Anti-Oxidative Effects of Melatonin Receptor Agonist and Omega-3 Polyunsaturated Fatty Acids in Neuronal SH-SY5Y Cells

Deciphering Synergic Effects on Anti-Depressant Mechanisms

Senthil Kumaran Satyanarayanan, Yin Hwa Shih, Yu Chuan Chien, Shih Yi Huang, Piotr Gałecki, Siegfried Kasper, Jane Pei Chen Chang, Kuan Pin Su

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Omega-3 polyunsaturated fatty acids (n-3 or omega-3 PUFAs) and melatonin receptor agonist ramelteon (RMT) both display antidepressant effects, while their cellular effects on anti-oxidative and neuroprotective mechanisms might be different. In this study, we aimed to decipher the individual and synergistic actions of n-3 PUFAs and RMT, as compared with the conventional antidepressant fluoxetine (FLX), in a cellular model of oxidative stress, which might play an important role in the pathophysiology of depression and associated disorders. We investigated the rescue and prevention effects of FLX, RMT, and n-3 PUFAs, e.g., eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), by using cell viability in SH-SY5Y cells under oxidative stress along with measurements of key cellular markers of oxidative stress, inflammatory, and neuroprotection. The results revealed that the RMT and EPA combination significantly increased the cell viability in a dose-dependent manner. RMT showed preventive effects, FLX and DHA possessed rescue effects, while EPA showed both rescue and preventive effects. We observed the dose-dependent activation and translocation of nuclear factor-κB to the nucleus augmented by the expressions of peroxisome proliferator activator receptor-gamma, tyrosine hydroxylase, c-Fos expression, and reactive oxygen species, implying that RMT and EPA combination reversed oxidative and neuroinflammatory pathophysiology and protected the neuronal cells from further damage. The results demonstrated that RMT and EPA synergistically provide effective neuroprotective, anti-oxidative/inflammatory effect against oxidative stress. Our study provides pre-clinical evidence to conduct future clinical trials of using n-3 PUFAs/RMT combination in depressive disorders.

Original languageEnglish
Pages (from-to)1-14
Number of pages14
JournalMolecular Neurobiology
DOIs
Publication statusAccepted/In press - Feb 3 2018

Fingerprint

Melatonin Receptors
Omega-3 Fatty Acids
Unsaturated Fatty Acids
Eicosapentaenoic Acid
Fluoxetine
Oxidative Stress
Docosahexaenoic Acids
Antidepressive Agents
Cell Survival
Peroxisome Proliferators
ramelteon
Tyrosine 3-Monooxygenase
Depressive Disorder
Reactive Oxygen Species
Anti-Inflammatory Agents
Clinical Trials
Depression

Keywords

  • Circadian rhythm
  • Depression
  • EPA DHA
  • Omega-3 fatty acids
  • Oxidative stress
  • Ramelteon

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

Cite this

Anti-Oxidative Effects of Melatonin Receptor Agonist and Omega-3 Polyunsaturated Fatty Acids in Neuronal SH-SY5Y Cells : Deciphering Synergic Effects on Anti-Depressant Mechanisms. / Satyanarayanan, Senthil Kumaran; Shih, Yin Hwa; Chien, Yu Chuan; Huang, Shih Yi; Gałecki, Piotr; Kasper, Siegfried; Chang, Jane Pei Chen; Su, Kuan Pin.

In: Molecular Neurobiology, 03.02.2018, p. 1-14.

Research output: Contribution to journalArticle

Satyanarayanan, Senthil Kumaran ; Shih, Yin Hwa ; Chien, Yu Chuan ; Huang, Shih Yi ; Gałecki, Piotr ; Kasper, Siegfried ; Chang, Jane Pei Chen ; Su, Kuan Pin. / Anti-Oxidative Effects of Melatonin Receptor Agonist and Omega-3 Polyunsaturated Fatty Acids in Neuronal SH-SY5Y Cells : Deciphering Synergic Effects on Anti-Depressant Mechanisms. In: Molecular Neurobiology. 2018 ; pp. 1-14.
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abstract = "Omega-3 polyunsaturated fatty acids (n-3 or omega-3 PUFAs) and melatonin receptor agonist ramelteon (RMT) both display antidepressant effects, while their cellular effects on anti-oxidative and neuroprotective mechanisms might be different. In this study, we aimed to decipher the individual and synergistic actions of n-3 PUFAs and RMT, as compared with the conventional antidepressant fluoxetine (FLX), in a cellular model of oxidative stress, which might play an important role in the pathophysiology of depression and associated disorders. We investigated the rescue and prevention effects of FLX, RMT, and n-3 PUFAs, e.g., eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), by using cell viability in SH-SY5Y cells under oxidative stress along with measurements of key cellular markers of oxidative stress, inflammatory, and neuroprotection. The results revealed that the RMT and EPA combination significantly increased the cell viability in a dose-dependent manner. RMT showed preventive effects, FLX and DHA possessed rescue effects, while EPA showed both rescue and preventive effects. We observed the dose-dependent activation and translocation of nuclear factor-κB to the nucleus augmented by the expressions of peroxisome proliferator activator receptor-gamma, tyrosine hydroxylase, c-Fos expression, and reactive oxygen species, implying that RMT and EPA combination reversed oxidative and neuroinflammatory pathophysiology and protected the neuronal cells from further damage. The results demonstrated that RMT and EPA synergistically provide effective neuroprotective, anti-oxidative/inflammatory effect against oxidative stress. Our study provides pre-clinical evidence to conduct future clinical trials of using n-3 PUFAs/RMT combination in depressive disorders.",
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AU - Chien, Yu Chuan

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