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The administration of Fructus Schisandrae attenuates dexamethasone-induced muscle atrophy in mice.

Abstract
In the present study, we aimed to determine whether ethanol extracts of Fructus Schisandrae (FS), the dried fruit of Schizandra chinensis Baillon, mitigates the development of dexamethasone-induced muscle atrophy. Adult SPF/VAT outbred CrljOri:CD1 (ICR) mice were either treated with dexamethasone to induce muscle atrophy. Some mice were treated with various concentrations of FS or oxymetholone, a 17α-alkylated anabolic-androgenic steroid. Muscle thickness and weight, calf muscle strength, and serum creatine and creatine kinase (CK) levels were then measured. The administration of FS attenuated the decrease in calf thickness, gastrocnemius muscle thickness, muscle strength and weight, fiber diameter and serum lactate dehydrogenase levels in the gastrocnemius muscle bundles which was induced by dexamethasone in a dose-dependent manner. Treatment with FS also prevented the dexamethasone-induced increase in serum creatine and creatine kinase levels, histopathological muscle fiber microvacuolation and fibrosis, and the immunoreactivity of muscle fibers for nitrotyrosine, 4-hydroxynonenal, inducible nitric oxide synthase and myostatin. In addition, the destruction of the gastrocnemius antioxidant defense system was also inhibited by the administration of FS in a dose-dependent manner. FS downregulated the mRNA expression of atrogin-1 and muscle ring-finger protein-1 (involved in muscle protein degradation), myostatin (a potent negative regulator of muscle growth) and sirtuin 1 (a representative inhibitor of muscle regeneration), but upregulated the mRNA expression of phosphatidylinositol 3-kinase, Akt1, adenosine A1 receptor and transient receptor potential cation channel subfamily V member 4, involved in muscle growth and the activation of protein synthesis. The overall effects of treatment with 500 mg/kg FS were comparable to those observed following treatment with 50 mg/kg oxymetholone. The results from the present study support the hypothesis that FS has a favorable ameliorating effect on muscle atrophy induced by dexamethasone, by exerting anti-inflammatory and antioxidant effects on muscle fibers, which may be due to an increase in protein synthesis and a decrease in protein degradation.
AuthorsJoo Wan Kim, Sae-Kwang Ku, Min Ho Han, Ki Young Kim, Sung Goo Kim, Gi-Young Kim, Hye Jin Hwang, Byung Woo Kim, Cheol Min Kim, Yung Hyun Choi
JournalInternational journal of molecular medicine (Int J Mol Med) Vol. 36 Issue 1 Pg. 29-42 (Jul 2015) ISSN: 1791-244X [Electronic] Greece
PMID25955031 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Aldehydes
  • Anti-Inflammatory Agents
  • Antioxidants
  • Drugs, Chinese Herbal
  • Muscle Proteins
  • Myostatin
  • RNA, Messenger
  • Receptor, Adenosine A1
  • TRPV Cation Channels
  • Tripartite Motif Proteins
  • Trpv4 protein, mouse
  • 3-nitrotyrosine
  • Tyrosine
  • Dexamethasone
  • L-Lactate Dehydrogenase
  • Nitric Oxide Synthase Type II
  • Fbxo32 protein, mouse
  • SKP Cullin F-Box Protein Ligases
  • Trim63 protein, mouse
  • Ubiquitin-Protein Ligases
  • Phosphatidylinositol 3-Kinase
  • Akt1 protein, mouse
  • Proto-Oncogene Proteins c-akt
  • Creatine Kinase
  • Sirt1 protein, mouse
  • Sirtuin 1
  • 4-hydroxy-2-nonenal
  • Oxymetholone
  • Creatine
Topics
  • Aldehydes (immunology)
  • Animals
  • Anti-Inflammatory Agents (therapeutic use)
  • Antioxidants (therapeutic use)
  • Creatine (blood)
  • Creatine Kinase (blood)
  • Dexamethasone (pharmacology)
  • Drugs, Chinese Herbal (therapeutic use)
  • Fibrosis (drug therapy, prevention & control)
  • L-Lactate Dehydrogenase (blood)
  • Mice
  • Mice, Inbred ICR
  • Muscle Proteins (genetics)
  • Muscle Strength (drug effects)
  • Muscle Tonus (drug effects)
  • Muscle, Skeletal (drug effects, pathology)
  • Muscular Atrophy (drug therapy, prevention & control)
  • Myostatin (biosynthesis, immunology)
  • Nitric Oxide Synthase Type II (immunology)
  • Oxymetholone (pharmacology)
  • Phosphatidylinositol 3-Kinase (genetics)
  • Protein Biosynthesis (genetics)
  • Proto-Oncogene Proteins c-akt (genetics)
  • RNA, Messenger (biosynthesis)
  • Receptor, Adenosine A1 (genetics)
  • SKP Cullin F-Box Protein Ligases (genetics)
  • Schisandra (metabolism)
  • Sirtuin 1 (genetics)
  • TRPV Cation Channels (genetics)
  • Tripartite Motif Proteins
  • Tyrosine (analogs & derivatives, immunology)
  • Ubiquitin-Protein Ligases (genetics)

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