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

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/hSOD1WT) and mutant-type (MT; NSC-34/hSOD1G93A) 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.

Multi-Targeting Neuroprotective Effects of Syzygium aromaticum Bud Extracts and Their Key Phytocompounds against Neurodegenerative Diseases

“…Eugenol scavenges free radicals by donating the phenolic hydroxyl group [23]. Much literature is unavailable on TMA, but Paeonol (2 -Hydroxy-4 -methoxyacetophenone), a structurally similar compound to TMA, has shown neuroprotection in vivo and in vitro by reducing oxidative stress [64,65]. A previous study suggested that eugenol, being lipophilic, influences the redistribution of protons across the membrane, thereby affecting membrane potential [66].…”

Protective mechanism of Paeonol on central nervous system

“…The anesthetic isoflurane has neurotoxicity, and its long-term use in the developing brain will lead to cognitive impairment and memory impairment (Culley et al, 2004;DiMaggio et al, 2011) et al, 2022). Similarly, it improves amyotrophic lateral sclerosis by reducing glutamate levels to inhibit oxidative stress (Latif et al, 2022).…”

“…It mainly upregulates MDA, ROS, and TNF‐α and downregulates GSH and SOD levels in the hippocampus to reduce oxidative stress and inflammatory response and at the same time reduces neutrophil infiltration (Pourmohammadi et al, 2022). Similarly, it improves amyotrophic lateral sclerosis by reducing glutamate levels to inhibit oxidative stress (Latif et al, 2022). It alleviates dry skin pruritus and reduces the expression of Chemokine C‐X‐C‐Motif receptor 3 (CXCR3) in spinal cord neurons, thus inhibiting the activation of astrocytes (Wang et al, 2021).…”

Pharmacological effects and mechanisms of paeonol on antitumor and prevention of side effects of cancer therapy

“…Paeonol, chemically known as 2-hydroxy-4-methoxy acetophenone, and the chemical structures are presented in Figure 1 . It has a low molecular weight of 166.17 g/mol and a melting point of 52°C ( Latif et al, 2022 ). It has been found to exert antitumor effects through various molecular mechanisms ( Fu et al, 2018 ; Cai et al, 2020 ; Zhang et al, 2020a ).…”