Anti-proliferative Effects of Pinocembrin Isolated From Anomianthus dulcis on Hepatocellular Carcinoma Cells.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most prevalent primary liver cancer. Anomianthus dulcis (Dunal) J.Sinclair (syn. Uvaria dulcis) has been used in Thai traditional medicine in various therapeutic indications. Phytochemical constituents of A. dulcis have been isolated and identified. However, their effects on liver cancer and the associated mechanisms have not been elucidated. METHODS: Dry flowers of A. dulcis were extracted using organic solvents, and chromatographic methods were used to purify the secondary metabolites. The chemical structures of the pure compounds were elucidated by analysis of spectroscopic data. Cytotoxicity against HCC cells was examined using SRB assay, and the effects on cell proliferation were determined using flow cytometry. The mechanisms underlying HCC inhibition were examined by molecular docking and verified by Western blot analysis. RESULTS: Among 3 purified flavonoids, pinocembrin, pinostrobin, and chrysin, and 1 indole alkaloid (3-farnesylindole), only pinocembrin showed inhibitory effects on the proliferation of 2 HCC cell lines, HepG2 and Li-7, whereas chrysin showed specific toxicity to HepG2. Pinocembrin was then selected for further study. Flow cytometric analyses revealed that pinocembrin arrested the HCC cell cycle at the G1 phase with a minimal effect on cell death induction. Pinocembrin exerted the suppression of STAT3, as shown by the molecular docking on STAT3 with a better binding affinity than stattic, a known STAT3 inhibitor. Pinocembrin also suppressed STAT3 phosphorylation at both Tyr705 and Ser727. Cell cycle regulatory proteins under the modulation of STAT3, namely cyclin D1, cyclin E, CDK4, and CDK6, are substantially suppressed in their expression levels. CONCLUSION: Pinocembrin extracted from A. dulcis exerted a significant growth inhibition on HCC cells via suppressing STAT3 signaling pathways and its downstream-regulated genes.

Acrotrione B, a Prenylated and Highly Oxidized Xanthenoid with Antibacterial and Anti-proliferative Activities from the Roots of Acronychia pedunculata.

A new prenylated xanthenoid with a highly oxidized core, acrotrione B (1: ), together with six previously reported acetophenones (2:  - 7: ), were isolated from the roots of Acronychia pedunculata. The structures of the isolated compounds were elucidated by thorough analysis of their 1D and 2D NMR spectroscopic data. The relative and absolute configurations of acrotrione B were determined by electronic circular dichroism (ECD) calculations. Acrotrione B is an unusual, oxidized xanthenoid with a cyclohexadienone core that has not been previously reported. It thus represents a new skeletal type within the xanthenoid class. Acrotrione B (1: ) exhibited anti-proliferative activity against Hela (IC50 = 16.0 µM) and A549 (IC50 = 16.3 µM) cell lines. 5'-Prenylacrovestone (4: ) and acrovestone (5: ) were even more potent with IC50 values of 5.1 µM and 0.77 µM, respectively, against Hela cells and 11.8 µM and 1.13 µM, respectively, against A549 cells. Moreover, acrotrione B (1: ) displayed moderate antibacterial activities against Staphylococcus aureus, Bacillus cereus, and Bacillus subtilis, with MIC values in the range of 16 - 64 µg/mL. Finally, acropyrone (6: ) showed a significant suppression of lipopolysaccharide (LPS) induced NO production in murine macrophage J774.A1 cells (IC50 = 8.9 µM).

Two new bioactive triterpenoids from the roots of Colubrina asiatica.

Two new ceanothane triterpenes, 3,7-O,O-dibenzoyl ceanothic acid methylester (1) and 3-O-acetyl-7-O-benzoyl ceanothic acid methylester (2), along with nine known compounds (3-11), were isolated from the roots of Colubrina asiatica. The isolated compounds were identified by spectroscopic evidence. Compounds 1 and 2 showed antimalarial activity against Plasmodium falciparum with IC50 values of 4.67 and 3.07 µg/mL, respectively. Compound 2 also showed antimycobacterial activity against Mycobacterium tuberculosis (MIC 6.25 µg/mL). In addition, compounds 1, 2, 10 and 11 showed cytotoxicity against three cancer cell lines (KB, NCI-H187 and MCF-7) with IC50 values ranging from 8.32 to 46.72 µg/mL.

Antimalarial polyoxygenated cyclohexene derivatives from the roots of Uvaria cherrevensis.

Three new polyoxygenated cyclohexene derivatives named cherrevenisyls A and B (1 and 2), and ellipeiopsol E (3), along with fifteen known compounds, were isolated from the roots of Uvaria cherrevensis. Their structures were determined by spectroscopic methods including 2D NMR techniques and mass spectrometry. The absolute configurations of 1 and 2 were assigned. Compounds 1, 2 and 5 showed antimalarial activity against Plasmodium falciparum with IC50 ranging from 3.34-7.34µg/mL. Compounds 5-18 exhibited cytotoxicity against three cancer cell lines (KB, MCF-7 and NCI-H187) with IC50 values in ranging from 1.26-49.03µg/mL.