Honokiol protects rats against eccentric exercise-induced skeletal muscle damage by inhibiting NF-κB induced oxidative stress and inflammation

Abstract

Honokiol, a bioactive component isolated from the Chinese herb Magnolia officinalis, is known for its potent antioxidative and anti-inflammatory effects. To study whether honokiol can protect skeletal muscle from sports injuries, we set up an eccentric exercise bout protocol for rats consisting of downhill running on a treadmill and examined the effect of oral administration of honokiol at 1 h before eccentric exercise at a dose of 5 mg/kg on day 1 (HK5 × 1) or 1 mg/kg/day for 5 consecutive days (HK1 × 5). Eccentric exercise was implemented for 3–5 consecutive days, and induced remarkable tissue damage. This damage was associated with an increase in serum creatine levels, increase in protein nitrotyrosylation, poly-ADP-ribose-polymerase (PARP) upregulation, lipid peroxidation, and leukocyte infiltration. The degree of muscle damage also paralleled dramatic gene expression for cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and inflammation-associated cytokines (interleukin (IL)-1β, IL-6, tumor necrosis factor-α, and monocyte chemoattractant protein-1), possibly through activation of nuclear factor kappa-B (NF-κB), a crucial proinflammatory transcription factor. Both honokiol treatments (HK5 × 1 and HK1 × 5) significantly ameliorated eccentric exercise-induced muscle damage as revealed by suppression of cell fragmentation, protein nitrotyrosylation and PARP upregulation, as well as reductions in lipid peroxidation and leukocyte infiltration, possibly through downregulating gene expression for COX-2, iNOS, and the proinflammatory cytokines by modulation of NF-κB activation. In conclusion, the present study demonstrates for the first time that honokiol exhibits protective effects against eccentric exercise-induced skeletal muscle damage in rats, probably by modulating inflammation-mediated damage to muscle cells.