Nguyen Hoai Nam

Pentacyclic triterpenoids from Mallotus apelta.

A new triterpene (1) and six known pentacyclic terpenoids (2-7) were isolated from the methanol extract of the dried leaves fromMallotus apelta. Based on the spectral and chemical evidence, their structures were determined to be 3α-hydroxyhop-22(29)-ene (1), hennadiol (2), friedelin (3), friedelanol (4), epifriedelanol (5), taraxerone (6), and epitaraxerol (7).

A new ursane-type triterpenoid glycoside from Centella asiatica leaves modulates the production of nitric oxide and secretion of TNF-α in activated RAW 264.7 cells.

One new ursane-type triterpenoid glycoside, asiaticoside G (1), five triterpenoids, asiaticoside (2), asiaticoside F (3), asiatic acid (4), quadranoside IV (5), and 2α,3β,6β-trihydroxyolean-12-en-28-oic acid 28-O-[α-L-rhamnopyranosyl-(1→4)-β-D-glucopyranosyl-(1→6)-β-D-glucopyranosyl] ester (6), and four flavonoids, kaempferol (7), quercetin (8), astragalin (9), and isoquercetin (10) were isolated from the leaves of Centella asiatica. Their chemical structures were elucidated by mass, 1D- and 2D-nuclear magnetic resonance (NMR) spectroscopy. The structure of new compound 1 was determined to be 2α,3β,23,30-tetrahydroxyurs-12-en-28-oic acid 28-O-[α-L-rhamnopyranosyl-(1→4)-β-D-glucopyranosyl-(1→6)-β-D-glucopyranosyl] ester. The anti-inflammatory activities of the isolated compounds were investigated on lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Asiaticoside G (1) potently inhibited the production of nitric oxide and tumor necrosis factor-α with inhibition rates of 77.3% and 69.0%, respectively, at the concentration of 100 μM.

Anti-inflammatory asterosaponins from the starfish Astropecten monacanthus.

Four new asterosaponins, astrosteriosides A-D (1-3 and 5), and two known compounds, psilasteroside (4) and marthasteroside B (6), were isolated from the MeOH extract of the edible Vietnamese starfish Astropecten monacanthus. Their structures were elucidated by chemical and spectroscopic methods including FTICRMS and 1D and 2D NMR experiments. The effects of the extracts and isolated compounds on pro-inflammatory cytokines were evaluated by measuring the production of IL-12 p40, IL-6, and TNF-α in LPS-stimulated bone marrow-derived dendritic cells. Compounds 1, 5, and 6 exhibited potent anti-inflammatory activity comparable to that of the positive control. Further studies are required to confirm efficacy in vivo and the mechanism of effects. Such potent anti-inflammatory activities render compounds 1, 5, and 6 important materials for further applications including complementary inflammation remedies and/or functional foods and nutraceuticals.

Inhibitors of osteoclastogenesis from Lawsonia inermis leaves

Ten phenolic compounds (1-10) were isolated from a methanol extract of Lawsonia inermis leaves including two new ones, lawsoniasides A (1) and B (2). Their structures were elucidated by spectroscopic methods (NMR and FTICRMS) in combination with acid hydrolysis and GC analyses. Compounds 4 and 5 showed a significant inhibition on receptor activator for nuclear factor-kappaB ligand-induced osteoclast formation in murine bone-marrow macrophages.

New anti-inflammatory cembranoid diterpenoids from the Vietnamese soft coral Lobophytum crassum.

Four new cembranoid diterpenes lobocrasols A-D (1-4), were isolated from the methanol extract of the soft coral Lobophytum crassum. Their structures were elucidated by spectroscopic analysis and by comparison of the spectroscopic data with those of similar compounds previously reported in literature. The anti-inflammatory effects of isolated compounds were evaluated using NF-κB luciferase and reverse transcription polymerase chain reaction (RT-PCR). Compounds 1 and 2 significantly inhibited TNFα-induced NF-κB transcriptional activity in HepG2 cells in a dose-dependent manner, with IC50 values of 6.30±0.42 and 6.63±0.11μM, respectively. Furthermore, the transcriptional inhibition of these compounds was confirmed by a decrease in cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) gene expression levels in HepG2 cells.

