Chang Yang, Rui Xue, Chuling Qin, Lingyue Huang, Rongrong Nie, Yuqin Luo, Siyuan Xu, Ke Tang, Jianning Chen, Lulu Jia, Qinyou Tan
{"title":"Celastrol Induces Ferroptosis by Regulating CERKL to Exert Anti-Gastric Cancer Effect.","authors":"Chang Yang, Rui Xue, Chuling Qin, Lingyue Huang, Rongrong Nie, Yuqin Luo, Siyuan Xu, Ke Tang, Jianning Chen, Lulu Jia, Qinyou Tan","doi":"10.1142/S0192415X25500351","DOIUrl":"https://doi.org/10.1142/S0192415X25500351","url":null,"abstract":"<p><p>Gastric cancer is a significant global health issue. Celastrol, a natural compound, has shown antitumor potential, but its molecular mechanism in gastric cancer remains unclear. In this study, we treated HGC-27 cells with celastrol and employed CCK8, colony formation, and Transwell assays, revealing its inhibitory effect on cell proliferation and migration. Flow cytometry assay results showed that celastrol could elevate the level of reactive oxygen species (ROS) in HGC-27 cells. By using the iron ion and malondialdehyde (MDA) detection kits, it was found that celastrol promoted the accumulation of iron ions (Fe[Formula: see text] in HGC-27 cells, increased the MDA content, and simultaneously decreased the glutathione (GSH) content. Additionally, Western blot analysis indicated that celastrol exerts an inhibitory effect on the expression of ferroptosis-marker proteins GPX4 and SLC7A11. PCR array and further experiments identified CERKL as a key factor, whose downregulation by celastrol was associated with enhanced ferroptosis. <i>In vivo</i>, celastrol inhibited tumor growth without affecting body weight or organ histology. Our findings suggest that celastrol may inhibit gastric cancer via CERKL-regulated ferroptosis, providing a potential therapeutic strategy.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":"53 3","pages":"931-949"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144082978","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":"Mechanisms of Dihydromyricetin for Improving Hepatic Fibrosis through the Integration of Metabolomics and Gut Microbiota.","authors":"Ying Gao, Hao Wu, Yanqun Luo, Xiaoliang Deng, Junming Chen, Tao Wu","doi":"10.1142/S0192415X25500338","DOIUrl":"https://doi.org/10.1142/S0192415X25500338","url":null,"abstract":"<p><p>It is crucial to prevent and treat liver fibrosis in patients with chronic liver disease. Dihydromyricetin (DMY) is a natural flavonoid compound from traditional Chinese medicine, known to alleviate chronic liver injury. However, its role in regulating inflammatory responses through gut microbiota and metabolic changes remains unclear. In this study, a mouse model of liver fibrosis was induced with carbon tetrachloride (CCl<sub>4</sub>), and DMY was administered via gavage. Histopathology, immunohistochemistry, Reverse Transcription Polymerase Chain Reaction (RT-PCR), 16S rRNA sequencing, and untargeted metabolomics were employed to evaluate DMY's pharmacological effects on CCl<sub>4</sub>-induced liver fibrosis and explore its underlying mechanisms. Our results show that DMY reduced the aspartate transaminase (AST) and alanine transaminase (ALT) serum levels in liver fibrosis model mice, and lowered the mRNA expression of pro-inflammatory cytokines and fibrosis markers. Additionally, DMY restored the richness and diversity of the gut microbiota, with several microbiota taxa significantly correlating with inflammatory markers. Metabolomic analysis of serum and liver tissue revealed that DMY significantly altered the liver metabolite disturbances induced by CCl<sub>4</sub>. Pearson correlation analysis demonstrated a strong relationship between microbial composition and liver metabolites. These results suggest that DMY alleviates liver fibrosis in mice by reshaping the gut microbiota and host metabolism, thereby improving the inflammatory response.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":"53 3","pages":"889-908"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144082981","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}
Ming Jiang, Zhuoneng Li, Xu Qin, Lili Chen, Guangxun Zhu
