Nguyen Thi Thanh Ngan

Inhibition of TNF-α-mediated NF-κB Transcriptional Activity in HepG2 Cells by Dammarane-type Saponins from Panax ginseng Leaves

Panax ginseng (PG) is a globally utilized medicinal herb. The medicinal effects of PG are primarily attributable to ginsenosides located in the root and leaf. The leaves of PG are known to be rich in various bioactive ginsenosides, and the therapeutic effects of ginseng extract and ginsenosides have been associated with immunomodulatory and anti-inflammatory activities. We examined the effect of PG leaf extract and the isolated ginsenosides, on nuclear factor (NF)-κB transcriptional activity and target gene expression by applying a luciferase assay and reverse transcription polymerase chain reaction in tumor necrosis factor (TNF)-α-treated hepatocarcinoma HepG2 cells. Air-dried PG leaf extract inhibited TNF-α-induced NF-κB transcription activity and NF-κB-dependent cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) gene expression more efficiently than the steamed extract. Of the 10 ginsenosides isolated from PG leaves, Rd and Km most significantly inhibited activity in a dose-dependent manner, with IC50 values of 12.05±0.82 and 8.84±0.99 μM, respectively. Furthermore, the ginsenosides Rd and Km inhibited the TNF-α-induced expression levels of the COX-2 and iNOS gene in HepG2 cells. Air-dried leaf extracts and their chemical components, ginsenoside Rd and Km, are involved in the suppression of TNF-α-induced NF-κB activation and NF-κB-dependent iNOS and COX-2 gene expression. Consequently, air-dried leaf extract from PG, and the purified ginsenosides, have therapeutic potential as anti-inflammatory.

Cytotoxic and anti-inflammatory cembranoids from the Vietnamese soft coral Lobophytum laevigatum

Four new cembranoids, namely laevigatol A-D (1-4), and six known metabolites (5-10), were isolated from the Vietnamese soft coral Lobophytum laevigatum. The structures of these compounds were elucidated by extensive spectroscopic analyses, and the absolute stereochemistry of 1 was determined using the modified Moshers method. Compounds 5, and 7-10 exhibited cytotoxic activity against selected human cancer cell lines. Compounds 1, 2, 8, and 9 showed dose-dependent inhibitory effects on the TNFα-induced NF-κB transcriptional activity in Hep-G2 cells. Moreover, compounds 1, 2, 8, and 9 significantly inhibited the induction of COX-2 and iNOS mRNA dose-dependently, indicating that these compounds attenuated the synthesis of these transcripts at the transcriptional level.

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 Triterpenoid Saponins from the Stem Bark of Kalopanax pictus

Five new compounds, 16,23,29-trihydroxy-3-oxo-olean-12-en-28-oic acid (1), 4,23,29-trihydroxy-3,4-seco-olean-12-en-3-oate-28-oic acid (2), 3β,6β,23-trihydroxyolean-12-en-28-oic acid 28-O-β-D-glucopyranoside (3), 3-O-[2,3-di-O-acetyl-α-L-arabinopyranosyl]hederagenin 28-O-α-L-rhamnopyranosyl-(1→4)-β-D-glucopyranosyl-(1→6)-β-D-glucopyranoside (4), and 3-O-[3,4-di-O-acetyl-α-L-arabinopyranosyl]hederagenin 28-O-α-L-rhamnopyranosyl-(1→4)-β-D-glucopyranosyl-(1→6)-β-D-glucopyranoside (5), as well as 10 known compounds (6-15), were isolated from the stem bark of Kalopanax pictus. Compounds 1-5 and 7-14 inhibited TNFα-induced NF-κB transcriptional activity in HepG2 cells in a dose-dependent manner, with IC50 values ranging from 0.6 to 16.4 μM. Furthermore, the transcriptional inhibitory function of these compounds was confirmed on the basis of decreases in COX-2 and iNOS gene expression in HepG2 cells. The structure-activity relationship of the compounds with respect to anti-inflammatory activity is also discussed.

