The American journal of Chinese medicine最新文献

{"title":"Gastrodin and Gastrodigenin as Potential Neuroprotectors for the Treatment of Neurodegenerative Diseases.","authors":"Jing Wang, Tingting Chen, Yudong Lin, Xiangchun Shen, Mingmei Zhou","doi":"10.1142/S0192415X26500199","DOIUrl":"10.1142/S0192415X26500199","url":null,"abstract":"<p><p>Neurodegenerative diseases (NDDs), characterized by a progressive neuronal loss that leads to cognitive and motor deficits, both pose a significant global health challenge and have limited treatment options. This review explores the therapeutic potential of gastrodin (GAS) and gastrodigenin (HBA), which are the key bioactive constituents of <i>Gastrodia elata</i> Blume (GEB). These compounds demonstrate significant neuroprotective effects across various NDD models which include Alzheimer's disease (AD) and Parkinson's disease (PD). Their mechanisms involve multi-target actions such as inhibiting pathological protein aggregation (Aβ, tau, α-synuclein), attenuating neuroinflammation via the TLR4/NF-κB and NLRP3 pathways, reducing oxidative stress through Nrf2 activation, mitigating mitochondrial dysfunction, inhibiting ferroptosis, and counteracting glutamate excitotoxicity. While pharmacokinetic studies reveal favorable brain distribution for HBA, its clinical translation faces challenges including blood-brain barrier penetration and the need for human trials. Advances in delivery systems, like focused ultrasound, show promise. This review both synthesizes the current evidence on GAS and HBA to highlight their multifaceted mechanisms and potential as multi-target agents for NDD intervention, and outlines future research directions for their clinical development.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":" ","pages":"529-554"},"PeriodicalIF":5.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146260499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tanshinone IIA Ameliorates Heart Failure by Inhibiting Ferroptosis via the Sirt1/p53/GPX4 Signaling Pathway.","authors":"Guo-Fu Zhong, Zhi-Wen Jiang, Xin Huang, Bo Lin, Qing-Hua Zhu, Ling Wang, Mujuan Xu, Yuxiang Liu, Maosheng Wang, Yue Han","doi":"10.1142/S0192415X26500564","DOIUrl":"10.1142/S0192415X26500564","url":null,"abstract":"<p><p>Heart failure (HF) is a high-mortality condition driven by cardiomyocyte death, and ferroptosis is a critical contributor to myocardial injury in this regard. Tanshinone IIA (Tan-IIA), a bioactive component from <i>Salvia miltiorrhiza</i>, has been shown to protect the heart, but its role in HF-related ferroptosis remains unclear. This study investigated whether Tan-IIA ameliorates HF by inhibiting ferroptosis and its underlying mechanism. We evaluated cardiac function, fibrosis, ferroptosis markers (such as ROS, Fe[Formula: see text], GSH, xCT, and GPX4), and Sirt1/p53 signaling using both a mouse model of HF induced by ligation of the left anterior descending (LAD) coronary artery and oxygen-glucose deprivation (OGD)-treated H9c2 cells. Direct binding of Tan-IIA to Sirt1 was verified by molecular docking, CETSA, and DARTS. Tan-IIA improved cardiac function, reduced fibrosis and inflammation, decreased ROS/Fe[Formula: see text], increased GSH, and upregulated xCT/GPX4 <i>in vivo</i> and <i>in vitro</i>. However, erastin reversed these effects. Tan-IIA upregulated Sirt1 and downregulated p53, while Sirt1 inhibition by EX527 abolished its cardioprotective and antiferroptotic actions. Tan-IIA ameliorates HF by inhibiting myocardial ferroptosis through the Sirt1/p53/GPX4 pathway thus in turn supports its potential clinical use in the treatment of HF.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":" ","pages":"1531-1550"},"PeriodicalIF":5.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148407668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Flaxseed and Linusorb Synergistically Ameliorate Menopausal Symptoms Through Non-Hormonal Activation of Estrogen Receptors and Suppression of Osteoclastogenesis.","authors":"Won Young Jang, Ji Hye Yoon, Seul Bi Lee, Sung-Jin Lee, Youn Young Shim, Martin J T Reaney, Byong Chul Yoo, Jongsung Lee, Jae Youl Cho","doi":"10.1142/S0192415X26500692","DOIUrl":"10.1142/S0192415X26500692","url":null,"abstract":"<p><p>Phytoestrogens derived from natural products have emerged as potential alternatives to hormone replacement therapy (HRT) for alleviating menopausal symptoms with reduced adverse effects. However, the therapeutic