Khan_2025_J.Toxicol_2025_3997995

The increasing popularity of herbal preparations has prompted people around the world to incorporate herbal products into their balanced diet, aiming to improve brain health and protect against neurological disorders. Erqember(Erq-Em) possesses a blend of various neuroprotective phytocompounds. The present study aimed to phytochemically analyze this polyherbal product and scientifically validate its neurological benefits. After chemical characterization through UHPLC-MS, in vivo studies involved the supplementation of mice with 10 and 20 mL/kg doses of Erq-Em in an AlCl(3)-induced amnesic mice model followed by behavioral assessment for anxiety and cognition in a battery of behavioral tests. Subsequently, whole brains were dissected for biochemical and histopathological analysis. Further, the study also included in silico studies to understand the interaction of detected phytocompounds with acetylcholinesterase protein. The outcomes revealed that mice treated with Eqr-Em were protected from anxiety-like behavior as they dose-dependently prefer innately frightening central, lightened, and elevated zones in OFT, L/D, and EPM tests. Moreover, the Erq-Em supplementation caused improved spontaneous learning in Y-maze and NOR tests, while their memory in passive avoidance and water maze tests was evident from longer step-through and shorter escape latencies, respectively. The biochemical analysis of brain homogenates showed a reduction in AchE and MDA while elevation in SOD and GPx levels in mice receiving Erq-Em. Moreover, the healthy and intact neuronal counts were markedly high in CA1 and DG regions of Nissl's-stained hippocampi of Erq-Em-treated mice. The compounds detected by UPLC-MS showed favorable BBB permeability and interacted well with acetylcholinesterase protein through in silico studies. Overall, the neurological benefits of Erqember might result from enhanced cholinergic neurotransmission and antioxidative activity of its phytocompounds, which together function as multimodal strategies against AlCl(3)-induced neurotoxicity.