{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T15:16:28Z","timestamp":1791645388486,"version":"4.3.4"},"reference-count":53,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,9,2]],"date-time":"2021-09-02T00:00:00Z","timestamp":1630540800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003710","name":"Korea Health Industry Development Institute","doi-asserted-by":"publisher","award":["HR14C0001"],"award-info":[{"award-number":["HR14C0001"]}],"id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2020R1I1A1A01058279"],"award-info":[{"award-number":["NRF-2020R1I1A1A01058279"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Type 1 diabetes mellitus is an autoimmune disease caused by the destruction of pancreatic beta cells. Many patients with type 1 diabetes experience skeletal muscle wasting. Although the link between type 1 diabetes and muscle wasting is not clearly known, insulin insufficiency and hyperglycemia may contribute to decreased muscle mass. In this study, we investigated the therapeutic effect of the ethanolic extract of Schisandrae chinensis Fructus (SFe) on muscle wasting in streptozotocin (STZ)-induced diabetic mice. STZ-diabetic C57BL\/6 mice (blood glucose level \u2265300 mg\/dL) were orally administered SFe (250 or 500 mg\/kg\/day) for 6 weeks. We observed that SFe administration did not change blood glucose levels but increased gastrocnemius muscle weight, cross-sectional area, and grip strength in STZ-induced diabetic mice. Administration of SFe (500 mg\/kg) decreased the expression of atrophic factors, such as MuRF1 and atrogin-1, but did not alter the expression of muscle synthetic factors. Further studies showed that SFe administration decreased the expression of KLF15 and p-CREB, which are upstream molecules of atrophic factors. Examination of the expression of molecules involved in autophagy\u2013lysosomal pathways (e.g., p62\/SQSTM1, Atg7, Beclin-1, ULK-1, LC3-I, and LC3-II) revealed that SFe administration significantly decreased the expression of p62\/SQSTM1, LC3-I, and LC3-II; however, no changes were observed in the expression of Atg7, Beclin-1, or ULK-1. Our results suggest that SFe ameliorated muscle wasting in STZ-induced diabetic mice by decreasing protein degradation via downregulation of the CREB-KLF15-mediated UPS system and the p62\/SQSTM1-mediated autophagy\u2013lysosomal pathway.<\/jats:p>","DOI":"10.3390\/cells10092283","type":"journal-article","created":{"date-parts":[[2021,9,2]],"date-time":"2021-09-02T10:02:11Z","timestamp":1630576931000},"page":"2283","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Schisandrae chinensis Fructus Extract Ameliorates Muscle Atrophy in Streptozotocin-Induced Diabetic Mice by Downregulation of the CREB-KLF15 and Autophagy\u2013Lysosomal Pathways"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9235-5500","authenticated-orcid":false,"given":"Ho-Jung","family":"Choi","sequence":"first","affiliation":[{"name":"Gachon Institute of Pharmaceutical Science, College of Pharmacy, Gachon University, 191 Hambakmoe-ro, Yeonsu-gu, Incheon 21936, Korea"},{"name":"Lee Gil Ya Cancer and Diabetes Institute, Gachon University, 155 Gaetbeol-ro, Yeonsu-gu, Incheon 21999, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3801-2464","authenticated-orcid":false,"given":"Myeong-Hoon","family":"Yeon","sequence":"additional","affiliation":[{"name":"Gachon Institute of Pharmaceutical Science, College of Pharmacy, Gachon University, 191 Hambakmoe-ro, Yeonsu-gu, Incheon 21936, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1166-4932","authenticated-orcid":false,"given":"Hee-Sook","family":"Jun","sequence":"additional","affiliation":[{"name":"Gachon Institute of Pharmaceutical Science, College of Pharmacy, Gachon University, 191 Hambakmoe-ro, Yeonsu-gu, Incheon 21936, Korea"},{"name":"Lee Gil Ya Cancer and Diabetes Institute, Gachon University, 155 Gaetbeol-ro, Yeonsu-gu, Incheon 21999, Korea"},{"name":"Gachon Medical Research Institute, Gil Hospital, 21 Namdong-daero 774 beon-gil, Namdong-gu, Incheon 21565, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1813","DOI":"10.2337\/db05-1183","article-title":"Decreased Muscle Strength and Quality in Older Adults with Type 2 Diabetes: The Health, Aging, and Body Composition Study","volume":"55","author":"Park","year":"2006","journal-title":"Diabetes"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1016\/j.jamda.2013.02.006","article-title":"Patients with type 2 diabetes show a greater decline in muscle mass, muscle strength, and functional capacity with aging","volume":"14","author":"Leenders","year":"2013","journal-title":"J. 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