Evaluation of anticholinesterase activity of orthoclase and Kaolin from selected Yemeni stones: potential anti-Alzheimer agents

Aluminum chloride (AlCl3) induces Alzheimer’s disease (AD)-like neurotoxicity and cognitive decline. This study evaluated whether Orthoclase (ORT) and Kaolin (KAO), two Yemeni aluminosilicate minerals, can mitigate AlCl3-induced impairments and inhibit acetylcholinesterase (AChE). In vitro AChE inhibition was quantified as the 50% inhibitory concentration (IC50). Male Rattus norvegicus Wistar rats (n = 6/group) were randomized to normal control, AlCl3 (17 mg/kg/day, p.o., 6 weeks), AlCl3 + donepezil (5 mg/kg/day), AlCl3 + ORT (5 mg/kg/day), or AlCl3 + KAO (5 mg/kg/day). The primary outcome was spatial learning and memory in the Morris Water Maze (MWM). Secondary outcomes were brain AChE activity and histopathological examination of brain, liver, and kidney tissues. Histopathological examinations were also carried out. Orthoclase showed stronger AChE inhibition than Kaolin (IC50 0.09 ± 0.04 vs. 0.47 ± 0.02 µg/mL; p < 0.001) and slightly higher potency than donepezil (IC50 0.13 ± 0.04 µg/mL). Chronic AlCl3 impaired MWM performance, whereas donepezil improved escape latency and probe trial indices versus the disease control. Orthoclase significantly improved behavioral performance and attenuated AlCl3-associated histological alterations, yielding effects comparable in direction and magnitude to donepezil. Kaolin produced modest, directionally favorable changes at the tested dose. Orthoclase, and to a lesser extent Kaolin, improved cognition and histological integrity in an AlCl3-induced AD-like model while exhibiting potent AChE inhibition in vitro. These findings support Orthoclase as a low-cost candidate for further mechanistic and safety studies in resource-constrained settings.