axinella carteri. Its structure was elucidated by interpretation of NMR spectral data of the intact compound and N-terminal Edman sequencing of linear peptide fragments obtained by partial hydrolysis of 1. The absolute configurations of the constituent amino acids were determined by acid hydrolysis, derivitization with FDAA, and LC-MS analyses.     

ent-Kaurane diterpenoids from Croton tonkinensis stimulate osteoblast differentiation

Four new ent-kaurane diterpenoids (1-4) were isolated from the leaves of Croton tonkinensis by bioactivity-guided fractionation using an in vitro osteoblast differentiation assay. Their structures were identified as ent-11β-acetoxykaur-16-en-18-ol (1), ent-11α-hydroxy-18-acetoxykaur-16-ene (2), ent-14β-hydroxy-18-acetoxykaur-16-ene (3), and ent-7α-hydroxy-18-acetoxykaur-16-ene (4). Compounds 1-4 significantly increased alkaline phosphatase activity and osteoblastic gene promoter activity. Compounds 1-3 also increased the levels of ALP and collagen type I alpha mRNA in C2C12 cells in a dose-dependent manner. These results suggest that ent-kaurane diterpenoids from C. tonkinensis have a direct stimulatory effect on osteoblast differentiation and may be potential therapeutic molecules against bone diseases such as osteoporosis.     

Hirsutide, a cyclic tetrapeptide from a spider-derived entomopathogenic fungus, Hirsutella sp

The entomopathogenic fungus Hirsutella sp., isolated from an infected spider, was found to produce the new cyclotetrapeptide hirsutide (1), cyclo-(L-NMe-Phe-L-Phe-L-NMe-Phe-L-Val), along with the known cytochalasin Q (2), using a cytotoxicity-guided isolation procedure. The structure of 1 was elucidated using one- and two-dimensional NMR experiments, mass spectrometry, and Marfey's method for analyzing the configuration of the amino acids.