Chinese Medicine最新文献

{"title":"Single-cell transcriptomics reveals how Shenfu Qiangxin pill ameliorates HFpEF by modulating cardiac cellular heterogeneity.","authors":"Yakun Yang, Haohao Gao, Zhifei Fu, Weiying Hu, Yijing Li, Haixia Li, Hanqing Lin, Aodi Fan, Ke Yang, Jingyu Ni, Guanwei Fan, Lan Li","doi":"10.1186/s13020-026-01456-3","DOIUrl":"10.1186/s13020-026-01456-3","url":null,"abstract":"<p><strong>Background: </strong>Heart failure with preserved ejection fraction (HFpEF) has currently emerged as a predominant and challenging subtype of heart failure, with high morbidity and mortality. However, the efficacy of current therapeutic strategies for HFpEF remains unsatisfactory. The traditional Chinese medicine formulation Shenfu Qiangxin pill (SFQX) ameliorates clinical symptoms in patients with heart failure, but its precise mechanisms for HFpEF remain to be elucidated. This study aimed to investigate the therapeutic potential of SFQX for HFpEF and to elucidate the mechanisms underlying its effects.</p><p><strong>Methods: </strong>UPLC-Q-TOF-MS/MS analysis was performed to identify the major active ingredients of SFQX. The HFpEF mouse model was established using a high-fat diet and an Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME) to evaluate the therapeutic efficacy of SFQX. We employed an integrated approach combining single-cell RNA sequencing (scRNA-seq) with functional and molecular validation to characterize SFQX-induced changes in cardiac cellular composition, cell-state remodeling, and tissue-level phenotypes in HFpEF.</p><p><strong>Results: </strong>We show that SFQX exerts therapeutic effects against HFpEF by coordinately modulating maladaptive cardiac cell subsets. Specifically, SFQX was associated with reprogramming of pathogenic immune cell polarization, normalization of fibroblast state heterogeneity, enhanced endothelial metabolic adaptability, and restoration of lymphatic endothelial homeostasis. These multicellular changes were accompanied by improved cardiac structure and function, reduced fibrosis and inflammation, enhanced lymphatic drainage capacity, and alleviated myocardial edema.</p><p><strong>Conclusion: </strong>Our findings highlight the ability of SFQX, as a multicomponent agent, to precisely regulate the highly heterogeneous pathology of HFpEF at a network level. This work not only establishes a mechanistic link between holistic principles of traditional medicine and modern biology but also provides a novel theoretical basis for SFQX's efficacy in multifactorial diseases.</p>","PeriodicalId":10266,"journal":{"name":"Chinese Medicine","volume":"21 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13383478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148535017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Wendan decoction modulates Parasutterella to influence fatty acid metabolism in MAFLD via the FXR/PPARα/CYP4A12A axis.","authors":"Yiheng Zhang, Jiahao Wang, Weihao Zhu, Yi Zhang, Tianle Ma, Huihua Fang, Jicong Du, Zhipeng Chen, Weidong Li, Xiao Zhang, Li Wu, Xin Chen, Haibing Hua","doi":"10.1186/s13020-026-01474-1","DOIUrl":"10.1186/s13020-026-01474-1","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;The host microbiota and hepatic drug-metabolizing enzymes are important mediators of the metabolism and biological effects of herbal components. Through bidirectional interactions, herbal medicines can also reshape the host microbial community. The clinical efficacy of Wendan Decoction (WDD) in treating metabolic dysfunction-associated fatty liver disease (MAFLD) has been well established. However, its interactions with the host microbiota through the gut-liver axis remain unclear.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Purpose: &lt;/strong&gt;This study aimed to investigate the mechanism by which WDD modulates host microbial activity through the gut-liver axis to ameliorate MAFLD.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;MAFLD models were established by high-fat diet (HFD) feeding and subsequently treated with WDD, Parasutterella excrementihominis (P. excrementihominis), or 7α-OH-T. The ABX group underwent antibiotic-mediated microbiota depletion before treatment. Multi-omics analyses were used to characterize the dynamic trajectories of microbiota-derived metabolites. These analyses included targeted bile acid (BA) profiling of serum, 16S rRNA gene sequencing and untargeted metabolomics of cecal contents, and proteomics and untargeted metabolomics of liver tissue. Hematoxylin and eosin, Oil Red O, and Alcian blue-periodic acid-Schiff staining were used to assess pathological changes in the liver and intestinal tissues during MAFLD. ELISA, Western blotting, and other assays were performed to quantify markers of inflammation and lipid metabolism. Following UPLC/UV detection of 7α-OH-T in portal vein serum, molecular docking and molecular dynamics simulations, together with cellular thermal shift assays (CETSA) and microscale thermophoresis (MST), were used to validate FXR as a target of 7α-OH-T.