AUTHOR=Gence Laura , Fernezelian Danielle , Bringart Matthieu , Veeren Bryan , Christophe Armelle , Brion François , Meilhac Olivier , Bascands Jean-Loup , Diotel Nicolas 

TITLE=Hypericum lanceolatum Lam. Medicinal Plant: Potential Toxicity and Therapeutic Effects Based on a Zebrafish Model

JOURNAL=Frontiers in Pharmacology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.832928

DOI=10.3389/fphar.2022.832928

ISSN=1663-9812

ABSTRACT=<p><italic>Hypericum lanceolatum</italic> Lam. (<italic>H. lanceolatum</italic>) is a traditional medicinal plant from Reunion Island used for its pleiotropic effects mainly related to its antioxidant activity. The present work aimed to 1) determine the potential toxicity of the plant aqueous extract <italic>in vivo</italic> and 2) investigate its putative biological properties using several zebrafish models of oxidative stress, regeneration, estrogenicity, neurogenesis and metabolic disorders. First, we characterized the polyphenolic composition by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and identified chlorogenic acid isomers, quercetin and kaempferol derivatives as the major compounds. We then evaluated for the first time the toxicity of an aqueous extract of <italic>H. lanceolatum</italic> and determined a maximum non-toxic concentration (MNTC) in zebrafish eleutheroembryos from 0 to 96 hpf following OECD (Organization for Economic Cooperation and Development) guidelines. This MNTC test was also determined on hatched eleutheroembryos after 2 days of treatment (from 3 to 5 dpf). In our study, the anti-estrogenic effects of <italic>H. lanceolatum</italic> are supported by the data from the EASZY assay. In a tail amputation model, we showed that <italic>H. lanceolatum</italic> at its MNTC displays antioxidant properties, favors immune cell recruitment and tissue regeneration. Our results also highlighted its beneficial effects in metabolic disorders. Indeed, <italic>H. lanceolatum</italic> efficiently reduces lipid accumulation and body mass index in overfed larva- and adult-models, respectively. In addition, we show that <italic>H. lanceolatum</italic> did not improve fasting blood glucose levels in a hyperglycemic zebrafish model but surprisingly inhibited neurogenesis impairment observed in diabetic conditions. In conclusion, our study highlights the antioxidant, pro-regenerative, anti-lipid accumulation and pro-neurogenic effects of <italic>H. lanceolatum in vivo</italic> and supports the use of this traditional medicinal plant as a potential alternative in the prevention and/or treatment of metabolic disorders.</p>