The American journal of Chinese medicine最新文献

{"title":"Emodin Inhibitsg Hepatocellular Carcinoma Invasion and Migration by Regulating the HDAC4/NF-κB (p65)/CXCL12 Signaling Axis and Suppressing M2 Macrophage Polarization.","authors":"Yi-Qiong Zhang, Yong-Jie Xu, Hai-Zhi Li, Shuang Wang, Cheng-Cheng Li, Chang-Yu-Dong Huang, Ya-Chun Shi, Xing Li, Shu-Yun Zhao, Li-Ying Zhu, Wei Pan","doi":"10.1142/S0192415X26500369","DOIUrl":"10.1142/S0192415X26500369","url":null,"abstract":"<p><p>This study aims to investigate how emodin, an active component of <i>Polygonum multiflorum</i>, regulates macrophage polarization through the HDAC4/NF-κB/CXCL12 pathway and impacts the progression of hepatocellular carcinoma (HCC). The inhibitory effect of emodin on M2 polarization was assessed by collecting conditioned cell culture medium from HepG2 cells and treating macrophages with emodin. Network pharmacology and other experiments were used to identify HDAC4 as a key target, and this was further validated through molecular docking, surface plasmon resonance (SPR), and Western blot analysis. Additional validation of the HDAC4/NF-κB(p65)/CXCL12 axis regarding HCC progression was conducted using single-cell RNA sequencing and an <i>in vivo</i> HCC model. The results demonstrate that macrophages with HepG2 supernatant after treating, including emodin, tetrahydroxy stilbene glucoside and physcion, were added to reduce macrophage M2 polarization and inhibit HepG2 invasion and migration. Network pharmacology and protein analysis were used to discover the role of HDAC4 as the target of three drugs in HCC. The feasibility of emodin as a drug target for HDAC4 was explored through molecular docking simulation and SPR, and then verified through Western blot and nuclear plasma separation analysis. Likewise, the HDAC4/NF-κB (p65) pathway reduces M2 polarization and inhibits the invasion and migration of HepG2. By using a single-cell sequencing database to predict the high expression of chemokines in HCC, and verifying the effect of emodin's ability to reduce M2 polarization and inhibit HepG2 invasion and migration via the HDAC4/NF-κB (p65)/CXCL12 pathway, the results were likewise validated <i>in vivo</i>. This study elucidates the novel role of emodin in HCC progression and macrophage polarization, and demonstrates how emodin-mediated HDAC4 inhibition effectively attenuates HCC invasion and migration.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":" ","pages":"975-1007"},"PeriodicalIF":5.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147793576","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":"Phycocyanin: Biomedical Activities and Related Mechanisms of Action.","authors":"Hongli Huang, Linhong Wang","doi":"10.1142/S0192415X26500308","DOIUrl":"10.1142/S0192415X26500308","url":null,"abstract":"<p><p>With global resources becoming increasingly strained, the development of novel sustainable resources has become particularly important. Spirulina has attracted considerable attention due to its exceptional nutritional value, abundant bioactive components, and superior environmental adaptability. A key functional component in spirulina, phycocyanin is a natural water-soluble protein pigment that exhibits diverse biological activities. In recent years, with advances in extraction and purification technologies, research on phycocyanin in the culinary, pharmaceutical, and cosmetic fields has both rapidly increased and significantly enhanced its commercial value. Despite its broad application prospects, research on its molecular mechanisms and systematic physiological effects requires further integration. This paper aims to comprehensively update the current research status of phycocyanin, systematically elucidate its biological activities as related to its anti-oxidative stress, immunomodulatory, anti-inflammatory, antitumor, and neuroprotective effects. To do so, this paper analyzes the molecular mechanisms through which phycocyanin exerts its effects, and in particular considers its regulation of key signaling pathways such as NRF2/HO-1, NF-κB, and PI3K/Akt. This review provides a detailed summary of the protective effects of phycocyanin on organs including the liver, cardiovascular system, and nervous system. It also summarizes the research progress on phycocyanin over the past 10 years, including findings related to its biological activities, functions, and related mechanisms. In conclusion, this review underscores the immense therapeutic potential of phycocyanin as a multi-target natural agent, and highlights the critical need for further clinical translation to fully harness its benefits in promoting human health and combating chronic diseases.