lignans and Muscular-Atrophy

Topics: Alnus; Dexamethasone; Lignans; Muscle Development; Muscle Fibers, Skeletal; Muscle, Skeletal; Muscular Atrophy; p38 Mitogen-Activated Protein Kinases

Schisandra chinensis fruit (Omiza in Korean), used for the production tea or liquor, and is known to enhance skeletal muscle function. However, the effect of Omiza extract (OM) on obesity-induced skeletal muscle atrophy remains unclear. This study investigated the effect of OM on skeletal muscle mass and performance in obese mice. OM increased skeletal muscle weight, size and improved skeletal muscle performance. Further, it also suppressed obesity-induced increases in proinflammatory cytokines, MuRF1, and Atrogin1 in mouse skeletal muscle and enhanced the expression of MHC and the phosphorylation of AKT/mTOR signaling molecules, thereby suppressing myostatin expression and regulating Smad-FOXO signaling. Schizandrin B, a major component of OM inhibited palmitic acid induced atrophy in C2C12 cells via Smad-FOXO regulation, suggesting that it partially contributed to the effects of OM against obesity-induced muscle atrophy. Taken together, OM may have the potential to prevent and treat obesity-induced muscle atrophy.

Topics: Animals; Cyclooctanes; Fruit; Lignans; Mice; Muscle, Skeletal; Muscular Atrophy; Obesity; Polycyclic Compounds; Schisandra

Topics: Animals; Hydrogen Peroxide; Lignans; Mice; Muscle Strength; Muscle, Skeletal; Muscular Atrophy; Muscular Diseases; Muscular Disorders, Atrophic; Organelle Biogenesis

Topics: Animals; Cells, Cultured; Cyclooctanes; Dexamethasone; Gene Expression; Lignans; Male; Mice, Inbred C57BL; Muscle Proteins; Muscle Strength; Muscle, Skeletal; Muscular Atrophy; Myosin Heavy Chains; Myostatin; Organ Size; Phytotherapy; Polycyclic Compounds; Proto-Oncogene Proteins c-akt; Schisandra; SKP Cullin F-Box Protein Ligases; Tripartite Motif Proteins; Ubiquitin-Protein Ligases

Cancer cachexia is a complex and multifactorial syndrome that influences about 50-80% of cancer patients and may lead to 20% of cancer deaths and muscle atrophy is the key characteristic of the syndrome. Recent researches have shown that myostatin is a negative regulator in the growth and differentiation of skeletal muscle. Herein, C2C12 cancer cachexia model was established with C26 conditioned culture medium (CCM), then treated with magnolol to evaluate the pharmacological activity of magnolol in myotube atrophy. Our results demonstrated that magnolol inhibited the activity of myostatin promotor and the myostatin signaling pathway. In C2C12 cancer cachexia model, magnolol decreased myostatin expression, inhibited the phosphorylation of SMAD2/3 activated by C26 conditioned culture medium (CCM), and elevated the phosphorylation of FOXO3a lowered by CCM. Myosin heavy chain (MyHC), myogenin (MyoG), and myogenic differentiation (MyoD), as three common myotube markers in C2C12 myotube, were decreased by CCM, which could be effectively reversed by magnolol via activation of AKT/mTOR-regulated protein synthesis and inhibition of ubiquitin-mediated proteolysis. This study reveals that magnolol inhibits myotube atrophy induced by CCM by increasing protein synthesis and decreasing ubiquitin-mediated proteolysis, so that magnolol is a promising leading compound in treating muscle atrophy induced by cancer cachexia.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Biological Products; Biphenyl Compounds; Cachexia; Cell Line, Tumor; Humans; Lignans; Mice; Muscle Fibers, Skeletal; Muscular Atrophy; Myostatin; Neoplasms; Transfection

Skeletal muscle atrophy, the most prominent phenotypic feature of cancer cachexia, is often observed in cancer patients undergoing chemotherapy. Magnolol (M) extracted from Magnolia officinalis exhibits several pharmacological effects including anti-inflammatory and anticancer activities. In this study, we investigated whether magnolol supplementation protects against the development of cachexia symptoms in bladder cancer-bearing mice undergoing chemotherapy. Combined treatment of magnolol with chemotherapeutic drugs, such as gemcitabine and cisplatin (TGCM) or gemcitabine (TGM), markedly attenuates the body weight loss and skeletal muscle atrophy compared with conventional chemotherapy (TGC). The antiatrophic effect of magnolol may be associated with inhibition of myostatin and activin A formation, as well as FoxO3 transcriptional activity resulting from Akt activation, thereby suppressing ubiquitin ligases MuRF-1 and MAFbx/atrogin-1 expression, as well as proteasomal enzyme activity. Notably, magnolol-induced insulin-like growth factor 1 (IGF-1) production and related protein synthesis may also contribute to its protective effects. The decreased food intake, and intestinal injury and dysfunction observed in the mice of TGC group were significantly improved in the TGCM and TGM groups. Moreover, the increased inflammatory responses evidenced by elevation of proinflammatory cytokine formation and NF-κB activation occurred in the atrophying muscle of TGC group were markedly inhibited in mice of combined treatment with magnolol. In summary, these findings support that magnolol is a promising chemopreventive supplement for preventing chemotherapy-induced skeletal muscle atrophy associated with cancer cachexia by suppressing muscle protein degradation, and inflammatory responses, as well as increasing IGF-1-mediated protein synthesis.

Topics: Animals; Biphenyl Compounds; Body Weight; Forkhead Box Protein O3; Forkhead Transcription Factors; Insulin-Like Growth Factor I; Interleukin-6; Lignans; Male; Mice; Mice, Nude; Muscular Atrophy; NF-kappa B; Proteasome Endopeptidase Complex; Tumor Necrosis Factor-alpha; Urinary Bladder Neoplasms