{"title":"Regulatory Role of Flavonoid Baicalin from <i>Scutellaria baicalensis</i> on AMPK: A Review.","authors":"Ming Jiang, Zhuoneng Li, Xu Qin, Lili Chen, Guangxun Zhu","doi":"10.1142/S0192415X25500296","DOIUrl":"https://doi.org/10.1142/S0192415X25500296","url":null,"abstract":"<p><p>AMP-activated protein kinase (AMPK) is a ubiquitous sensor of cellular energy and nutrient status in eukaryotic cells. It serves an essential function in the modulation of energy balance and metabolism homeostasis through its regulation of carbohydrate metabolism, lipid metabolism and protein metabolism. The dysregulation of AMPK is closely related to a series of systemic diseases, affecting multiple organs and tissues. Baicalin is a natural compound derived from the dry raw root of <i>Scutellaria baicalensis</i>, and it has been found to exhibit several potential pharmacological actions. These include hepatoprotective effects, anti-inflammation effects and anti-tumor effects. These biological activities are related to the regulatory effect of baicalin on the host metabolism, which is closely associated with AMPK modulation. In this review, we provide an overview of the regulatory effect of baicalin on AMPK and its upstream and downstream signaling pathways. The pharmacological properties and underlying mechanism of baicalin for regulating AMPK were summarized with regards to four aspects: regulatory effect of baicalin on AMPK in lipid metabolism and glucose metabolism, regulatory effect of baicalin on AMPK in its pharmacological effect of anti-tumor and anti-inflammation. As a natural compound, baicalin has the potential for the management of certain AMPK-related diseases.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":"53 3","pages":"771-801"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144082986","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":"Chinese Medicine in the Era of Artificial Intelligence: Challenges and Development Prospects.","authors":"Chaoyu Wang, Guowei Dai, Yue Luo, Chuanbiao Wen, Qingfeng Tang","doi":"10.1142/S0192415X25500144","DOIUrl":"10.1142/S0192415X25500144","url":null,"abstract":"<p><p>Traditional Chinese medicine (TCM) has protected the health of Chinese people for thousands of years. With the rapid development of artificial intelligence (AI), various fields of TCM are facing both opportunities and challenges. This review discusses the development prospects and challenges of Chinese medicine in the AI era, emphasizing that AI, as an important tool in the process of Chinese medicine healthcare services, can assist doctors in making objective, rational and professional treatment decisions, and that AI has a strong potential for development in the field of Chinese medicine. However, the emotions, complex thoughts, and humanistic values of doctors are qualities that AI is currently unable to realize, so as the dominant player, the doctor is indispensable to the medical process. By summarizing and analyzing the current development status of AI in diagnosis, drug research, health management and education in TCM, this paper reveals the development prospects and potential risks of combining TCM with AI, and suggests that AI is an important aid for modernizing and improving the quality of TCM medical care in a coordinated manner.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":" ","pages":"353-384"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143652978","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":"Intestinal Absorption Characteristics and Reciprocal Interactions of <i>Forsythiae Fructus</i> and <i>Lonicerae Japonicae Flos</i>-Containing Chinese Herbal Formulation with Human Gut Microbiome.","authors":"Jia-Yuan He, Fu-Lan Xiao, Qin-Yue Zheng, Chang-Hong Wang, Yi-Yue Tang, Jun-Xuan Fu, Jia-Yi Huang, Lian-Di Zhou, Qi-Hui Zhang","doi":"10.1142/S0192415X25500211","DOIUrl":"10.1142/S0192415X25500211","url":null,"abstract":"<p><p>The intestinal absorption of active herbal constituents plays an important role in the biomedical efficacy of Traditional Chinese Medicine (TCM) formulations after oral administration. TCM compounds with low oral bioavailability can reach the distal intestine and then interact with intestinal flora, influencing the botanical pharmacological effects. In this study, <i>in vitro</i> digestion and an <i>ex vivo</i> Ussing chamber model were utilized to evaluate the intestinal absorption behavior of <i>Forsythiae Fructus</i>-<i>Lonicerae Japonicae