Natural Products and Traditional Chinese Medicine in Hepatocellular Carcinoma: From Pharmacological Mechanisms to Clinical Translation.

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-drug 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.