potential and mechanistic basis of flaxseed-derived lignan secoisolariciresinol diglucoside polymer (SDGP) remain largely unexplored. This study aimed to investigate the synergistic effects of SDGP and a linusorb mixture (LOMIX) on menopausal symptoms and to elucidate their underlying molecular mechanisms. Estrogen receptor (ER) activation was evaluated using ERE-luciferase reporter assays and Western blot analysis in MCF-7 cells. Anti-osteoclastogenic effects were assessed in RANKL-induced RAW264.7 cells. An ovariectomized (OVX) rat model was used to examine <i>in vivo</i> efficacy on reproductive tissues and bone metabolism. Co-treatment with SDGP and LOMIX synergistically enhanced ERα/ERβ phosphorylation and Akt activation, leading to increased transcription of ER target genes. The combination also suppressed osteoclast differentiation by inhibiting NF-κB and MAPK signaling pathways, including c-Fos and NFATc1. In OVX rats, oral administration of the mixture restored vaginal cornification and uterine morphology, and significantly improved trabecular bone structure and bone mineral density. Notably, these effects were achieved without significant alterations in circulating estrogen, FSH, or LH levels. The combination of SDGP and LOMIX alleviates menopausal symptoms through non-hormonal activation of ER signaling and inhibition of osteoclastogenesis. These findings suggest a promising phytotherapeutic strategy for managing postmenopausal disorders with reduced risk of hormone-related side effects.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":" ","pages":"1853-1873"},"PeriodicalIF":5.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148715180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Icariin: Unraveling Ferroptosis Mechanisms, Metabolic Networks, and Innovative Therapy Strategies.","authors":"Xiaojiao Yang, Lijun Li, Jilin Wang, Longxiang Xie, Yuhan Chen, Jieying Wang, Xianbin You, Xiaoqin Ye","doi":"10.1142/S0192415X26500655","DOIUrl":"10.1142/S0192415X26500655","url":null,"abstract":"<p><p>Ferroptosis is an iron-dependent form of cell death driven by lipid peroxidation. This concept reshapes our understanding of tissue degenerative lesions and oncogenesis. Icariin (ICA) is an isoprenyl flavonol glycoside derived from plants of the genus Epimedium. Acting as a bidirectional regulator of this pathway, it precisely modulates cellular sensitivity to ferroptosis across distinct disease states. This review systematically synthesizes literature from PubMed, ScienceDirect, Web of Science, and Google Scholar (2015-2025). Search keywords included \"Icariin\", \"ferroptosis\", \"pharmacological mechanism\", \"pharmacokinetics\" and \"toxicology\", while excluding conference abstracts, non-English studies, and reports lacking raw data. We systematically elucidated the role of ICA across a continuous \"mechanism-treatment-metabolism\" spectrum: in neurodegenerative disease models, ICA exerts an anti-oxidant effect to maintain cellular homeostasis, whereas in drug-resistant cancer cells, it functions as a pro-oxidant, promoting the elimination of malignant cells. This context-dependent effect is primarily attributed to its modulation of the nuclear factor erythroid 2-related factor 2 (Nrf2)/glutathione peroxidase 4 (GPX4) axis, which serves as the critical \"molecular switch\" of redox homeostasis. Beyond direct signaling, ICA functions as a natural precursor. Its safety profile and therapeutic window are governed by the metabolic network, potentially conferring advantages over synthetic inhibitors. Although low systemic bioavailability limits clinical translation, nanodelivery systems and synthetic biology strategies offer viable approaches for optimizing its metabolic profile. Ultimately, ICA provides an exquisite molecular blueprint, charting a course for the development of ferroptosis-targeted therapies that can precisely sense and adapt to the microenvironments of complex diseases.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":" ","pages":"1749-1781"},"PeriodicalIF":5.