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

Sana Latif; Seung-Hye Choi; Asmita Gyawali; Seung Jae Hyeon; Young-Sook Kang; Hoon Ryu

doi:10.3390/antiox11071392

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

Antioxidants (Basel). 2022 Jul 18;11(7):1392. doi: 10.3390/antiox11071392.

Authors

Sana Latif¹, Seung-Hye Choi², Asmita Gyawali¹, Seung Jae Hyeon², Young-Sook Kang¹, Hoon Ryu²

Affiliations

¹ Research Institute of Pharmaceutical Sciences and College of Pharmacy, Sookmyung Women's University, Seoul 04310, Korea.
² Brain Science Institute, Korea Institute of Science and Technology, Seoul 02792, Korea.

Abstract

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^WT) and mutant-type (MT; NSC-34/hSOD1^G93A) motor neuron-like amyotrophic lateral sclerosis (ALS) cell lines. Cytotoxicity induced by glutamate, lipopolysaccharides, and H₂O₂ reduced viability of cell; however, the addition of paeonol improved cell viability against neurotoxicity. The [³H]paeonol uptake was increased in the presence of H₂O₂ 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. [³H]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.

Keywords: NSC-34 cell lines; amyotrophic lateral sclerosis (ALS); carrier-mediated transport system; neuroprotection; organic anion transporter 1 (Oat1); paeonol; plasma membrane monoamine transporter (Pmat); reduction-oxidation reactions.

Grants and funding

This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (Grant Number 2019R1F1A1044048 to YSK, 2020M3E5D9079744 and 2022R1A2C3013138 to HR), and K-Lab Grants from Korea Institute of Science and Technology (2E31504 and 2E31505) from the Korea Institute of Science and Technology of South Korea.