本研究建立并验证了超高效液相色谱-三重四极杆串联质谱（UPLC-MS/MS）法同步测定栀子柏皮汤中栀子苷、甘草苷、甘草酸、小檗碱和黄柏碱5种关键活性成分在佐剂性关节炎（adjuvant arthritis， AA）模型大鼠血浆中的药代动力学特征，及其在主要组织中的分布规律。通过灌胃AA模型大鼠栀子柏皮汤后，在不同时间点采集血浆及主要脏器（心、肝、脾、肺、肾）样品；并在完成方法学考察后，测定上述5种关键成分含量，以识别其药代动力学参数及组织分布轨迹。结果表明，所建立的方法专属性、线性关系、准确度、精密度、稳定性、提取回收率与基质效应均符合生物样品分析要求。其中，黄柏碱达峰浓度(Cmax)最大（1 019.31 μg/L）；栀子苷达峰时间(Tmax)最短，半衰期(t1/2)最长（8.42 h）；而甘草酸、小檗碱和黄柏碱的血药浓度-时间曲线均呈现双峰现象，提示其吸收或代谢可能涉及多途径机制。组织分布表明，栀子苷主要分布于肾、肝、脾（肾＞肝＞脾＞心＞肺）；甘草苷、甘草酸、小檗碱均主要富集于肝、肾；黄柏碱在肝、肾中的浓度最高，且其...

Scutellaria baicalensis Georgi (SBG) serves as a widely used dietary and medicinal ingredient. Intrinsic quality and nutritional variations in SBG are inevitable due to ecological factors and extraction process discrepancies. To evaluate authentic quality differences and guide practical material selection, this study proposes a novel "multi-model integration strategy" focused on chemical activity. Using chemometric approaches, seven key active markers were identified from diverse SBG extract fingerprints. Frontier molecular orbital energy and electronegativity analyses unveiled the chemical basis of their bioactivities. Multi-criteria decision-making models (VIKOR, Entropy weight-TOPSIS, and RSR) collectively revealed that Gansu-originated SBG exhibited superior overall quality compared to Inner Mongolia samples, designating Gansu as the premier quality source. Traditional pharmacological experiments further validated the enhanced quality and activity of Gansu SBG. These modeling methods enable efficient quality assessment for clinical and market applications, addressing the time-consuming limitations of conventional pharmacological assays through mathematical modeling. Finally, discriminant function models were developed to distinguish SBG by origin. This integrated strategy, rooted in characteristic substances' chemical activity, offers insights for quality optimization and traceability of food-herbal products. © 2025 The Authors

Background: Angiogenesis is essential for pannus formation and maintenance in rheumatoid arthritis (RA). Heat shock protein 70 kDa (HSP70) can induce angiogenesis by being released extracellularly through exosomes. Geniposide (GE) is the primary pharmacological component of the fruit of Gardenia jasminoides Ellis (GJ). In vivo, we have found that GE is able to reduce HSP70 levels in the synovium and serum of CIA-S and has antiangiogenic effects. However, the mechanism by which GE inhibits HSP70 to improve angiogenesis is still unclear. This study aims to explore how GE inhibits the extracellular release of HSP70 and its impact on angiogenesis in human umbilical vein endothelial cells (HUVECs). Methods: HUVECs' exosomes were extracted using ultracentrifugation and characterized through transmission electron microscope, nanoparticle tracer technology, nano-flow cytometry and Western blotting. The proliferative ability of HUVECs was assessed by EdU and CCK8 assay. Transwell and wound healing assays were used to measure the migration ability of HUVECs, while tube formation assay was employed to evaluate their tube- forming ability. The TNF-alpha-induced HSP70 release model in HUVECs was established, with extracellular HSP70 levels serving as an evaluation index. Immunofluorescence and co-immunoprecipitation assay were used to analyze the interaction between HSP70 and the lipid raft marker Caveolin-1 (Cav-1). Western blotting was employed to investigate the expression of SphK1/S1P/S1PRs/G alpha i pathway-related proteins, and ELISA was utilized to detect extracellular S1P and HSP70 levels. Results: The exosomes of HUVECs contained HSP70. HUVECs were stimulated by extracellular HSP70, which enhanced their proliferation, migration, and tube-forming abilities. TNF-alpha (10 ng/mL) significantly increased the release of HSP70, which was inhibited by GE (25 mu M-100 mu M) in a concentration-dependent manner. GE reduced HSP70 in lipid rafts without affecting Cav-1. GE (100 mu M) inhibited proteins in the SphK1/S1P/S1PRs/G alpha i pathway, preventing HSP70 release and improving HUVECs' functions compared to the K6PC-5 (SphK1-specific agonist) and TNF-alpha groups. Conclusion: This study found that GE inhibited the extracellular release of HSP70 by suppressing the SphK1/S1P/ S1PRs/G alpha i pathway, thereby producing anti-angiogenic effects in vitro. This provides a novel direction and strategy for anti-angiogenesis therapy for RA.

