1,3-Dicaffeoylquinic Acid as an Active Compound of <i>Arctium lappa</i> Root Extract Ameliorates Depressive-Like Behavior by Regulating Hippocampal Nitric Oxide Synthesis in Ovariectomized Mice

• Main Authors: Dong Wook Lim, Minji Kim, Minseok Yoon, Jaekwang Lee, Changho Lee, Min Young Um
• Format: Article
• Language: English
• Published: MDPI AG 2021-08-01
• Series: Antioxidants
• Subjects: <i>Arctium lappa</i> root; menopause; depression; nitric oxide; neuronal nitric oxide synthase; ERK–CREB–BDNF signaling
• Online Access: https://www.mdpi.com/2076-3921/10/8/1281

Menopause is a risk factor for depression. Although 1,3-dicaffeoylquinic acid (1,3-diCQA), a phenolic compound in <i>Arctium lappa</i> (<i>A. lappa</i>) root, has various health benefits, its effects on menopausal depression remain to be determined. Therefore, this study investigates the antidepressant-like effects of 1,3-diCQA from an <i>A. lappa</i> root extract (AE) and the associated molecular mechanisms. Ovariectomized (OVX) mice were orally administered AE for 20 weeks, following which depression-like behaviors were assessed. Although the mice exhibited depression-like behaviors, AE administration mitigated these symptoms by activating the ERK–CREB–BDNF pathway and increasing nNOS levels in the hippocampus. Similarly, a significant increase in nNOS-derived NO production and activation of the ERK–CREB–BDNF pathway was observed in the primary hippocampal neurons. Although this stimulatory effect of 1,3-diCQA was not significantly affected by treatment with estrogen receptor agonist or antagonist, it was inhibited by 7-NI, an nNOS inhibitor. Moreover, mice treated with 1,3-diCQA exhibited a marked improvement in their forced swimming test and tail suspension test immobility, while pretreatment with 7-NI reversed the antidepressant-like effects of 1,3-diCQA. Our results suggest that 1,3-diCQA regulates nNOS in an estrogen recepters-independent manner to increase NO production in OVX mice.