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148809663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Natural Products for Alzheimer's Disease: A New Twist Impacting Ferroptosis.","authors":"Yaqiao Yi, Pu Jia, Peipei Xie, Xiru Peng, Xuan Zhu, Shuting Yin, Cong Yan, Ganpeng Yu","doi":"10.1142/S0192415X26500266","DOIUrl":"10.1142/S0192415X26500266","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline. Despite significant advances in AD research, effective disease-modifying therapies remain unavailable. In recent years, ferroptosis has gained increasing attention for its potential role in the pathogenesis of AD. Accumulating evidence indicates that substantial iron accumulation, dysregulation of anti-oxidant defense systems, and elevated levels of lipid peroxidation are present in the brains of AD patients. These alterations create a conducive environment for ferroptosis and are closely associated with neuronal death and cognitive dysfunction. Therefore, targeting ferroptosis-related signaling pathways holds promise as a novel strategy to delay or halt the progression of AD. Natural products, such as flavonoids, phenolic compounds, and terpenoids, have become a focus of research in the intervention of neurodegenerative diseases due to their structural diversity, broad biological activities, and relatively low toxicity. Increasing studies have demonstrated that various herbal medicines, including <i>Rhodiola rosea</i>, <i>Polygala tenuifolia</i>, <i>Ginkgo biloba</i>, and <i>Poria cocos</i>, can effectively suppress ferroptosis through multiple mechanisms. These mechanisms include scavenging free radicals, enhancing anti-oxidant capacity, modulating iron metabolism, and restoring the function of key regulators like GPX4 or system Xc^-, to thereby ameliorate AD-related neural damage. This review systematically summarizes recent advances in understanding the role of ferroptosis in AD and highlights the therapeutic potential of natural products that target ferroptotic pathways. We aim to provide theoretical support and candidate molecules for the development of novel AD treatment strategies based on ferroptosis regulation, and thus offer valuable insights for future research into new ferroptosis inhibitors.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":" ","pages":"707-731"},"PeriodicalIF":5.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147793581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Research Progress on the Molecular Mechanisms of Cordycepin in Modulating Inflammation.","authors":"Yali Zhao, Shihao Zheng, Mengxue Liu, Dan Ma","doi":"10.1142/S0192415X2650031X","DOIUrl":"10.1142/S0192415X2650031X","url":null,"abstract":"<p><p>Cordycepin is a bioactive compound isolated from the <i>Cordyceps</i> fungi. It is structurally analogous to adenosine and possesses potent anti-inflammatory and immunomodulatory properties. Its anti-inflammatory effects are mainly mediated by regulating key signaling pathways, including nuclear factor-kappa B, mitogen-activated protein kinase, phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin, and nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 inflammasome pathways. Cordycepin inhibits the production of pro-inflammatory mediators such as tumor necrosis factor-α, interleukin (IL)-1β, IL-6, inducible nitric oxide synthase, and cyclooxygenase-2. It promotes the secretion of anti-inflammatory cytokines such as IL-10 and transforming growth factor-β. Cordycepin modulates immune cell functions via mechanisms including the induction of M2 polarization of macrophages, suppression of microglial activation, regulation of T lymphocyte differentiation, and inhibition of neutrophil infiltration. This review summarizes the anti-inflammatory effects of cordycepin on oxidative stress. These findings indicate that cordycepin exerts favorable anti-inflammatory effects during inflammatory responses.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":" ","pages":"859-880"},"PeriodicalIF":5.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147793617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Research Progress in Traditional Chinese Medicine for the Treatment of Breast Cancer.","authors":"Lankang Wang, Baoyi Ni, Lutuo Han, Wencheng Chi, Yang Wu, Jiakang Jiang","doi":"10.1142/S0192415X26500151","DOIUrl":"10.1142/S0192415X26500151","url":null,"abstract":"<p><p>Breast cancer (BC) is a major cause of cancer-related mortality worldwide. While mainstream anticancer therapies have improved clinical outcomes, they are often associated with significant toxicity and drug resistance. Traditional Chinese medicine (TCM) has received increasing recognition as a valuable complementary approach in oncology. This review summarizes the current evidence supporting the integrative use of TCM in BC management. Clinical studies indicate that TCM formulations