{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T10:48:28Z","timestamp":1788432508685,"version":"build-2803163510"},"reference-count":61,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,3,23]],"date-time":"2022-03-23T00:00:00Z","timestamp":1647993600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2020R1A2C1102078"],"award-info":[{"award-number":["2020R1A2C1102078"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Muscle atrophy in postmenopausal women is caused by estrogen deficiency and a variety of inflammatory factors, including tumor necrosis factor alpha (TNF\u03b1). Paeoniflorin (PNF), a natural compound with anti-inflammatory properties, improves estradiol synthesis. Here, we demonstrate that PNF inhibits the progression of TNF\u03b1-induced skeletal muscle atrophy after menopause by restoring mitochondrial biosynthesis. Differentiated myoblasts damaged by TNF\u03b1 were restored by PNF, as evident by the increase in the expression of myogenin (MyoG) and myosin heavy chain 3 (Myh3)\u2014the markers of muscle differentiation. Moreover, diameter of atrophied myotubes was restored by PNF treatment. TNF\u03b1-repressed nuclear respiratory factor 1 (NRF1) and mitochondrial transcription factor A (TFAM) (a major regulator of mitochondrial biosynthesis) were restored by PNF, via regulation by estrogen receptor alpha (ER\u03b1), an upregulator of NRF1. This mechanism was confirmed in ovariectomized (OVX) mice with a ~40% reduction in the cross-sectional area of the anterior tibialis muscle. OVX mice administered PNF (100, 300 mg\/kg\/day) for 12 weeks recovered more than ~20%. Behavioral, rotarod, and inverted screen tests showed that PNF enhances reduced muscle function in OVX mice. ER\u03b1 restored expression of mitofusin 1 (MFN1) and mitofusin 2 (MFN2) (mitochondrial fusion markers) and dynamin-related protein (DRP1) and fission 1 (FIS1) (mitochondrial fission markers). Therefore, PNF can prevent muscle atrophy in postmenopausal women by inhibiting dysfunctional mitochondrial biogenesis.<\/jats:p>","DOI":"10.3390\/ph15040390","type":"journal-article","created":{"date-parts":[[2022,3,23]],"date-time":"2022-03-23T22:08:06Z","timestamp":1648073286000},"page":"390","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Paeoniflorin Alleviates Skeletal Muscle Atrophy in Ovariectomized Mice through the ER\u03b1\/NRF1 Mitochondrial Biogenesis Pathway"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1322-767X","authenticated-orcid":false,"given":"Ki-Sun","family":"Park","sequence":"first","affiliation":[{"name":"KM Science Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyungjun","family":"Kim","sequence":"additional","affiliation":[{"name":"KM Science Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hye Jin","family":"Kim","sequence":"additional","affiliation":[{"name":"KM Convergence Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kang-In","family":"Lee","sequence":"additional","affiliation":[{"name":"KM Science Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seo-Young","family":"Lee","sequence":"additional","affiliation":[{"name":"KM Science Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jieun","family":"Kim","sequence":"additional","affiliation":[{"name":"KM Science Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1007\/s00223-014-9915-y","article-title":"Skeletal muscle: A brief review of structure and function","volume":"96","author":"Frontera","year":"2015","journal-title":"Calcif. 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