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

Donald G Matthews,Armando Alcazar Magana,Claudia S Maier,Joseph F Quinn,Jan F Stevens,Maya Caruso,Nora E Gray,Kirsten M Wright,Amala Soumyanath

doi:10.3390/nu12113488

Donald G Matthews, Armando Alcazar Magana + Show 7 more

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https://doi.org/10.3390/nu12113488

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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.

Highlights

Centella asiatica (L.) Urban (CA), family Apiaceae, known as Indian Pennywort, Mandukaparni, or Brahmi is an edible herb and popular botanical dietary supplement
We demonstrated that a CA water extract (CAW) dose-dependently reversed memory deficits in novel object recognition and conditioned fear response (CFR) in both male and female 5XFAD transgenic mice, an amyloid-β-driven model of Alzheimer’s disease (AD) [3]
TT and caffeoylquinic acids (CQA) content in CAW was determined by LC-HRMS/MS (Table 1)

Summary

Introduction

Centella asiatica (L.) Urban (CA), family Apiaceae, known as Indian Pennywort, Mandukaparni, or Brahmi is an edible herb and popular botanical dietary supplement. It is an important Ayurvedic herb used for memory improvement [1]. We demonstrated that a CA water extract (CAW) dose-dependently reversed memory deficits in novel object recognition and conditioned fear response (CFR) in both male and female 5XFAD transgenic mice, an amyloid-β-driven model of Alzheimer’s disease (AD) [3]. We treated male and female 5XFAD mice with CAW, or CAW-equivalent amounts of TT and CQA compounds, to explore the role of these two groups of compounds in the cognitive effects of CAW. Cognitive function was assessed using CFR, as in our earlier study on CAW [3]

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