can alleviate the adverse effects induced by chemotherapy and targeted therapy to thereby enhance patients' quality of life and treatment adherence. As an adjuvant, TCM also shows the potential to improve both the efficacy of conventional treatments and survival outcomes. Preclinical investigations reveal that bioactive herbal compounds exert multi-target antitumor effects by modulating key mechanisms such as programmed cell death, proliferation, metastasis, cell-cycle progression, drug resistance, aerobic glycolysis, and antitumor immunity. Furthermore, advanced drug delivery systems are being developed to overcome the inherent limitations of herbal compounds. However, challenges which warrant further investigation, including heterogeneous study designs, the standardization of formulations, and potential herb-drug interactions, remain under-explored. Overall, TCM represents a promising complementary strategy for BC. Future efforts should prioritize well-designed clinical trials, mechanistic elucidation, and the development of integrated precision medicine models to optimize patient care.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":" ","pages":"411-444"},"PeriodicalIF":5.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147313683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cepharanthine Triggers Ferroptosis in Gastric Cancer by PINK1/FUNDC1-Mediated Mitophagy-Dependent GPX4 Degradation.","authors":"Fubo Jing, Bing Yan, Chunlan Liu, Wenshuai Zhu, Muhua Luan, Zhaotian Feng, Yuanxin Xing, Xiaoli Ma, Liang Zhang, Yunshan Wang, Yanfei Jia","doi":"10.1142/S0192415X26500126","DOIUrl":"10.1142/S0192415X26500126","url":null,"abstract":"<p><p>Cepharanthine (CEP), a natural compound derived from the plant <i>Stephania cephalantha Hayata</i>, demonstrates pharmacological properties including anti-inflammatory, immuno-regulatory, antiviral, antitumor and antiparasitic effects. Due to its insidious progression and drug resistance, gastric cancer (GC) continues to have a high incidence and mortality rate worldwide. While the great potential of ferroptosis in cancer therapy is well-established, and CEP has shown potential antitumor activity, the role of ferroptosis in CEP's impact on GC remains unknown. Our aim in this study is to uncover what role ferroptosis has in the impact of CEP on GC. To investigate this, cell viability was measured by CCK-8 assay, and the effect of CEP on GC cell ferroptosis was assessed by Fe2[Formula: see text], DCFH-DA, and TEM. Integrated transcriptomic analyses revealed the critical pathways involved in CEP-induced ferroptosis, and JC-1, MitoSOX Red, Mito-Tracker, and immunofluorescence staining were used to evaluate mitophagy. The interaction between CEP and PINK1 was further confirmed by molecular docking, CETSA, and DARTS, and a xenograft tumor was used both to evaluate the effect of CEP on GC and to verify its mechanism through immunohistochemistry and western blotting. It was found that CEP could induce ferroptosis in GC cells by inducing an increase in reactive oxygen species, malondialdehyde, and intracellular Fe[Formula: see text] levels, and that it had little effect on normal gastric epithelial cells. Mechanistically, CEP binds directly to RUNX2, PINK1, and FUNDC1 to thereby activate PINK1-mediated mitophagy, prompt FUNDC1 to recruit GPX4 into mitochondria, and ultimately lead to the autophagic degradation of GPX4 and ferroptosis. A subcutaneous tumor model in nude mice confirmed the ferroptosis-associated antitumor efficacy of CEP <i>in vivo</i>. This study highlights that the natural compound CEP exerts its antitumor effects by activating mitophagy-dependent ferroptosis through a multi-target effect. CEP thus shows great promise as a potential drug candidate for GC treatment.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":"54 1","pages":"329-348"},"PeriodicalIF":5.