Liver fibrosis results from an imbalance between the deposition and the degradation of the extracellular matrix in the liver, for which there are currently no effective therapeutic drugs available. In this study, we demonstrated that baicalin, a major active component of the traditional Chinese medicine Scutellaria baicalensis, was able to inhibit the activation of hepatic stellate cells and attenuate liver fibrosis in various mouse models. In order to elucidate the molecular basis of its antifibrotic effects, we designed a novel baicalin photo-cross-linking probe and applied a quantitative chemoproteomic strategy based on dimethyl labeling to profile baicalin-interacting proteins. Aided by systematic gene knockouts of these potential baicalin interactors, we identified STAT3 as a key target in mediating the antifibrotic function of baicalin. Mechanistically, baicalin primarily binds to the N-terminal domain of STAT3, inhibits its interaction with JAK2 and thereby suppresses STAT3 phosphorylation. Our findings reveal the molecular mechanism of the antifibrotic effects of baicalin and provide a theoretical basis for the design of new antifibrotic drugs based on the structure of baicalin.

AbstractEthnopharmacological relevance : Sanren decoction (SRD) is a classic Traditional Chinese Medicine (TCM) formula historically recorded for treating "dampness-heat" related gastrointestinal and metabolic dysfunction. Despite its clinical efficacy in managing obesity and lipid metabolism disorders, how SRD regulates the gut microbiota-lipid metabolism axis has not been fully characterized.Aim of the study : This study aimed to evaluate the therapeutic effects of SRD on high-fat diet (HFD)-induced obesity and associated lipid metabolism disorders, and to elucidate the underlying mechanisms through which SRD exerts its anti-obesity effects by reshaping the gut microbiota-lipid metabolism axis, especially through the enrichment of the [Eubacterium] coprostanoligenes group.Materials and methods : The chemical profile of SRD was standardized according to the Pharmacopoeia of the People's Republic of China (2025 Edition). A total of 50 rats were randomly assigned to five groups: normal control, model control, SRD low-dose (22.5 g/kg/d), SRD high-dose (45 g/kg/d), and orlistat (60 mg/kg/d). The obesity model was established by feeding a HFD, followed by a 9-week oral intervention. Metabolic status was evaluated via serum biochemical indices—including triacylglycerol (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C)—and histological analysis using hematoxylin and eosin (H&E) staining. To investigate the underlying mechanisms, an integrated multi-omics approach was employed, comprising 16S rRNA gene sequencing for gut microbiota, ultra-high performance liquid chromatography-quadrupole Exactive HF-X (UHPLC-Q Exactive HF-X) based untargeted lipidomics for serum lipid profiling, and tandem mass tag (TMT)-based proteomics for adipose tissue analysis, aimed at exploring interactions within the microbiota-lipid-protein axis.Result s: Compared with the normal control group, the model group showed significantly increased body fat percentage and serum levels of TG, TC, and LDL-C; these changes were significantly reversed by both SRD and orlistat. Gut microbiota analysis revealed that SRD restored the HFD-induced depletion of core dominant phyla and specifically enriched the cholesterol-reducing bacteria, [Eubacterium] coprostanoligenes group. Untargeted lipidomics demonstrated that SRD reversed serum lipidomic abnormalities, notably by downregulating 11 differential triacylglycerol species. TMT-based proteomics identified 16 key target proteins in adipose tissue regulated by SRD, which were primarily involved in the activation of adenosine monophosphate-activated protein kinase (AMPK) and PPAR signaling pathways. Integrated analysis identified the [Eubacterium] coprostanoligenes group as a central hub, with its abundance significantly correlating with obesity phenotypes, lipid profiles, and metabolic proteins.Conclusions : By integrating traditional TCM theory with multi-omics evidence, this study demonstrates that SRD alleviates obesity and lipid metabolism disorders by enriching functional gut microbiota (notably the [Eubacterium] coprostanoligenes group) and modulating host lipid metabolism via AMPK and PPAR signaling pathways. These findings position SRD as a promising microflora-targeted candidate for the treatment of metabolic syndrome.

