Traditional Chinese Medicine and Ferroptosis in Alzheimer’s Disease: A Potential Therapeutic Approach

Abstract: Alzheimer’s disease (AD) represents a prevalent neurodegenerative disorder associated with considerable morbidity and mortality. Currently, no therapeutic agents exist that can achieve a fundamental reversal or complete cure for this condition. Consequently, the identification of novel molecular targets and the development of innovative treatment modalities aimed at slowing progression and alleviating symptoms represent pressing priorities within AD clinical research. Ferroptosis, a regulated cell death process driven by intracellular iron dysregulation and excessive lipid peroxidation, is now recognized as a critical contributor to AD pathogenesis. Traditional Chinese medicine (TCM) has demonstrated beneficial outcomes in managing AD, and emerging evidence suggests its regulatory effects may extend to modulating ferroptotic pathways. This review summarizes and analyzes the therapeutic efficacy of various TCM strategies against AD, including herbal extracts, monomers (eg, alkaloids, terpenoids, glycosides, phenolic derivatives, quinones), compound formulas, and acupuncture. It highlights how these interventions target key ferroptosis-related axes—such as iron homeostasis, the system Xc−/GSH/GPX4 antioxidant system, and the Keap1/Nrf2/ARE pathway—to collectively address the pathological foundation of the disease. However, current evidence is predominantly preclinical, and the translational potential of TCM is constrained by challenges including blood-brain barrier penetration, pharmacokinetic profiles, standardization, and safety assessments. In conclusion, TCM exhibits substantial potential for both research and clinical application in AD by targeting and attenuating the ferroptosis pathway, offering promising avenues for disease modification and symptomatic relief. Keywords: Alzheimer’s disease, ferroptosis, traditional Chinese medicine, cell death, Chinese herbal compounds