Spectroscopic analysis, kinetic mechanism, computational docking, and molecular dynamics of active metabolites from the aerial parts of Astragalus membranaceusBunge as tyrosinase inhibitors.

A new isoflavane derivative (2), a new natural isoflavane (6), four new oleanane-type triterpenoid saponins (23, 25, 28, and 29), and twenty three known secondary metabolites (1, 3-5, 7-22, 24, 26, and 27) were isolated from the aerial parts of Astragalus membranaceus Bunge. The chemical structures of these compounds were elucidated through spectroscopic analysis and compared with those identified in previous studies. Tyrosinase inhibition ability of isolated compounds (1-29) was evaluated. Of these, compounds 3, 4, 6, and 14 exhibited inhibitory effects, with IC50 values ranging from 24.6 to 59.2 µM. According to kinetic analysis, compounds 3 and 4 were non-competitive inhibitors of tyrosinase, whereas compounds 6 and 14 inhibited tyrosinase in uncompetitive and competitive modes, respectively. Molecular docking analysis identified that compounds 3, 4, and 6 could bind to allosteric sites and compound 14 could bind to the catalytic site of tyrosinase, which is consistent with the results of kinetic studies. Molecular dynamics behaviors of the active compounds in complex with tyrosinase were investigated via 60 ns simulation which demonstrated their high stability. These findings indicate that the aerial parts of A. membranaceus are a potential source of natural tyrosinase inhibitors.

Anti-inflammatory activity and cytotoxicity against ovarian cancer cell lines by amide alkaloids and piperic esters isolated from Piper longum fruits: In vitro assessments and molecular docking simulation.

Three new amide alkaloids, piperlongumamides D-F (14, 19, and 32); a new piperic ester, piperlongumester A (45); and two new natural compounds, methyl (2E,4Z)-5-(1,3-benzodioxol-5-yl)penta-2,4-dienoate (46) and trans-piperolein B ester (47), along with 41 known compounds were isolated from the fruits of Piper longum L. Their structures were identified by analyzing spectroscopic data, including mass spectrometry, 1D, and 2D NMR data. The anti-inflammatory and cytotoxic activities of all isolated compounds (1-47) were evaluated. Compounds 3, 6, and 19 inhibited nitric oxide production with IC50 values of 16.1 ± 0.94, 14.5 ± 0.57, and 27.3 ± 1.11 µM, respectively, whereas compound 1 exhibited strong cytotoxic activity toward three ovarian cancer cell lines A2780, TOV-112D, and SK-OV3, with IC50 values of 6.7 ± 0.77, 5.8 ± 0.29, and 48.3 ± 0.40 µM, respectively. Molecular docking simulations were performed to identify the interaction and binding mechanisms of these active metabolites with proteins related to inflammation and cancer.

Bioactive triterpene glycosides from the fruit of Stauntonia hexaphylla and insights into the molecular mechanism of its inflammatory effects.

Chromatography of the ethanol extract of the medicinal fruit Stauntonia hexaphylla resulted in the purification of 26 compounds (1-26), including two undescribed triterpene saponins 1 and 2 (hexaphylosides A and B). Their structures were confirmed by spectroscopic data, including IR, HR QTOF MS, 1H, 13C NMR, COSY, HMQC, HMBC, and TOCSY, and HPLC sugar analysis after acid hydrolysis. The anti-inflammatory effects of the high-purity constituents (1-26) on lipopolysaccharide (LPS)-induced RAW264.7 macrophage cells were investigated by screening nitric oxide production. The NO inhibitory activity of compounds 6 and 10 with the IC50 values of 1.33 and 1.10 µM, respectively. The structure-activity relationships (SAR) of the isolated compounds were also analyzed. Furthermore, compounds 6 and 10 inhibited the protein expression inducible nitric oxide synthase (iNOS), and cyclooxygenase (COX)-2 via Western blotting analysis. This showed that compounds 6 and 10 contributed to the anti-inflammatory effects of S. hexaphylla fruit, which could be developed as a natural nutraceutical and functional food ingredient.