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;WDD alleviated hepatic steatosis, intestinal inflammation, and barrier dysfunction in MAFLD, but these effects depended on the integrity of the host microbiota. 16S rRNA gene sequencing showed that WDD promoted the growth of beneficial bacteria, including Bacteroides and Parasutterella. Combined analysis of targeted serum BA metabolomics and untargeted metabolomics of cecal contents indicated that WDD-mediated modulation of the host microbiota reduced the total serum BA load, increased alternative-pathway metabolites, including CDCA and TCDCA, in the liver and intestine, and decreased toxic secondary BAs, including DCA and LCA. Steroid and fatty acid metabolites, such as 7α-OH-T, were also increased. Pearson correlation analysis and P. excrementihominis transplantation experiments suggested that the increase in 7α-OH-T was closely associated with P. excrementihominis. Untargeted liver metabolomics and serological analyses confirmed that gut-derived 7α-OH-T entered the liver through the portal vein and acted on hepatic targets via the gut-liver axis. In animal experiments involving exogenous 7α-OH-T supplementation and in MAFLD THLE","PeriodicalId":10266,"journal":{"name":"Chinese Medicine","volume":"21 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13383561/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148535036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacological manipulation of Sema4D by salvianolic acid A mitigates diabetic retinopathy via inhibiting PlexinB1/RhoA/ROCK/pMLC2 signaling cascade involved in endothelial dysfunction.","authors":"Weiwei Zheng, Ling Ning, Peiliang Shen, Jing Ma, Chang Yu, Ruiqin Jia, Liwenyu Chen, Wei Zou, Yuhua Xu, Yanhong Pan, Zhonghong Wei, Qiuhong Shen, Chongjin Zhong, Aiyun Wang, Wenxing Chen, Juan Chen, Suyun Yu, Jia Li, Yin Lu, Yang Zhao","doi":"10.1186/s13020-026-01468-z","DOIUrl":"10.1186/s13020-026-01468-z","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Diabetic retinopathy (DR) is a leading cause of blindness. While anti-vascular endothelial growth factor (VEGF) therapy is effective, its utility is limited by variable patient response and the need for frequent injections. Therefore, identifying new therapeutic targets for DR is imperative. Emerging evidence indicates that astrocytes contribute to endothelial dysfunction in DR, suggesting that targeting astrocyte-endothelial cell crosstalk represents a promising therapeutic strategy.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Purpose: &lt;/strong&gt;To evaluate the therapeutic potential of Salvianolic acid A (Sal A) for DR, elucidate the molecular mechanisms by which it modulates astrocyte-endothelial cell interactions, and develop a liposome-based nanodelivery system to enhance its efficacy.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design: &lt;/strong&gt;The protective effects and mechanisms of Sal A were systematically investigated using a streptozotocin (STZ)-induced diabetic mouse model, complemented by a suite of in vitro and molecular approaches including co-culture models, transcriptomic analysis, and target validation assays.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Retinal vascular structure and barrier function were assessed in vivo via immunofluorescence staining and Evans Blue leakage assays. Endothelial cell behaviors were examined in vitro using wound healing, Transwell migration, tube formation, and spheroid sprouting assays. Transcriptomic profiling was performed by RNA sequencing (RNA-seq). The direct target of Sal A was identified and validated using MS-based drug-affinity responsive target stability (DARTS) screening, cellular thermal shift assay (CETSA), and microscale thermophoresis (MST). Expression of key signaling molecules was measured by western blotting, enzyme-linked immunosorbent assay (ELISA), and quantitative real-time PCR (qRT-PCR). Liposome@Sal A was prepared and characterized for its physicochemical properties (dynamic light scattering, transmission electron microscopy), stability, and therapeutic efficacy in vitro and in vivo.