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 (Author), Minji Kim (Author), Minseok Yoon (Author), Jaekwang Lee (Author), Changho Lee (Author), Min Young Um (Author)
• Format: Book
• Published: MDPI AG, 2021-08-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 10.3390/antiox10081281; 2076-3921
• Keywords: <i>Arctium lappa</i> root; menopause; depression; nitric oxide; neuronal nitric oxide synthase; ERK-CREB-BDNF signaling; Therapeutics. Pharmacology; RM1-950
• Source: Antioxidants, Vol 10, Iss 8, p 1281 (2021)

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.