Emam_2024_Pharmaceuticals.(Basel)_17_

BACKGROUND/OBJECTIVES: Marrubium vulgare L. (M. vulgare), the white horehound, is well known for treating inflammation-related diseases. METHODS: In this context, we investigated the efficacy of M. vulgare ingredients in treating Alzheimer's disease using various in vitro and in silico antioxidant, anti-inflammatory, anti-cholinesterase, and anti-tyrosinase mechanisms. RESULTS: In our results, sixty-one components were tentatively identified using gas and liquid chromatography (GC-MS and LC-MS(n)) and categorized as hydrocarbons, fatty acids, and polyphenolics. The extract inhibited linoleic oxidation with an IC(50) value of 114.72 microg/mL, captured iron (Fe(2+)) ions with an IC(50) value of 164.19 microg/mL, and displayed reducing power. In addition, the extract showed radical-scavenging ability towards DPPH( ), NO( ), ABTS( +), and H(2)O(2) assays compared to L-ascorbic acid and butylated hydroxytoluene. The DPPH( ) was scavenged by 77.62% at 100 microg/mL, and NO( ), ABTS( +), and H(2)O(2) were scavenged with IC(50) values of 531.66, 117.51, and 143.10 microg/mL, respectively. M. vulgare also exhibited discriminating anti-inflammatory potency against cyclooxygenase (COX-2) with IC(50) values of 619.15 microg/mL compared to celecoxib (p > 0.05). Notably, three Alzheimer's biomarkers, acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and tyrosinase were significantly inhibited. The molecular docking study supposed that the phenylethanoid glycosides of samioside and forsythoside B inhibited AChE and tyrosinase enzymes with low binding affinities of -9.969 and -8.804 kcal/mol, respectively. Marruboside was a proper inhibitor of COX and BChE enzymes with a binding score of -10.218 and -10.306 kcal/mol, respectively. CONCLUSIONS: M. vulgare extract showed significant inhibitory actions, which suggest that it could have a promising potential as an anti-Alzheimer agent.