title: 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.
authors.affiliation: Research Institute, Bio-Port Korea INC, Marine Bio-industry Development Center, Busan 619-912, Republic of Korea.
authors.forename: Joo Wan
authors.initials: JW
authors.lastname: Kim
authors.affiliation: Department of Anatomy and Histology, College of Korean Medicine, Daegu Haany University, Gyeongsan 712‑715, Republic of Korea.
authors.forename: Sae-Kwang
authors.initials: SK
authors.lastname: Ku
authors.affiliation: Department of Biochemistry, Dongeui University College of Korean Medicine, Busan 614-052, Republic of Korea.
authors.forename: Min Ho
authors.initials: MH
authors.lastname: Han
authors.affiliation: Research Institute, Bio-Port Korea INC, Marine Bio-industry Development Center, Busan 619-912, Republic of Korea.
authors.forename: Ki Young
authors.initials: KY
authors.lastname: Kim
authors.affiliation: Research Institute, Bio-Port Korea INC, Marine Bio-industry Development Center, Busan 619-912, Republic of Korea.
authors.forename: Sung Goo
authors.initials: SG
authors.lastname: Kim
authors.affiliation: Laboratory of Immunobiology, Department of Marine Life Sciences, Jeju National University, Jeju 690-756, Republic of Korea.
authors.forename: Gi-Young
authors.initials: GY
authors.lastname: Kim
authors.affiliation: Anti-Aging Research Center and Blue-Bio Industry RIC, Dongeui University, Busan 614-714, Republic of Korea.
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Hwang
authors.affiliation: Anti-Aging Research Center and Blue-Bio Industry RIC, Dongeui University, Busan 614-714, Republic of Korea.
authors.forename: Byung Woo
authors.initials: BW
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, Busan National University College of Medicine, Yangsan 626-870, Republic of Korea.
authors.forename: Cheol Min
authors.initials: CM
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, Dongeui University College of Korean Medicine, Busan 614-052, Republic of Korea.
authors.forename: Yung Hyun
authors.initials: YH
authors.lastname: Choi
mesh_terms: D000447:Aldehydes / Q000276:immunology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D000975:Antioxidants / Q000627:therapeutic use; D003401:Creatine / Q000097:blood; D003402:Creatine Kinase / Q000097:blood; D003907:Dexamethasone / Q000494:pharmacology; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D005355:Fibrosis / Q000188:drug therapy / Q000517:prevention & control; D007770:L-Lactate Dehydrogenase / Q000097:blood; D051379:Mice; D008813:Mice, Inbred ICR; D009124:Muscle Proteins / Q000235:genetics; D053580:Muscle Strength / Q000187:drug effects*; D009129:Muscle Tonus / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects / Q000473:pathology*; D009133:Muscular Atrophy / Q000188:drug therapy* / Q000517:prevention & control; D055435:Myostatin / Q000096:biosynthesis / Q000276:immunology; D052247:Nitric Oxide Synthase Type II / Q000276:immunology; D010110:Oxymetholone / Q000494:pharmacology; D058539:Phosphatidylinositol 3-Kinase / Q000235:genetics; D014176:Protein Biosynthesis / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D043682:Receptor, Adenosine A1 / Q000235:genetics; D044843:SKP Cullin F-Box Protein Ligases / Q000235:genetics; D032141:Schisandra / Q000378:metabolism*; D056564:Sirtuin 1 / Q000235:genetics; D050916:TRPV Cation Channels / Q000235:genetics; D000070584:Tripartite Motif Proteins; D014443:Tyrosine / Q000031:analogs & derivatives / Q000276:immunology; D044767:Ubiquitin-Protein Ligases / Q000235:genetics
chemical_list: D000447:Aldehydes; D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D004365:Drugs, Chinese Herbal; D009124:Muscle Proteins; D055435:Myostatin; D012333:RNA, Messenger; D043682:Receptor, Adenosine A1; D050916:TRPV Cation Channels; D000070584:Tripartite Motif Proteins; C486576:Trpv4 protein, mouse; C002744:3-nitrotyrosine; D014443:Tyrosine; D003907:Dexamethasone; D007770:L-Lactate Dehydrogenase; D052247:Nitric Oxide Synthase Type II; C486691:Fbxo32 protein, mouse; D044843:SKP Cullin F-Box Protein Ligases; C499084:Trim63 protein, mouse; D044767:Ubiquitin-Protein Ligases; D058539:Phosphatidylinositol 3-Kinase; C514862:Akt1 protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D003402:Creatine Kinase; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1; C027576:4-hydroxy-2-nonenal; D010110:Oxymetholone; D003401:Creatine