Background Ulcerative colitis (UC) is a chronic inflammatory bowel disease closely related to gut microbiota dysbiosis and intestinal homeostasis imbalance. Sishen Pill&Tongxieyaofang (SSP-TXYF) has a long history of application in traditional Chinese medicine and is widely used in UC clinics. However, its mechanism of action is still unclear. Purpose This study aimed to explore the potential regulatory role of SSP-TXYF in protecting against UC through metabolites produced by the intestinal microbiota, and elucidate its underlying molecular mechanism. Study design and Methods 16S rRNA and UPLC-QE-Orbitrap-MS were used to assess the microbiota and short-chain fatty acids (SCFAs). A rat model of 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced gut microbiota dysbiosis was used to study the effects of SSP-TXYF on UC in vivo. Intestinal epithelial cells-6 (IEC-6) were treated with lipopolysaccharide (LPS). The intestinal mucosal barrier (IMB) functions were investigated by alcian blue staining and western blot analysis. The mechanism of SSP-TXYF influenced the HIF-1α acetylation pathway was examined by real-time fluorescence quantitative PCR (qPCR), Western blotting, and Co-immunoprecipitation. Results Using 16S rRNA gene-based microbiota analysis, we found that SSP-TXYF ameliorated TNBS-induced gut microbiota dysbiosis. We found that SSP-TXYF significantly inhibited the decreased abundance of Firmicutes in UC rats, in addition, the abundance of Actinobacteria was also improved. The mechanism of SSP-TXYF-treated TNBS-induced UC resulted from improved IMB functions via the activation of hypoxia-inducible factor-1 (HIF-1α) acetylation. Notably, SSP-TXYF Enriched microbiota-derived metabolites propionate and butyrate, which could activate HIF-1α acetylation in IEC. Furthermore, exogenous treatment of propionate and butyrate reproduced similar protective effects as SSP-TXYF to UC through improving HIF-1α-dependent IMB functions. Conclusions Overall, our findings suggest that the gut microbiota-propionate/butyrate-HIF-1α-IMB axis plays an important role in SSP-TXYF-maintaining intestinal homeostasis, which may represent a novel approach for UC prevention via the intervention of any link in this axis.

Background: Ulcerative colitis (UC) is a stubborn disease that occurs globally. SSP-TXYF is a traditional Chinese medicine (TCM) compound, which is widely used in the treatment of UC, but its picking and preparation is complicated. Therefore, this work analyzes the components of SSP-TXYF to find an natural compound that can treat UC, and verifies its efficacy and mechanism, aiming to explore new natural compound with the same efficacy as SSP-TXYF. Methods and results: In this study, we used the quality markers (Q-marker) strategy to analyze the SSP-TXYF. We obtained that angelicin (Ang) is the main active ingredient. Combined with reductive dimethyl labeling and tandem orthogonal proteolysis-activity-based protein profiling (rdTOP-ABPP) and network pharmacology, we found that ERK1/2 and HDAC1 may be the binding proteins. Then, we demonstrated that Ang not only suppresses inflammation in lipopolysaccharide-induced IEC-6 but also effectively inhibits 2,4,6-trinitrobenzenesulfonic acid-induced UC in vivo. Increasing the concentration of propionate and butyrate, activating GPR43 and GPR109A receptors, increasing ERK1/2 activity, promoting Sp1 phosphorylation, thus competitively inhibiting the combination of HIF-1 alpha and HDAC1, and finally increasing the acetylation of HIF-1 alpha is the molecular signaling mechanism for Ang. Conclusions: In conclusion, Ang can improve the symptoms of UC in rats and activate the GPR/ERK/SP1/HDAC1/ HIF-1 alpha pathway in colonic epithelial cells to repair the damaged intestinal mucosal barrier (IMB). The key pharmacodynamic mechanism of Ang is consistent with SSP-TXYF, and it is preliminarily believed that Ang can be used as a new natural medicine for treating UC.

Influenza A virus (IAV) infection triggers excessive activation of PANoptosis—a coordinated form of programmed cell death integrating pyroptosis, apoptosis, and necroptosis—which contributes to severe immunopathology and acute lung injury. However, the molecular regulators that drive PANoptosis during IAV infection remain poorly understood. In this study, we integrated bulk and single-cell RNA sequencing (scRNA-seq) datasets to dissect the cellular heterogeneity and transcriptional dynamics of PANoptosis in the influenza-infected lung. PANoptosis-related gene activity was quantified using the AUCell, ssGSEA, and AddModuleScore algorithms. Machine learning approaches, including Support Vector Machine (SVM), Random Forest (RF), and Least Absolute Shrinkage and Selection Operator (LASSO) regression, were employed to identify key regulatory genes. scRNA-seq analysis revealed that PANoptosis activity was primarily enriched in macrophages and neutrophils. Integration of transcriptomic and computational data identified cathepsin B (CTSB as a central regulator of PANoptosis. In vivo validation in an IAV-infected mouse model confirmed elevated expression of PANoptosis markers and upregulation of CTSB. Mechanistically, CTSB may facilitate NLRP3 inflammasome activation and promote lysosomal dysfunction-associated inflammatory cell death. These findings identify CTSB as a critical mediatoCTSBr linking lysosomal integrity to innate immune-driven lung injury and suggest that targeting CTSB could represent a promising therapeutic strategy to alleviate influenza-associated immunopathology.

