Aristolactam derivatives from Fissistigma glaucescens

The phytochemical investigation of stems of Fissistigma glaucescens (Hance) Merr. led to the isolation of a new aristolactam derivative aristolactam AIb (1), together with eleven known aristolactam derivatives (2–12). Structure elucidation of these compounds were performed on the basis of NMR spectral data and MS. Compounds 2–7 were isolated from the F. glaucescens for the first time. The chemotaxonomic significance of the isolates was also discussed.     

Guaiane-Type Sesquiterpenes from the Stems of Fissistigma oldhamii

Two new guaiane-type sesquiterpenes dysodensiols J and L, one new natural product dysodensiol K together with four known biogenetically related guaiane-type sesquiterpenes were isolated from the stems of Fissistigma oldhamii. Their structures were elucidated by detailed analysis of NMR, HR-ESI-MS, IR and Optical rotations data. Compound 1 contains an uncommon five-membered ether ring. The inhibitory effect of all compounds on the proliferation of primary synovial cells was evaluated. Compound 3 showed inhibitory activity with an IC₅₀ value of 6.8 μM. Compounds 5–7 exhibited moderate inhibitory activity with IC₅₀ values of 23.8, 26.6, and 27.1 μM, respectively.     

Novelties in Fissistigma (Annonaceae) from Borneo

Five new species of Fissistigma are described from Borneo. Fissistigma brevistipitatum sp. nov. is a species of lowland and hill forest mostly recorded from Sabah. Fissistigma bygravei sp. nov. is similar to F. hypoglaucum (Miq.) Merr. of the Malay Peninsula and Sumatra. Fissistigma carrii sp. nov. is from Mount Kinabalu. Fissistigma crassicaule is a robust plant known from a couple of collections from Sarawak. Fissistigma montanum sp. nov. is a species from hill and montane forest recorded from Brunei, Sabah and Sarawak. A new combination in Fissistigma is made for Melodorum multivenium Diels. Two recently described species of Fissistigma from Borneo ( F. cordifolium Irawan and F. magnisepalum Irawan) are reduced to synonymy of Friesodielsia excisa (Miq.) Steenis and Friesodielsia affinis (Hook. f. & Thomson) D. Das, respectively. Both species of Friesodielsia are lectotypified.     

Eudesmane-type sesquiterpenes and aporphine-type alkaloids from Fissistigma maclurei

The phytochemical investigation of the stems of Fissistigma maclurei Merr. led to the isolation of a new eudesmane-type sesquiterpene 6α,12-dihydroxy-4(15)-eudesmen- 1-one (1), together with seven known eudesmane-type sesquiterpenes (2–8) and four known aporphine-type alkaloids (9–12). The structures of these compounds were elucidated using comprehensive spectroscopic methods. All compounds were isolated from the F. maclurei for the first time. The chemotaxonomic significance of the isolates was also discussed.     

Four New Polyhydroxy Cyclohexanes from the Stems of Fissistigma tientangense

Four undescribed polyhydroxy cyclohexanes, fissoxhydrylenes A–D ( 1–4 ), together with two known biogenetically related polyhydroxy cyclohexanes ( 5 and 6 ) were isolated from the stems of Fissistigma tientangense Tsiang et P. T. Li. Their structures were elucidated by detailed analysis of NMR, HR-ESI-MS, IR, UV and Optical rotations data. The absolute configuration of 1 was confirmed by X-ray crystallographic. The absolute configurations of 2–4 were confirmed by chemical reaction and optical rotations. Compound 4 represent the first example of a no substituent polyhydroxy cyclohexanes from natural products. All isolated compounds were evaluated for their anti-inflammatory activities against the lipopolysaccharide-induced nitric oxide (NO) production in mouse macrophage RAW 264.7 cells in vitro. Compounds 3 and 4 showed inhibitory activities with the IC₅₀ values of 16.63±0.06 μM and 14.38±0.08 μM, respectively.     

中国瓜馥木属(番荔枝科)一新记录

在对中国科学院植物研究所、华南植物研究所、昆明植物研究所、西双版纳热带植物园以及中山大学、西南林学院等地标本馆番荔枝科Annonaceae标本研究的基础上,笔者又详细研究了阔叶瓜馥木Fissistigma chloroneurum (Hand._Mazz.) Tsiang的模式照片(IBSC)和李秉滔(1965)引证为阔叶瓜馥木的张宏达1097、毛品一3915和5295、王孝等100017、高锡朋55422、陈少卿12648和156、曾怀德26659等标本,后又在网上查阅了纽约植物园标本馆F. petelotii Merr.的模式,认为毛品一3915、5295是F. petelotii Merr.在中国的新分布,现予以报道,并作了果的拉丁文补充描述.     

