Plant-derived bioactive compounds produced by Streptomyces variabilis LCP18 associated with Litsea cubeba (Lour.) Pers as potential target to combat human pathogenic bacteria and human cancer cell lines.

To date, endophytic actinomycetes have been well-documented as great producers of novel antibiotics and important pharmaceutical leads. The present study aimed to evaluate potent bioactivities of metabolites synthesized by the strain LCP18 residing in the Vietnamese medicinal plant Litsea cubeba (Lour.) Pers towards human pathogenic bacteria and human cancer cell lines. Endophytic actinomycete strain LCP18 showed considerable inhibition against seven bacterial pathogens and three human tumor cell lines and was identified as species Streptomyces variabilis. Strain S. variabilis LCP18 was phenotypically resistant to fosfomycin, trimethoprim-sulfamethoxazole, dalacin, cefoxitin, rifampicin, and fusidic acid and harbored the two antibiotic biosynthetic genes such as PKS-II and NRPS. Further purification and structural elucidation of metabolites from the LCP18 extract revealed five plant-derived bioactive compounds including isopcrunetin, genistein, daidzein, syringic acid, and daucosterol. Among those, isoprunetin, genistein, and daidzein exhibited antibacterial activity against Salmonella typhimurium ATCC 14,028 and methicillin-resistant Staphylococcus epidermidis ATCC 35,984 with the MIC values ranging from 16 to 128 µg/ml. These plant-derived compounds also exhibited cytotoxic effects against human lung cancer cell line A549 with IC50 values of less than 46 µM. These findings indicated that endophytic S. variabilis LCP18 can be an alternative producer of plant-derived compounds which significantly show potential applications in combating bacterial infections and inhibition against lung cancer cell lines.

New dammarane-type triterpenoid glycosides from Gynostemma burmanicum.

The chemical composition of Gynostemma burmanicum King ex Chakrav. was investigated for the first time in this study. Nine dammarane glycosides (1‒9) were isolated from the EtOH extract of the aerial parts of G. burmanicum. Their structures were elucidated by 1D and 2D NMR spectroscopic interpretation as well as by chemical studies. The new compounds were 3ß,20S-dihydroxydammar-24-ene-3-O-ß-D-glucopyranosyl-20-O-[ß-D-xylopyranosyl-(1→6)-ß-D-glucopyranoside] (1), 3ß,12ß,20S-trihydroxydammar-24-ene-3-O-ß-D-xylopyranosyl-20-O-[ß-D-xylopyranosyl-(1→6)-ß-D-glucopyranoside] (2), and 12-oxo-3ß,20S-dihydroxydammar-24-ene-3-O-[ß-D-glucopyranosyl(1→2)-ß-D-glucopyranosyl]-20-O-[ß-D-xylopyranosyl-(1→6)-ß-D-glucopyranoside] (3).

New dianthramide and cinnamic ester glucosides from the roots of Aconitum carmichaelii.

Four new compounds N-salicyl-3-hydroxyanthranilic acid methyl ester (1), N-(2'-dehydroxysalicyl)-3-hydroxyanthranilic acid methyl ester (2), methyl-4-ß-D-allopyranosyl-ferulate (3), and methyl-4-ß-D-gulopyranosyl-cinnamate (4), along with six known compounds (5-10), were isolated from the roots of Aconitum carmichelii Debx. Their structures were elucidated on the basis of spectral data analysis, including 1D, 2D-NMR, and HR-ESI-MS. Compounds 1 and 2 showed the inhibition of nitric oxide (NO) production with IC50 values of 9.13 and 19.94 µM, respectively.

Anticyanobacterial phenolic constituents from the aerial parts of Eupatorium fortunei Turcz.

Four thymol derivatives and two phenolic compounds were isolated from the aerial parts of Eupatorium fortunei. The new structures were elucidated to be 7,8,9-trihydroxythymol (1), and 8,10-didehydro-7,9-dihydroxythymol (2) by means of MS and NMR analysis. The known compounds were identified as 8,9,10-trihydroxythymol (3), 10-acetoxy-8,9-dihydroxythymol (4), o-coumaric acid (5) and 4-(2-hydroxyethyl)benzaldehyde (6). Compound 3 showed strongest inhibitory effect on the growth of Microcystis aeruginosa in comparison with CuSO4.

