Preprint / Version 1

Caffeoylquinic Acids in Centella asiatica Reverse Cognitive Deficits in Male 5XFAD Alzheimer’s Disease Model Mice

Authors

Keywords:

Centella asiatica, family Apiaceae, 5XFAD, conditioned fear response, triterpenes, caffeoylquinic acids

Abstract

Centella asiatica (CA) is an edible plant and a popular botanical dietary supplement. It is reputed, in Ayurveda, to mitigate age-related cognitive decline. There is a considerable body of preclinical literature supporting CA’s ability to improve learning and memory. This study evaluated the contribution of CA’s triterpenes (TT), widely considered its active compounds, and caffeoylquinic acids (CQA) to the cognitive effects of CA water extract (CAW) in 5XFAD mice, a model of Alzheimer’s disease. 5XFAD mice were fed a control diet alone, or one containing 1% CAW or compound groups (TT, CQA, or TT + CQA) equivalent to their content in 1% CAW. Wild-type (WT) littermates received the control diet. Conditioned fear response (CFR) was evaluated after 4.5 weeks. Female 5XFAD controls showed no deficit in CFR compared to WT females, nor any effects from treatment. In males, CFR of 5XFAD controls was attenuated compared to WT littermates (p = 0.005). 5XFAD males receiving CQA or TT + CQA had significantly improved CFR (p < 0.05) compared to 5XFAD male controls. CFR did not differ between 5XFAD males receiving treatment diets and WT males. These data confirm a role for CQA in CAW’s cognitive effects. Keywords: Centella asiatica, family Apiaceae, 5XFAD, conditioned fear response, triterpenes, caffeoylquinic acids

Author Biographies

Armando Magana, Department of Chemistry, Oregon State University, Corvallis, OR 97331, USA; [email protected] (A.A.M.); [email protected] (C.S.M.)

Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA; [email protected]

Claudia Maier, Department of Chemistry, Oregon State University, Corvallis, OR 97331, USA; [email protected] (A.A.M.); [email protected] (C.S.M.)

Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA; [email protected]

Jan Stevens, Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA; [email protected]

Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, OR 97331, USA

Joseph Quinn, Department of Neurology, School of Medicine, Oregon Health &amp; Science University, Portland, OR 97239, USA; [email protected] (D.G.M.); [email protected] (M.C.); [email protected] (K.M.W.); [email protected] (N.E.G.); [email protected] (J.F.Q.)

Parkinson’s Disease Research Education and Clinical Care Center, Veterans’ Administration Portland Health Care System, Portland, OR 97239, USA

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