Discovery and synthesis of new immunosuppressive alkaloids from the stem of Fissistigma oldhamii (Hemsl.) Merr

Three new alkaloids (1-3) and twenty-one known compounds were isolated from the stem of Fissistigma oldhamii (Hemsl.) Merr. which was the ruler herb in an approved Traditional Chinese herbal formula used for treatment of rheumatoid arthritis in China and synthesis of one new immunosuppressive alkaloid was achieved. These compounds, including the crude extracts of this herb, exhibited strong activities in the inhibition of T and B cell proliferation.     

Bioassay-guided isolation of an alkaloid with antiangiogenic and antitumor activities from the extract of Fissistigma cavaleriei root

Fissistigma cavaleriei (Levl) Rehd (Annonaceae) is used as a folklore medicine for treatment of inflammation, arthritis, and tuberculosis by Miao people in China. In the present study, the antiangiogenic activity of F. cavaleriei was investigated. The chorioallantoic membrane of the fertilized hen's egg (CAM assay) was used to determine antiangiogenic activity of the plant extract. Compound (1), a compound with antiangiogenic activity, was isolated by bioassay-guided fractionation from F. cavaleriei for the first time. The structure of compound (1) was elucidated on the basis of spectroscopic methods. Colorimetric COX (ovine) inhibitor screening assay was used to determine its inhibitory effect on COX-1 and COX-2. MTT and Sulforhodamine B assays were used to investigate its cytotoxic effects on tumor cell lines. As a result, compound (1) showed a selectively inhibiting effect on COX-2 and could inhibit the growth of tumor cells in vitro. The antitumor activity of compound (1) was further confirmed by the observation that compound (1) administration significantly inhibited the growth of S-180 cells in mice. Moreover, compound (1) was able to enhance the antitumor activity of doxorubicin in the mice bearing with S-180 cells while combined with doxorubicin. In conclusion, compound (1) is a multi-target molecule and further experimental investigations are needed to determine whether it can be used as a lead molecule for tumor treatment.     

A novel flavonoid from Fissistigma cupreonitens, 5‑hydroxy‑7,8‑dimethoxyflavanone,competitively inhibited the efflux function of human P-glycoprotein and reversed cancer multi-drug resistance

BackgroundP-glycoprotein (P-gp) over-expression plays a vital role in not only systemic drug bioavailability but also cancer multi-drug resistance (MDR). Develop functional inhibitors of P-gp can conquer both problems.Purpose and study designThe aim of the present study was to research the P-gp modulating effects and MDR reversing ability of a novel flavonoid from Fissistigma cupreonitens, the underlying inhibitory mechanisms were further elucidated as well.MethodsCalcein-AM, rhodamine 123, and doxorubicin were fluorescent substrates for the evaluation of P-gp inhibitory function and detailed drug binding modes. Docking simulation was performed to reveal the in silico molecular bonding. ATPase assay and MDR1 shift assay were adopted to reveal the ATP consumption and conformational change of P-gp. The MDR reversing effects were demonstrated through cytotoxicity, cell cycle, and apoptosis analyses.Results5‑hydroxy‑7,8‑dimethoxyflavanone inhibited the efflux of rhodamine 123 and doxorubicin in a competitive manner, and increased the intracellular fluorescence of calcein at a concentration as low as 2.5 μg/ml. 5‑hydroxy‑7,8‑dimethoxyflavanone slightly changed P-gp's conformation and only stimulated ATPase at very high concentration (100 μg/ml). The docking results showed that 5‑hydroxy‑7,8‑dimethoxyflavanone and verapamil exhibited similar binding affinity to P-gp. The MDR reversing effects were prominent in the vincristine group, the reversal folds were 23.01 and 13.03 when combined with 10 μg/ml 5‑hydroxy‑7,8‑dimethoxyflavanone in the P-gp over-expressing cell line (ABCB1/Flp-In™-293) and MDR cancer cell line (KB/VIN), respectively.ConclusionThe present study demonstrated that 5‑hydroxy‑7,8‑dimethoxyflavanone was a novel effective flavonoid in the P-gp efflux inhibition and in vitro cancer MDR reversion.     

Potent inhibition of superoxide anion production in activated human neutrophils by isopedicin,a bioactive component of the Chinese medicinal herb Fissistigma oldhamii

Fissistigma oldhamii is widely used in traditional Chinese medicine to treat rheumatoid arthritis. Activation of neutrophils is a key feature of inflammatory diseases. Herein, the anti-inflammatory functions of isopedicin, a flavanone derived from F. oldhamii, and its underlying mechanisms were investigated in human neutrophils. Isopedicin potently and concentration-dependently inhibited superoxide anion (O₂^?) production in formyl-l-methionyl-l-leucyl-l-phenylalanine (FMLP)-activated human neutrophils with an IC₅₀ value of 0.34 ± 0.03 μM. Furthermore, isopedicin displayed no superoxide-scavenging ability, and it failed to alter subcellular NADPH oxidase activity. The inhibitory effect of isopedicin on O₂^? production was reversed by protein kinase A (PKA) inhibitors. Moreover, isopedicin increased cAMP formation and PKA activity in FMLP-activated human neutrophils, which occurred through the inhibition of phosphodiesterase (PDE) activity but not an increase in adenylate cyclase function. In addition, isopedicin reduced FMLP-induced phosphorylation of extracellular regulated kinase and c-Jun N-terminal kinase, which was reversed by the PKA inhibitor. In contrast, isopedicin failed to alter FMLP-induced phosphorylation of p38 mitogen-activated protein kinase and calcium mobilization. In summary, these results demonstrate that inhibition of O₂^? production in human neutrophils by isopedicin is associated with an elevation of cellular cAMP and activation of PKA through its inhibition of cAMP-specific PDE.     

