In vitro and in silico cytotoxic activities of triterpenoids from the leaves of Aralia dasyphylla Miq. and the assessment of their ADMET properties.

From the methanol extract of the leaves of Aralia dasyphylla Miq. (Araliaceae), ten triterpenoids including five ursane-type triterpenoids, ursolic acid (1), 3-O-α-l-arabinopyranosyl ursolic acid (2), ursolic acid 28-O-ß-D-glucopyranosyl ester (3), 3-O-[ß-D-glucopyranosyl (l→3)]-α-L-arabinopyranosyl ursolic acid (4), and matesaponin 1 (5), and five oleanane-type triterpenoids, elatoside E (6), elatoside F (7), 3-O-[ß-D-glucopyranosyl (l→3)]-α-L-arabinopyranosyl oleanolic acid (8), 3-O-α-L-arabinopyranosyl oleanolic acid (9) and oleanolic acid 28-O-ß-D-glucopyranosyl ester (10) were isolated. Their structures were elucidated based on 1D-, 2D-NMR and ESI-MS spectra as well as by comparison with those reported in the literature. All isolated compounds were evaluated in vitro for their cytotoxic activities against three human cancer cell lines (HepG2, LU-1 and RD) and in silico by molecular docking studies on human glucose transporter 1 (hGLUT1) protein. The triterpenoids 2, 4, 6, 8 and 9 exhibited good growth inhibition of HepG2 and LU-1 cancer cell lines with IC50 values in the range 1.76 - 7.21 (µM). The oleanane type triterpenoid 8 was the highest cytotoxic compound to inhibit all the tested cancer cell lines with IC50 values of 2.73 ± 0.12, 1.76 ± 0.11, 2.63 ± 0.10 µM, respectively. The in silico molecular docking study results showed that compounds 4 and 6 had the highest binding affinity. Compounds 1-10 were evaluated for their in silico ADMET of absorption, distribution, metabolism, excretion and oral toxicity parameters. Compounds 6, 8, 9 and 10 from A. dasyphylla are potential hGLUT1 inhibitors and worth of further investigation for the prevention or treatment of diabetes and cancer.Communicated by Ramaswamy H. Sarma.

Dammarane triterpenes and phytosterols from Dysoxylum tpongense Pierre and their anti-inflammatory activity against liver X receptors and NF-κB activation.

Dysoxylum tpongense Pierre (local name 'Huynh Dan Bap') belonging to family Meliaceae, is a tree (3-10 m height), distributed in the mountainous areas (ca. 1000 m a.s.l.) in North Vietnam. From the dichloromethane fraction of the methanol extract of the leaves and stems of this plant, six dammarane triterpenes, one furanoid diterpene together with three sterols were isolated. Evaluation of biological activities of isolated compounds showed that cabraleahydroxylactone (5), cabraleahydroxylactone 3-acetate (6), and stigmast-4-en-3-one (10) possessed an anti-inflammatory effect against Liver X receptor (LXR) activation in HepG2 cell line model with IC50 values of 20.29 ± 3.69, 24.32 ± 2.99, and 7.09 ± 0.97 (µM), respectively. While three other triterpenoid compounds aglinin C 3- acetate (1), aglinin C (2), and 24-epi-cabraleadiol (4) presented the most significant inhibitory effect against TNF-α induced NF-κB activation in HepG2 cell line in a dose-dependent manner with IC50 values of 12.45 ± 2.37, 23.32 ± 3.25, and 13.95 ± 1.57 µM, respectively. As stigmast-4-en-3-one (10), with structure closely similar to cholesterol, acted selectively on LXRs but not on NF-kB activation pathway, this suggests that stigmast-4-en-3-one (10) can be potentially applied as an agonist on LXR signaling pathway. Pathways LXRs-NF-κB-iNOS expression have a close relationship and play a crucial role in proceeding metabolic abnormalities like atherosclerosis, obesity, inflammation, etc. Thus, the findings showed that dammarane-type triterpenoids from D. tpongense are worthy of further investigation for potential LXR agonists and potent anti-atherogenic agents against atherosclerotic lesion progression.

Identification of Soluble Epoxide Hydrolase Inhibitors from the Seeds of Passiflora edulis Cultivated in Vietnam

Soluble epoxide hydrolases (sEH) are enzymes present in all living organisms, metabolize epoxy fatty acids to 1,2-diols. sEH in the metabolism of polyunsaturated fatty acids plays a key role in inflammation. In addition, the endogenous lipid mediators in cardiovascular disease are also broken down to diols by the action of sEH that enhanced cardiovascular protection. In this study, sEH inhibitory guided fractionation led to the isolation of five phenolic compounds trans-resveratrol (1), trans-piceatannol (2), sulfuretin (3), (+)-balanophonin (4), and cassigarol E (5) from the ethanol extract of the seeds of Passiflora edulis Sims cultivated in Vietnam. The chemical structures of isolated compounds were determined by the interpretation of NMR spectral data, mass spectra, and comparison with data from the literature. The soluble epoxide hydrolase (sEH) inhibitory activity of isolated compounds was evaluated. Among them, trans-piceatannol (2) showed the most potent inhibitory activity on sEH with an IC₅₀ value of 3.4 µM. This study marks the first time that sulfuretin (3) was isolated from Passiflora edulis as well as (+)-balanophonin (4), and cassigarol E (5) were isolated from Passiflora genus.