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Sal A treatment ameliorated retinal vascular abnormalities in diabetic mice, evidenced by increased VE-cadherin and NG2 expression, decreased α-smooth muscle actin (α-SMA) expression, and reduced acellular capillary formation, collectively restoring vascular integrity. Mechanistically, astrocyte-derived soluble Semaphorin 4D (sSema4D) promoted endothelial hyperactivation via the PlexinB1/RhoA/ROCK/pMLC2 signaling cascade. Sal A directly bound to the Arg92 residue of membrane-bound Sema4D on astrocytes, significantly inhibiting sSema4D shedding and its subsequent deleterious effects on endothelial cells. Furthermore, Liposome@Sal A enhanced retinal drug delivery and demonstrated superior therapeutic efficacy compared to free Sal A in diabetic mice.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Sal A preserves retinal vascular structure and function in DR by binding to astrocytic Sema4D at Arg92, thereby inh","PeriodicalId":10266,"journal":{"name":"Chinese Medicine","volume":"21 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13383426/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148535589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Co-production of high-purity floridoside and isofloridoside ameliorates MASH via Parabacteroides goldsteinii-UDCA-FXR enterohepatic axis.","authors":"Shuang Li, Rong Guo, Linxiao Sun, Peng Zhu, Tingting Wang, JianJun Zheng, Haimin Chen, Hongshan Li","doi":"10.1186/s13020-026-01450-9","DOIUrl":"10.1186/s13020-026-01450-9","url":null,"abstract":"<p><strong>Background: </strong>Metabolic dysfunction-associated steatohepatitis (MASH), the progressive form of metabolic dysfunction-associated fatty liver disease (MAFLD), is tightly linked to gut microbiota dysbiosis and disrupted bile acid (BA) homeostasis. Floridoside (Flor), a marine glycoside from the edible seaweed Pyropia haitanensis (P. haitanensis), exerts promising biological activities. However, protocols for its high-purity preparation and the mechanisms underlying its anti-MASH effects remain unclear.</p><p><strong>Purpose: </strong>To develop a protocol for the preparation of high-purity Flor and its isomer isofloridoside (Isoflor) from P. haitanensis, and to elucidate how Flor alleviates MASH via regulating gut microbiota and BA metabolism.</p><p><strong>Methods: </strong>High-purity Flor and Isoflor were isolated via integrated chromatography, with their chemical structures confirmed by LC-MS and NMR. Anti-MASH efficacy was evaluated in a high-fat diet (HFD)-induced murine MASH model. The underlying mechanisms were explored using multi-omics analyses, including transcriptomics, gut microbiota metagenomics and BA-targeted metabolomics, and further validated by molecular docking, molecular dynamics simulation and western blotting; the compounds' biosafety was evaluated using zebrafish.</p><p><strong>Results: </strong>High-purity Flor and Isoflor were successfully isolated, each with a purity of ≥ 99.0%. Both compounds exhibited a favorable biosafety profile and comparable lipid-lowering activity in zebrafish. In HFD-induced murine MASH models, Flor robustly ameliorated HFD-driven obesity, hepatic steatosis, and chronic inflammation, and restored systemic BA homeostasis characterized by a markedly increased non-12-OH/12-OH BA ratio. Meanwhile, Flor treatment dramatically enriched the relative abundance of intestinal Parabacteroides goldsteinii (P. goldsteinii), which showed a significant positive correlation with MASH alleviation and beneficial BAs (e.g., ursodeoxycholic acid (UDCA)). Mechanistically, UDCA exerted its therapeutic effects by antagonizing FXR signaling, upregulating the hepatic protein and mRNA expression of CYP7B1 and CYP27A1, and ultimately promoting the activation of the alternative BA synthesis pathway.</p><p><strong>Conclusion: </strong>High-purity Flor and Isoflor were obtained via an integrated co-production process from P. haitanensis. We hypothesize that Flor may ameliorate MASH by enriching P. goldsteinii and modulating the UDCA-FXR axis to activate the alternative bile acid synthesis pathway, positioning Flor as a promising prebiotic candidate for MASH management.