Anti-inflammatory constituents from Psychotria prainii H. Lév.

One new and three known compounds were isolated from the ethanol extract of Psychotria prainii aerial parts. By means of spectroscopic methods, their structures were elucidated to be deacetylasperulosidic acid 6-ethyl ether (1), asperulosidic acid (2), asperuloside (3) and obtucarbamates C (4). The isolated compounds were evaluated for their inhibitory effect on NO production in LPS-stimulated RAW264.7 cells. Among them, compounds 2 and 4 exhibited strong effect with the IC50 values of 5.75 ± 0.85 and 6.92 ± 0.43 µM, respectively. This is the first report for the chemical composition and biological activity of P. prainii.

A new megastigmane sulphoglycoside and polyphenolic constituents from pericarps of Garcinia mangostana.

A megastigmane sulphoglycoside together with three phenolic compounds were isolated from the water-soluble fraction of the pericarps of Garcinia mangostana. The structure of the new compound was determined as 4-O-sulpho-ß-d-glucopyranosyl abscisate (1) by spectroscopic data. Proanthocyanidin A2 (2) showed potent α-glucosidase inhibitory and DPPH scavenging activities with IC50 values of 3.46 and 11.6 µM, respectively.

A new anti-inflammatory ß-carboline alkaloid from the hairy-root cultures of Eurycoma longifolia.

One new ß-carboline alkaloid 7-methoxy-(9H-ß-carbolin-1-il)-(E)-1-propenoic acid (1) together with 9-methoxycanthin-6-one (2) and 9-hydroxycanthin-6-one (3) were isolated from the hairy-root cultures of Eurycoma longifolia. The effects of these compounds on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW264.7 cells were investigated. Compound 1 strongly inhibited the production of NO while 2 and 3 having weak or inactive effect. Consistently, compound 1 decreased the expression of cyclooxygenase-2 and inducible nitric oxide synthase.

7-Methoxy-(9H-ß-Carbolin-1-il)-(E)-1-Propenoic Acid, a ß-Carboline Alkaloid From Eurycoma longifolia, Exhibits Anti-Inflammatory Effects by Activating the Nrf2/Heme Oxygenase-1 Pathway.

Eurycoma longifolia is an herbal medicinal plant popularly used in Southeast Asian countries. In the present study, we show that 7-methoxy-(9H-ß-carbolin-1-il)-(E)-1-propenoic acid (7-MCPA), a ß-carboline alkaloid isolated from E. longifolia, exerted anti-inflammatory effects by activating the nuclear factor-E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway. 7-MCPA inhibited lipopolysaccharide (LPS)-induced production of nitric oxide (NO), prostaglandin E2 (PGE2 ), and interleukin-6 (IL-6) in RAW264.7 cells and rescued C57BL/6 mice from LPS-induced lethality in vivo. LPS-induced expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and IL-6 was also significantly suppressed by treatment of 7-MCPA in RAW264.7 cells. 7-MCPA induced nuclear translocation of Nrf2 and increased transcription of its target genes, such as HO-1. Treating RAW264.7 cells with 7-MCPA increased the intracellular level of reactive oxygen species (ROS) and the phosphorylation level of p38 mitogen-activated protein kinase (MAPK); however, co-treatment with the antioxidant N-acetyl-cysteine (NAC) blocked 7-MCPA-induced p38 MAPK phosphorylation. Moreover, NAC or SB203580 (p38 MAPK inhibitor) blocked 7-MCPA-induced nuclear translocation of Nrf2, suggesting that 7-MCPA activated Nrf2 via a ROS-dependent p38 pathway. 7-MCPA induced HO-1 protein and mRNA expression and knockdown of Nrf2 with siRNA or SB203580 blocked 7-MCPA-mediated induction of HO-1 expression. Inhibiting Nrf2 or HO-1 abrogated the anti-inflammatory effects of 7-MCPA in LPS-stimulated RAW264.7 cells. We also demonstrated that 7-MCPA suppressed LPS-induced nuclear factor κB (NF-κB) activation. These results provide the first evidence that 7-MCPA exerts its anti-inflammatory effect by modulating the Nrf2 and NF-κB pathways and may be a potential Nrf2 activator to prevent or treat inflammatory diseases.