INTRODUCTION: Rheumatoid arthritis (RA) is a chronic autoimmune disease that primarily manifests with symptoms such as heat and toxin. However, the key components and molecular mechanisms of Zhizi Baipi decoction (ZBD) in the treatment of RA are still unclear.; OBJECTIVES: The study aimed to explore the mechanism of action of ZBD for treating RA through ingredient analysis, network pharmacology, and experimental validation.; MATERIAL AND METHODS: The chemical constituents of ZBD were identified by ultra-high performance liquid chromatography coupled with Q-TOF-mass spectrometry (UPLC-Q-TOF-MSE). Additionally, the active ingredients of ZBD treating RA were screened by network pharmacology and using molecular docking to verify the binding energy of the active ingredients and ZBD's targets. Then we elucidated ZBD's mechanism of action on collagen-induced arthritis (CIA) model rats. Subsequently, experimental validations were used to validate the findings of network pharmacology.; RESULTS: A total of 84 chemical constituents was identified by UPLC-Q-TOF-MSE. The results of network pharmacology indicated that ZBD could exert its therapeutic effect on RA through the vascular endothelial growth factor (VEGF) pathway. Molecular docking revealed a strong binding capacity between the target KDR and the active ingredients. Additionally, we quantified the five active ingredients of ZBD. Invivo experiments demonstrated that ZBD inhibited synovial angiogenesis and alleviated the occurrence and progression of RA.; CONCLUSION: Overall, ZBD has a significant therapeutic effect on RA. The results of qualitative analysis, network pharmacology, molecular docking, and invivo experiments indicated that the main active components of ZBD could modulate the VEGF pathway to treat RA. © 2025 John Wiley & Sons Ltd.

Rheumatoid arthritis (RA) is a metabolically active disease, with shifts in fatty acid metabolism during disease progression profoundly affecting the systemic inflammatory response. Altered fatty acid biomarker metabolism may be a key target for the treatment of RA. To investigate the changes of fatty acid metabolism in RA, collagen- induced arthritis (CIA) model was established. Microdialysis sampling was utilized to overcome the characteristic of occlusive joint cavity in vivo synovial fluid (SF) sampling. Lipidomic methods were established with the UHPLC-Orbitrap Exploris120 platform, and lipid measurements were performed on serum and SF samples. Then, multivariate statistical analyses were performed to detect changes in lipid metabolites induced by CIA. Consequently, a total of 22 potential biomarkers associated with differential fatty acids were screened and identified in serum, and 13 were identified in SF. Notably, alterations were observed in metabolites such as Hexadecanoic acid, Octadecanoic acid, Arachidonic acid, (+/-)11,12-EpETrE, +/-)11,12-EpETrE, DHA, DPA, Myristic acid, Suberic acid, and others. This study explored a new mechanism of the RA disease process from the perspective of fatty acid metabolism. It provided a new strategy for experimental research on determining the optimal time for establishing CIA model and screening clinical diagnostic biomarkers.