</p>","PeriodicalId":10266,"journal":{"name":"Chinese Medicine","volume":"21 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13377823/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148469425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond chemical composition: solvent pretreatment modulates supramolecular assembly and interactions with MRSA to enhance antibacterial efficacy of Scutellariae Radix-Coptidis Rhizoma.","authors":"Yiqing Huang, Yihang Zhao, Jichang Wei, Jihui Lu, Zhiwei Wang, Gen Li, Helong Xu, Yuanhua Li, Xuemei Huang, Penglong Wang","doi":"10.1186/s13020-026-01460-7","DOIUrl":"10.1186/s13020-026-01460-7","url":null,"abstract":"<p><strong>Background: </strong>Scutellariae Radix-Coptidis Rhizoma herb pair is a classic traditional Chinese medicine (TCM) combination with heat-clearing, dampness-drying and detoxifying effects, extensively applied clinically against bacterial infections. Traditional water decoction and ethanol pretreatment are mainstream extraction approaches, whereas existing comparisons merely emphasize quantitative variations of bioactive compounds, neglecting the underlying supramolecular assembly differences of effective substances. Comparative analysis of solvent-induced supramolecular variations provides a novel perspective to interpret differential pharmacodynamic material bases of TCM formulas.</p><p><strong>Methods: </strong>Macroscopic and microscopic morphologies of HH-0 and HH-50 were firstly characterized by visual inspection, SEM and DLS. Their phytochemical profiles were subsequently analyzed by UHPLC-Q-Orbitrap HRMS and HPLC. Antibacterial activities against MRSA were further quantified via turbidimetry and plate assays. UV, FT-IR and MD simulations revealed divergent supramolecular assembly behaviors. Finally, untargeted metabolomics and assembly-peptidoglycan interaction simulations elucidated the underlying anti-MRSA mechanisms.</p><p><strong>Results: </strong>The solvent pretreatment endowed HH-0 and HH-50 supramolecules with distinct characteristics. HH-50 featured rougher supramolecular surfaces and higher Zeta potential with favorable dispersibility. The two supramolecules shared consistent active constituents, and HH-50 showed elevated berberine abundance and enhanced anti-MRSA activity. Notably, HH-50 maintained superior antibacterial efficacy and interference against peptidoglycan synthesis and energy metabolism even at identical berberine doses. This confirmed that divergent supramolecular conformations determined antibacterial differences, as diminished hydrogen bonds and weakened van der Waals and electrostatic interactions enhanced the binding affinity between assemblies and MRSA.</p><p><strong>Conclusion: </strong>Beyond chemical composition, solvent pretreatment (water versus 50% ethanol) markedly modulates supramolecular assembly behaviors and subsequent assembly-bacteria interactions, thereby regulating the anti-MRSA efficacy of the Scutellariae Radix-Coptidis Rhizoma herb pair. This work emphasizes that supramolecular configurations, rather than simple differences in chemical contents, dominate the pharmacological activities of traditional Chinese medicine preparations.</p>","PeriodicalId":10266,"journal":{"name":"Chinese Medicine","volume":"21 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13378121/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148469380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modeling symptom-acupoint interactions via a heterogeneous graph learning framework for intelligent acupoint recommendation.","authors":"Wei Lin, Jiaqi Chen, Zhuo Chen, Tao Yin, Jing Guo, Fang Zeng","doi":"10.1186/s13020-026-01458-1","DOIUrl":"10.1186/s13020-026-01458-1","url":null,"abstract":"<p><strong>Objective: </strong>Acupuncture prescriptions involve complex compatibility mechanisms grounded in multi-symptom and multi-acupoint interactions, embodying millennia of clinical experience. Despite growing interest in computational acupoint recommendations, significant challenges persist due to sparse clinical data and the insufficient modelling of symptom-acupoint relationships, posing considerable hurdles to effective prediction.</p><p><strong>Methods: </strong>We introduced an acupoint compatibility prediction framework with graph neural networks (GNN) and fine-tuned bidirectional encoder representations from transformers (termed GNN-BERT-Attention). The heterogeneous feature interaction learning mechanism was introduced to model symptom-acupoint interactions through heterogeneous graph construction, capturing semantic features and relational patterns in a unified space, which alleviated the sparsity of data. Neural collaborative filtering is utilised via label-aware fusion to iteratively refine the confidence of predictions, while Focal Loss and randomised augmentation strategies enhance robustness against imbalanced label distribution.