Affiliations: [a] Department of Anatomy and Cell Biology, College of Medicine, The University of Illinois at Chicago, Chicago, IL, USA
| [b] Department of Food Quality and Safety, Volcani Center, Agricultural Research Organization, Rishon Lezion, Israel
Correspondence:
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Correspondence to: Orly Lazarov, PhD, Professor, Department of Anatomy and Cell Biology, College of Medicine Research Building, University of Illinois at Chicago, 909 S. Wolcott St., Chicago, IL 60612, USA. Tel.: +1 312 355 0548; E-mail: [email protected].
Abstract: Plant derivatives offer a novel and natural source of therapeutics. The desert plant Achillea fragrantissima (Forssk) Sch. Bip (Af) is characterized by protective antioxidative and anti-inflammatory properties. Here, we examined the effect of two Af-derived phytochemicals on learning and memory, amyloid-β protein precursor (AβPP) metabolism, and tau phosphorylation in the familial Alzheimer’s disease-linked APPswe/PS1ΔE9 mouse model. We observed that mice that were injected with the phytochemicals showed a trend of improvement, albeit statistically insignificant, in the Novel Object Recognition task. However, we did not observe improvement in contextual fear conditioning, suggesting that the benefits of treatment may be either indirect or task-specific. In addition, we observed an increase in the full-length form of AβPP in the brains of mice treated with Af–derived phytochemicals. Interestingly, both in vivo and in vitro, there was no change in levels of soluble Aβ, oligomeric Aβ, or the carboxyl terminus fragments of AβPP (APP-CTFs), suggesting that the increase in full length AβPP does not exacerbate AβPP pathology, but may stabilize the full-length form of the molecule. Together, our data suggest that phytochemicals present in Af may have a modest positive impact on the progression of Alzheimer’s disease.
Keywords: Achillolide A, Alzheimer’s disease, amyloid-β protein precursor, flavonoids, sesquiterpene lactones, 3, 5, 4’-trihydroxy-6, 7, 3’-trimethoxyflavone