Angelicin (Ang), a natural tricyclic aromatic compound and quality marker derived from Fructus Psoraleae, exhibits significant anti-inflammatory efficacy. Fructus Psoraleae has long been utilized clinically for treating ulcerative colitis (UC). However, the specific role of Ang in UC remains poorly characterized. The present study aimed to elucidate the anti-UC effects of Ang and its underlying mechanisms. The anti-UC activity of Ang was evaluated using two UC models induced by dextran sulfate sodium (DSS) and 2,4,6-trinitrobenzenesulfonic acid (TNBS). Results demonstrated that Ang markedly inhibited the progression of UC. Microbial profiling indicated that the Ang-treated microbiome, particularly Lactobacillus murinus, provided protective effects against UC. Mechanistically, Ang facilitated proliferation of normal colonic epithelial cells, thus enhancing the intestinal mucosal barrier (IMB). Cysteine (Cys) played a crucial intermediary role by promoting glutathione (GSH) synthesis, maintaining redox homeostasis, and consequently facilitating cell proliferation. Additionally, increased Cys levels supported ribosomal biogenesis, enhancing protein translation and further stimulating cell proliferation. G-rich RNA sequence-binding factor 1 (GRSF1) was identified as a direct molecular target of Ang during ribosomal biogenesis. These findings indicated that Ang is a promising agent for promoting Cys-mediated cell proliferation, highlighting its role in maintaining redox homeostasis and protein translation. This study provides evidence supporting the future development of Ang as a therapeutic candidate for UC.

Colitis-associated colorectal cancer (CAC) is fatal and can develop spontaneously or as a complication of inflammatory bowel diseases. Although co-administration of azoxymethane/dextran sulfate sodium (AOM/DSS) is a classic method for CAC modeling, its limitations need to be addressed. Accordingly, we aimed to optimize the AOM/DSS model to study CAC extensively and further investigate its pathogenic mechanisms relative to microbiota and metabolism. We optimized the CAC model via a single or enhanced injection of AOM combined with different administration modes and varying DSS concentrations. Subsequently, the fecal-microbiota composition was examined using 16S RNA sequencing, and fecal-colon-metabolome profiles were evaluated via ultra-high performance liquid chromatography-mass spectrometry. Two interval injections of AOM combined with 1.5 % DSS-free drinking resulted in a high tumor formation rate, uniform tumor formation, and low mortality. Based on this model, we innovatively divided the pathogenesis of CAC into three stages, namely inflammation induction, proliferation initiation, and tumorigenesis, and examined the pathological characteristics in each stage. Gut microbial dysbiosis and metabolic alteration drove colorectal tumorigenesis by aggravating inflammation while promoting cell proliferation and carcinogenesis in mice. For the first time, we dynamically demonstrated the process of colon "inflammation to cancer" transformation and provided novel insights to clarify the role of amino acid metabolism in the formation of CAC.

Purpose: Many studies have shown that the imbalance of the intestinal flora and metabolite can lead to the development of ulcerative colitis (UC), but their role in recurrent-UC is still unclear. We studied the intestinal flora and metabolites associated with recurrent-UC to elucidate the mechanism and biomarkers of recurrent-UC.Methods: Ulcerative colitis (UC) models in active, remission, and recurrence stages were established, and the abundance of intestinal flora was determined by 16 S rRNA sequencing. The changes in the metabolites present in feces and serum were analyzed by UPLC-MS/MS.Results: We identified 24 metabolites in feces and serum, which might be used as diagnostic and predictive biomarkers of recurrent-UC. The dominant flora of recurrent-UC included Romboutsia, UCG-005, etc. The results of a network analysis found that long-chain fatty acids and phenylalanine were strongly correlated with Fir-micutes and Proteobacteria, which indicated that the recurrence of UC might be closely related to metabolites and microorganisms.Conclusion: The changes in intestinal microbiota and metabolites are closely related to the development of UC. Microbiota is an important inducer of UC, which can regulate metabolites through the 'microorganism-gut -metabolite' axis. It may provide a new method for the prediction and treatment of UC.