</p><p><strong>Results: </strong>Comprehensive experiments demonstrate the superiority of the proposed GNN-BERT-Attention model over State-of-the-Art (SOTA) baselines in precision, recall, ranking-based metrics and robustness. Ablation studies validate the effectiveness of each architectural module, and hyperparameter tuning confirms models' stability. A web-based demonstration system further validates clinical applicability, enabling real-time, interpretable acupoint recommendations.</p><p><strong>Conclusion: </strong>This study contributes to enhancing the performance of acupoint prediction, ultimately benefiting the efficiency and precision of acupuncture treatment while providing a theoretical foundation for optimising prescriptions and advancing evidence-based traditional Chinese medicine interventions.</p>","PeriodicalId":10266,"journal":{"name":"Chinese Medicine","volume":"21 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13374231/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148469433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lycorine ameliorates diabetic nephropathy by targeting RAGE and inhibiting the HMGB1/RAGE/NF-κB signaling axis.","authors":"Zheng Xu, Xuejin Jin, Miao Yuan, Huanyan Tao, Yutong Wang, Jingnan Zhang, Guang Liang, Qian Zhou","doi":"10.1186/s13020-026-01469-y","DOIUrl":"10.1186/s13020-026-01469-y","url":null,"abstract":"<p><strong>Background: </strong>Diabetic nephropathy (DN) is a major microvascular complication of diabetes and a leading cause of end-stage renal disease. Chronic inflammation plays a pivotal role in the pathogenesis of DN. Lycorine (LY), a complex tetracyclic pyrrolo[de]phenanthridine alkaloid derived from the Amaryllidaceae family, possesses notable anti-inflammatory activity, yet its therapeutic potential in DN remains insufficiently defined.</p><p><strong>Methods: </strong>We evaluated the renoprotective effects of LY both in vivo and in vitro. Streptozotocin (STZ)-induced diabetic mice were treated with LY, and renal function and histopathological alterations were assessed. In vitro, human renal tubular epithelial HK-2 cells were exposed to high glucose plus palmitic acid (HG + PA) with or without LY. RNA-seq analysis was performed to identify LY-regulated pathways. Molecular docking, surface plasmon resonance (SPR) assay, and cellular thermal shift assay (CETSA) were used to evaluate the interaction between LY and receptor for advanced glycation end products (RAGE). RAGE siRNA-mediated knockdown was further conducted to determine whether RAGE is required for the protective effects of LY. Activation of the HMGB1/RAGE/NF-κB signaling axis and associated inflammatory mediators was analyzed by Western blotting and RT-PCR.</p><p><strong>Results: </strong>LY markedly alleviated renal injury in STZ-induced diabetic mice, as evidenced by reduced albuminuria, improved renal function, and attenuated renal fibrosis, apoptosis, oxidative stress, and inflammation. Notably, LY did not significantly alter blood glucose levels or body weight, indicating that its renoprotective effect was independent of glycemic control. In HG + PA-treated HK-2 cells, LY significantly suppressed apotosis, oxidative stress, and inflammatory cytokine expression. Mechanistically, RNA-seq analysis identified AGE-RAGE and NF-κB signaling pathways as key pathways modulated by LY. Molecular docking, SPR, and CETSA confirmed that LY directly interacted with RAGE. Moreover, RAGE knockdown largely abolished the additional protective effects of LY, supporting RAGE as a critical molecular target. LY inhibited HMGB1/RAGE-mediated NF-κB activation, as reflected by reduced HMGB1, RAGE, p-p65, and p-IκBα levels.</p><p><strong>Conclusion: </strong>LY ameliorates diabetic nephropathy without affecting blood glucose levels by directly targeting RAGE and suppressing the HMGB1/RAGE/NF-κB signaling axis. These findings identify LY as a potential RAGE-targeting therapeutic candidate for inflammation-driven diabetic kidney injury.