Nguyen Hai Dang

Two New Triterpene Glycosides from the Vietnamese Sea CucumberHolothuria scabra

Two new triterpene glycosides, namely holothurin A3 (1) and A4 (2) were isolated from the methanol extract of the sea cucumber,Holothuria scabra, with their structures elucidated from the spectroscopic evidence (1D NMR, 2D NMR, ESI-MS and HRESI-MS). Compounds1 and2 were found to be strongly cytotoxic to both cancer cell lines, KB and Hep-G2, with 50% inhibitory concentrations (IC50) of 0.87 and 0.32 μg/mL (for compound 1) and of 1.12 and 0.57 μg/mL (for compound2), respectively.

Phenolic glycosides from Alangium salviifolium leaves with inhibitory activity on LPS-induced NO, PGE2, and TNF-α production

Three new phenolic glycosides, salviifosides A-C (13), and three known compounds salicin (4), kaempferol (5), and kaempferol 3-O-beta-d-glucopyranoside (6) were isolated from the leaves of Alangium salviifolium (L.f.) Wangerin (Alangiaceae). The structures of the new metabolites were determined on the basic of spectroscopic analyses including two dimensional NMR. The anti-inflammatory activities of new compounds (1-3) were investigated on lipopolysaccharide (LPS)-induced murine macrophage cells line, RAW 264.7. Salviifoside B (2) potentially inhibits the productions of nitric oxide (NO), prostaglandin E(2) (PGE(2)), and tumor necrosis factor-alpha (TNF-alpha).

7‐Methoxy‐(9H‐β‐Carbolin‐1‐il)‐(E)‐1‐Propenoic Acid, a β‐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‐β‐carbolin‐1‐il)‐(E)‐1‐propenoic acid (7‐MCPA), a β‐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. J. Cell. Biochem. 117: 659–670, 2016.

Alkaloids from roots of Stephania rotunda and their cholinesterase inhibitory activity.

In the course of screening plants used in folk medicine as memory enhancers, a 70% ethanolic extract of Stephania rotunda roots showed significant AChE inhibitory activity. Repeated column chromatography led to the isolation of a new protoberberine alkaloid, which we named stepharotudine (1), and seven known compounds (2-8). The chemical structures of the isolated compounds were elucidated based on extensive 1D and 2D NMR spectroscopic data. Compounds 1-8 were investigated in vitro for their anticholinesterase activity using a rat cortex AChE enzyme.

New cytotoxic benzopyrans from the leaves ofMallotus apelta

Two new benzopyrans 6-[1′-oxo-3′(R)-hydroxy-butyl]-5, 7-dimethoxy-2,2-dimethyl-2H-1-benzopyran (1) and 6-[1′-oxo-3′(R)-methoxy-butyl]-5,7-dimethoxy-2,2-dimethyl-2H-1-benzopyran (2) were isolated from the leaves ofMallotus apelta Muell.-Arg., (Euphorbiaceae). Their chemical structures were elucidated by spectroscopic analyses, especially by 1D- 2D-NMR and MS spectra. Compound1 was found to have strong cytotoxic effect against two human cancer cell lines as human hepatocellular carcinoma (Hep-2, IC50: 0.49 μg/mL) and rhabdosarcoma (RD, IC50: 0.54 μg/mL), while compound2 showed moderate activity against Hep-2 cell line (IC50, 4.22μg/mL), byin vitro assay.

Two new C-Glucosyl benzoic acids and flavonoids from mallotus nanus and their antioxidant activity

Two new 2-C-β-D-glucopyranosyl benzoic acid derivatives named mallonanosides A (1) and B (2) were isolated from the methanolic extract of the leaves of Mallotus nanus along with five known flavonoids, kaempferin (3), juglanin (4), quercitrin (5), myricitrin (6), and rhoifolin (7). Their structures were established on the basis of spectral and chemical evidence. Their antioxidant activities were shown to depend on the number of hydroxyl groups, and the location and species of sugar moiety.

Anti-amnesic effect of alkaloid fraction from Lycopodiella cernua (L.) Pic. Serm. on scopolamine-induced memory impairment in mice.

Lycopodiella cernua (L.) Pic. Serm. (Licopodiaceae) has been used in Vietnamese folk medicine for treating central nervous system conditions. In this study, the alkaloid fraction from the methanol extract of this plant (VLC) was evaluated for in vitro acetylcholinesterase (AChE) inhibitory activity in cognition-relevant brain areas of mice. In in vivo study, the cognitive-enhancing effect of VLC on amnesic mice induced by scopolamine was investigated by assessing a passive avoidance and a Morris water maze test. VLC inhibited AChE activity in mouse frontal cortex, hippocampus and striatum with IC50 values of 26.7, 32.2 and 25.7μg/mL, respectively. Administration of VLC (10, 20, 50 and 100mg/kg, p.o.) significantly reversed cognitive impairments in mice by passive avoidance test. Treating with VLC (50mg/kg) reduced escape latencies in training trials and prolonged swimming times in the target quadrant during the probe trial in the water maze task (P<0.05). These results indicated that L. cernua originated from Vietnam has anti-cholinesterase activity and might be useful for the treatment of cognitive impairment.

Cytotoxic Steroids from the Vietnamese Soft Coral Sinularia conferta

Twelve steroids, including five new compounds 1-5, were isolated and structurally elucidated from a methanol extract of the Vietnamese soft coral Sinularia conferta. Their cytotoxic effects against three human cancer cell lines, lung carcinoma (A-549), cervical adenocarcinoma (HeLa), and pancreatic epithelioid carcinoma (PANC-1), were evaluated using 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) assays. Among isolated compounds, 10 exhibited potent cytotoxic effects on all three tested cell lines with IC50 values of 3.64±0.18, 19.34±0.42, and 1.78±0.69 µM, respectively.

New flavonoid and pentacyclic triterpene from Sesamum indicum leaves

Two new and one known compounds were isolated from the methanol extract of Sesamum indicum leaves. By means of spectroscopic methods, their structures were elucidated and identified to be 3-epibartogenic acid (1), kaempferol 3-O-[2-O-(trans-p-coumaroyl)-3-O-α-L-rhamnopyranosyl]-β-d-glucopyranoside (2) and epigallocatechin (3). Compound 1 and 3 strongly inhibited α-amylase with the IC50 values of 146.7 and 303.9 μM, respectively, in comparison with acarbose (IC50 124.0 μM).

Cytotoxic Activity of New Phenolic Compounds from Vietnamese Caesalpinia sappan

Two new phenolic compounds, caesalpiniaphenols G–H (1 and 2), were isolated from Vietnamese Caesalpinia sappan heartwood. The chemical structures were established mainly by extensive spectroscopic studies and chemical evidence. Compounds 1 and 2 showed potent inhibitory activity against HL-60 cancer cell lines with respective IC50 values of 16.7 and 22.5 µg/mL. Treating HL-60 cells with various concentrations of 1 resulted in growth inhibition and the induction of apoptosis.