Mechanisms and Translational Prospects of Active Components of Traditional Chinese Medicine in Modulating Lipid Metabolism Reprogramming to Induce Ferroptosis in Hepatocellular Carcinoma
10.13422/j.cnki.syfjx.20260669
- VernacularTitle:中药活性成分调控脂质代谢重编程诱导肝细胞癌铁死亡的机制与转化前景
- Author:
Jianfei YANG
1
;
Huanhuan LIN
1
;
Xiaoli SHI
1
;
Jikai MA
1
;
Wenwen YANG
1
;
Yubei LU
2
Author Information
1. School of Clinical Medicine，Gansu University of Chinese Medicine，Lanzhou 730000，China
2. The First Affiliated Hospital of Gansu University of Chinese Medicine，Lanzhou 730050，China
- Publication Type:Journal Article
- Keywords:
lipid metabolism reprogramming;
hepatocellular carcinoma;
ferroptosis;
active components of traditional Chinese medicine;
mechanism
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2026;32(23):283-291
- CountryChina
- Language:Chinese
-
Abstract:
Lipid metabolism reprogramming is a metabolic hallmark of hepatocellular carcinoma （HCC） initiation and progression. It encompasses aberrant activation of de novo lipogenesis （DNL）， remodeling of the membrane phospholipid polyunsaturated fatty acid （PUFA）/monounsaturated fatty acid （MUFA） ratio， upregulation of the mevalonate （MVA） pathway， and compensatory activation of subcellular antioxidant networks. Together with liver-specific dysregulation of iron homeostasis， these alterations shape a dual metabolic landscape in which ferroptosis susceptibility and resistance coexist， thereby driving malignant progression and therapeutic tolerance. In traditional Chinese medicine （TCM）， the core pathogenesis of HCC is conceptualized as the interplay of dampness， heat， stasis， toxin， and deficiency， which is intrinsically consistent at the biological level with the aforementioned lipid accumulation， redox imbalance， and disordered iron metabolism. According to the three therapeutic principles of clearing heat， detoxifying， and resolving dampness， activating blood to dispel stasis and counteract toxins， and reinforcing healthy Qi to consolidate the root， this review systematically delineates the molecular mechanisms by which the active components of traditional Chinese medicine modulate the lipid-ferroptosis network. Active components including berberine， tanshinone ⅡA， and ginsenosides cooperatively induce ferroptosis in HCC by disrupting the cystine/glutamate antiporter-glutathione-glutathione peroxidase 4 （System Xc-/GSH/GPX4） antioxidant axis， upregulating long-chain acyl-CoA synthetase 4 （ACSL4） to promote PUFA-containing membrane lipid peroxidation， perturbing nuclear factor erythroid 2-related factor 2/Kelch-like ECH-associated protein 1 （NRF2/KEAP1） and protein kinase R-like endoplasmic reticulum kinase/activating transcription factor 4 （PERK/ATF4） signaling pathways， and disrupting ferritin homeostasis. On this basis， the review evaluates the translational prospects of these components in reversing tyrosine kinase inhibitor （TKI） resistance， sensitizing immune checkpoint inhibitor therapy， and enabling nanocarrier-mediated delivery， with the aim of providing a pharmacological basis for the development of TCM candidate agents targeting the lipid-ferroptosis axis and for the optimization of therapeutic strategies integrating Chinese and Western medicine.