</p>","PeriodicalId":10266,"journal":{"name":"Chinese Medicine","volume":"21 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13374191/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148454850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Guiqi Baizhu prescription attenuates 5-FU-induced intestinal mucositis by targeting IKKβ to inhibit M1 macrophage polarization.","authors":"Yu-Cen Zhou, Ya-Ling Li, Jing Ma, Junjie Li, Qi Si, Shunzhi Wang, Dan Huang, Xiao-Xia Wa, Hui Cai, Yong-Qi Liu","doi":"10.1186/s13020-026-01406-z","DOIUrl":"10.1186/s13020-026-01406-z","url":null,"abstract":"<p><strong>Background: </strong>Chemotherapy-induced intestinal mucositis (CIM), particularly that induced by agents such as 5-fluorouracil (5-FU), frequently leads to chemotherapy discontinuation. However, effective treatment options remain limited. Guiqi Baizhu prescription (GQBZP), a traditional Chinese medicine formula, has been reported to possess anticancer, analgesic, and anti-inflammatory activities.</p><p><strong>Purpose: </strong>This study aimed to evaluate the therapeutic efficacy of GQBZP against 5-FU-induced intestinal mucositis (IM) and to clarify its underlying molecular mechanisms and material basis.</p><p><strong>Methods: </strong>The protective effects and mechanistic actions of GQBZP were investigated using a murine model of 5-FU-induced IM. Potential IKKβ-targeting compounds within GQBZP were screened through virtual docking combined with CCK-8 assays and subsequently evaluated in 5-FU-stimulated human intestinal epithelial cells (HIECs) and lipopolysaccharide/interferon-γ (LPS/IFN-γ)-stimulated THP-1 macrophages. Target specificity and binding characteristics were further validated by molecular dynamics (MD) simulations, surface plasmon resonance (SPR) analysis, and experiments using IKKβ-overexpressing HEK293T cells.</p><p><strong>Results: </strong>In vivo experiments demonstrated that GQBZP significantly alleviated 5-FU-induced IM by suppressing M1 macrophage polarization within intestinal tissues and restoring intestinal barrier integrity, effects closely associated with modulation of the IKKβ/NF-κB signaling pathway. Virtual screening and CCK-8 assays identified five IKKβ-targeting compounds in GQBZP: Rhamnocitrin, Toralactone, Naringenin, Liquiritigenin, and Carvacrol. These compounds markedly reduced apoptosis and pro-inflammatory cytokine production in 5-FU-treated HIECs. In addition, they inhibited M1 macrophage polarization and cytokine release in LPS/IFN-γ-stimulated THP-1 cells, accompanied by attenuation of IKKβ/NF-κB pathway activation. MD simulations, SPR assays, and functional studies in IKKβ-overexpressing HEK293T cells further confirmed that Toralactone directly binds to and suppresses IKKβ activation, whereas Rhamnocitrin modulates IKKβ activity through an indirect regulatory mechanism.</p><p><strong>Conclusion: </strong>GQBZP alleviates 5-FU-induced IM by promoting recovery of the intestinal epithelial barrier and inhibiting M1 macrophage polarization through an IKKβ/NF-κB-dependent mechanism, thereby exerting synergistic anti-inflammatory effects. Toralactone was identified as a key active constituent responsible for direct inhibition of IKKβ-mediated M1 polarization. These findings suggest that targeting IKKβ to regulate macrophage polarization represents a promising therapeutic strategy for the management of CIM.</p>","PeriodicalId":10266,"journal":{"name":"Chinese Medicine","volume":"21 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13374300/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148469418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Atractylodis Macrocephalae Rhizoma ameliorates diarrhea induced by cold drinks and a high-fat diet by remodeling gut microecology and restoring barrier function.","authors":"Yajuan Tian, Chenxing Wang, Yuzhong Du, Jiayi Zheng, Su Gao, Hengpu Zhou, Meiqiu Yan, Jingjing Yu, Bai Tao, Zengguang Gao, Rui Wu, Jie Su, Suhong Chen, Guiyuan Lv","doi":"10.1186/s13020-026-01467-0","DOIUrl":"10.1186/s13020-026-01467-0","url":null,"abstract":"<p><strong>Background: </strong>Atractylodis Macrocephalae Rhizoma (AMR) has traditionally been utilized for treating spleen deficiency diarrhea. Nevertheless, the effects and mechanisms of AMR on diarrhea caused by the consumption of cold drinks and a high-fat diet (CDHFD) remain insufficiently understood.</p><p><strong>Aim: </strong>This study aimed to explore the therapeutic effects and mechanisms of AMR in treating CDHFD-induced diarrhea.</p><p><strong>Methods: </strong>AMR was prepared as an aqueous extract, and its chemical composition was analyzed using UPLC-ESI-MS. A diarrhea model was established in ICR mice by exposure to CDHFD for four weeks, with AMR (low/high doses) administered concurrently via oral gavage. Bowel movements were evaluated using indicators such as fecal water content. Systemic inflammation was assessed by measuring pro-inflammatory cytokines via ELISA and performing peripheral blood cell counts. Intestinal barrier integrity was examined via H&E, AB-PAS staining, and immunofluorescence of tight junction proteins. Gut microbiota profiling was performed using 16S rDNA sequencing. Serum lipopolysaccharide (LPS) levels were measured via ELISA to assess translocation. Finally, the regulatory effects of AMR on the A20/TRAF6/NF-κB signaling pathway were validated using Western blotting. Spearman's correlation analysis was employed to integrate microbiota changes with host inflammatory phenotypes.