Involvement of serotonergic system in the antidepressant-like effect of a novel curcumin derivative CUD003

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K15902
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General internal medicine(including psychosomatic medicine)
• Research Institution: Josai University
• Principal Investigator: MATSUZAKI HIROKAZU 城西大学, 薬学部, 助教 (80582238)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 抗うつ効果 / フェルラ酸誘導体 / クルクミン誘導体 / 抗酸化作用 / 5-HT神経系

Outline of Final Research Achievements

In this study, we investigated the antidepressant-like effect of a novel synthetic derivate of curcumin CUD003 and the possible mechanism of its action. Treatment with CUD003 (3 mg/kg, p.o.) decreased the immobility time in the forced swim test (FST) without affecting locomotor activity in the open field test. CUD003 was more effective than curcumin in the FST. The antidepressant-like effect of CUD003 was abolished by the pretreatment with pCPA (a tryptophan hydroxylase inhibitor), WAY-100635 (a 5-HT1A antagonist), ketanserin (a 5-HT2A/C antagonist), or ondansetron (a 5-HT3 antagonist). Moreover, social defeat stress-induced depressive behaviors as evidenced by an increased immobility time in the FST, and a decreased grooming time in the sucrose splash test were attenuated by the treatment of CUD003. These results suggest that CUD003 has more potent antidepressant-like effect than curcumin, which may be mediated by the serotonergic systems through 5-HT1A, 5-HT2A/2C and 5-HT3 receptors.

Free Research Field

神経薬理学

Academic Significance and Societal Importance of the Research Achievements

うつ病は様々な病因仮説が提唱されていることからも、一つの機序のみを特異的に増強した薬物では効果に限界があり、複数の作用をバランスよく有していることが重要であると考える。本研究では、強い抗酸化作用や抗炎症作用を示す新規誘導体から候補化合物を絞り込み、強い抗うつ作用を有するCUD003を発見できた。本研究によって得られる知見により、将来的に既存の抗うつ薬とは作用機序の異なる、より優れた抗うつ作用を示す化合物の創出が可能になると考えている。