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Background <p>Aluminum chloride (AlCl<sub>3</sub>) 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 AlCl<sub>3</sub>-induced impairments and inhibit acetylcholinesterase (AChE).</p> Methods <p>In vitro AChE inhibition was quantified as the 50% inhibitory concentration (IC<sub>50</sub>). Male <i>Rattus norvegicus</i> Wistar rats (<i>n</i> = 6/group) were randomized to normal control, AlCl<sub>3</sub> (17&#xa0;mg/kg/day, p.o., 6 weeks), AlCl<sub>3</sub> + donepezil (5&#xa0;mg/kg/day), AlCl<sub>3</sub> + ORT (5&#xa0;mg/kg/day), or AlCl<sub>3</sub> + KAO (5&#xa0;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.</p> Results <p>Orthoclase showed stronger AChE inhibition than Kaolin (IC<sub>50</sub> 0.09 ± 0.04 vs. 0.47 ± 0.02&#xa0;µg/mL; <i>p</i> &lt; 0.001) and slightly higher potency than donepezil (IC<sub>50</sub> 0.13 ± 0.04&#xa0;µg/mL). Chronic AlCl<sub>3</sub> impaired MWM performance, whereas donepezil improved escape latency and probe trial indices versus the disease control. Orthoclase significantly improved behavioral performance and attenuated AlCl<sub>3</sub>-associated histological alterations, yielding effects comparable in direction and magnitude to donepezil. Kaolin produced modest, directionally favorable changes at the tested dose.</p> Conclusions <p>Orthoclase, and to a lesser extent Kaolin, improved cognition and histological integrity in an AlCl<sub>3</sub>-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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月9日

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  • Wafa M. Al-Madhagi,
  • Mohammed A. Alkhawlani,
  • Majed Alwan,
  • Maged Al-Najar

摘要

Background

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).

Methods

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.

Results

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.

Conclusions

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.