Flos</i>-containing Yinqiao Jiedu Granule (YQJDG). It was found that the jejunum exhibited active absorption effects for some components of the formula, while the oral bioavailability of other herbal ingredients was low. Through further research using a combined UPLC-MS/MS and 16S rDNA sequencing technique, we studied the existence of the reciprocal interactions between YQJDG and gut microbiome. The <i>in vitro</i> fecal fermentation results showed that YQJDG significantly impacted the microbial community composition. The YQJDG markedly increased the abundance of beneficial microorganisms, such as <i>Parabacteroides distasonis</i> and <i>Streptococcus gallolyticus</i> subsp. <i>Macedonicus,</i> and suppressed the abundance of conditional pathogens including <i>Prevotella steorerea, Haemophilus parainfluenzae</i>, and <i>Bacteroides</i>. These effects may potentially contribute to the body's immune functions and anti-inflammatory capacities. UPLC-MS/MS analysis suggested that the fecal microbiota chemically transformed constituents with low bioavailability to more readily absorbed potentially active metabolites. These findings provided valuable insights into the absorption characteristics of YQJDG and its interaction with the gut microbiome, further facilitating our understanding of precise pharmacological mechanisms of action of this Chinese herbal formulation.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":" ","pages":"543-566"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143722818","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}
Lan Wang, Kaiqiang Tang, Yan Wang, Peng Zhang, Shao Li
{"title":"Advancements in Artificial Intelligence-Driven Diagnostic Models for Traditional Chinese Medicine.","authors":"Lan Wang, Kaiqiang Tang, Yan Wang, Peng Zhang, Shao Li","doi":"10.1142/S0192415X25500259","DOIUrl":"10.1142/S0192415X25500259","url":null,"abstract":"<p><p>Traditional Chinese medicine (TCM) is an ancient medical system with distinctive ethnic characteristics. TCM diagnosis, underpinned by unique theoretical frameworks and methodologies, continues to play a significant role in contemporary healthcare. The four fundamental diagnostic methods, inspection, auscultation-olfaction, inquiry and palpation, are inherently subjective, relying on practitioner experience. Despite its unique advantages and practical value, TCM must still take advantage of modern advancements to enhance its effectiveness and accessibility. With the rapid development of computer technology, intelligent TCM diagnosis has emerged as a promising frontier. Integrating artificial intelligence (AI), particularly through large language models (LLMs), offers new avenues for enhancing TCM diagnostic practices. However, the systematic review and analysis of these technologies remains limited. This paper provides a comprehensive overview of the development and recent advancements in TCM diagnostic technologies, focusing on the applications of ML across various data modalities, and including images, text, and waveforms. Additionally, it explores the latest applications of LLMs within the TCM diagnostic field. Furthermore, the review discusses the prospects and challenges associated with AI-based TCM diagnosis. By systematically summarizing the latest research achievements and technological advancements, this study aims to provide directional guidance and decision support for future research and practical applications in the intersection of AI and TCM. Ultimately, this review seeks to foster the continued development and integration of intelligent TCM diagnosis into modern healthcare.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":"53 3","pages":"647-673"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144082977","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}
Xiaoyun Ye, Xiaohong Wu, Siheng Lian, Ruina Cai, Xianni Wei, Tingting Nan, Yumei Cai, Yonglong Su, Jinbao Wei
