Antioxidant and Neuroprotective Effects of Paeonol against Oxidative Stress and Altered Carrier-Mediated Transport System on NSC-34 Cell Lines

Paeonol is a naturally occurring phenolic agent that attenuates neurotoxicity in neurodegenerative diseases. We aimed to investigate the antioxidant and protective effects of paeonol and determine its transport mechanism in wild-type (WT; NSC-34/hSOD1<sup>WT</sup>) and mutant-type (MT; N...

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Main Authors: Sana Latif, Seung-Hye Choi, Asmita Gyawali, Seung Jae Hyeon, Young-Sook Kang, Hoon Ryu
Format: Article
Language:English
Published: MDPI AG 2022-07-01
Series:Antioxidants
Subjects:
Online Access:https://www.mdpi.com/2076-3921/11/7/1392
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author Sana Latif
Seung-Hye Choi
Asmita Gyawali
Seung Jae Hyeon
Young-Sook Kang
Hoon Ryu
author_facet Sana Latif
Seung-Hye Choi
Asmita Gyawali
Seung Jae Hyeon
Young-Sook Kang
Hoon Ryu
author_sort Sana Latif
collection DOAJ
description Paeonol is a naturally occurring phenolic agent that attenuates neurotoxicity in neurodegenerative diseases. We aimed to investigate the antioxidant and protective effects of paeonol and determine its transport mechanism in wild-type (WT; NSC-34/hSOD1<sup>WT</sup>) and mutant-type (MT; NSC-34/hSOD1<sup>G93A</sup>) motor neuron-like amyotrophic lateral sclerosis (ALS) cell lines. Cytotoxicity induced by glutamate, lipopolysaccharides, and H<sub>2</sub>O<sub>2</sub> reduced viability of cell; however, the addition of paeonol improved cell viability against neurotoxicity. The [<sup>3</sup>H]paeonol uptake was increased in the presence of H<sub>2</sub>O<sub>2</sub> in both cell lines. Paeonol recovered ALS model cell lines by reducing mitochondrial oxidative stress induced by glutamate. The transport of paeonol was time-, concentration-, and pH-dependent in both NSC-34 cell lines. Kinetic parameters showed two transport sites with altered affinity and capacity in the MT cell line compared to the WT cell line. [<sup>3</sup>H]Paeonol uptake increased in the MT cell line transfected with organic anion transporter1 (Oat1)/Slc22a6 small interfering RNA compared to that in the control. Plasma membrane monoamine transporter (Pmat) was also involved in the uptake of paeonol by ALS model cell lines. Overall, paeonol exhibits neuroprotective activity via a carrier-mediated transport system and may be a beneficial therapy for preventing motor neuronal damage under ALS-like conditions.
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spelling doaj.art-f79c1d4aa421454aa60ab939a4b4ae2f2023-12-03T14:34:26ZengMDPI AGAntioxidants2076-39212022-07-01117139210.3390/antiox11071392Antioxidant and Neuroprotective Effects of Paeonol against Oxidative Stress and Altered Carrier-Mediated Transport System on NSC-34 Cell LinesSana Latif0Seung-Hye Choi1Asmita Gyawali2Seung Jae Hyeon3Young-Sook Kang4Hoon Ryu5Research Institute of Pharmaceutical Sciences and College of Pharmacy, Sookmyung Women’s University, Seoul 04310, KoreaBrain Science Institute, Korea Institute of Science and Technology, Seoul 02792, KoreaResearch Institute of Pharmaceutical Sciences and College of Pharmacy, Sookmyung Women’s University, Seoul 04310, KoreaBrain Science Institute, Korea Institute of Science and Technology, Seoul 02792, KoreaResearch Institute of Pharmaceutical Sciences and College of Pharmacy, Sookmyung Women’s University, Seoul 04310, KoreaBrain Science Institute, Korea Institute of Science and Technology, Seoul 02792, KoreaPaeonol is a naturally occurring phenolic agent that attenuates neurotoxicity in neurodegenerative diseases. We aimed to investigate the antioxidant and protective effects of paeonol and determine its transport mechanism in wild-type (WT; NSC-34/hSOD1<sup>WT</sup>) and mutant-type (MT; NSC-34/hSOD1<sup>G93A</sup>) motor neuron-like amyotrophic lateral sclerosis (ALS) cell lines. Cytotoxicity induced by glutamate, lipopolysaccharides, and H<sub>2</sub>O<sub>2</sub> reduced viability of cell; however, the addition of paeonol improved cell viability against neurotoxicity. The [<sup>3</sup>H]paeonol uptake was increased in the presence of H<sub>2</sub>O<sub>2</sub> in both cell lines. Paeonol recovered ALS model cell lines by reducing mitochondrial oxidative stress induced by glutamate. The transport of paeonol was time-, concentration-, and pH-dependent in both NSC-34 cell lines. Kinetic parameters showed two transport sites with altered affinity and capacity in the MT cell line compared to the WT cell line. [<sup>3</sup>H]Paeonol uptake increased in the MT cell line transfected with organic anion transporter1 (Oat1)/Slc22a6 small interfering RNA compared to that in the control. Plasma membrane monoamine transporter (Pmat) was also involved in the uptake of paeonol by ALS model cell lines. Overall, paeonol exhibits neuroprotective activity via a carrier-mediated transport system and may be a beneficial therapy for preventing motor neuronal damage under ALS-like conditions.https://www.mdpi.com/2076-3921/11/7/1392paeonolneuroprotectionreduction-oxidation reactionscarrier-mediated transport systemorganic anion transporter 1 (Oat1)plasma membrane monoamine transporter (Pmat)
spellingShingle Sana Latif
Seung-Hye Choi
Asmita Gyawali
Seung Jae Hyeon
Young-Sook Kang
Hoon Ryu
Antioxidant and Neuroprotective Effects of Paeonol against Oxidative Stress and Altered Carrier-Mediated Transport System on NSC-34 Cell Lines
Antioxidants
paeonol
neuroprotection
reduction-oxidation reactions
carrier-mediated transport system
organic anion transporter 1 (Oat1)
plasma membrane monoamine transporter (Pmat)
title Antioxidant and Neuroprotective Effects of Paeonol against Oxidative Stress and Altered Carrier-Mediated Transport System on NSC-34 Cell Lines
title_full Antioxidant and Neuroprotective Effects of Paeonol against Oxidative Stress and Altered Carrier-Mediated Transport System on NSC-34 Cell Lines
title_fullStr Antioxidant and Neuroprotective Effects of Paeonol against Oxidative Stress and Altered Carrier-Mediated Transport System on NSC-34 Cell Lines
title_full_unstemmed Antioxidant and Neuroprotective Effects of Paeonol against Oxidative Stress and Altered Carrier-Mediated Transport System on NSC-34 Cell Lines
title_short Antioxidant and Neuroprotective Effects of Paeonol against Oxidative Stress and Altered Carrier-Mediated Transport System on NSC-34 Cell Lines
title_sort antioxidant and neuroprotective effects of paeonol against oxidative stress and altered carrier mediated transport system on nsc 34 cell lines
topic paeonol
neuroprotection
reduction-oxidation reactions
carrier-mediated transport system
organic anion transporter 1 (Oat1)
plasma membrane monoamine transporter (Pmat)
url https://www.mdpi.com/2076-3921/11/7/1392
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