Background: Enhancing white adipose tissue (WAT) browning combats obesity. The RII(3 subunit of cAMP-dependent protein kinase (PKA) is primarily expressed in the brain and adipose tissue. Deletion of the hypothalamic RII(3 gene centrally induces WAT browning, yet the peripheral mechanisms mediating this process remain unexplored. Methods: This study investigates the mechanisms underlying WAT browning in RII(3-KO mice. Genetic approaches such as (33-adrenergic receptors ((33ARs) deletion and sympathetic denervation of WAT were utilized. Genome-wide transcriptomic sequencing and bioinformatic analysis were employed to identify potential mediators of WAT browning. siRNA assays were employed to knock down mTOR and lipin1 in vitro, , while AAV-shRNAs were used for the same purpose in vivo. Results: We found that WAT browning substantially contributes to the lean and obesity-resistant phenotypes of RII(3-KO mice. The WAT browning can be dampened by (33ARs 3 ARs deletion or WAT sympathetic denervation. We identified that adipocytic mTOR and lipin1 may act as mediators of the WAT browning. Inhibition of mTOR or lipin1 abrogates WAT browning and hinders the lean phenotype of RII(3-KO mice. In human subcutaneous white adipocytes and mouse white adipocytes, (33AR 3 AR stimulation can activate mTOR and causes lipin1 nuclear translocation; knockdown of mTOR and Lipin1 mitigates WAT browning-associated gene expression, impedes mitochondrial activity. Moreover, mTOR knockdown reduces lipin1 level and nuclear translocation, indicating that lipin1 may act downstream of mTOR. Additionally, in vivo knockdown of mTOR and Lipin1 diminished WAT browning and increased adiposity. Conclusions: The beta 3AR-activated 3 AR-activated mTOR-lipin1 axis mediates WAT browning, offering new insights into the molecular basis of PKA-regulated WAT browning. These findings provide potential adipose target candidates for the development of drugs to treat obesity.

ETHNOPHARMACOLOGICAL RELEVANCE:Huangqin Tang (HQT), a traditional Chinese medicine formula, is commonly used in clinical practice for the treatment of inflammatory bowel diseases. It has been reported that HQT exerts antitumor effects on colitis-associated colorectal cancer (CAC). However, the mechanism by which HQT interferes with the inflammation-to-cancer transformation remains unclear. AIMS OF THE STUDY:The purpose of this study was to dynamically evaluate the efficacy of HQT in alleviating or delaying CAC and to reveal the underlying mechanism. METHODS:We established a mouse model of CAC using azoxymethane combined with 1.5% dextran sodium sulphate. The efficacy of HQT was evaluated based on pathological sections and serum biochemical indices. Subsequently, amino acids (AAs) metabolism analyses were performed using ultra-performance liquid chromatography-tandem mass spectrometry, and the phosphatidylinositol 3 kinase/protein kinase B/mechanistic target of rapamycin (PI3K/AKT/mTOR) pathway was detected by western blotting. RESULTS:The data demonstrated that HQT could alleviate the development of CAC in the animal model. HQT effectively reduced the inflammatory response, particularly interleukin-6 (IL-6), in the inflammation induction stage, as well as in the stages of proliferation initiation and tumorigenesis. During the proliferation initiation and tumorigenesis stages, immunohistochemistry staining showed that the expression of the proliferation marker Ki67 was reduced, while apoptosis was increased in the HQT group. Accordingly, HQT substantially decreased the levels of specific AAs in the colon with CAC, including glutamic acid, glutamine, arginine, and isoleucine. Furthermore, HQT significantly inhibited the activated PI3K/AKT/mTOR pathway, which may contribute to suppression of cell proliferation and enhancement of apoptosis. CONCLUSION:HQT is effective in alleviating and delaying the colon "inflammation-to-cancer". The mechanism of action may involve HQT maintained AAs metabolism homeostasis and regulated PI3K/AKT/mTOR pathway, so as to maintain the balance between proliferation and apoptosis, and then interfere in the occurrence and development of CAC.

