2. Academic Validation
  3. Oxyphylla A exerts antiparkinsonian effects by ameliorating 6-OHDA-induced mitochondrial dysfunction and dyskinesia in vitro and in vivo

Oxyphylla A exerts antiparkinsonian effects by ameliorating 6-OHDA-induced mitochondrial dysfunction and dyskinesia in vitro and in vivo

  • Chem Biol Interact. 2024 Sep 3:403:111224. doi: 10.1016/j.cbi.2024.111224.
Min Shao 1,  Chen Zhao 2,  Zhijian Pan 1,  Xuanjun Yang 3,  Cheng Gao 2,  Gloria Hio-Cheng Kam 4,  Hefeng Zhou 5,  Simon Ming-Yuen Lee 6
Affiliations

Affiliations

  • 1 School of Bioengineering, Zhuhai Campus of Zunyi Medical University, Zhuhai, China.
  • 2 State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, Macau, China.
  • 3 State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, Macau, China; Department of Food Science and Nutrition, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, China.
  • 4 Department of Food Science and Nutrition, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, China.
  • 5 School of Bioengineering, Zhuhai Campus of Zunyi Medical University, Zhuhai, China. Electronic address: zhf@zmu.edu.cn.
  • 6 State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, Macau, China; Department of Food Science and Nutrition, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, China; Research Centre for Chinese Medicine Innovation, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, China; State Key Laboratory of Chemical Biology and Drug Discovery, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, China; Research Institute for Smart Ageing, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, China; Research Institute for Future Food, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, China; PolyU-BGI Joint Research Centre for Genomics and Synthetic Biology in Global Deep Ocean Resource, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, China. Electronic address: simon-my.lee@polyu.edu.hk.
PMID: 39233265 DOI: 10.1016/j.cbi.2024.111224
Abstract

Parkinson's disease (PD) poses a formidable challenge in neurology, marked by progressive neuronal loss in the substantia nigra. Despite extensive investigations, understanding PD's pathophysiology remains elusive, with no effective therapeutic intervention identified to alter its course. Oxyphylla A (OPA), a natural compound extracted from Alpinia oxyphylla, exhibits promise in experimental models of various neurodegenerative disorders (ND), notably through novel mechanisms like α-synuclein degradation. The purpose of this investigation was to explore the neuroprotective potential of OPA on 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in PD models, with a focus on mitochondrial functions. Additionally, potential OPA targets for neuroprotection were explored. PC12 cells and C57BL/6 mice were lesioned with 6-OHDA as PD models. Impaired mitochondrial membrane potential (Δψm) was assessed using JC-1 staining. The oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) were also detected to evaluate mitochondrial function and glucose metabolism in PC12 cells. Behavioral analysis and immunohistochemistry were performed to evaluate pathological lesions in the mouse brain. Moreover, bioinformatics tools predicted OPA targets. OPA restored cellular energy metabolism and mitochondrial biogenesis, preserving Δψm in 6-OHDA-induced neuronal damage. Pre-treatment mitigated loss of tyrosine hydroxylase (TH)-positive neurons in the substantia nigra and striatal dopaminergic fibers, restoring dopamine levels and ameliorating motor deficits in PD mice. Mechanistically, OPA may activate PKA/Akt/GSK-3β and CREB/PGC-1α/NRF-1/TFAM signaling cascades. Bioinformatics analysis identified potential OPA targets, including CTNNB1, ESR1, MAPK1, MAPK14, and Src. OPA, derived from Alpinia oxyphylla, exhibited promising neuroprotective activity against PD through addressing mitochondrial dysfunction, suggesting its potential as a multi-targeted therapeutic for PD.

Keywords

6-OHDA; Mitochondria; Neuroprotection; Oxyphylla A; Parkinson's disease; Target prediction.

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