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Triptolide obtained from\n                      <jats:italic>Tripterygium wilfordii<\/jats:italic>\n                      Hook F possesses potent anti\u2010inflammatory and immunosuppressive effects. The present study aims to evaluate the protective effects and molecular mechanisms of triptolide on inflammation\u2010induced skeletal muscle atrophy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>The effects of triptolide on skeletal muscle atrophy were investigated in LPS\u2010treated C2C12 myotubes and C57BL\/6 mice. Protein expressions and mRNA levels were analysed by western blot and qPCR, respectively. Skeletal muscle mass, volume and strength were measured by histological analysis, micro\u2010CT and grip strength, respectively. Locomotor activity was measured using the open field test.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>KEY RESULTS<\/jats:title>\n                    <jats:p>\n                      Triptolide (10\u2013100\u2009fM) up\u2010regulated protein synthesis signals (IGF\u20101\/p\u2010IGF\u20101R\/IRS\u20101\/p\u2010Akt\/p\u2010mTOR) and down\u2010regulated protein degradation signal atrogin\u20101 in C2C12 myotubes. In LPS (100\u2009ng\u00b7ml\n                      <jats:sup>\u22121<\/jats:sup>\n                      )\u2010treated C2C12 myotubes, triptolide up\u2010regulated MyHC, IGF\u20101, p\u2010IGF\u20101R, IRS\u20101 and p\u2010Akt. Triptolide also down\u2010regulated ubiquitin\u2010proteasome molecules (n\u2010FoxO3a\/atrogin\u20101\/MuRF1), proteasome activity, autophagy\u2010lysosomal molecules (LC3\u2010II\/LC3\u2010I and Bnip3) and inflammatory mediators (NF\u2010\u03baB, Cox\u20102, NLRP3, IL\u20101\u03b2 and TNF\u2010\u03b1). However, AG1024, an IGF\u20101R inhibitor, suppressed triptolide\u2010mediated effects on MyHC, myotube diameter, MuRF1 and p62 in LPS\u2010treated C2C12 myotubes. In LPS (1\u00a0mg\u00b7kg\n                      <jats:sup>\u22121<\/jats:sup>\n                      , i.p.)\u2010challenged mice, triptolide (5 and 20\u2009\u03bcg\u00b7kg\n                      <jats:sup>\u22121<\/jats:sup>\n                      \u00b7day\n                      <jats:sup>\u22121<\/jats:sup>\n                      , i.p.) decreased plasma TNF\u2010\u03b1 levels and it increased skeletal muscle volume, cross\u2010sectional area of myofibers, weights of the gastrocnemius and tibialis anterior muscles, forelimb grip strength and locomotion.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Implications<\/jats:title>\n                    <jats:p>These findings reveal that triptolide prevented LPS\u2010induced inflammation and skeletal muscle atrophy and have implications for the discovery of novel agents for preventing muscle wasting.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.15472","type":"journal-article","created":{"date-parts":[[2021,3,31]],"date-time":"2021-03-31T06:53:51Z","timestamp":1617173631000},"page":"2998-3016","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":171,"title":["Triptolide prevents LPS\u2010induced skeletal muscle atrophy via inhibiting NF\u2010\u03baB\/TNF\u2010\u03b1 and regulating protein synthesis\/degradation pathway"],"prefix":"10.1111","volume":"178","author":[{"given":"Wei\u2010Yu","family":"Fang","sequence":"first","affiliation":[{"name":"Department of Pharmacology, School of Medicine, College of Medicine Kaohsiung Medical University  Kaohsiung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu\u2010Ting","family":"Tseng","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, College of Medicine Kaohsiung Medical University  Kaohsiung Taiwan"},{"name":"Menzies Health Institute Queensland Griffith University  Southport Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tzu\u2010Ying","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, College of Medicine Kaohsiung Medical University  Kaohsiung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yin\u2010Chih","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Kaohsiung Medical University Hospital Kaohsiung Medical University  Kaohsiung Taiwan"},{"name":"Department of Orthopedics, College of Medicine Kaohsiung Medical University  Kaohsiung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan\u2010Hsuan","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, College of Medicine Kaohsiung Medical University  Kaohsiung Taiwan"},{"name":"Graduate Institute of Medicine, College of Medicine Kaohsiung Medical University  Kaohsiung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan\u2010Wen","family":"Lo","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, College of Medicine Kaohsiung Medical University  Kaohsiung Taiwan"},{"name":"Graduate Institute of Medicine, College of Medicine Kaohsiung Medical University  Kaohsiung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih\u2010Lung","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Kaohsiung Medical University Hospital  Kaohsiung Taiwan"},{"name":"Department of Neurosurgery, College of Medicine Kaohsiung Medical University  Kaohsiung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1745-655X","authenticated-orcid":false,"given":"Yi\u2010Ching","family":"Lo","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, College of Medicine Kaohsiung Medical University  Kaohsiung Taiwan"},{"name":"Graduate Institute of Medicine, College of Medicine Kaohsiung Medical University  Kaohsiung Taiwan"},{"name":"Department of Medical Research Kaohsiung Medical University Hospital  Kaohsiung Taiwan"},{"name":"School of Pharmacy, College of Pharmacy Kaohsiung Medical University  Kaohsiung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,5,21]]},"reference":[{"issue":"1","key":"e_1_2_12_2_1","first-page":"S297","article-title":"The concise guide to pharmacology 2019\/20: Enzymes","volume":"176","author":"Alexander S. 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