Inhibition of Nuclear Transcription Factor-κB and Activation of Peroxisome Proliferator-Activated Receptors in HepG2 Cells by Cucurbitane-Type Triterpene Glycosides from Momordica charantia

Momordica charantia is used to treat various diseases, including inflammatory conditions. Previous reports indicated that the extract of this plant inhibits activation of nuclear transcription factor-κB (NF-κB) but activates peroxisome proliferator-activated receptor (PPAR). Additionally, cucurbitane-type triterpene glycosides are the main bioactive components of the fruit of M. charantia. Therefore, we investigated the anti-inflammatory activity of 17 cucurbitane-type triterpene glycosides (1-17) isolated from this plant. Their inhibition of NF-κB and activation of PPAR activities in HepG2 cells were measured using luciferase reporter and PPAR subtype transactivation assays. Compounds 6 and 8 were found to inhibit NF-κB activation stimulated by tumor necrosis factor-α (TNFα) in a dose-dependent manner. With 50% inhibition concentration (IC(50)) values of 0.4 μM, compounds 6 and 8 were more potent inhibitors than the positive control, sulfasalazine (IC(50)=0.9 μM). Compounds 4, 6, and 8 also inhibited TNFα-induced expressions of inducible nitric oxide synthase and cyclooxygenase-2 mRNA. However, only compound 13 significantly increased PPARγ transactivation.

Protein Tyrosine Phosphatase 1B Inhibitors from the Roots of Cudrania tricuspidata

A chemical investigation of the methanol extract from the roots of Cudrania tricuspidata resulted in the isolation of 16 compounds, including prenylated xanthones 1–9 and flavonoids 10–16. Their structures were identified by NMR spectroscopy and mass spectrometry and comparisons with published data. Compounds 1–9 and 13–16 significantly inhibited PTP1B activity in a dose dependent manner, with IC50 values ranging from 1.9–13.6 μM. Prenylated xanthones showed stronger PTP1B inhibitory effects than the flavonoids, suggesting that they may be promising targets for the future discovery of novel PTP1B inhibitors. Furthermore, kinetic analyses indicated that compounds 1 and 13 inhibited PTP1B in a noncompetitive manner; therefore, they may be potential lead compounds in the development of anti-obesity and -diabetic agents.

Anti‐Inflammatory and PPAR Transactivational Properties of Flavonoids from the Roots of Sophora flavescens

Anti‐inflammatory and peroxisome proliferator‐activated receptors (PPARs) transactivational effects of nine compounds (1 − 9) from the roots of Sophora flavescens were evaluated using NF‐κB‐luciferase, reverse transcriptase polymerase chain reaction, peroxisome proliferator response element (PPRE)‐luciferase, and GAL‐4‐PPAR chimera assays. Compounds 4 and 8 significantly inhibited TNFα‐induced NF‐κB transcriptional activity in HepG2 cells in a dose‐dependent manner, with IC50 values of 4.0 and 4.4 μM, respectively. Furthermore, the transcriptional inhibitory function of these compounds was confirmed by a decrease in cyclooxgenase 2 and inducible nitric oxide synthase gene expression levels in HepG2 cells. Compounds 1, 3, 5, 6, 8, and 9 significantly activated the transcription of PPARs in a dose‐dependent manner, with EC50 values ranging from 1.1 to 13.0 μM. Compounds 1, 3, 5, 6, 8, and 9 exhibited dose‐dependent PPARα transactivational activity, with EC50 values in a range of 0.9 − 16.0 μM. Compounds 1, 3, 8, and 9 also significantly upregulated PPARγ activity in a dose‐dependent manner, with EC50 values of 10.5, 6.6, 15.7, and 1.6 μM, whereas compounds 1, 8, and 9 demonstrated transactivational PPARβ(δ) effects with EC50 values of 11.4, 10.3, and 1.5 μM, respectively. These results provide a scientific rationale for the use of the roots of S. flavescens and warrant further studies to develop new agents for the prevention and treatment of inflammatory and metabolic diseases. Copyright

Effect of triterpenes and triterpene saponins from the stem bark of Kalopanax pictus on the transactivational activities of three PPAR subtypes.

