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Isoquercitrin isolated from newly bred Green ball apple peel in lipopolysaccharide-stimulated macrophage regulates NF-κB inflammatory pathways and cytokines

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Abstract

Apple peel has several bioactive properties. The fruit is grown worldwide, and its ingredients are used medicinally. However, its anti-inflammatory activities are poorly characterized. In this study, isoquercitrin isolated from newly bred Green ball apple peel from Korea showed anti-inflammatory effects. To confirm its anti-inflammatory effects, isoquercitrin was treated with lipopolysaccharide, which induces proinflammatory factors in Raw 264.7 macrophage cells. Proinflammatory effects were measured by real-time polymerase chain reaction and Western blotting as well as enzyme-linked immunosorbent assay. Cell viability was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay to define the isoquercitrin concentration nontoxic to cells. Nitric oxide (NO) production, prostaglandin E2, inducible NO synthase, cyclooxygenase-2 (COX-2), and nuclear factor-κB p65 protein expression decreased in a concentration-dependent manner by isoquercitrin. mRNA expression of tumor necrosis factor-α, interleukin (IL)-1β, IL-6, monocyte chemoattractant protein-1, and prostaglandin E synthase 2 (PTGES2) as proinflammatory factors significantly decreased. PTGES2, which was stimulated by COX-2 and involved in PGE2 expression, was inhibited. Therefore, this study rendered isoquercitrin isolated from the newly bred Green ball apple peel as a potential pharmacological alternative to treat inflammation-related diseases.

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Availability of data and materials

All data analyzed during this study are included in this published article.

Abbreviations

COX-2:

Cyclooxygenase-2

DMSO:

Dimethyl sulfoxide

HA:

Hyaluronic acid

HAase:

Hyaluronidase

IL:

Interleukin

iNOS:

Inducible nitric oxide synthase

LPS:

Lipopolysaccharide

MCP-1:

Monocyte chemoattractant protein-1

MTT:

3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

NF-κB:

Nuclear factor-κB

NO:

Nitric oxide

PBS:

Phosphate-buffered saline

PCR:

Polymerase chain reaction

PGE2 :

Prostaglandin E2

PTGES2:

Prostaglandin E synthase 2

TNF-α:

Tumor necrosis factor-α

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Authors

Contributions

EL contributed to conceptualization, methodology, visualization, and writing––original draft. HP was involved in conceptualization, investigation, writing––review and editing. HJ contributed to validation and data curation. IK and BK were involved in visualization and formal analysis. YC contributed to supervision and writing––review and editing.

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Correspondence to Young-Je Cho.

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The authors declare that they have no competing interests.

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Lee, EH., Park, HJ., Jung, HY. et al. Isoquercitrin isolated from newly bred Green ball apple peel in lipopolysaccharide-stimulated macrophage regulates NF-κB inflammatory pathways and cytokines. 3 Biotech 12, 100 (2022). https://doi.org/10.1007/s13205-022-03118-1

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