Characterization and evaluation of antimicrobial and cytotoxic effects of Streptomyces sp. HUST012 isolated from medicinal plant Dracaena cochinchinensis Lour.

A highly potent secondary metabolite producing endophytic strain, Streptomyces sp. HUST012 was isolated from the stems of the medicinal plant Dracaena cochinchinensis Lour. Strain HUST012 showed antimicrobial and antitumor activities which were significantly much higher than those of dragon's blood extracted from D. cochinchinensis Lour. On further analysis, the strain was found to produce two metabolites, SPE-B11.8 (elucidated to be a novel metabolite (Z)-tridec-7-ene-1,2,13-tricarboxylic acid) and SPE-B5.4 (elucidated as Actinomycin-D). The Minimum Inhibitory Concentration values of SPE-B11.8 against a set of test bacterial organisms (Methicillin-resistant Staphylococcus epidermis ATCC 35984, Methicillin-resistant Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, and Klebsiella pneumoniae ATCC 13883) ranged between 15.63 and 62.5 µg/ml while that for SPE-B5.4 ranged between 0.04 and 2.24 µg/ml. The compound SPE-B11.8 showed cytotoxic effect at 41.63 and 29.54 µg/ml IC 50-values against Hep G2 and MCF-7, respectively, while the compound SPE-B5.4 exhibited stronger activities against them at 0.23 and 0.18 µg/ml IC 50-values.

Cytotoxic constituents from the seeds of Vietnamese Caesalpinia sappan.

CONTEXT: Caesalpinia sappan Linn. (Leguminosae) has been used in folk medicines for the treatment of many diseases. The heartwood of this plant contains various phenolic components with interesting biological applications; however, the chemical and biological potentials of the seed of this plant have not been fully explored. OBJECTIVE: This study identified the cytotoxic activity of compounds from the seeds of C. sappan. MATERIALS AND METHODS: The methanol extract of the seed of C. sappan was suspended in H2O and then partitioned with CH2Cl2, EtOAc, and n-BuOH, successively. Diterpenoid compounds were isolated from the CH2Cl2-soluble fraction by silica gel column chromatography methods using organic solvents. The compound structures were determined by detailed analysis of NMR and MS spectral data. Cytotoxic activity was measured using a modified MTT assay against HL-60, HeLa, MCF-7, and LLC cancer cells. The activation of caspase-3 enzyme and western blotting assay were performed to confirm inhibitory mechanism of active compound. RESULTS: Five cassane-type diterpenoids were isolated and identified as phanginin I (1), phaginin A (2), phanginin D (3), phanginin H (4), and phanginin J (5). Compounds 1-4 showed effective inhibition against HL-60 cells with the IC50 values of 16.4 ± 1.5, 19.2 ± 2.0, 11.7 ± 1.6, and 22.5 ± 5.1 µM. Compounds 1-3 exhibited cytotoxic activity against HeLa cells with the IC50 values of 28.1 ± 3.6, 37.2 ± 3.4, and 22.7 ± 2.8 µM. Treatment of HL-60 cell lines with various concentrations of 3 (0-30 µM) resulted in the growth inhibition and induction of apoptosis. CONCLUSION: These findings demonstrate that compound 3 (phanginin D) is one of the main active components of the seed of C. sappan activating caspases-3 which contribute to apoptotic cell death.

Inhibitors of α-glucosidase and α-amylase from Cyperus rotundus.

CONTEXT: A methanol extract of Cyperus rotundus L. (Cyperaceae) rhizomes showed inhibitory activity against α-glucosidase and α-amylase, two enzymes involve in carbohydrate digestion. OBJECTIVE: Identification of compounds from C. rotundus rhizomes responsible for the inhibition of α-glucosidase and α-amylase. MATERIALS AND METHODS: Compounds were identified by a phytochemical investigation using combined chromatographic and spectroscopic methods. α-glucosidase and α-amylase inhibitory activities were evaluated by in vitro enzyme inhibition assays. RESULTS: A new (2RS,3SR)-3,4',5,6,7,8-hexahydroxyflavane (1), together with three known stilbene dimers cassigarol E (2), scirpusin A (3) and B (4) were isolated. Compound 2 inhibited both α-glucosidase and α-amylase activities while the flavane 1 only showed effect on α-amylase, and compounds 3 and 4 were active on α-glucosidase. All four compounds showed significant 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity. DISCUSSION: The inhibitory activities against α-amylase and α-glucosidase of the C. rotundus rhizomes were reported for the first time. Stilbene dimers are considered as potent inhibitors of α-glucosidase and promising antihyperglycemic agents. CONCLUSION: The isolated compounds may contribute to the antidiabetic property of C. rotundus.