Background:Ulcerative colitis(UC)is a diffuse nonspecific intestinal inflammation.Spleen-kidney Yang deficiency combined with liver stagnation is the most common symptom.Sishen Pills-Tongxie Yaofang(SSP-TXYF)is a traditional Chinese medicine(TCM)that is widely used in the treatment of this symptom.However,its pharmacological mechanism and active components remain unclear. Objective:This study elucidated the potential mechanism and active components of SSP-TXYF in the treatment of UC from the per-spective of TCM syndrome. Methods:Metascape,STRING,and Cytoscape were used to explore the SSP-TXYF-compound-target-UC network and biological en-richment pathways,so as to screen the active compounds,key targets,and pathways of SSP-TXYF.Through the construction of a rat model with UC,the key targets and active components were verified after SSP-TXYF administration. Results:A total of 77 effective active chemical components,208 potential targets,and 5 core target genes were screened out.Gene Ontology biological process items and Kyoto Encyclopedia of Genes and Genomes signaling pathways showed that SSP-TXYF played a role in regulating nerve-endocrine,cell proliferation and apoptosis,and immune-related pathways.The main compounds and the tar-get protein exhibited a good binding ability in molecular docking.The results of animal experiments showed that SSP-TXYF could im-prove UC through IL-6,AKT1,PTGS2,CASP3,and JUN,and nobiletin and wogonin were identified as the main active components. Conclusions:This study suggests that nobiletin and wogonin are the main components of SSP-TXYF in the treatment of UC,which provides effective therapeutic targets and drugs for future clinical treatment of UC.

Background: Enhancing white adipose tissue (WAT) browning combats obesity. The RIIβ subunit of cAMP-dependent protein kinase (PKA) is primarily expressed in the brain and adipose tissue. Deletion of the hypothalamic RIIβ gene centrally induces WAT browning, yet the peripheral mechanisms mediating this process remain unexplored. Methods: This study investigates the mechanisms underlying WAT browning in RIIβ-KO mice. Genetic approaches such as β3-adrenergic receptors (β3ARs) deletion and sympathetic denervation of WAT were utilized. Genome-wide transcriptomic sequencing and bioinformatic analysis were employed to identify potential mediators of WAT browning. siRNA assays were employed to knock down mTOR and lipin1 in vitro, while AAV-shRNAs were used for the same purpose in vivo. Results: We found that WAT browning substantially contributes to the lean and obesity-resistant phenotypes of RIIβ-KO mice. The WAT browning can be dampened by β3ARs deletion or WAT sympathetic denervation. We identified that adipocytic mTOR and lipin1 may act as mediators of the WAT browning. Inhibition of mTOR or lipin1 abrogates WAT browning and hinders the lean phenotype of RIIβ-KO mice. In human subcutaneous white adipocytes and mouse white adipocytes, β3AR stimulation can activate mTOR and causes lipin1 nuclear translocation; knockdown of mTOR and Lipin1 mitigates WAT browning-associated gene expression, impedes mitochondrial activity. Moreover, mTOR knockdown reduces lipin1 level and nuclear translocation, indicating that lipin1 may act downstream of mTOR. Additionally, in vivo knockdown of mTOR and Lipin1 diminished WAT browning and increased adiposity. Conclusions: The β3AR-activated mTOR-lipin1 axis mediates WAT browning, offering new insights into the molecular basis of PKA-regulated WAT browning. These findings provide potential adipose target candidates for the development of drugs to treat obesity.

