2. Academic Validation
  3. Hordenine improves Parkinsonian-like motor deficits in mice and nematodes by activating dopamine D2 receptor-mediated signaling

Hordenine improves Parkinsonian-like motor deficits in mice and nematodes by activating dopamine D2 receptor-mediated signaling

  • Phytother Res. 2023 Mar 8. doi: 10.1002/ptr.7790.
Hongli Li 1,  Min Gao 1,  Ziyu Chen 2,  Zhenyu Zhou 1,  Wei Li 3,  Xiaoyang Zhang 3,  Xi Jiang 1,  Lingling Luo 1,  Fei Li 1,  Gaorui Wang 2,  Yu Zhang 4,  Xingxu Huang 4,  Jingning Zhu 3,  Shengjie Fan 1,  Xiaojun Wu 2,  Cheng Huang 1
Affiliations

Affiliations

  • 1 Drug Discovery Laboratory, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
  • 2 Shanghai Key Laboratory of Compound Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
  • 3 State Key Laboratory of Pharmaceutical Biotechnology, Department of Physiology, and Institute for Brain Sciences, School of Life Sciences, Nanjing University, Nanjing, China.
  • 4 School of Life Science and Technology, ShanghaiTech University, Shanghai, China.
PMID: 36883794 DOI: 10.1002/ptr.7790
Abstract

Parkinson's disease (PD) is a chronic neurodegenerative disease characterized by selective loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the striatum, leading to dopamine (DA) deficiency in the striatum and typical motor symptoms. A small molecule as a dietary supplement for PD would be ideal for practical reasons. Hordenine (HOR) is a phenolic phytochemical marketed as a dietary supplement found in cereals and germinated barley, as well as in beer, a widely consumed beverage. This study was aimed to identify HOR as a dopamine D2 receptor (DRD2) agonist in living cells, and investigate the alleviative effect and mechanism of HOR on PD-like motor deficits in mice and nematodes. Our results firstly showed that HOR is an agonist of DRD2, but not DRD1, in living cells. Moreover, HOR could improve the locomotor dysfunction, gait, and postural imbalance in MPTP- or 6-OHDA-induced mice or Caenorhabditis elegans, and prevent α-synuclein accumulation via the DRD2 pathway in C. elegans. Our results suggested that HOR could activate DRD2 to attenuate the PD-like motor deficits, and provide scientific evidence for the safety and reliability of HOR as a dietary supplement.

Keywords

Parkinson's disease; dietary supplement; dopamine D2 receptor; gait disorders; hordenine; locomotor deficits.

Figures
Products