Identification and nitric oxide production inhibitory activity of phenolic derivatives from the trunks of Gnetum latifolium.

Phytochemical investigation of the trunks from Gnetum latifolium led to the isolation of a novel phenolic glucoside, 2E-2,4-di-(3,4-dihydroxyphenyl)but-2-en-1-yl-O-ß-D-glucopyranoside (1), along with five known stilbene derivatives (2-6). Their structures were determined mainly using high-resolution electrospray ionisation mass spectrometry and nuclear magnetic resonance spectroscopic analyses, followed by comparisons of observed spectral data with reported values. The novel compound 1 in G. latifolium was found to be useful as a chemotaxonomic marker. Biological evaluation revealed that compound 6 had remarkable inhibitory effects on nitric oxide production, with a half-maximal inhibitory concentration (IC50) value of 4.85 ± 0.20 µM, which was much higher than that of the positive control dexamethasone (IC50 = 14.20 ± 0.54 µM).

Oleanane-type triterpenoid sulphates, two new α-glucosidase inhibitors from Elaeocarpus hainanensis.

In connection with our interest in the phytochemical investigation of Elaeocarpus hainanensis Oliv. (Elaeocarpaceae) growing in Vietnam, two new sulphated oleanane triterpenes were obtained herein and structurally identified. Based on the combination of the extensive 1D-, 2D NMR and HR ESI MS spectroscopic data analysis, their chemical structures have been elucidated as 1α,3ß-dihydroxy-olean-18-ene 1-sulphate (1) and 1α,3ß-dihydroxy-olean-12-ene 1-sulphate (2). Notably, compounds 1 and 2 are corroborating the proposition that triterpenoid sulphates serve as chemosystematic markers of the Elaeocarpus genus. Additionally, all these two new compounds 1 and 2 strongly inhibited α-glucosidase in vitro with the respective IC50 values of 3.81 ± 0.33 µM and 21.27 ± 0.48 µM, which were significantly better than that obtained from positive control, acarbose (IC50 247.73 ± 11.85 µM).

Acetylcholinesterase inhibitory activities of some flavonoids from the root bark of Pinus krempfii Lecomte: in vitro and in silico study.

From the root bark of Pinus krempfii Lecomte, four flavonoids were isolated and evaluated for their inhibitory activities against AChE and BChE enzymes in vitro and in silico. Tectochrysin (1) was found to inhibit AChE with an IC50 value of 33.69 ± 2.80 µM. The docking study results also showed agreement with the in vitro test results. All four compounds also showed the best binding affinity for the AChE enzyme, characterised by binding energy (ΔG) values as low as -8.1 to -9.3 kcal/mol, in which, the compound tectochrysin had the best binding affinity for the AChE protein with a ΔG value of -9.329 kcal/mol. Tectochrysin (1) was also bound to the amino acid Phe295 of AChE with a bond length of 2.8 Å, similar to the control dihydrotanshinone-I. Galangin (2) also showed its in vitro inhibitory activity against BChE with an IC50 value of 82.21 ± 2.70 µM. In silico, it also had the best binding energy value of -9.072 kcal/mol with BChE and formed hydrogen bonds with the His438 (2.85 Å) residues of BChE like the positive control (tacrine). The steered molecular dynamics (SMD) simulation results of these two complexes revealed a mechanistic insight that the protein-ligand complexes showed stable trajectories throughout the 20 and 150 ns simulations. Moreover, the drug likeliness suggested that both flavonoids (1 and 2) were expected to be drug-like and have an LD50 toxicity level of 5. This study has contributed new results for drug discovery and the development of substances with neuroprotective effects, especially for the treatment of Alzheimer's disease.Communicated by Ramaswamy H. Sarma.

Two new norlignans from the aerial parts of Pouzolzia sanguinea (Blume) Merr.

Two new norlignans, pouzolignan N (1) and pouzolignan O (2), together with five known norlignans, pouzolignan F (3), pouzolignan G (4), pouzolignan H (5), pouzolignan L (6), and gnetifolin F (7) were isolated from the aerial parts of Pouzolzia sanguinea (Blume) Merr. Their chemical structures were elucidated via HR-ESI-MS and NMR spectroscopic methods. Absolute configurations at stereocenters were confirmed by comparisons of CD spectra with those of TD-DFT calculations. Compounds 1-6 exhibited chemical structures unique to Pouzolzia species. At a concentration of 30 µM, compounds 1-7 exhibited weak cytotoxic activity toward CAL27 and MDA-MB-231 cell lines (cell viability from 65.3 ± 0.86 to 98.8 ± 1.23%). They also inhibited anoctamin-1 activity with inhibitory rates from 8.1 ± 0.87 to 24.3 ± 1.41%.

Predominant HLA Alleles and Haplotypes in Mild Adverse Drug Reactions Caused by Allopurinol in Vietnamese Patients with Gout.