BackgroundDiabetic kidney disease (DKD) is a common microvascular complication and one of the main causes of death in diabetes. Ferroptosis, an iron-dependent mode of cell death characterized by lipid ROS accumulation, was found to be associated with a number of diseases and has great potential for kidney diseases. It has great value to identify potential ferroptosis-related genes and their biological mechanisms in DKD.MethodsWe obtained the GSE30122 dataset from Gene Expression Omnibus (GEO) database and ferroptosis-related genes from the Ferrdb database. After differential expression analysis, and three machine learning algorithms, the hub ferroptosis-related gene EZH2 was identified. In order to investigate the function of EZH2, Gene Set Enrichment Analysis (GSEA), Gene Set Variation Analysis (GSVA) and single cell analysis were conducted. The expression of EZH2 was validated in DKD patients, HK-2 cell models and DKD mouse models. EZH2 knockdown HK-2 cells and HK-2 cells treated with GSK126 were performed to verify whether EZH2 affected ferroptosis in DKD. CHIP assay was used to detect whether EZH2 regulated ferroptosis by suppressing SLC7A11. Molecular docking was performed to explore EZH2 and four traditional Chinese medicine (Sennoside A, Berberine, Umbelliferone, Platycodin D) related to ferroptosis in DKD treatment.ResultsAccording to the GSE30122 dataset in GEO and ferroptosis-related genes from the Ferrb database, we obtained the hub ferroptosis-related gene EZH2 in DKD via diversified machine learning methods. The increasing of EZH2 expression was shown in single cell analysis, DKD patients, DKD mouse models and high glucose induced DKD cell models. Further study showed that EZH2 knockdown and inhibition can alleviate HG-induced ferroptosis in vitro. CHIP assay showed EZH2-mediated epigenetic silencing regulated the expression of SLC7A11. Molecular docking results showed that EZH2 had strong binding stability with Sennoside A, Berberine, Umbelliferone, and Platycodin D.ConclusionOverall, our data shouwed that histone H3K27 methyltransferase EZH2 could regulate the renal tubular epithelial cell ferroptosis by suppressing SLC7A11 in DKD, which may serve as a credible reliable indicator for diagnosing DKD and a potential target for treatment.

目的:研究黄芩汤对溃疡性结肠炎(UC)模型小鼠的药效,并探究黄芩汤在UC中是否能调节肠道菌群,发挥屏障保护作用.方法:雄性Balb/c小鼠按体质量随机分为正常组、模型组、黄芩汤高(20g·kg-1)、中(10g·kg-1)、低(5g·kg-1)剂量组、菌群干扰组、菌群干扰模型组、菌群干扰黄芩汤组(黄芩汤,20 g·kg-1).灌胃抗生素(杆菌肽200 mg·kg-1、万古霉素200 mg·kg-1)8 d构建菌群干扰模型,自由饮用3％葡聚糖硫酸钠(DSS)溶液7 d构建UC模型,黄芩汤给药治疗7 d.实验结束后处死小鼠,取血、结肠及粪便,苏木素-伊红(HE)染色观察结肠病变,酶联免疫吸附测定法(ELISA)检测血清白细胞介素-4(IL-4)、白细胞介素-6(IL-6)、白细胞介素-10(IL-10)、肿瘤坏死因子-α(TNF-α)含量,实时荧光定量聚合酶链式反应(Real-time PCR)及蛋白免疫印迹法(Westernblot)检测结肠组织中紧密连接蛋白1(Claudin1)、黏蛋白1(MUC1)、咬合蛋白(Occludin)、闭锁小带蛋白-1(ZO-1)mRNA和蛋白的表达,提取小鼠粪便DNA进行高通量测序分析.结果:与正常组比较,模型组小鼠血清IL-4、IL-6、TNF-α含量明显升高(P＜0.05,P＜0.01),IL-10明显降低(P＜0.05);与模型组比较,黄芩汤给药组IL-4、IL-6、TNF-α含量下降(P＜0.05,P＜0.01),IL-10含量显著上升(P＜0.01),Claudin1、MUC1、Occludin、ZO-1 mRNA和蛋白表达明显上升(P＜0.05,P＜0.01).菌群干扰后,小鼠肠道菌物种多样性及丰度降低,变形菌门(Proteobacteria)增多(P＜0.01),厚壁菌门(Firmicutes)、拟杆菌门(Bacteroidetes)减少(P＜0.01);DSS诱发UC后,拟杆菌门和柔壁菌门(Tenericutes)明显减少(P＜0.05);黄芩汤高、中、低3个剂量组中拟杆菌门、柔壁菌门明显增多(P＜0.05,P＜0.01),厚壁菌门减少(P＜0.05),乳酸菌属(Lactobacillus)、毛螺菌属(Lachnospiraceae NK4A136 group)、大肠埃希菌志贺属(Escherichiia-Shigella)、螺杆菌(Helicobacter)的丰度与黄芩汤剂量呈正比.结论:黄芩汤可以抑制UC小鼠的炎症反应,回调失衡的肠道菌群,修复损伤的肠黏膜屏障.

