Highlights
- •Kaempferol suppressed the bleomycin-induced dermal fibrosis in mice.
- •Kaempferol reduced oxidative stress in the bleomycin-induced fibrotic skin in vivo.
- •Kaempferol reduced inflammatory/fibrotic cytokines in bleomycin-treated skin.
- •Kaempferol reduced bleomycin-induced apoptosis in vivo.
- •Kaempferol reduced oxidant-induced ROS and apoptosis in SSc fibroblasts in vitro.
Abstract
Background
There is growing evidence that vasculopathy-induced hypoxia and oxidative stress enhance
the process of fibrosis in systemic sclerosis (SSc). Kaempferol is a natural flavonoid
widely found in various vegetables and fruits, and has been reported to have excellent
antioxidant activity.
Objective
Objective was to elucidate the effect of kaempferol on skin fibrosis and the mechanism
of the inhibitory regulation of fibrosis by kaempferol.
Methods
We assessed the effect of intraperitoneally administered kaempferol on bleomycin-induced
dermal fibrosis in mice. The effect of kaempferol on oxidative stress in bleomycin-treated
mice and SSc fibroblasts was assessed in vivo and in vitro.
Results
We identified that kaempferol injection significantly inhibited bleomycin-induced
dermal fibrosis in mice. The number of αSMA+ myofibroblasts, CD3+ T-cells, and CD68+ macrophages in lesional skin was significantly decreased by kaempferol injections.
Kaempferol administration also significantly suppressed the bleomycin-induced oxidative
stress signal in OKD48 mice. Additionally, mRNA levels of oxidative stress-associated
factors, such as HO-1 and NOX2, as well as inflammatory and pro-fibrotic cytokines,
including IL-6, TGF-β and TNFα in sclerotic skin were significantly decreased by kaempferol.
Kaempferol also reduced bleomycin-induced TUNEL+ apoptotic cells in the lesional skin of bleomycin-treated mice. Furthermore, the
oxidant-induced intracellular accumulation of reactive oxygen species (ROS) in SSc
fibroblasts was inhibited by kaempferol treatment. In addition, the oxidant-induced
apoptosis of SSc fibroblasts was decreased by kaempferol in vitro.
Conclusion
Kaempferol might improve bleomycin-induced fibrosis by reducing oxidative stress,
inflammation, and oxidative cellular damage. Administration of kaempferol might be
an alternative treatment for skin fibrosis in SSc.
Abbreviations:
ATP (adenosine triphosphate), ECs (endothelial cells), HO-1 (Heme Oxygenase 1), IL-6 (interleukin-6), Nox (nicotinamide adenine dinucleotide phosphate (NADPH) oxidase), Nrf2 (NF-E2-related factor 2), ROS (reactive oxygen species), SSc (systemic sclerosis), TGF-β (transforming growth factor-β), TNF-α (tumor necrosis factor-α), Trx2 (thioredoxin 2), TUNEL (terminal deoxynucleotide transferase dUTP nick end-labeling)Keywords
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Article Info
Publication History
Published online: August 16, 2019
Accepted:
August 14,
2019
Received in revised form:
July 30,
2019
Received:
May 13,
2019
Identification
Copyright
© 2019 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.
