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 x 1) or 1 mg/kg/day for 5 consecutive days (HK1 x 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)-1beta, IL-6,
tumor necrosis factor-alpha, and
monocyte chemoattractant protein-1), possibly through activation of
nuclear factor kappa-B (
NF-kappaB), a crucial proinflammatory
transcription factor. Both
honokiol treatments (HK5 x 1 and HK1 x 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-kappaB 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.