Anacardium Occidentale L. Leaf Extracts Protect Against Glutamate/H2O2-Induced Oxidative Toxicity and Induce Neurite Outgrowth: The Involvement of SIRT1/Nrf2 Signaling Pathway and Teneurin 4 Transmembrane Protein

Chatrawee Duangjan; Panthakarn Rangsinth; Shaoxiong Zhang; Michael Wink; Tewin Tencomnao

doi:10.3389/fphar.2021.627738

Anacardium Occidentale L. Leaf Extracts Protect Against Glutamate/H₂O₂-Induced Oxidative Toxicity and Induce Neurite Outgrowth: The Involvement of SIRT1/Nrf2 Signaling Pathway and Teneurin 4 Transmembrane Protein

Front Pharmacol. 2021 Apr 23:12:627738. doi: 10.3389/fphar.2021.627738. eCollection 2021.

Authors

Chatrawee Duangjan^{1

2

3}, Panthakarn Rangsinth^{1

2}, Shaoxiong Zhang^{4

5}, Michael Wink⁵, Tewin Tencomnao^{1

2

6}

Affiliations

¹ Graduate Program in Clinical Biochemistry and Molecular Medicine, Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok, Thailand.
² Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok, Thailand.
³ Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, United States.
⁴ College of Horticulture, Fujian Agriculture and Forestry University, Fuzhou, China.
⁵ Institute of Pharmacy and Molecular Biotechnology, Im Neuenheimer Feld 364, Heidelberg University, Heidelberg, Germany.
⁶ Natural Products for Neuroprotection and Anti-Ageing Research Unit, Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok, Thailand.

Abstract

Neurodegenerative diseases are linked to neuronal cell death and neurite outgrowth impairment that are often caused by oxidative stress. Natural products, which have neuroprotective against oxidative stress and neurite outgrowth inducing activity, could be potential candidates for alternative treatment of neurodegenerative diseases. This study aims to investigate the neuroprotective effects and neuritogenesis properties of Anacardium occidentale leaf extracts in cultured neuronal (HT22 and Neuro-2a) cells. We found gallic acid, catechin and quercetin as the main compounds in A. occidentale extracts. The extracts have a protective effect against glutamate/H₂O₂-mediated oxidative stress-induced cell toxicity. The gene expression of cellular antioxidant enzymes (SODs, GPx and, GSTs) were up-regulated by this treatment. The treatment also triggered SIRT, Nrf2 proteins as well as the mRNA transcriptions of relevant anti-oxidation genes (NQO1, GCLM, and EAAT3). We demonstrated that the extracts promote antioxidant defense in neuronal cells via the SIRT1/Nrf2 signaling pathway. Moreover, the extracts increase neurite outgrowth and Ten-4 expression in Neuro-2a cells. However, the neuritogenesis properties did not occur, when Ten-4 expression was knocked down by corresponding siRNA. These results suggest that the leaf extracts have an interesting neuritogenesis and neuroprotective potential against glutamate/H₂O₂-mediated toxicity and could be a potential therapeutic candidate for neurodegenerative diseases.

Keywords: H2O2; Nrf2/SIRT1; anacardium occidentale; glutamate; neurite outgrowth; teneurin-4.