溃疡性结肠炎是一种病因尚不明确的慢性肠道疾病,主要症状为腹痛、腹泻、黏液脓血便等,并可伴有多种并发症,转化为结肠癌的风险较高.近年来溃疡性结肠炎和相关结肠癌的发病率有上升的趋势,严重影响人体健康和生活质量.手术和免疫抑制剂等是现代临床治疗溃疡性结肠炎和相关结肠癌的主要方法,但这些方法均有不同的不良反应,治疗效果不理想.多年来,中医药由于其不良反应小,疗效显著,在治疗溃疡性结肠炎和相关结肠癌方面备受关注.黄芩汤出自《伤寒论》,由黄芩、芍药、甘草和大枣组成,具有清热止利、和中止痛之功效,用于治疗溃疡性结肠炎疗效显著.黄芩汤成分复杂,以多靶点多途径发挥作用.经文献查阅并结合本课题组多年的研究成果,发现黄芩汤治疗溃疡性结肠炎和相关结肠癌的作用机制可能与保护肠黏膜屏障,抑制炎症反应,促进线粒体自噬,抑制氧化应激,调控肠道菌群、细胞周期、基因表达,抑制细胞增殖和促进细胞凋亡等多种机制相关.现将近年来的研究情况进行较为详尽的综述,以期能够为黄芩汤作用机制的深入研究及临床用药提供理论参考.

目的 探讨伴免疫球蛋白(Ig)G沉积原发性膜性肾病(PMN)病人疾病缓解影响因素及与肾小球IgG4表达强度的关系.方法 回顾性纳入山西省运城市中心医院2014年1月至2020年1月收治伴IgG沉积PMN病人共500例,根据有无IgG4表达和表达强度分组,分析临床病理及随访预后资料,采用单因素和多因素Cox回归模型评价伴IgG沉积PMN病人疾病缓解独立影响因素.结果 阳性组24 h尿蛋白量和M型磷脂酶A2受体(PLA2R)表达强度比例显著高于阴性组(P<0.05);弱阳性组、中阳性组及强阳性组血浆白蛋白、IgG1强度比例及IgA强度比例比较差异有统计学意义(P<0.05);阴性组、弱阳性组、中阳性组及强阳性组随访3个月(30.0％比17.3％比15.9％比9.5％)和6个月(38.4％比30.6％比26.5％比13.0％)累积缓解率比较差异有统计学意义(P<0.05);Cox回归模型单因素和多因素分析结果显示,IgG4阳性高强度、男性、基线高24 h尿蛋白量均是伴IgG沉积PMN病人疾病未缓解独立危险因素[RR=1.33,95％CI:(1.05,1.61);RR=1.80,95％CI:(1.17,3.04);RR=1.51,95％CI:(1.09,2.80).P<0.05].结论 伴IgG沉积PMN病人疾病缓解效果与IgG4表达强度、性别及基线24 h尿蛋白量密切相关;而肾小球IgG4表达强度可作为PMN治疗反应性潜在评估指标加以应用.

重度抑郁症(MDD)目前高度流行,以高级神经障碍为主要病理表现.大脑灰质作为高级神经活动的生理功能承载者,成为MDD治疗的重点.但近年来文献表明,中枢神经系统(CNS)中白质与灰质彼此相对独立,功能整合联动.MDD除灰质损伤外,白质损伤同样是疾病进展的核心驱动事件,决定了疾病转归.治疗层面,目前MDD的药物治疗主要以灰质修复为主要焦点之一,而忽略了白质完整性对于疾病治疗的重要性,成为目前MDD治疗的短板.中医药在白质修复中具有良好的应用潜能.该文从以下3点展开论述:①总结梳理白质损伤在MDD发生发展中的作用;②以小胶质细胞的微环境调节为切入点,阐述MDD中白质修复的关键环节;③分析中医药在MDD中白质修复的应用价值.该综述旨在凸显白质完整性在MDD治疗中的重要性,有望从白质修复的角度拓展相关中药在MDD中的活性认识维度,解析其潜在应用价值.

