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KMID : 0613820210310090818
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Journal of Life Science
2021 Volume.31 No. 9 p.818 ~ p.826
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Attenuation of Lipopolysaccharide-induced Inflammatory and Oxidative Response by 5-Aminolevulinic Acid Phosphate in RAW 264.7 Macrophages
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Ji Seon-Yeong
Kim Min-Yeong
Hwangbo Hyun
Lee Hye-Sook
Hong Su-Hyun
Cha Hee-Jae
Kim Heui-Soo
Kim Suhk-Mann
Choi Yung-Hyun
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Abstract
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5-Aminolevulinic acid phosphate (5-ALA-p) is a substance obtained by eluting 5-ALA (a natural delta amino acid) with aqueous ammonia, adding phosphoric acid to the eluate, and then adding acetone to confer properties suitable for use in photodynamic therapy applications. However, its pharmacological efficacy, including potential mechanisms of antioxidant and anti-inflammatory reactions, remains unclear. This study aimed to investigate the effects of 5-ALA-p on oxidative and inflammatory stresses in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Our data showed that 5-ALA-p significantly inhibited excessive phagocytic activity via LPS and attenuated oxidative stress in LPS-treated RAW 264.7 cells. Furthermore, 5-ALA-p improved mitochondrial biogenesis reduced by LPS, suggesting that 5-ALA-p restores mitochondrial damage caused by LPS. Additionally, 5-ALA-p significantly suppressed the release of nitric oxide (NO) and pro-inflammatory cytokines, such as tumor necrosis factor α (TNF-α), interleukin (IL)-1β, and IL-6, which are associated with the inhibition of inducible NO synthase and respective cytokine expression. Furthermore, 5-ALA-p reduced the nuclear translocation of nuclear factor-kappa B (NF-κB) and inhibited phosphorylation of mitogen-activated protein kinases (MAPKs), indicating that the anti-inflammatory effect of 5-ALA-p is mediated through the suppression of NF-κB and MAPK signaling pathways. Based on these results, 5-ALA-p may serve as a potential candidate to reduce inflammation and oxidative stress.
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KEYWORD
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5-Aminolevulinic acid phosphate, inflammation, MAPKs, NF-κB, oxidative stress
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