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":" ","pages":"827-858"},"PeriodicalIF":5.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147793620","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":"Isoliquiritigenin from Licorice Attenuates Metastatic Development of Pancreatic Cancer by Regulation of Selective Autophagy-Mediated Ferroptosis and the Tumor Microenvironment.","authors":"Zhu Zhang, Yingyi Liu, Ai-Wei Chang, Ching-Yeung Lai, Aiping Lyu, Qilei Chen, Hubiao Chen, Joshua Ka-Shun Ko","doi":"10.1142/S0192415X26500710","DOIUrl":"10.1142/S0192415X26500710","url":null,"abstract":"<p><p>Isoliquiritigenin (ISL) is a bioactive chalcone obtained from licorice, the ground root of <i>Glycyrrhiza glabra</i>. We previously identified ISL as a late-phase autophagy inhibitor in pancreatic cancer treatment. This study aimed to further explore the involvement of selective autophagy and tumor immunity in its antineoplastic action. Network pharmacology revealed that ISL would downregulate biological processes associated with pancreatic ductal adenocarcinoma (PDAC) including cell migration, extracellular matrix organization and wound healing. Our experimental findings further confirmed ISL's role in inhibiting the epithelial-mesenchymal transition, a key mechanism involved in these processes. ISL also increased the production of reactive oxygen species in both PANC-1 and MIA PaCa-2 PDAC cells, which was intensified through inhibition of autophagy. Furthermore, ISL downregulated glutathione peroxidase 4 (GPX4) and the system Xc^- counter-transporter of cystine SLC3A2, while increasing the expression of nuclear receptor coactivator 4 (NCOA4) and decreasing that of ferritin heavy chain 1 (FTH1), thereby promoting ferritinophagy-activated ferroptosis. Alternatively, ISL could induce mitophagy by facilitating mitochondrial dynamics toward fusion through an increase in Parkin and MFN1 gene expression. ISL also modulated the robust transcriptional stress response associated with autophagy and ferroptosis through regulation of CREB1 and VMP1. In the tumor microenvironment, ISL decreased the number of myeloid-derived suppressor cells (MDSCs) while increasing the number of CD4[Formula: see text] and CD8[Formula: see text] T cells in the spleen, tumor tissues and blood of Pan02-xenografted mice. ISL also impaired M2 polarization of macrophages in tumor tissues. The inhibitory effects of ISL could be attenuated by interferon-[Formula: see text] through STAT1 signaling. These results demonstrate that ISL regulates selective autophagy-mediated ferroptosis associated with modulation of the tumor microenvironment when treating pancreatic cancer.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":" ","pages":"1899-1930"},"PeriodicalIF":5.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148852295","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":"Astragaloside IV Ameliorates Diabetic Kidney Disease via Inhibiting MAPK Pathway and Alleviating Metabolic Dysregulation.","authors":"You Wang, Guang-Rui Huang, Bao-Sheng Zhao, Zhu-Qing Yang, Miao Xu, Yu-Zhuo Chang, Li-Jia Wu, Xin-Cui Bao, Jing Yang, Zhe Liu, Ling-Ling Qin, Hai-Yan Wang, Gui-Min Zheng, Ming Gao, Cui-Yan Lv, Tong-Hua Liu","doi":"10.1142/S0192415X26500473","DOIUrl":"10.1142/S0192415X26500473","url":null,"abstract":"<p><p>Diabetic kidney disease (DKD) is a severe diabetic microvascular complication with a complex pathogenesis and progression driven by renal fibrosis and inflammation. As a condition, DKD imposes a heavy clinical burden. Astragaloside IV (AS-IV), the main active component of <i>Astragalus membranaceus</i>, exhibits renoprotective potential in DKD, but its molecular mechanisms remain unclear. This study combined network pharmacology, molecular docking, and <i>in vivo</i> validation in db/db mice in order to explore AS-IV's therapeutic effect on DKD and the mechanisms by which it alleviates inflammation and fibrosis. The efficacy of AS-IV was evaluated via glucose metabolism, urinary protein, hepatic/renal function, and renal histopathology using H&E, PAS, Masson staining, and transmission electron microscopy. The expressions of the MAPK pathway, fibrosis and inflammation-related molecules were detected by ELISA, Western blot, RT-qPCR, immunohistochemistry and immunofluorescence. In addition, non-targeted