7'-(3',4'-dihydroxyphenyl)-N-[(4-methoxyphenyl)ethyl]propenamide (Z23), an effective compound from the Chinese herb medicine Fissistigma oldhamii (Hemsl.) Merr, suppresses T cell-mediated immunity in vitro and in vivo

Fissistigma oldhamii (Hemsl.) Merr [F. oldhamii], a traditional Chinese herb medicine, is widely used for treating rheumatoid arthritis (RA) in China. Following bioactivity-guided isolation, a representative immunosuppressive compound with low cytotoxicity, 7'-(3',4'-dihydroxyphenyl)-N-[(4-methoxyphenyl)ethyl]propenamide (Z23), was been identified in this herb medicine. We investigated the immunosuppressive effects of Z23 on T cells in vitro and in vivo. The results showed that Z23 in a dose-dependent manner significantly inhibited the proliferation of splenocytes induced by concanavalin A (ConA) and by the mixed lymphocyte culture reaction (MLR), with half inhibitive concentration (IC(50)) values of 6.22 microM and 0.78 microM, respectively. Z23 also dose-dependently inhibited the proliferation and type 1 cytokine (IFN-gamma and IL-2) production of primary T cells stimulated by anti-CD3/CD28 mAbs, but did not affect IL-12 production by mouse peritoneal macrophages (pMphi) stimulated with LPS plus IFN-gamma in vitro. Administration of Z23 (6.25 mg/kg, 12.5 mg/kg, 25 mg/kg, i.p.) dose-dependently suppressed 2,4-dinitrofluorobenzene (DNFB)-induced delayed-type hypersensitivity (DTH) reactions. Furthermore, administration of Z23 (25 mg/kg, i.p.) significantly reduced the incidence and severity of type II bovine collagen (CII)-induced arthritis (CIA), which was associated with the inhibition of CII-specific T cell proliferation and type 1 cytokine (IFN-gamma and IL-2) production. In this study, we report that a representative immunosuppressive compound from F. oldhamii, Z23, effectively inhibits murine immune responses in vitro and in vivo, and that the immunosuppressive effects of Z23 might be attributed to suppression of T cell activation and function and Th1 type cytokine production.     

Mycotoxin production from fungi isolated from grapes

AIMS: In order to assess the potential for producing mycotoxins, fungi were isolated from wine producing grapes. METHODS AND RESULTS: The isolates were identified and Penicillium expansum, the most well recognized mycotoxin producer, was analysed for mycotoxin production by TLC. Many of the strains produced patulin and/or citrinin, often depending on whether they were grown on a grape or yeast extract sucrose media. CONCLUSION: Citrinin was produced by all strains grown in the yeast extract sucrose medium, but only one strain (from 51) was able to produce this compound in grape juice medium. Patulin was produced in the yeast extract medium by 20 strains and in grape juice medium by 33 strains. SIGNIFICANCE AND IMPACT OF THE STUDY: The presence of mycotoxins in wine producing grapes is discussed. Grapes contamination with patulin seems not to contribute to wine contamination, and no ochratoxin producing fungi was identified.     

Diterpenes derived from clerodanes from Pulicaria angustifolia

The investigation of Pulicaria angustifolia afforded, in addition to known triterpenes and caryophyllene epoxide, four methyl esters of diterpenes, all derived from clerodane. Three of them are derivatives of seco-nidoresedic acid. The structures were elucidated by spectroscopic methods.     

Chemiluminescence from an erythrocyte folic acid oxidase from normal individuals and from cancer patients

Folic acid oxidase from erythrocytes oxidatively cleaves folic acid at the C-9-N-10 bond to yield pterin-6-aldehyde and p-aminobenzoyl glutamic acid, with the concomitant generation of singlet oxygen. The emission from singlet oxygen is proportional to the enzyme activity. DABCO was used as a singlet oxygen emission enhancer to increase the sensitivity of the measurement. In general, pregnant women show high enzymatic activity, but the emission is strongly quenched by DABCO. This is contrary to normal and cancer cases in which an increase in the emission was observed. This effect is larger in cancer cases. These results are presented as a potential method for detecting physiological and pathological human conditions.