</p><p><strong>Results: </strong>AMR significantly ameliorated CDHFD-induced diarrhea. Mechanistically, AMR remodeled the gut microecology by enriching beneficial bacteria, particularly Lachnospiraceae_NK4A136 and norank_f_Muribaculaceae. Concurrently, it increased the number of goblet cells and regulated the expression of tight junction proteins to repair intestinal barrier damage and reverse hyperpermeability. The restoration of barrier function effectively blocked the systemic translocation of LPS, which subsequently inhibited the hyperactivation of the NF-κB signaling pathway, thereby reducing systemic inflammation and ultimately alleviating diarrhea.</p><p><strong>Conclusion: </strong>AMR exerts protective effects against CDHFD-induced diarrhea through microbiota-driven intestinal barrier restoration, which sequentially blocks the activation of the LPS/NF-κB inflammatory pathway.</p>","PeriodicalId":10266,"journal":{"name":"Chinese Medicine","volume":"21 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13371211/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148454875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Esophageal epithelial cell-derived kynurenine drives Th17 inflammation in reflux esophagitis and is targeted by Xuanfu Daizhe decoction.","authors":"Jing Xun, Qi Gao, Huichao Yang, Jinlu Zhang, Yu Wang, Bin Liu, Xiaolin Jiang, Dihua Li, Lin Lang, Haiwei Mei, Ximo Wang, Qi Zhang, Yu Wu","doi":"10.1186/s13020-026-01413-0","DOIUrl":"10.1186/s13020-026-01413-0","url":null,"abstract":"<p><strong>Background: </strong>The role of immunometabolic dysregulation in reflux esophagitis (RE), particularly the metabolic drivers of pathogenic T helper 17 (Th17) cell differentiation, is not fully understood. Although Xuanfu Daizhe Decoction (XDD) is a clinically effective Traditional Chinese Medicine (TCM) formula for RE, its potential to modulate these immunometabolic pathways remains unelucidated.</p><p><strong>Objective: </strong>This study aimed to investigate the mechanism by which tryptophan metabolic dysregulation in RE influences Th17 cell differentiation and to evaluate whether XDD exerts therapeutic effects by targeting this pathway.</p><p><strong>Methods: </strong>Metabolomic analysis was performed to assess alterations in the tryptophan metabolic pathway in serum from RE patients and RE rat models. Inflamed human esophageal epithelial cells (HEECs) model was established using acidified bile salts to observe kynurenine (KYN) secretion and its effect on Th17 differentiation. siRNA-mediated silencing of the aryl hydrocarbon receptor repressor (AHRR) was employed to clarify the role of AHRR in KYN-AhR-mediated Th17 differentiation. The interventional effects of XDD and its impact on the KYN-AHRR-AhR-Th17 axis were further examined in both cellular and rat models.</p><p><strong>Results: </strong>Metabolomic profiling of clinical samples and RE rat models demonstrated significant dysregulation in the KYN pathway. Furthermore, we identified that inflamed HEECs induced high expression of IDO/TDO to elevate KYN secretion, which promoted Th17 cell differentiation. Mechanistically, KYN disrupted aryl hydrocarbon receptor (AhR) signaling via upregulation of its repressor, AHRR, thereby driving Th17 differentiation. Finally, we demonstrated that XDD treatment alleviated inflammation and tissue injury of RE by modulating the KYN-AHRR-AhR-Th17 axis.</p><p><strong>Conclusion: </strong>This study reveals a novel mechanism in RE whereby esophageal epithelial-derived KYN promotes Th17 differentiation via the AHRR-AhR signaling axis. Furthermore, XDD exerts therapeutic effects by modulating this immunometabolic pathway. These findings provide new insights into RE pathogenesis and experimental evidence supporting the application of XDD in immunometabolic disorders.</p>","PeriodicalId":10266,"journal":{"name":"Chinese Medicine","volume":"21 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13371025/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148454848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}