{"title":"Recent Advances of Shikonin in the Molecular Mechanisms of Anticancer, Anti-Inflammation and Immunoregulation.","authors":"Xiaoyun Ye, Xiaohong Wu, Siheng Lian, Ruina Cai, Xianni Wei, Tingting Nan, Yumei Cai, Yonglong Su, Jinbao Wei","doi":"10.1142/S0192415X25500417","DOIUrl":"https://doi.org/10.1142/S0192415X25500417","url":null,"abstract":"<p><p>Shikonin, a natural bioactive compound derived from medicinal plants, demonstrates extensive pharmacological properties in traditional Chinese medicine, and exhibits significant therapeutic potential for modern diseases such as cancers and immune-related disorders. Over the past decades, research has focused on its anticancer, anti-inflammatory, and immunomodulatory activities. <i>In vitro</i> and <i>in vivo</i> studies have elucidated its mechanisms at cellular and molecular levels. Shikonin exerts antitumor effects by inducing multiple cell death modalities through caspase-3 activation, ROS generation, modulation of ATF3 expression, modulation of RIP1/RIP3 signaling, and activation of the BAX/caspase-3/GSDME pyroptosis axis. Furthermore, it suppresses tumor cell proliferation, inhibits metastasis, and blocks cell cycle progression by downregulating oncogenic c-Myc and MMP2 while upregulating the cell cycle inhibitor P21. It also enhances chemosensitivity via β-catenin modulation. Furthermore, shikonin inhibits PD-L1 expression through the NF-κB/STAT3 and NF-κB/CSN5 pathways, and mediates tumor immunomodulation as a result. Its anti-inflammatory capacity is attributed to the regulation of immune cells, signaling pathways (e.g., TLR4/MyD88/NF-κB), and pro-inflammatory cytokines (e.g., TNF-α, IL-6). The regulation of these processes thereby enhances anti-inflammatory responses in target organs and mitigates autoimmune diseases. This review systematically deciphers shikonin's mechanisms in tumor suppression, inflammation resolution, and immune regulation, offering novel insights for interdisciplinary research bridging oncology, immunology, and inflammation biology, and laying a foundation for advancing immune-modulating cancer therapies and autoimmune disease management.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":"53 4","pages":"1093-1118"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144532188","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":"Ophiopogonin D from <i>Ophiopogon japonicas</i>-induced USP25 Activity to Reduce Ferroptosis of Macrophage in Acute Lung Injury by the Inhibition of Bound Rac1 and Nox1 Complex.","authors":"Zhichen Pu, Yingjing Gui, Wenhui Wang, Yinping Shui, Haitang Xie, Min Zhao","doi":"10.1142/S0192415X25500193","DOIUrl":"10.1142/S0192415X25500193","url":null,"abstract":"<p><p>Acute lung injury (ALI) can lead to severe respiratory system damage, characterized by extensive inflammation and lung tissue injury. Ophiopogonin D (OD), from <i>Ophiopogon japonicus</i>, has pharmacological effects such as anti-inflammatory and anti-oxidant, hypoglycemic, anti-aging, and immune regulation properties. This study attempts to identify the protective mechanism of OD against ALI by the inhibition of ferroptosis of macrophages. The tissue-specific expression of USP25 in patients with COVID-19 was evaluated using single-cell data from the China National GeneBank and the GSE147507 dataset from Gene Expression Omnibus (GEO). C57BL/6 mice, Murine bone marrow derived macrophages (BMDM) or RAW264.7 cells were induced by Lipopolysaccharide (LPS). OD prevented ALI, and reduced inflammation levels and oxidative stress in mice models. OD significantly decreased the number of monocyte/macrophages (CD11b [Formula: see text]Ly6G-cells) in the peritoneal cavity after ALI induction. OD-mitigated inflammation and oxidative stress of macrophages in the ALI model. OD-reduced ferroptosis of macrophages in a model of ALI through the inhibition of ROS-induced mitochondrial damage. USP25 is significantly expressed in macrophages in patients with COVID-19 using single-cell analysis. OD-suppressed Rac1/NOX1-derived ROS to reduce the mitochondrial damage of macrophages in a model of ALI by the induction of USP25 activity. OD-identified USP25 at 907-VAL and 975-ARG in an ALI model to suppress USP25 Ubiquitination. OD from <i>Ophiopogon japonicus</i> induces USP25 activity to reduce ferroptosis of macrophages in ALI by binding the Rac1 and Nox1 complex. Therefore, it can be concluded that OD may be a potential therapeutic drug for the treatment of ALI.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":" ","pages":"501-522"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143653031","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}
