Toxicological Evaluation and In Silico Identification of Acetylcholinesterase Inhibitors in a Commercial Polyherbal Formulation (KWAPF01) .

This study investigated the toxicological implications of a commercial polyherbal formulation, KWAPF01. Twenty-four Wistar rats were randomized into six groups of four animals per group. The animals in Group 1 were administered placebo and designated as control, while the rats in Groups 2 to 6 were administered 1000, 1500, 2000, 2500, and 3000 mg/kg bodyweight single oral dose of KWAPF01, respectively, and subsequently monitored for gross morphological and behavioural changes for 72 h. Piloerection, reduced motility, and tremor were observed in experimental groups, and the median lethal dose (LD 50 ) of the extract was 2225.94 mg/kg bodyweight. The 11 compounds identified through HPLC analysis of the extract were docked against acetylcholinesterase (AChE), and the docking scores ranged from -5.3 to -10.8 kcal/mol, with catechol (-5.3 kcal/mol) and berberine (-10.8 kcal/mol) having the highest and lowest binding energies, respectively. Judging by the results, it could be inferred that some of the constituents of KWAPF01 have a direct impact on the nervous system and this is possibly elicited via the cholinergic system as it contains a nicotinic acetylcholine receptors agonist and potential inhibitors of AChE. Therefore, the use of KWAPF01 needs to be cautiously guided.