Orange peel extract reduces the inflammatory state of skeletal muscle after downhill running via an increase in IL-1RA

• Published in: Bioscience, biotechnology, and biochemistry biotechnology, and biochemistry, 2021-05, Vol.85 (6), p.1506-1513
• Main Authors: Suzuki, Toshihide, Shimizu, Makoto, Yamauchi, Yoshio, Sato, Ryuichiro
• Format: Article
• Language: English
• ISSN: 1347-6947; 1347-6947
• DOI: 10.1093/bbb/zbab049

ABSTRACT It has been reported that orange peel extract (OPE) and the 4 major polymethoxyflavones (PMFs) in OPE have a protective effect against downhill running (DR)-induced skeletal muscle inflammation. However, the mechanism is not well understood. We investigated the potential of OPE and PMF compounds for increasing anti-inflammatory cytokine levels. The plasma interleukin-1 receptor antagonist (IL-1RA) level was increased 1 and 8 h after OPE administration in rats. Nobiletin induced the secretion of IL-1RA from C2C12 myotubes. In the inflammatory state of skeletal muscle after DR, OPE administration reduced nuclear factor kappa-light-chain enhancer of activated B cells (NF-κB) expression, NF-κB-DNA binding, and monocyte chemotactic protein-1 mRNA levels, but these effects were all abrogated by the intravenous administration of IL-1RA neutralizing antibody. These results indicated that OPE reduces skeletal muscle inflammatory state after DR via an increase in IL-1RA, and that IL-1 receptor signaling is important for skeletal muscle inflammation after DR.