metabolomics was used to explore metabolic regulation. Network pharmacology identified the MAPK pathway as a core target, and molecular docking confirmed AS-IV's strong binding to MAPK1/MAPK3. <i>In vivo,</i> AS-IV improved glucose metabolism, reduced albuminuria, alleviated renal histological damage, inhibited ERK/JNK/p38 phosphorylation in the MAPK pathway, downregulated fibrosis-related proteins (TGF-β1, α-SMA, Collagen I/IV) and suppressed NF-κB-mediated inflammation. It furthermore ameliorated metabolic disorders, and exhibited a particular efficacy in doing so for amino acid metabolism. Collectively, AS-IV retards DKD progression by both exerting antifibrotic/anti-inflammatory effects and correcting metabolic dysregulation via inhibition of the MAPK pathway. These mechanisms provide a theoretical basis for the clinical application of AS-IV in DKD.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":" ","pages":"1281-1307"},"PeriodicalIF":5.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148255097","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":"Ginsenoside Rg3 in Cancer Therapy: Pharmacokinetics, Molecular Mechanisms, and Synergistic Combinations.","authors":"Yue Cui, Jingming Li, Chunyan Liu, Guohua Yu, Jiaru Shi, Xueyan Li, Jinchai Qi, Ruofan Guo, Huixia Fan, Shuo Zhang, Chen Wang, Kang Chen, Zhiqiang Luo","doi":"10.1142/S0192415X26500552","DOIUrl":"10.1142/S0192415X26500552","url":null,"abstract":"<p><p>Ginsenoside Rg3, a rare protopanaxadiol-type saponin enriched during the heat processing of Panax ginseng, has attracted increasing attention as a multitarget anticancer agent. This systematic review examines the anticancer potential of Rg3 through comprehensive searches of the PubMed and Web of Science databases, with a focus on peer-reviewed preclinical and clinical studies. The therapeutic efficacy of Rg3 is critically influenced by its stereochemical configuration, concentration-dependent bidirectional regulation, and pharmacokinetic constraints, including poor oral bioavailability, rapid clearance, and gut microbiota-mediated metabolism. Nanocarrier-based and targeted delivery systems have substantially improved its pharmacokinetic profile and tumor accumulation, supporting its further development for anticancer applications. Within this pharmacological context, Rg3 exhibits broad-spectrum anticancer activity across multiple solid tumors, including hepatocellular carcinoma, melanoma, lung, ovarian, breast, colon, gastric, and prostate cancers, as well as osteosarcoma, renal cancer, lung adenocarcinoma, glioblastoma, gallbladder, nasopharyngeal, cervical, and pancreatic cancers, and the hematological malignancy multiple myeloma. Mechanistically, Rg3 suppresses cancer progression through coordinated regulation of proliferation, apoptosis, autophagy, ferroptosis, angiogenesis, epithelial-mesenchymal transition, cancer stemness, immune evasion, and redox homeostasis, primarily involving the PI3K/AKT/mTOR, NF-[Formula: see text]B, MAPK, Wnt/[Formula: see text]-catenin, EGFR, and p53 pathways. These effects reflect transferable network-level mechanisms rather than tumor type-restricted actions. Moreover, Rg3 demonstrates synergistic effects with chemotherapy, radiotherapy, targeted therapy, and immunotherapy, while reversing drug resistance and attenuating treatment-related toxicity in multiple cancer models and clinical settings. Overall, this review systematically integrates current evidence on the pharmacokinetics, anticancer spectrum, molecular mechanisms, synergistic combinations, immunomodulatory effects, and clinical applications of Rg3, providing a concise framework for the rational development of Rg3-based combination strategies in precision cancer therapy.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":" ","pages":"1499-1530"},"PeriodicalIF":5.