Preprint / Version 1

Chlorogenic Acids, Acting via Calcineurin, Are the Main Compounds in Centella asiatica Extracts That Mediate Resilience to Chronic Stress in Drosophila melanogaster

Authors

Keywords:

Gotu Kola, caffeoylquinic acids, triterpenes, chronic stress, anhedonia

Abstract

Common symptoms of depressive disorders include anhedonia, sleep problems, and reduced physical activity. Drugs used to treat depression mostly aim to increase serotonin signaling but these can have unwanted side effects. Depression has also been treated by traditional medicine using plants like Centella asiatica (CA) and this has been found to be well tolerated. However, very few controlled studies have addressed CA’s protective role in depression, nor have the active compounds or mechanisms that mediate this function been identified. To address this issue, we used Drosophila melanogaster to investigate whether CA can improve depression-associated symptoms like anhedonia and decreased climbing activity. We found that a water extract of CA provides resilience to stress induced phenotypes and that this effect is primarily due to mono-caffeoylquinic acids found in CA. Furthermore, we describe that the protective function of CA is due to a synergy between chlorogenic acid and one of its isomers also present in CA. However, increasing the concentration of chlorogenic acid can overcome the requirement for the second isomer. Lastly, we found that chlorogenic acid acts via calcineurin, a multifunctional phosphatase that can regulate synaptic transmission and plasticity and is also involved in neuronal maintenance. Keywords: Gotu Kola, caffeoylquinic acids, triterpenes, chronic stress, anhedonia

Author Biographies

Helen Holvoet, Institut für Entwicklungsbiologie und Neurobiologie, Johannes Gutenberg-Universität Mainz, 55128 Mainz, Germany; [email protected] (H.H.);

Formal analysis, Investigation, Writing – original draft, Visualization

Doris Kretzschmar, BENFRA Botanical Dietary Supplements Research Center, Oregon Health & Science University, Portland, OR 97239, [email protected] (L.Y.); [email protected] (J.C.); [email protected] (A.S.)

Conceptualization, Methodology, Validation, Writing – original draft, Writing – review & editing, Visualization, Supervision, Project administration, Funding acquisition

Amala Soumyanath, BENFRA Botanical Dietary Supplements Research Center, Oregon Health & Science University, Portland, OR 97239, [email protected] (L.Y.); [email protected] (J.C.); [email protected] (A.S.)

Conceptualization, Methodology, Validation, Data curation, Writing – review & editing, Supervision, Project administration, Funding acquisition

Claudia Maier, BENFRA Botanical Dietary Supplements Research Center, Oregon Health & Science University, Portland, OR 97239, [email protected] (L.Y.); [email protected] (J.C.); [email protected] (A.S.)

Conceptualization, Methodology, Validation, Writing – review & editing, Supervision, Funding acquisition

Burkhard Poeck, Institut für Entwicklungsbiologie und Neurobiologie, Johannes Gutenberg-Universität Mainz, 55128 Mainz, Germany; [email protected] (H.H.);

Methodology, Validation, Formal analysis, Data curation, Writing – review & editing

Luke Marney, BENFRA Botanical Dietary Supplements Research Center, Oregon Health & Science University, Portland, OR 97239, [email protected] (L.Y.); [email protected] (J.C.); [email protected] (A.S.)

Formal analysis, Visualization

Jaewoo Choi, BENFRA Botanical Dietary Supplements Research Center, Oregon Health & Science University, Portland, OR 97239, [email protected] (L.Y.); [email protected] (J.C.); [email protected] (A.S.)

Formal analysis, Writing – review & editing, Visualization

Liping Yang, BENFRA Botanical Dietary Supplements Research Center, Oregon Health & Science University, Portland, OR 97239, [email protected] (L.Y.); [email protected] (J.C.); [email protected] (A.S.)

Formal analysis, Investigation, Writing – review & editing

Dani Long, BENFRA Botanical Dietary Supplements Research Center, Oregon Health & Science University, Portland, OR 97239, [email protected] (L.Y.); [email protected] (J.C.); [email protected] (A.S.)

Formal analysis, Investigation, Visualization

Roland Strauss, Institut für Entwicklungsbiologie und Neurobiologie, Johannes Gutenberg-Universität Mainz, 55128 Mainz, Germany; [email protected] (H.H.);

Conceptualization, Methodology, Writing – review & editing, Supervision, Funding acquisition

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