Natural Compounds Isolated from African Mistletoes (Loranthaceae) Exert Anti-Inflammatory and Acetylcholinesterase Inhibitory Potentials: In Vitro and In Silico Studies

Abstract

Despite the medicinal uses of Phragmanthera capitata, Globimetula dinklagei and Tapinanthus bangwensis against memory loss, convulsions and pain, their efficacy against brain-dysfunction diseases and inflammation models has not yet been studied. Therefore, this study aims to investigate the anti-inflammatory and acetylcholinesterase (AChE) inhibitory potentials of their crude extracts and isolated natural compounds by combining in vitro and in silico experiments. Crude extracts and isolated compounds were tested in vitro for their AChE inhibitory activity by using Ellman’s method. Additionally, their anti-inflammatory activity was determined by evaluating the nitric oxide (NO) production inhibitory activity in lipopolysaccharide-stimulated RAW 264.7 macrophage cells and the 15-lipoxygenase (15-LOX) inhibitory activity by using the ferrous oxidation xylenol orange assay. Furthermore, the in silico efficacy of natural compounds was investigated against ten putative target enzymes relevant in Alzheimer’s disease (AD) pathogenesis and inflammation. It was found that the crude extracts had weak to moderate inhibitory potential against AChE, with the extract of T. bangwensis being the most active (50% inhibitory concentration (IC50) = 48.97 µg/mL). Six natural compounds, namely, 3-O-β-D-glucopyranosyl-28-hydroxy-α-amyrin (2), apigenin- 8-C-β-D-glucopyranoside (3), globimetulin B (5), globimetulin C (6), bangwaursene B (8) and 3β-acetoxy-11,12-epoxytaraxerol (9), were identified for the first time as having anti-AChE potential, among which (9) had the highest efficacy with an IC50 of 13.89 µM. Among the anti-AChE compounds, (5) was also efficient against NO production and 15-LOX, and the data are in agreement with the docking score. In summary, compounds (5) and (9) are the most prominent lead compounds that should be further tested experimentally against molecular targets of AD and inflammation.

In vitro antiproliferative, anti-inflammatory effects and molecular docking studies of natural compounds isolated from Sarcocephalus pobeguinii (Hua ex Pobég)

“…Additionally, the cell viability of treated cells was determined by using the MTT assay as previously described ( Mosmann, 1983 ). The whole experiment was repeated at different concentrations (100, 50, 25, 10 and 5 μg/mL) only for tested compounds that were able to inhibit at 50% of NO production, and the IC 50 values was calculated as previously described ( Mfotie Njoya et al, 2023 ).…”

“…Thereafter, standard precision ligand docking was performed using the same software. The best of nine binding poses based on the docking scores were visualized and captured in BIOVIA Discovery Studio Visualizer 2021 ( Mfotie Njoya et al, 2023 ).…”