The results of in silico screening of the 50 isolated compounds from Millettia dielsiana against the target proteins PDE4 (PDE4A, PDE4B, and PDE4D) showed binding affinity ranges from −5.81 to −11.56, −5.27 to −13.01, and −5.80 to −12.12 kcal mol⁻¹, respectively, with median values of −8.83, −8.84, and −8.645 kcal mol⁻¹, respectively. Among these compounds, Millesianin F was identified as the most promising PDE4A inhibitor due to its strongest binding affinity with the target protein PDE4A. (−11.56 kcal mol⁻¹). This was followed by the compound 5,7,4′-trihydroxyisoflavone 7-O-β-d-apiofuranosyl-(1→6)-β-d-glucopyranoside (D50) with the binding affinity value of −11.35 kcal mol⁻¹. For the target protein PDE4B, compound D50 exhibited the strongest binding affinity value of −13.01 kcal mol⁻¹, while showing poorer inhibition ability for PDE4D. The 100 ns MD simulation examination (radius of gyration, Solvent Accessible Surface Area (SASA), Root-Mean-Square Deviation (RMSD), Root-Mean-Square Fluctuation (RMSF), and hydrogen bonding) was carried out to examine the overall stability and binding efficiency of the protein–ligand complex between compounds (Millesianin F, Millesianin G, Claclrastin-7-O-β-d-glucopyranoside, 7-hydroxy-4′,6 dimethoxyisoflavone-7-O-β-d-apiofuranosyl-(1→6)-β-d-glucopyranoside, 7-hydroxy-4′,8-dimethoxyisoflavone 7-O-β-d-apiofuranosyl-(1→6)-β-d-glucopyranoside, Odoratin-7-O-β-d-glucopyranoside, and 5,7,4′-trihydroxyisoflavone 7-O-β-d-apiofuranosyl-(1→6)-β-d-glucopyranoside) and PDE4 (A, B) subtype proteins. Compound D50 has shown strong anti-inflammatory activity, as evidenced by experimental results. It effectively inhibits PDE4B and PDE4D, with IC₅₀ values of 6.56 ± 0.7 µM and 11.74 ± 1.3 µM, respectively. Additionally, it reduces NO production, with an IC₅₀ value of 5.40 ± 0.9 µM. Based on these findings, it is promising and considered a potential novel anti-inflammatory drug for future development.

From the root bark of Pinus krempfii Lecomte, four flavonoids were isolated and evaluated for their inhibitory activities against AChE and BChE enzymes in vitro and in silico. Tectochrysin (1) was found to inhibit AChE with an IC₅₀ value of 33.69 ± 2.80 μM. The docking study results also showed agreement with the in vitro test results. All four compounds also showed the best binding affinity for the AChE enzyme, characterised by binding energy (ΔG) values as low as -8.1 to -9.3 kcal/mol, in which, the compound tectochrysin had the best binding affinity for the AChE protein with a ΔG value of -9.329 kcal/mol. Tectochrysin (1) was also bound to the amino acid Phe295 of AChE with a bond length of 2.8 Å, similar to the control dihydrotanshinone-I. Galangin (2) also showed its in vitro inhibitory activity against BChE with an IC₅₀ value of 82.21 ± 2.70 μM. In silico, it also had the best binding energy value of -9.072 kcal/mol with BChE and formed hydrogen bonds with the His438 (2.85 Å) residues of BChE like the positive control (tacrine). The steered molecular dynamics (SMD) simulation results of these two complexes revealed a mechanistic insight that the protein-ligand complexes showed stable trajectories throughout the 20 and 150 ns simulations. Moreover, the drug likeliness suggested that both flavonoids (1 and 2) were expected to be drug-like and have an LD₅₀ toxicity level of 5. This study has contributed new results for drug discovery and the development of substances with neuroprotective effects, especially for the treatment of Alzheimer's disease.Communicated by Ramaswamy H. Sarma.

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-β-D-glucopyranosyl ester (3), 3-O-[β-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-[β-D-glucopyranosyl (l→3)]-α-L-arabinopyranosyl oleanolic acid (8), 3-O-α-L-arabinopyranosyl oleanolic acid (9) and oleanolic acid 28-O-β-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 Graphical Abstract