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Honokiol protects rats against eccentric exercise-induced skeletal muscle damage by inhibiting NF-kappaB 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 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.
AuthorsJasson Chiang, Yuh-Chiang Shen, Yea-Hwey Wang, Yu-Chang Hou, Chien-Chih Chen, Jyh-Fei Liao, Min-Chien Yu, Chi-Wen Juan, Kuo-Tong Liou
JournalEuropean journal of pharmacology (Eur J Pharmacol) Vol. 610 Issue 1-3 Pg. 119-27 (May 21 2009) ISSN: 1879-0712 [Electronic] Netherlands
PMID19303869 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Biphenyl Compounds
  • Chemokine CCL2
  • Interleukin-1beta
  • Interleukin-6
  • Lignans
  • Proteins
  • Tumor Necrosis Factor-alpha
  • honokiol
  • Creatinine
  • Cyclooxygenase 2
  • Poly(ADP-ribose) Polymerases
Topics
  • Animals
  • Biphenyl Compounds (pharmacology)
  • Chemokine CCL2 (metabolism)
  • Creatinine (blood)
  • Cyclooxygenase 2 (metabolism)
  • Dose-Response Relationship, Drug
  • Gene Expression
  • Inflammation (metabolism)
  • Interleukin-1beta (metabolism)
  • Interleukin-6 (metabolism)
  • Lignans (pharmacology)
  • Lipid Peroxidation (drug effects)
  • Male
  • Muscle, Skeletal (injuries)
  • Oxidative Stress (drug effects)
  • Physical Conditioning, Animal
  • Poly(ADP-ribose) Polymerases (metabolism)
  • Proteins (metabolism)
  • Rats
  • Rats, Wistar
  • Time Factors
  • Tumor Necrosis Factor-alpha (genetics, metabolism)
  • Up-Regulation (drug effects)

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