Pharmacological Research - Modern Chinese Medicine · Published 2026-07-14 · DOI 10.1016/j.prmcm.2026.100847
Pranal Chhetri, Ananta Choudhury
Introduction: Currently, alcohol-associated liver disease (ALD) is considered a major cause of liver-related disorders and mortality globally, with limited therapeutic options. Recent evidence has identified ferroptosis as a key pathological mechanism of ALD, characterised by iron imbalance, mitochondrial dysfunction, lipid peroxidation, and inflammatory responses. Concurrently, phytochemicals from various Cuscuta species have gathered increasing attention for their diverse pharmacological activities. In this review, the primary focus is on Cuscuta chinensis (Tu Si Zi), a key medicinal species utilised in Traditional Chinese Medicine (TCM), while examining its potential relevance in ALD-induced ferroptosis as a mechanistic framework for therapeutic intervention. Along with Cuscuta chinensis, another species from the same genus, i.e., Cuscuta reflexa, is also included for comparative and translational purposes to emphasise species-specific pharmacological relevance and existing research gaps. Methods: Relevant studies published from 2014 to 2026 were identified and retrieved from PubMed, Web of Science, Scopus, and Google Scholar, following manual screening for relevance. Several reports related to ALD, ferroptosis, TCM, and medicinal Cuscuta species, with particular emphasis on Cuscuta chinensis (Tu Si Zi) and Cuscuta reflexa, were reviewed and critically synthesised. Results: Currently available reports suggest that ferroptosis may be an important pathological mechanism in ALD, which is characterised by iron dysregulation, lipid peroxidation, impaired antioxidant function, and mitochondrial damage. Key phytochemicals found in Cuscuta species, such as quercetin, kaempferol, luteolin, and hyperoside, may influence the ferroptosis-related pathways, thereby modulating them through regulation of Nuclear factor erythroid 2- related factor 2/Heme Oxygenase-1 (Nrf2/HO-1) signalling, Solute Carrier Family 7 Member 11- Glutathione Peroxidase 4 (SLC7A11-GPX4) antioxidant defences, lipid metabolism, iron homeostasis, and mitochondrial activities. In addition, ferroptosis, inflammation, and mitochondrial dysfunction are considered to be interconnected through a pathogenic network that amplifies hepatic damage, providing a potential framework for multifactorial therapeutic intervention. Discussion: Although experimentally, Cuscuta reflexa has been studied and investigated more extensively, its inclusion in this review provides a comparative framework that strengthens the TCM-centred emphasis on Cuscuta chinensis and further demonstrates species-specific pharmacological distinctions. Overall, Cuscuta species may represent a promising therapeutic candidate for targeting ferroptosis- related pathways in ALD, although this has not been proven clinically. Future research should focus on phytochemical standardising, advanced drug delivery strategies, and the conduct of detailed mechanistic preclinical and clinical validation. The conceptual systems-level framework presented in this review is largely based on the integration of already published mechanistic evidence and reports rather than formal system pharmacology analyses, and should therefore be regarded as hypothesis-generating.
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Chhetri, P., Choudhury, A. (2026). Cuscuta species as potential ferroptosis-modulating agents in alcohol-associated liver disease: A conceptual systems-level perspective. Pharmacological Research - Modern Chinese Medicine. https://doi.org/10.1016/j.prmcm.2026.100847