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146183915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Codonopsis pilosula</i> (Dangshen) Alleviates Ulcerative Colitis Through Activation of the Aromatic Hydrocarbon Receptor Signaling Pathway by the Gut Bacterium <i>Alistipes onderdonkii</i> and Its Metabolite, 5-HIAA.","authors":"Qian Yang, Wentai Pang, Lin Ma, Qianru Zhao, Yu Wang, Rui Shao","doi":"10.1142/S0192415X26500230","DOIUrl":"10.1142/S0192415X26500230","url":null,"abstract":"<p><p>Ulcerative colitis (UC) is a growing global health concern, but there remains a lack of natural food sources and multi-targeted drugs to effectively it. <i>Codonopsis pilosula</i> (dangshen, DS), a medicinal food used in traditional Chinese medicine, offers more comprehensive benefits than conventional drugs due to the numerous active compounds, such as lobetyolin, tangshenoside I, codonopsine, succinic acid, and raffinose, it contains. DS can be safely incorporated into diets to enhance UC treatment compliance and continuous management. This study explored the therapeutic effects and mechanisms of DS using microbial sequencing, metabolomics, and experimental validation. DS alleviated UC symptoms in mice to ultimately achieve reduced weight loss, colon shortening, disease activity, and histopathology scores. It lowered pro-inflammatory cytokine levels (IL-6, IL-1β, TNF-[Formula: see text], balanced Th17 and Treg cells, and enhanced the intestinal barrier integrity by upregulating tight junction proteins (ZO-1, occludin, E-cadherin). In addition, DS significantly reduced the abundance of pathogenic <i>Escherichia</i>-<i>Shigella</i> by modulating the composition of the intestinal flora and increasing the production of tryptophan metabolites (5-hydroxyindole-3-acetic acid (5-HIAA) and kynurenic acid (KYNA)) through probiotic bacteria, like <i>Alistipes</i> and <i>Lactobacillus</i>, which act as aromatic hydrocarbon receptor (AhR) ligands. We found that <i>Alistipes onderdonkii</i> cultured <i>in vitro</i> produced 5-HIAA, and that DS could further increase 5-HIAA levels. In addition, both 5-HIAA and DS activated AhR in turn. The diminished efficacy of DS in UC after colony clearance was accompanied by a decrease in the level of AhR, which suggests the importance of bacterial-derived metabolites as mediators of the efficacy of DS. The metabolomics results showed that DS mainly exerted its regulatory effects by modulating arachidonic acid metabolism and tryptophan metabolism. Based on our data, which elucidated the relationship between AhR and anti-inflammatory effects, we identified the AhR/NF-κBp65 signaling pathway as a potential pharmacological mechanism by which DS is associated with UC amelioration.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":" ","pages":"627-659"},"PeriodicalIF":5.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146204552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Andrographolide Suppresses Head and Neck Squamous Cell Carcinoma Progression via EGR1-ACSL4 Axis-Mediated Ferroptosis.","authors":"Guo Cheng, Xin Zhu, Chenping Zhang","doi":"10.1142/S0192415X26500485","DOIUrl":"10.1142/S0192415X26500485","url":null,"abstract":"<p><p>Head and neck squamous cell carcinoma (HNSCC) is a highly aggressive malignancy with high rates of recurrence and metastasis that result in poor clinical outcomes. Ferroptosis, an iron-dependent, lipid peroxidation-driven regulated cell death pathway, offers a therapeutic strategy to enhance antitumor effects by exploiting cancer cell vulnerability to iron-mediated lipid peroxidation. Andrographolide (ADE), the major bioactive component extracted from <i>Andrographis paniculata</i>, demonstrates extensive antitumor activities. However, its specific role and mechanisms in HNSCC are unclear. The <i>in vitro</i> effects of ADE on HNSCC were evaluated using comprehensive experimental approaches which included CCK8, clonogenic survival analysis, wound healing, transwell migration, western blotting, omics analysis, and ferroptosis assessment. Its <i>in vivo</i> antitumor effects were confirmed using C57BL/6J mouse and patient-derived xenograft models. The results showed that ADE suppresses HNSCC growth by inducing ferroptosis. Mechanistically, ADE transcriptionally upregulates acyl-CoA synthetase long-chain family member 4 (ACSL4) by increasing the nuclear accumulation of early growth response 1 (EGR1) to thereby trigger ferroptosis. Furthermore, <i>in vivo</i> studies corroborated the finding that ADE attenuates tumor progression through ACSL4-dependent ferroptosis. In conclusion, our study reveals that ADE induces ferroptosis in HNSCC via the EGR1-ACSL4 axis. This finding highlights the potential of ADE as a therapeutic agent, and provides a mechanistic foundation for its future clinical applications in HNSCC.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":" ","pages":"1309-1330"},"PeriodicalIF":5.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148201965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}