Chemical compositions of essential oils from Xyloselinum vietnamense and X. selinum leonidii.

The chemical compositions of essential oils obtained by hydrodistillation from leaves and stems of Xyloselinum vietnamense and X. leonidii, two new species belonging to the family Apiaceae, were analyzed by GC-MS. The major components in both species were sabinene, alpha- and beta-pinene, myrcene, beta-phellandrene, (Z)-beta-ocimene, and terpinen-4-ol. The monoterpene sabinene was most abundant in the leaves of X. vietnamense (75.0%). These compounds might be considered as chemotaxonomic markers of Xyloselinum species. In the DPPH radical scavenging assay, all four essential oils showed moderate activity, while the water extracts exhibited stronger effects. The strong DPPH scavenging activity of the water residues of X. vietnamens and X. leonidii might be due to their phenolic components. This paper is the first report on the chemical compositions and antioxidant activity of X. vietnamens and X. leonidii.

Toxicity and anticancer effects of an extract from Selaginella tamariscina on a mice model.

The toxicity and antitumour effect of the ethanol extract of Selaginella tamariscina (STE), a plant widely used in folk medicine, were examined in a mice model. In the single-dose acute toxicity test, an oral administration of 10,000 mg kg(-1) STE did not cause any lethality. The sub-acute toxicity study showed that the treatment by 250, 1000 and 3000 mg kg(-1 )day(-1) for 30 continuous days did neither alter the body weights nor the haematological parameters in BALB/c mice. The anticancer effect of STE was evaluated in BALB/c mice inoculated with Lewis lung carcinoma cells. Oral administration of STE could not prevent the tumour formation but provided strong inhibition of tumour growth.

Anti-inflammatory effects of fatty acids isolated from Chromolaena odorata

OBJECTIVE@#To identify inhibitors of nitric oxide production and NF-κB activity from Chromolaena odorata (C. odorata).@*METHODS@#The compounds isolated from the aerial parts of C. odorata by bioassay-guided fractionation were investigated for their inhibitory effects on the NO production and NF-κB activity in LPS-stimulated RAW264.7 cells.@*RESULTS@#Six fatty acids (S)-coriolic acid (1), (S)-coriolic acid methyl ester (2), (S)-15,16-didehydrocoriolic acid (3), (S)-15,16-didehydrocoriolic acid methyl ester (4), linoleamide (5) and linolenamide (6) were isolated. All compounds inhibited the NO production at concentrations consistent with those required for NF-κB inhibition. Compound 2 was the most active with the IC(50) values of 5.22 and 5.73 μM. The addition of a double bond in the fatty chain decreased the inhibitory effects while the methyl esterification increased the activities.@*CONCLUSIONS@#The fatty acid components in C. odorata with NF-κB inhibitory activity could explain the anti-inflammation property of this plant in traditional medicine. This study could also contribute to the better use of C. odorata for human health care.

Aporphine alkaloids, clerodane diterpenes, and other constituents from Tinospora cordifolia.

Phytochemical investigation of the methanol extract of Tinospora cordifolia aerial parts led to the isolation of four new and seven known compounds. The structures of two new aporphine alkaloids, N-formylasimilobine 2-O-beta-D-glucopyranosyl-(1-->2)-beta-D-glucopyranoside (tinoscorside A, 1) and N-acetylasimilobine 2-O-beta-D-glucopyranosyl-(1-->2)-beta-D-glucopyranoside (tinoscorside B, 2), a new clerodane diterpene, tinoscorside C (3), and a new phenylpropanoid, sinapyl 4-O-beta-D-apiofuranosyl-(1-->6)-O-beta-D-glucopyranoside (tinoscorside D, 6) were determined by extensive spectroscopic methods including FTICR-MS and 1D and 2D NMR.