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148431779","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":"Curcumin for the Treatment of Inflammatory Bowel Disease: From Mechanism to Clinic.","authors":"Yushan Wu, Jiangmei Pang, Jiaxin Li, Mingshan Jiang, Hao Lin, Hu Zhang","doi":"10.1142/S0192415X26500217","DOIUrl":"10.1142/S0192415X26500217","url":null,"abstract":"<p><p>Inflammatory bowel disease (IBD) is characterized by chronic symptoms, frequent relapses, and an increased risk of complications such as colorectal cancer. These qualities significantly impair patients' quality of life, and while various treatment options are available, they are often limited by inconsistent responses, unclear long-term safety, considerable individual variability, restricted drug accessibility, high costs, and the complexity of combination therapies. Such challenges thus highlight the urgent need for novel, safer, and more effective treatments. Curcumin, a natural compound with diverse biological activities, shows promise in IBD management. This review discusses the mechanisms of curcumin in IBD, highlights its multi-target regulation of both signaling pathways and various immune cell populations, and emphasizes its potent anti-oxidant and anti-inflammatory effects. In addition, curcumin has been shown to strengthen intestinal barrier function and modulate the intestinal microbiota. While clinical studies indicate that curcumin can improve symptoms, endoscopic findings, and laboratory markers in IBD patients, its low bioavailability remains a challenge. Recent research has focused on enhancing curcumin's stability, targeting, and bioavailability to optimize its therapeutic potential. Insights from curcumin's use in other diseases further support its potential in IBD treatment. Despite these promising findings, further high-quality clinical trials and the development of novel curcumin formulations are necessary to enable its practical clinical application in IBD.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":" ","pages":"573-602"},"PeriodicalIF":5.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147313698","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":"Quercetin Alleviates Endothelial Dysfunction in Atherosclerosis by Inhibiting Ferroptosis Through PACS2/HMOX-1 Pathway.","authors":"Hai-Jiao Long, Quan-Jun Liu, Shi-Ying Qin, Hong Xiang, Jie Ouyang, Jun-Xi Liao, Ye Tao, Jiao-Qian Huang, Shu-Hua Chen, Hong-Wei Lu","doi":"10.1142/S0192415X26500229","DOIUrl":"10.1142/S0192415X26500229","url":null,"abstract":"<p><p>Atherosclerosis is a leading cause of worldwide cardiovascular morbidity and mortality, and endothelial ferroptosis has emerged as a key mechanism in driving vascular injury. This study aimed to investigate whether quercetin (QCT), a natural dietary flavonoid with potent anti-oxidant activity, protects against atherosclerosis-associated endothelial dysfunction by modulating ferroptosis. In order to test this, ApoE[Formula: see text] mice fed a high-fat diet were treated with QCT or ferrostatin-1, and their aortic plaque burden, stability, and macrophage infiltration were then assessed. To evaluate ferroptosis, human umbilical vein endothelial cells (HUVECs) were exposed to oxidized low-density lipoprotein (Ox-LDL), with or without QCT, and their reactive oxygen species (ROS), Fe[Formula: see text] accumulation, and heme oxygenase-1 (HMOX-1) expression were measured. While functional assays examined endothelial barrier integrity and monocyte adhesion, gene modulation studies explored the role of phosphofurin acidic cluster sorting protein 2 (PACS2). QCT treatment markedly reduced plaque area, necrotic core size, and macrophage infiltration while enhancing plaque stability. <i>In vitro</i>, QCT suppressed Ox-LDL-induced ferroptosis by decreasing ROS and Fe[Formula: see text] levels and downregulating HMOX-1 to thereby restore endothelial integrity and reduce monocyte adhesion. Mechanistically, QCT restored PACS2 expression suppressed by Ox-LDL. However, PACS2 knockdown or HMOX-1 activation abrogated QCT's protective effects. These findings identify QCT as a promising dietary anti-oxidant that mitigates atherosclerosis via the PACS2-HMOX-1 ferroptosis pathway.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":" ","pages":"603-625"},"PeriodicalIF":5.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146204564","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":"Triptolide from <i>Tripterygium wilfordii</i> Suppresses Glycolysis and Induces Cuproptosis via the HK2/DLAT Signaling Pathway in Colorectal Cancer.","authors":"Hui-Hui Liang, Lu-Lu Jia, Ke Tang, Rui Xue, Rong-Rong Nie, Jian-Ning Chen, Hui-Min Xu, Xuan-Jie Qin, Shi-Kun Cai, Qin-You Tan","doi":"10.1142/S0192415X26500242","DOIUrl":"10.1142/S0192415X26500242","url":null,"abstract":"<p><p>Colorectal cancer (CRC) exhibits high mortality due to tumor cell dissemination. Surgical resection combined with chemotherapy is the primary treatment, but chemoresistance often limits its efficacy against metastasis. Cuproptosis, a novel cell death mechanism regulating mitochondrial and lipid metabolism, may suppress metastasis