Shikonin inhibits TNF-α production through suppressing PKC-NF-κB-dependent decrease of IL-10 in rheumatoid arthritis-like cell model.

Abstract

Shikonin, a major effective component in the Chinese herbal medicine Lithospermum erythrorhizon Sieb., exhibits an anti-inflammatory property towards rheumatoid arthritis (RA), but the potential mechanism is unclear. Our aim was to investigate the mechanism of shikonin on the lipopolysaccharide (LPS)-induced fibroblast-like synoviocyte (LiFLS) inflammation model. Fibroblast-like synoviocytes (FLSs) were treated with 200 μg/ml of LPS for 24 h to establish the RA-like model, LiFLS. FLSs were pretreated with shikonin (0.1-1 μM) for 30 min in the treatment groups. Quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assays were used to detect mRNA and protein levels of interleukin (IL)-10 and tumor necrosis factor (TNF)-α. Signal proteins involved in IL-10 production were analyzed by Western blotting. Shikonin significantly reversed the inhibitory effects of LPS on IL-10 expression in FLSs by inactivating the PKC-NF-κB pathway. In addition, shikonin inhibited LPS-induced TNF-α expression in FLSs, and this effect was markedly diminished by IL-10-neutralizing antibody. The IL-10-mediated suppression of TNF-α transcription was demonstrated by no response to the protein synthesis inhibitor cyclohexamide and no mRNA decay. Shikonin inhibits LPS-induced TNF-α production in FLSs through suppressing the PKC-NF-κB-dependent decrease in IL-10, and this study also highlights the potential application of shikonin in the treatment of RA.

• Authors: Wen-Xiao Sun, Yan Liu, Wei Zhou, He-Wei Li, Jian Yang, Zhen-Bing Chen
• Journal: Journal of natural medicines (J Nat Med) Vol. 71 Issue 2 Pg. 349-356 (Apr 2017) ISSN: 1861-0293 [Electronic] Japan
• PMID: 27943122 (Publication Type: Journal Article)

Chemical References

• Drugs, Chinese Herbal
• NF-kappa B
• Naphthoquinones
• Tumor Necrosis Factor-alpha
• Interleukin-10
• shikonin

Topics

• Arthritis, Rheumatoid (drug therapy, immunology)
• Drugs, Chinese Herbal (analysis)
• Humans
• Interleukin-10 (metabolism)
• NF-kappa B (metabolism)
• Naphthoquinones (therapeutic use)
• Tumor Necrosis Factor-alpha (antagonists & inhibitors, metabolism)