以生物活性為導向之 Glycosmis parviflora (Sims) Little 莖和 Crotalaria pallida Aiton 根之活性成分物質研究

A dereplication system was utilized to rapidly identify and characterize acetylcholinesterase-interacting compounds by comparing UPLC-MS/MS profile screening approach and molecular docking analysis, derived from the extracts and fractions of the stem of Glycosmis parviflora (Sims) Little. Eleven potential AChE inhibitors were isolated and identified from the ethyl acetate extract of G. parviflora, including an undescribed alkaloid (9), namely glybomine D, eight known alkaloids (18), a flavonoid (10), and a phytosterol (11). The inhibitory potential of these compounds against AChE was assessed, with O-methylglycosolone (6), 1,3-dimethoxy-2-hydroxy-10-methyl-9(10H)-acridinone (1), skimmianine (4) and arborine (2), regarded as effective inhibitors, yielding IC50 values of 39.81, 41.53, 49.40, and 59.92 μM, respectively. Notably, O-methylglycosolone exhibited the highest potency. Four of these potent AChE inhibitors exhibited mixed-type inhibition. However, O-methylglycosolone (6), 1,3-dimethoxy-2-hydroxy-10-methyl-9(10H)-acridinone (1), and arborine (2) were first reported modulating with acetylcholinesterase activity. Furthermore, molecular docking revealed O-methylglycosolone (6) superior binding affinity (-23.749 kcal/mol) compared to other compounds, mainly by interacting with the peripheral anionic site of AChE, which forms hydrogen bonds and hydrophobic forces may play an important role, interaction with amino acid residues such as Tyr341, Tyr72, Ser293, and Arg296 in the active cavity, which is crucial for effective and selective inhibition of AChE activity. ADMET predictions suggest that arborine (2), skimmianine (4), and O-methylglycosolone (6) demonstrate favorable permeability across the blood-brain barrier, while 1,3-dimethoxy-2-hydroxy-10-methyl-9(10H)-acridinone (1) exhibits comparatively reduced permeability. These findings highlight the potential of these compounds as natural AChE inhibitors for treating neurodegenerative diseases.
In the root of Crotalaria pallida Aiton, a bioactivity-guided isolation was used to obtain seven (12‒18) undescribed compounds, namely crotapalliflavones AG together with fourteen known flavonoids (19‒32) from the fraction Fr.1 of the root of C. pallida that had the most effective anti-proliferative activity against human hepatocarcinoma cells (HepG2). Additionally, five previously described triterpenoid saponins (33‒37) were first extracted from three other fractions of species C. pallida. The structures were identified by a variety of spectroscopic methods as well as by comparison with the literature. The separated and purified flavonoids showed appreciable cytotoxicity in HepG2 cells and might attenuate the damage induced by acetaminophen (APAP) in these cells. Erythrinin B (22), 13, crotadihydrofuran C (19), 15, crotafuran C (31), 12, 14, 17 and erythrinin C (28) exhibited cytotoxic activities. Erythrinin B (22) possessed the most potential effect with IC50 values of 9.02 ± 2.01 µM against HepG2 cells. Isoflavonoids 16 and 18 and triterpenoid saponins kaikasaponin II (33) and abrisaponin So1 (37) dramatically decreased APAP toxicity in HepG2 cells.
Overall, our findings suggest that stem of G. parviflora is a promising natural source for potent acetylcholinesterase inhibitors, and the root of C. pallida shows the potential to be implemented as a natural medication to treat liver cancer as well as other diseases of the liver.