{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T08:30:33Z","timestamp":1786696233223,"version":"build-2736575974"},"reference-count":40,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Food Laboratory of Zhongyuan Major Innovation Project of Henan Province","award":["241110110100"],"award-info":[{"award-number":["241110110100"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Age-related skeletal muscle atrophy (sarcopenia) poses a major public health challenge, emphasizing the need for safe and effective interventions. Our previous studies demonstrated that C-C chemokine receptor type 5 (CCR5) is a key therapeutic target for skeletal muscle atrophy, as its activation by C-C motif chemokine ligand 11 (CCL11) promotes the dissociation and degradation of the structural protein \u03b1-actin, ultimately contributing to muscle loss. To identify potential CCR5 inhibitors, a database of 7860 natural alkaloids was constructed for pharmacophore-based virtual screening using the CCR5\u2013Maraviroc crystal structure. Screening yielded 789 candidates, and subsequent batch molecular docking analysis identified Isoliensinine (ISO), a lotus seed alkaloid, as a potential CCR5 inhibitor with low binding energy (\u221210 kcal\/mol) and stable hydrogen bonding interactions with Glu283 and Tyr251. Molecular dynamics simulations further confirmed the structural stability of the ISO\u2013CCR5 complex. Molecular dynamics simulations further confirmed the structural stability of the ISO-CCR5 complex. In vitro, ISO dose-dependently inhibited CCL11-induced CCR5 activity (IC50 = 1.314 \u03bcM) with low cytotoxicity in C2C12 myotubes, and markedly alleviated CCL11-induced myotube atrophy by suppressing CCR5 activation and the upregulation of the muscle atrophy\u2013related markers MAFbx and MuRF1. These findings provide preliminary evidence for ISO as a potential CCR5-targeting candidate for further investigation in sarcopenia.<\/jats:p>","DOI":"10.3390\/molecules31162837","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T08:08:29Z","timestamp":1786694909000},"page":"2837","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification of Isoliensinine as a Novel CCR5 Inhibitor for the Prevention of Skeletal Muscle Atrophy Through Virtual Screening and Experimental Validation"],"prefix":"10.3390","volume":"31","author":[{"given":"Taiqi","family":"Qu","sequence":"first","affiliation":[{"name":"Key Laboratory of Functional Dairy, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujuan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Health, China Agricultural University, Beijing 100091, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yijia","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Functional Dairy, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-7491-3726","authenticated-orcid":false,"given":"Yuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Health, China Agricultural University, Beijing 100091, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixuan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Health, China Agricultural University, Beijing 100091, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanan","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Health, China Agricultural University, Beijing 100091, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1007\/s11357-023-01016-9","article-title":"Sarcopenia: No consensus, no diagnostic criteria, and no approved indication-How did we get here?","volume":"46","author":"Evans","year":"2024","journal-title":"Geroscience"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1152\/physrev.00061.2017","article-title":"Sarcopenia: Aging-Related Loss of Muscle Mass and Function","volume":"99","author":"Larsson","year":"2019","journal-title":"Physiol. 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