目的:以RAW264.7细胞为炎症模型,探究黄芩汤的抗炎作用机制.方法:制备黄芩汤,筛选对RAW264.7细胞的安全剂量;将RAW264.7细胞接种于24孔板中,先后加入黄芩汤和脂多糖(LPS),分别采用Griess法和酶联免疫吸附测定法(ELISA)测定一氧化氮(NO)和白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、前列腺素E2(PGE2)的含量;将RAW264.7细胞接种于6孔板中,设空白组、LPS组、LPS+黄芩汤组、核转录因子-κB p65(NF-κB p65)抑制剂(PDTC)组、p38丝裂原活化蛋白激酶(p38 MAPK)抑制剂(SB203580)组、细胞外信号调节激酶(ERK)抑制剂(PD98059)组、c-Jun氨基末端激酶(JNK)抑制剂(SP600125)组、Janus酪氨酸蛋白激酶(JAK)抑制剂(AG490)组,先后加入相应的抑制剂和黄芩汤,并经LPS刺激后,提取RNA和蛋白,分别采用实时荧光定量聚合酶链式反应(Real-time PCR)和蛋白免疫印迹法(Western blot)检测NF-κB p65、p38 MAPK、ERK、JNK和JAK mRNA及蛋白的表达水平,探究黄芩汤通过调控NF-κB、丝裂原活化蛋白激酶(MAPK)和JAK/信号转导及转录激活因子(STAT)信号通路发挥抗炎作用的机制.结果:与空白组比较,LPS刺激后,模型组细胞中NO、IL-6、TNF-α、PGE2的浓度明显增加(P＜0.05,P＜0.01),与模型组比较,加入黄芩汤后,NO、IL-6、TNF-α、PGE2分泌量有减少趋势(P＜0.05,P＜0.01);与空白组比较,模型组细胞内p38 MAPK、ERK、JNK、JAK和NF-κB p65 mRNA及总蛋白表达明显升高(P＜0.05,P＜0.01),与模型组比较,黄芩汤孵育后,炎症细胞内p38MAPK、ERK、JNK、JAK和NF-KB p65总蛋白及mRNA的表达明显降低(P＜0.05,P＜0.01);同时各抑制剂组细胞内NF-κB p65总蛋白及mRNA表达均有下降趋势(P＜0.05,P＜0.01).结论:黄芩汤能够通过NF-κB、MAPK和JAK/STAT信号通路抑制炎症反应.

目的:以Caco-2细胞为载体,结合基因干扰(RNAi)技术,通过体外实验进一步验证黄芩汤基于核因子E,相关因子2(Nrf2)通路发挥的抗氧化应激作用.方法:将处于对数生长期的Caco-2细胞,经siRNA转染,构建siRNACaco-2细胞;将正常Caco-2细胞和siRNA Caco-2细胞与不同浓度的黄芩汤共同孵育后,提取RNA和蛋白,采用实时荧光定量聚合酶链式反应(Real-time PCR)和蛋白免疫印迹法(Western blot)技术检测血红素氧合酶-1(HO-1)、醌氧化还原酶1(NQO1)、谷胱甘肽疏基转移酶(GST)、接头蛋白Kelch样ECH相关蛋白l(Keap1)及Nrf2 mRNA和蛋白的表达;同时,采用比色法和探针法检测各组细胞中超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)的活力及丙二醛(MDA)、活性氧(ROS)的表达水平.结果:与空白组比较,仅有黄芩汤400 mg·L-1组与萝卜硫素(SFN)组可降低正常Caco-2细胞内ROS、MDA含量(P＜0.01);而黄芩汤各剂量组与SFN组细胞内SOD与GSH-Px活力均有增加的趋势,且黄芩汤400 mg·L-1组和SFN组与空白组比较差异有显著统计学意义(P＜0.01);同时,各组细胞HO-1、GST、Keap1、NQO1和Nrf2蛋白及mRNA的表达量均有明显升高的趋势(P＜0.05,P＜0.01).经转染后,与空白组比较,模型组细胞内MDA和ROS的含量升高,而GSH-Px和SOD的活力及HO-1、GST、Keap1和NQO1蛋白及mRNA的表达量均有不同程度地降低(P＜0.05,P＜0.01),与药物孵育后,与模型组比较,SFN组细胞内SOD活力和SFN组、黄芩汤各给药组GSH-Px活力显著升高(P＜0.01),黄芩汤400 mg·L-1组、200 mg·L-1组和SFN组细胞内SOD和GSH-Px活力均有升高的趋势(P＜0.01),黄芩汤400 mg·L-1组和SFN组MDA有降低的趋势,且各给药组ROS均有降低(P＜0.01);HO-1、GST、Keap1、NQO1和Nrf2的蛋白及mRNA表达均有不同程度增加(P＜0.05,P＜0.01).结论:黄芩汤可以通过调控Nrf2通路发挥抗氧化应激的作用.