Anti-inflammatory norditerpenoids from the soft coral Sinularia maxima

Chemical investigation of the soft coral Sinularia maxima resulted in the isolation of seven norditerpenoids, including two new compounds, 12-hydroxy-scabrolide A (2) and 13-epi-scabrolide C (6). The structures of the isolated compounds were elucidated based on extensive spectroscopic evidence including Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) and both one- and two-dimensional nuclear magnetic resonance (1D and 2D NMR, respectively), in comparison with reported data. Compound 6 potently inhibited IL-12 and IL-6 production in LPS-stimulated bone marrow derived dendritic (BMDCs) with IC(50) values of 5.30 ± 0.21 and 13.12 ± 0.64 μM, respectively. Compound 1 exhibited moderate inhibitory activity against IL-12 and IL-6 production with IC(50) values of 23.52 ± 1.37 and 69.85 ± 4.11 μM, respectively.

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.

Anti-Inflammatory Components of the Starfish Astropecten polyacanthus

Inflammation is important in biomedical research, because it plays a key role in inflammatory diseases including rheumatoid arthritis and other forms of arthritis, diabetes, heart disease, irritable bowel syndrome, Alzheimer’s disease, Parkinson’s disease, allergies, asthma, and even cancer. In the present study, we describe the inhibitory effect of crude extracts and steroids isolated from the starfish Astropecten polyacanthus on pro-inflammatory cytokine (Interleukin-12 (IL-12) p40, interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α)) production in lipopolysaccharide (LPS)-stimulated bone marrow-derived dendritic cells (BMDCs). Among those tested, compounds 5 and 7 showed potent inhibitory effects on the production of all three pro-inflammatory cytokines with IC50 values ranging from 1.82 ± 0.11 to 7.00 ± 0.16 μM. Potent inhibitory activities were also observed for compound 1 on the production of IL-12 p40 and IL-6 with values of 3.96 ± 0.12 and 4.07 ± 0.13 μM, respectively, and for compounds 3 and 4 on the production of IL-12 p40 with values of 6.55 ± 0.18 and 5.06 ± 0.16 μM, respectively. Moreover, compounds 2 (IC50 = 34.86 ± 0.31 μM) and 6 (IC50 = 79.05 ± 2.05 μM) exhibited moderate inhibitory effects on the production of IL-12 p40, whereas compounds 3 (IC50 = 22.80 ± 0.21 μM) and 4 (IC50 = 16.73 ± 0.25 μM) moderately inhibited the production of TNF-α and IL-6, respectively.

Rat intestinal sucrase inhibition of constituents from the roots of Rosa rugosa Thunb.

A new octanordammarane triterpene, 3β,15α-dihydroxymansumbinol (1) and a novel A-ring contracted oleanane triterpenoid, 2-formyl-(A)1-19α-hydroxy-1-norolean-2,12-dien-28-oic acid (2) were isolated from the roots extract of Rosa rugosa along with fifteen known compounds (3-17). Their structures were elucidated by extensive spectroscopic analysis, including 1D and 2D NMR, and FTICRMS. The MeOH extract, as well as CH2Cl2 and EtOAc fractions at a concentration of 0.5mg/mL showed potent sucrase inhibitory activity, with inhibition percentage values of 84.67±5.37%, 87.50±2.78%, and 81.91±2.90%, respectively. In addition, compounds 7-13 (1.0 mM) showed potent sucrase inhibitory activity (61.88±3.19% to 84.70±3.07% inhibition), which was comparable to that of the positive control, acarbose, with an inhibition percentage value of 50.96±2.97%. Compounds 1, 2, 4, and 14-17 showed moderate and/or weak inhibitory activities at the same concentration. The α-glucosidase inhibitory activities of the extracts and purified compounds may provide a novel opportunity to develop a new class of antidiabetic agents.

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.