Allopurinol (ALP) is commonly used as a drug for gout treatment. However, ALP is known to cause cutaneous adverse reactions (CARs) in patients. The HLA-B*58:01 allele is considered a biomarker of severe CAR (SCAR) in patients with gout, with symptoms of Stevens Johnson syndrome, and with toxic epidermal necrolysis. However, in patients with gout and mild cutaneous adverse drug reactions (MCARs), the role of HLA-allele polymorphisms has not been thoroughly investigated. In this study, 50 samples from ALP-tolerant patients and ALP-induced MCARs patients were genotyped in order to examine the polymorphisms of their HLA-A and HLA-B alleles. Our results showed that the frequencies of HLA-A*02:01/HLA-A*24:02 and HLA-A*02:01/HLA-A*29:01, the dual haplotypes in HLA-A, in patients with ALP-induced MCARs were relatively high, at 33.3% (7/21), which was HLA-B*58:01-independent, while the frequency of these dual haplotypes in the HLA-A locus in ALP-tolerant patients was only 3.45% (1/29). The HLA-B*58:01 allele was detected in 38% (8/21) of patients with ALP-induced MCARs, and in 3.45% (1/29) of ALP-tolerant patients. Notably, although HLA-B*58:01 may be a cause for the occurrence of MCARs in patients with gout, this correlation was not as strong as that previously reported in patients with SCAR. In conclusion, in addition to the HLA-B*58:01 allele, the presence of the dual haplotypes of HLA-A*02:01/HLA-A*24:02 and/or HLA-A*02:01/HLA-A*29:01 in the HLA-A locus may also play an important role in the appearance of ALP-induced MCARs in the Vietnamese population. The obtained primary data may contribute to the development of suitable treatments for patients with gout not only in Vietnam but also in other Asian countries.

New phenolics from Dianella ensifolia.

Phytochemical investigation and chromatographic separation of extracts from the aerial parts of Dianella ensifolia (L.) DC. (synonym Dianella nemorosa Lam. Ex. Schiler f.) led to the isolation of 10 compounds, the structures of which were determined by HR-ESI-MS and 1 D- and 2 D-NMR spectroscopies, and by comparisons with published studies. Among the isolated compounds were three flavans, a biflavan, a biflavone, a tetralone, a naphthalen glycoside, an aromatic compound, and two steroids. Six of these were known chemicals, while three were identified as new compounds: 7-acetyl-4R,8-dihydroxy-6-methyl-1-tetralone, 2(S),2',4'-dihydroxy-7-methoxyflavan, and diaensi-biflavan. 2(S),7,4'-dimethoxy flavan was obtained for the first time as a natural product.

Anti-proliferative diterpenes from Dacrycarpus imbricatus.

A new diterpene, cassipouryl hexadecanoate (2), in addition to the cassipourol (1) and four terpenes (3-6) were isolated from the twigs and leaves of Dacrycarpus imbricatus (Blume) de Laub. The structures of the two monocyclic diterpenes (1, 2), were elucidated on the basic of 1D and 2D NMR spectroscopic data and compared with the literature. These two monocyclic diterpenes (1, 2) were tested for their anti-proliferative activity on acute myeloid leukemia (OCI-AML) cells. The results showed that 1 had significantly anti-proliferative activity whereas 2 was weakly active.

Isolation, characterisation and biological evaluation of a phenoxazine, a natural dyestuff isolated from leaves of Peristrophe bivalvis.

Peristrophe bivalvis (L.) Merr. (Acanthaceae) is a wild growing and cultivated plant used for dyeing of foods by the ethnic minorities of Vietnam. The major component of the colour aqueous extract (CAE) of its leaves was identified as peristrophine by spectral analysis, especially the 2D NMR spectra (HSQC, HMBC and NOESY). Considering the widespread utilisation of the decoction of this plant for food dyeing, we evaluated the acute oral toxicity of the CAE. Based on the results in an acute toxicity study in mice, the LD50 value of the CAE was determined as 9100 ± 290 mg kg(-1) body weight. Additionally, in vitro cytotoxic assay showed an inhibition of peristrophine against Hepatocellular carcinoma (HepG2, IC503.90 µg mL(-1)). CAE and peristrophine (1) have also been tested for their ability to affect the cell number of the OCI acute myeloid leukaemia cell line. CAE and peristrophine significantly decreased the OCI cell number at different concentrations and times of treatment.

Transcriptional regulatory networks associated with self-renewal and differentiation of neural stem cells.

Neural stem cells (NSCs) are self-renewing, multipotent cells that can generate neurons, astrocytes, and oligodendrocytes of the nervous system. NSCs have been extensively studied because they can be used to treat impaired cells and tissues or improve regenerative power of degenerating cells in neurodegenerative diseases or spinal cord injuries. For successful clinical applications of NSCs, it is essential to understand the mechanisms underlying self-renewal and differentiation of NSCs, which involve complex interplays among key factors including transcription factors, epigenetic control, microRNAs, and signaling pathways. Despite numerous studies on such factors, a holistic view of their interplays during neural development still remains elusive. In this review, we present recently identified potential regulatory factors and their targets by genomics and proteomics technologies and then integrate them into regulatory networks that describe their complex interplays to achieve self-renewal and differentiation of NSCs.

Chemical constituents of Acanthus ilicifolius L. and effect on osteoblastic MC3T3E1 cells.

A new coumaric acid derivative called acancifoliuside (1) and six known compounds as acteoside (2), isoacteoside (3), acanthaminoside (4), (+)-lyoniresinol 3a-O-beta-glucopyranoside (5), (-)-lyoniresinol (6), and alpha-amyrin (7), were isolated from the methanolic extract of the leaves of Acanthus ilicifolius L. (Acanthaceae). Their structures were determined by spectroscopic methods and a comparison with the spectral data reported in the literature. The effects of the compounds on the function of osteoblastic MC3T3-E1 cells were tested. Compounds 2, 3, and 5 (30 microM) increased the growth and differentiation of osteoblasts significantly (P<0.05), indicating that A. ilicifolius leaves may help prevent osteoporosis.