Risks, Benefits, and Molecular Targets of Fenugreek Administration in the Treatment of Hepatocellular Carcinoma

Fenugreek (Trigonella foenum-graecum) has attracted growing interest as a complementary agent in the management of hepatocellular carcinoma (HCC), a leading cause of cancer-related mortality worldwide. Its rich botanical and phytochemical profile, including key bioactive compounds such as diosgenin, trigonelline, saponins, and flavonoids, underpins a spectrum of biological activities relevant to liver cancer therapy. This review critically examines the risks, benefits, and molecular targets of fenugreek administration in HCC, synthesising current evidence on extraction methods, standardisation, pharmacokinetics, and mechanisms of action. Preclinical studies highlight fenugreek's antitumor efficacy, mediated by apoptosis induction, cell cycle regulation, and modulation of oxidative stress and inflammatory pathways, while its hepatoprotective effects are supported by robust antioxidant and anti-inflammatory properties. However, the safety profile is nuanced, with potential risks including reproductive toxicity, rare hypersensitivity reactions, and herb-drug interactions, particularly in patients with compromised hepatic function or polypharmacy. The review identifies critical gaps in clinical evidence, especially regarding long-term safety and synergistic effects with conventional therapies and underscores the need for rigorous standardisation and patient monitoring. We describe the potential integration of fenugreek into multimodal HCC treatment strategies, if safety concerns are addressed. Future research should elucidate precise molecular targets, optimise formulations, and conduct well-controlled clinical trials to fully realise fenugreek's therapeutic potential in HCC management.