Pepper component 7-ethoxy-4-methylcoumarin, a novel dopamine D2 receptor agonist, ameliorates experimental Parkinson's disease in mice and Caenorhabditis elegans.

Abstract

Parkinson's disease (PD) is a progressive neurodegenerative disease resulting from the degeneration of dopaminergic (DAergic) neurons in the substantia nigra pars compacta (SNpc) and subsequent deficit of dopamine in the striatum. PD is inversely associated with consumption of peppers; however, the constituent and the underlying mechanism remain unclear. This study aimed to investigate the effects of 7-ethoxy-4-methylcoumarin (EMC), a pepper constituent, on PD-like disorders in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mice and 6-hydroxydopamine (6-OHDA)-exposed C. elegans. In this study, EMC was identified as an agonist of dopamine D2 receptor (DRD2) and increased the expression of P-CREB and BDNF in SH-SY5Y cells. In MPTP-treated PD mice, EMC was shown to apparently ameliorate the motor and gait disorders, and restore the depressed TH expression in SNpc and striatum. Meanwhile, it recovered the locomotor deficit caused by 6-OHDA in wild type N2 and CAT-2-transgenic UA57 of C. elegans, and relieved the degeneration of DAergic neurons resulting from 6-OHDA or with ageing. Moreover, EMC inhibited α-synuclein accumulation in C. elegans strain NL5901 overexpressing human α-synuclein gene. Taken together, EMC was identified as a novel DRD2 agonist and improved experimental PD in mice and C. elegans. These findings suggest that EMC may be beneficial to PD patients, further supporting that the consumption of peppers may have favorable effect on PD progression.

• Authors: Hongli Li, Yaru Feng, Ziyu Chen, Xi Jiang, Zhenyu Zhou, Jinfeng Yuan, Fei Li, Yu Zhang, Xingxu Huang, Shengjie Fan, Xiaojun Wu, Cheng Huang
• Journal: Pharmacological research (Pharmacol Res) Vol. 163 Pg. 105220 (01 2021) ISSN: 1096-1186 [Electronic] Netherlands
• PMID: 33007422 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 Elsevier Ltd. All rights reserved.

Chemical References

• Coumarins
• Dopamine Agonists
• Neuroprotective Agents
• Receptors, Dopamine D2
• 4-methyl-7-ethoxycoumarin
• Oxidopamine
• 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine

Topics

• 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
• Animals
• Animals, Genetically Modified
• Behavior, Animal (drug effects)
• Caenorhabditis elegans
• Cell Line
• Coumarins (pharmacology, therapeutic use)
• Disease Models, Animal
• Dopamine Agonists (pharmacology, therapeutic use)
• Humans
• Locomotion (drug effects)
• Male
• Mice, Inbred C57BL
• Neuroprotective Agents (therapeutic use)
• Oxidopamine
• Parkinsonian Disorders (chemically induced, drug therapy)
• Receptors, Dopamine D2 (metabolism)
• Mice