Kalopanax pictus (Araliaceae) is a deciduous tree that grows in East Asian countries. Its stem bark and leaves have been used in traditional medicine to treat rheumatic arthritis, neurotic pain, and diabetes mellitus. A phytochemical study on a methanol extract of the stem bark of K. pictus resulted in the isolation of three new compounds, 6β,16α-dihydroxy-hederagenin 3-O-β-D-glucuronopyranoside (1), 3-O-β-D-glucuronopyranosyl-28-O-β-D-glucopyranosyl-6β,16α-dihydroxy-oleanolic acid (2), and 3-O-β-D-galactopyranosyl(1→3)-α-L-arabinopyranosyl hederagenin 28-O-β-D-glucopyranosyl-(1→6)-β-D-glucopyranosyl ester (3), along with eight known compounds (4-11). Their structures were established on the basis of chemical and spectroscopic methods (IR, 1D and 2D NMR, and HRESITOFMS). Compounds 1-6 and 8-10 upregulated PPARs transcriptional activity in a dose-dependent manner in HepG2 cells, with EC(50) values in the range 0.20-15.5 μM. Moreover, the specific PPAR transactivational effects of compounds 1-6 and 8-10 on separate PPAR subtypes, PPARα, -γ, and -β(δ) were further investigated. Compounds 4, 5, 8, and 10 showed significant PPARα transactivational activity, with EC(50) values of 7.8, 8.0, 10.3, and 17.3 μM, respectively. Compounds 2, 4, 6, and 8-10 exhibited PPARγ dose-dependent transactivational activity, with EC(50) values of 14.7, 15.5, 14.8, 10.9, 17.1, and 16.3 μM, whereas compounds 8 and 10 significantly upregulated PPARβ(δ) transcriptional activity, with EC(50) values of 15.7 and 17.7 μM, respectively.

A new iridoid and effect on the rat aortic vascular smooth muscle cell proliferation of isolated compounds from Buddleja officinalis

A new iridoid, named methylscutelloside (1) together with 19 known compounds belonging to the iridoids (2-4), monoterpenoids (5), flavonoids (6-8), triterpenoids (9-14), and phenylethanoids (15-20) were isolated from the flowers of Buddleja officinalis. Their chemical structures were elucidated on the basis of physicochemical properties, and by spectroscopic methods including 1D, 2D NMR, and MS. All isolated compounds were tested in vitro for their effects on the proliferation of rat aortic vascular smooth muscle cells (VSMCs). Among them, iridoids were the main active components and showed significant inhibitory effects on PDGF-BB-induced proliferation in rat aortic VSMCs.

Cytotoxic and PPARs transcriptional activities of sterols from the Vietnamese soft coral Lobophytum laevigatum

A new unusual sterol, named lobophytosterol (1), and five known metabolites (2-6) were isolated from the methanol extract of the soft coral Lobophytum laevigatum. Their chemical structures were elucidated by extensive spectroscopic analysis and comparison with those reported in the literature. The absolute stereochemistry of 1 was determined using a modified Moshers method. Compounds 1-3 showed cytotoxic activity against HCT-116 cells with IC(50) values of 3.2, 6.9 and 18.1 μM, respectively. Compound 1 additionally displayed cytotoxic effects on A549 and HL-60 cells with IC(50) values of 4.5 and 5.6 μM, respectively. Treatment of these cells with compound 1 resulted in an induction of apoptosis evident by chromatin condensation in treated cells. Besides, compounds 2, 4, and 6 significantly upregulated PPARs transcriptional activity dose-dependently in Hep-G2 cells. Taken together, these data suggest that compound 1 might inhibit the growth of the cancer cells by the induction of apoptosis, and compounds 2, 4, and 6 might act as specific agonists for PPARα, PPARδ, and PPARγ and may therefore regulate cellular glucose, lipid, and cholesterol metabolism.