{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:59:55Z","timestamp":1790125195286,"version":"4.0.1"},"reference-count":187,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T00:00:00Z","timestamp":1766966400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100017596","name":"Natural Science Basic Research Program of Shaanxi Province","doi-asserted-by":"crossref","award":["2025JC-YBMS-868"],"award-info":[{"award-number":["2025JC-YBMS-868"]}],"id":[{"id":"10.13039\/501100017596","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Clinical Research Project of Traditional Chinese Medicine of Shaanxi Provincial Administration of Traditional Chinese Medicine","award":["SZY-KJCYC-2025-LC-003"],"award-info":[{"award-number":["SZY-KJCYC-2025-LC-003"]}]},{"name":"Scientific Research and Innovation Talent Program of Traditional Chinese Medicine of Shaanxi Province","award":["2025-CXRC-09"],"award-info":[{"award-number":["2025-CXRC-09"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Cancer cachexia (CC) is a multifactorial, multi-organ syndrome characterized by systemic inflammation, metabolic dysregulation, anorexia, and progressive depletion of skeletal muscle and adipose tissue. Despite its high prevalence among patients with advanced malignancies, effective therapeutic options remain limited. Recent studies have elucidated the molecular underpinnings of CC and the therapeutic potential of natural herbs, highlighting the involvement of central nervous system regulation, adipose tissue, immune responses, gut microbiota, skeletal muscle, and disruptions in anabolic\u2013catabolic signaling pathways such as mTOR, UPS, NF-\u03baB, and STAT3. Persistent inflammation induces E3 ubiquitin ligases (Atrogin-1\/MuRF-1) through cytokines including IL-6 and TNF-\u03b1, thereby impairing muscle homeostasis, while suppression of anabolic cascades such as IGF-1\/mTOR further aggravates muscle atrophy. The limited efficacy and adverse effects of synthetic agents like megestrol acetate underscore the value of herbal therapies as safer adjunctive strategies. Botanicals such as Coicis Semen, Scutellaria baicalensis, and Astragalus demonstrate anti-inflammatory and muscle-preserving activities by modulating NF-\u03baB, IL-6, and oxidative stress signaling. Numerous investigations indicate that these herbs downregulate MuRF-1 and Atrogin-1 expression, enhance appetite, and attenuate muscle loss, though they exhibit minimal influence on tumor suppression. While promising, current evidence remains largely preclinical and mechanistic validation is incomplete. This review consolidates contemporary insights into CC pathogenesis and the bioactivity of herbal interventions, highlighting the need for translational research to bridge preclinical findings with clinical applicability.<\/jats:p>","DOI":"10.3390\/cancers18010104","type":"journal-article","created":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T13:30:52Z","timestamp":1767187852000},"page":"104","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Systematic Exploration of Molecular Mechanisms and Natural Herbal Therapeutic Strategies for Cancer Cachexia"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-3498-880X","authenticated-orcid":false,"given":"Pengyu","family":"Han","sequence":"first","affiliation":[{"name":"Department of Traditional Chinese Medicine, Tangdu Hospital, Fourth Military Medical University, Xi\u2019an 710023, China"},{"name":"Shaanxi Provincial Key Laboratory of Integrated Traditional Chinese and Western Medicine in Oncology Diagnosis and Treatment, Fourth Military Medical University, Xi\u2019an 710023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingyu","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Traditional Chinese Medicine, Tangdu Hospital, Fourth Military Medical University, Xi\u2019an 710023, China"},{"name":"Shaanxi Provincial Key Laboratory of Integrated Traditional Chinese and Western Medicine in Oncology Diagnosis and Treatment, Fourth Military Medical University, Xi\u2019an 710023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guomin","family":"Dong","sequence":"additional","affiliation":[{"name":"College of Traditional Chinese Medicine, Shaanxi University of Chinese Medicine, Middle Section of Century Avenue, Xianyang 712046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Litian","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Tangdu Hospital, Fourth Military Medical University, Xi\u2019an 710023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Han","sequence":"additional","affiliation":[{"name":"College of Traditional Chinese Medicine, Shaanxi University of Chinese Medicine, Middle Section of Century Avenue, Xianyang 712046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donghu","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Traditional Chinese Medicine, Tangdu Hospital, Fourth Military Medical University, Xi\u2019an 710023, China"},{"name":"Shaanxi Provincial Key Laboratory of Integrated Traditional Chinese and Western Medicine in Oncology Diagnosis and Treatment, Fourth Military Medical University, Xi\u2019an 710023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Traditional Chinese Medicine, Tangdu Hospital, Fourth Military Medical University, Xi\u2019an 710023, China"},{"name":"Shaanxi Provincial Key Laboratory of Integrated Traditional Chinese and Western Medicine in Oncology Diagnosis and Treatment, Fourth Military Medical University, Xi\u2019an 710023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Traditional Chinese Medicine, Tangdu Hospital, Fourth Military Medical University, Xi\u2019an 710023, China"},{"name":"Shaanxi Provincial Key Laboratory of Integrated Traditional Chinese and Western Medicine in Oncology Diagnosis and Treatment, Fourth Military Medical University, Xi\u2019an 710023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1038\/s41467-020-20760-6","article-title":"Perspectives on skeletal muscle stem cells","volume":"12","author":"Relaix","year":"2021","journal-title":"Nat. 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