by inhibiting cellular metabolism. Triptolide (TP), a potential antitumor agent derived from <i>Tripterygium wilfordii</i>, can reverse chemoresistance. This study investigated the link between TP's anti-CRC effects and cuproptosis. Cell Counting Kit-8 (CCK-8), colony formation, wound healing, and transwell migration/invasion assays demonstrated that TP inhibited the proliferation, migration, and invasion of SW480 and HCT116 cells in a dose-dependent manner. Bioinformatic analysis implicated glycolysis and cuproptosis in TP's anti-CRC action. Subsequent validation via glucose metabolism assays, reactive oxygen species (ROS) detection, JC-1 staining, copper ion measurement, morphological observation, qRT-PCR, and Western blotting confirmed that TP had a significant effect in both suppressing glycolysis and inducing cuproptosis in SW480 and HCT116 cells. In addition, <i>in vivo</i> studies have shown that TP significantly inhibits tumor growth and promotes copper accumulation within tumors. Furthermore, hematoxylin-eosin (H&E) staining and biochemical analysis have indicated that it has no obvious liver or kidney toxicity. These results suggest that TP may both inhibit the glycolysis of CRC and induce cuprotosis via the Hexokinase 2 (HK2)/Dihydrolipoamide S-acetyltransferase (DLAT) pathway. Future research should systematically verify its effectiveness and safety through <i>in vivo</i> studies and clinical trials to promote the application of TP in CRC treatment.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":" ","pages":"661-683"},"PeriodicalIF":5.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146222536","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":"CORRIGENDUM - <i>Rhus verniciflua and Eucommia ulmoides</i> Protects Against High-Fat Diet-Induced Hepatic Steatosis by Enhancing Anti-Oxidation and AMPK Activation.","authors":"Hwa-Young Lee, Geum-Hwa Lee, Young Yoon, Han-Jung Chae","doi":"10.1142/S0192415X26920023","DOIUrl":"10.1142/S0192415X26920023","url":null,"abstract":"","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":" ","pages":"1979-1980"},"PeriodicalIF":5.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148820742","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":"Nobiletin Ameliorated the Development of Diabetic Kidney Disease via Modulating Ferroptosis and Epithelial-Mesenchymal Transition Involving Gut-Kidney Axis.","authors":"Tingting Zhao, Chuyun Zhao, Qian Xiang, Xi Zhang, Kin-Fong Hong, Peiyu Liu, Zhongyan Sun, Yadi Liu, Ruiting Huang, Yiran Li, Hio-Fai Cheong, Yuwei Wu, Yingqiu Mo, Yiduo Xu, Yingxi Zhao, Qiruo Huang, Ying Xie, Youhua Xu","doi":"10.1142/S0192415X26500114","DOIUrl":"10.1142/S0192415X26500114","url":null,"abstract":"<p><p>Diabetic kidney disease (DKD) is one of the most common microvascular complications associated with diabetes mellitus. However, the existing treatment approaches, aimed at delaying the onset of DKD, exhibit limited efficacy. The flavonoid nobiletin has demonstrated substantial lipid-lowering and insulin-sensitizing effects in mice exhibiting metabolic dysfunction, but the therapeutic potential and mechanism of nobiletin in the context of DKD remains to be comprehensively elucidated. In this study, the active components of polymethoxylated flavonoids (PMFs) were identified via UPLC. A DKD rat model was established through a high-fat diet and the administration of streptozotocin via intraperitoneal injection. The effect and mechanism of nobiletin on DKD was evaluated by histological, biochemical, molecular, and multi-omics analysis. We found that treatment with PMFs and nobiletin inhibited ferroptosis and EMT in high glucose and insulin-induced models, protected the glomerular filtration barrier integrity, and concurrently suppressed ROS, Fe[Formula: see text], and MDA while increasing the GSH level. Animal experiments indicated that nobiletin treatment markedly impeded the progression of DKD and alleviated both EMT and endothelial dysfunction. Moreover, nobiletin significantly preserved the integrity of the intestinal barrier and enriched the diversity of gut microbiota. In conclusion, our findings indicate that nobiletin could attenuate DKD and concomitantly limit ferroptosis and EMT, and that the gut-kidney axis played an important role in its effects.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":" ","pages":"303-328"},"PeriodicalIF":5.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146047722","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}