Wen Liu, Zhibin Jiang, Ruirui Wang, Xiongjian Zhang, Xiaoqing Jiang, Can Chen, Pengfei Guo, Ming Yi, Wei Li
{"title":"Targeting EGFR-Mcl-1 Axis by Piperlongumine as a Novel Strategy for Non-Small Cell Lung Cancer Therapy.","authors":"Wen Liu, Zhibin Jiang, Ruirui Wang, Xiongjian Zhang, Xiaoqing Jiang, Can Chen, Pengfei Guo, Ming Yi, Wei Li","doi":"10.1142/S0192415X25500235","DOIUrl":"10.1142/S0192415X25500235","url":null,"abstract":"<p><p>Non-small cell lung cancer (NSCLC) is a malignancy that faces serious resistance challenges in treatment. In this study, we identified Piperlongumine as a promising therapeutic candidate to overcome Osimertinib resistance in NSCLC. We systematically investigated the inhibitory effect of Piperlongumine on NSCLC cells and confirmed that it could effectively inhibit the <i>in vitro</i> kinase activity of wild-type (WT), exon 19 deletion, and L858R/T790M-mutated EGFR. We also found that Piperlongumine-induced intrinsic apoptosis by interfering with the EGFR signaling pathway, which was characterized by the down-regulation of the anti-apoptotic protein Mcl-1. Further mechanistic studies revealed that Piperlongumine-induced degradation of Mcl-1 was dependent on the Akt-GSK3β signaling pathway. Additionally, Piperlongumine-promoted interaction between Mcl-1 and β-TRCP, thereby enhancing β-TRCP-mediated ubiquitination and the degradation of Mcl-1. Furthermore, Piperlongumine significantly inhibited tumor growth in both Osimertinib-sensitive and resistant NSCLC xenograft models. These findings highlight the potential of Piperlongumine as an effective agent in overcoming EGFR-targeted therapy resistance and suggest new avenues for its clinical application in NSCLC treatment.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":" ","pages":"597-619"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143722899","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}
Chun-Mei Qian, Liu Yang, Yi-Ying Wang, Zi-Liang Wang, Zi-Hang Xu, Mi-Die Xu, Xing Zhang, Xiao-Yu Wang
{"title":"Gambogic Acid Induces Ferroptosis via miR-1291/FOXA2 Axis in Gastric Cancer.","authors":"Chun-Mei Qian, Liu Yang, Yi-Ying Wang, Zi-Liang Wang, Zi-Hang Xu, Mi-Die Xu, Xing Zhang, Xiao-Yu Wang","doi":"10.1142/S0192415X25500363","DOIUrl":"https://doi.org/10.1142/S0192415X25500363","url":null,"abstract":"<p><p>Gastric cancer (GC) remains a leading cause of cancer-related mortality worldwide, posing a significant threat to human health. Recently, gambogic acid (GA) has garnered attention for its anticancer properties in GC. However, it remains unclear whether GA can regulate other forms of cell death beyond apoptosis. In this study, we found that GA inhibited proliferation and induced ferroptosis in GC cells. Western blot analysis was employed to assess ferroptosis and endoplasmic reticulum (ER) stress-related proteins, as well as forkhead box A2 (FOXA2) expression. Additionally, malondialdehyde (MDA) and glutathione (GSH) levels were measured following GA treatment, and quantitative real-time polymerase chain reaction (RT-qPCR) was used to evaluate miR-1291 expression. Our findings revealed that GA treatment elevated reactive oxygen species (ROS) levels and promoted intracellular Fe[Formula: see text], MDA, and GSH accumulation. Furthermore, GA upregulated SLC7A11 and ferritin expression while suppressing glutathione peroxidase 4 (GPX4) in AGS and HGC27 cells, suggesting its role in ferroptosis induction. Notably, GA increased miR-1291 levels and downregulated FOXA2 expression. Subsequent analyses showed FOXA2 as a direct target of miR-1291. Functional experiments involving miR-1291 and FOXA2 knockdown or overexpression further suggested that the miR-1291/FOXA2 axis mediates ferroptosis. Finally, tumor xenograft models showed that GA effectively inhibited tumor growth by inducing ferroptosis. In conclusion, our study provides compelling evidence that GA induces ferroptosis in GC through the miR-1291/FOXA2 axis, highlighting its potential as a novel therapeutic strategy and preventive target for gastric cancer treatment.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":"53 3","pages":"951-971"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144082979","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}