{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T13:23:11Z","timestamp":1787750591014,"version":"build-2784847793"},"reference-count":79,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Hainan Provincial Health Commission","award":["WSJK2024MS162"],"award-info":[{"award-number":["WSJK2024MS162"]}]},{"award":["WSJK2024MS162"],"award-info":[{"award-number":["WSJK2024MS162"]}],"id":[{"id":"https:\/\/ror.org\/04nm1xm49","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007935","name":"Hainan Medical University","doi-asserted-by":"publisher","award":["XSTS2025166"],"award-info":[{"award-number":["XSTS2025166"]}],"id":[{"id":"10.13039\/501100007935","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007935","name":"Hainan Medical University","doi-asserted-by":"publisher","award":["X202611810060"],"award-info":[{"award-number":["X202611810060"]}],"id":[{"id":"10.13039\/501100007935","id-type":"DOI","asserted-by":"publisher"}]},{"award":["XSTS2025166"],"award-info":[{"award-number":["XSTS2025166"]}],"id":[{"id":"https:\/\/ror.org\/004eeze55","id-type":"ROR","asserted-by":"publisher"}]},{"award":["X202611810060"],"award-info":[{"award-number":["X202611810060"]}],"id":[{"id":"https:\/\/ror.org\/004eeze55","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Hepatocellular carcinoma (HCC) remains difficult to control because recurrence, impaired hepatic reserve, and treatment resistance limit durable benefit. Natural products and traditional Chinese medicine (TCM) provide resources that range from drug-lead discovery to adjunctive multicomponent therapy. This review integrates pharmacological and clinical evidence for purified compounds, semisynthetic derivatives, extracts, formulas, and delivery systems. It focuses on metabolic reprogramming and redox homeostasis, stress responses and regulated cell death, tumor cell plasticity and vascular remodeling, and the immune microenvironment and host response. Recent studies have strengthened selected mechanistic claims through chemical probes, functional perturbation, and resistance models. Clinical research has concentrated on recurrence control after surgery or minimally invasive treatment and on combinations with transarterial chemoembolization, targeted agents, and immunotherapy. Randomized trials and prospective cohorts suggest potential benefit in specific settings, although product standardization, external validation, and long-term follow-up remain limited. Major translational barriers include uncertain active constituents, inadequate batch comparability, missing tumor-exposure data, and sparse herb\u2013drug interaction studies. Future development should match target validation, pharmacokinetics, safety assessment, and clinical endpoints to each product class and clarify whether a candidate is best positioned as a drug lead, adjunctive therapy, or supportive intervention.<\/jats:p>","DOI":"10.3390\/ph19091350","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T12:59:57Z","timestamp":1787749197000},"page":"1350","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Natural Products and Traditional Chinese Medicine in Hepatocellular Carcinoma: From Pharmacological Mechanisms to Clinical Translation"],"prefix":"10.3390","volume":"19","author":[{"given":"Jingyi","family":"Shen","sequence":"first","affiliation":[{"name":"Key Laboratory of Tropical Translational Medicine of Ministry of Education, College of Basic Medical Sciences, Hainan Academy of Medical Sciences, Hainan Medical University, Haikou 571199, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoya","family":"Liu","sequence":"additional","affiliation":[{"name":"The First Department of Clinical Medicine, Chongqing Medical University, Chongqing 400016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuanyan","family":"Yan","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tropical Translational Medicine of Ministry of Education, College of Basic Medical Sciences, Hainan Academy of Medical Sciences, Hainan Medical University, Haikou 571199, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tropical Translational Medicine of Ministry of Education, College of Basic Medical Sciences, Hainan Academy of Medical Sciences, Hainan Medical University, Haikou 571199, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianfang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tropical Translational Medicine of Ministry of Education, College of Basic Medical Sciences, Hainan Academy of Medical Sciences, Hainan Medical University, Haikou 571199, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiquan","family":"Gu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tropical Translational Medicine of Ministry of Education, College of Basic Medical Sciences, Hainan Academy of Medical Sciences, Hainan Medical University, Haikou 571199, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weimin","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tropical Translational Medicine of Ministry of Education, College of Basic Medical Sciences, Hainan Academy of Medical Sciences, Hainan Medical University, Haikou 571199, China"},{"name":"Department of Pharmacology, College of Basic Medical Sciences, Hainan Medical University, Haikou 571199, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengwen","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Surgery, Hepatobiliary and Pancreatic Cancer Center, Affiliated Cancer Hospital of Hainan Medical University (Hainan Provincial Cancer Hospital), Hainan Provincial Clinical Medical Research Center for Liver Diseases and Liver Critical Care, Haikou 570311, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0602-7872","authenticated-orcid":false,"given":"Qiang","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tropical Translational Medicine of Ministry of Education, College of Basic Medical Sciences, Hainan Academy of Medical Sciences, Hainan Medical University, Haikou 571199, China"},{"name":"The First Department of Clinical Medicine, Chongqing Medical University, Chongqing 400016, China"},{"name":"School of Biomedical Sciences, The University of Queensland, Brisbane, QLD 4068, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,26]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. 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