利用UHPLC-TOF-MS技术分析三妙化学成分，通过网络药理学和动物实验研究三妙丸治疗类风湿性关节炎的作用机制。利用UHPLC-TOF-MS技术检测三妙丸所含化学成分，结合DisGeNET、SwissTargetPrediction等数据库筛选类风湿性关节炎与三妙丸化学成分的交集靶点，构建蛋白-蛋白相互作用（protein-protein interaction， PPI）网络。将关键靶点导入MATESCAPE平台进行基因本体论（Gene Ontology， GO）分析和京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes， KEGG）通路注释，结合成分、靶点和通路，利用Cytoscape 3.8软件构建“成分-靶点-通路”网络，预测三妙丸治疗类风湿性关节炎的主要活性成分、关键靶点及通路。建立HPLC-DAD法同时测定三妙丸中小檗碱，苍术内酯-I，苍术内酯-Ⅱ，人参皂苷Ro，三七皂苷R1的含量。建立大鼠胶原诱导型（collagen-induced arthritis， CIA）模型，进行行为学实验，HE检测SMP对大鼠滑膜病理形态的影响，Western blot检测PI3K/AKT通路的变化。结果鉴定出三妙丸化学成分共126个。化学成分与疾病共有交集靶点332个，根据PPI网络结果筛选排名前十的为核心靶点，其中包括AKT1、TNF等，KEGG富集结果显示主要涉及PI3K/AKT样受体通路等20条典型通路。5种成分在各自范围内线性关系良好，RSD ≤ 2%。动物实验研究结果显示，三妙丸有效改善CIA大鼠滑膜异常增生，降低滑膜PI3K和p-AKT表达水平。综上所述，三妙丸可能通过调控PI3K/AKT通路，缓解RA病情。

作为一种新型铁依赖性细胞死亡方式， 铁死亡特定过程就是含有多不饱和脂肪酸 (polyunsaturated fatty acid， PUFA) 的磷脂在胞膜上过度积累发生过氧化。脂滴时刻处于生成和分解的动态转换， 在调节脂质代谢中起着核心作用， 并时刻处于生成和分解的动态转换。脂滴代谢与铁死亡的发生密切相关， 在铁死亡异常导致疾病中发挥重要作用。本综述首先着重介绍脂滴代谢过程及其对PUFA存储和释放的影响， 并进一步阐明脂滴代谢对铁死亡调控机制及关键调节蛋白， 以期揭示脂滴与铁死亡间的内在联系， 为铁死亡相关疾病的临床治疗提供新思路。

Resident synoviocytes and synovial microvasculature, together with immune cells from circulation, contribute to pannus formation, the main pathological feature of rheumatoid arthritis (RA), leading to destruction of adjacent cartilage and bone. Seeds, fibroblast-like synoviocytes (FLSs), macrophages, dendritic cells (DCs), B cells, T cells and endothelial cells (ECs) seeds with high metabolic demands undergo metabolic reprogramming from oxidative phosphorylation to glycolysis in response to poor soil of RA synovium with hypoxia, nutrient deficiency and inflammatory stimuli. Glycolysis provides rapid energy supply and biosynthetic precursors to support pathogenic growth of these seeds. The metabolite lactate accumulated during this process in turn condition the soil microenvironment and affect seeds growth by modulating signalling pathways and directing lactylation modifications. This review explores in depth the survival mechanism of seeds with high metabolic demands in the poor soil of RA synovium, providing useful support for elucidating the etiology of RA. In addition, we discuss the role and major post-translational modifications of proteins and enzymes linked to glycolysis to inspire the discovery of novel anti-rheumatic targets.

目的 探讨栀子苷(geniposide,GE)改善风湿热痹证胶原性关节炎(collagen induced arthritis,CIA)大鼠血管新生的作用是否与调控热休克蛋白70 (heat shock proteins 70,HSP70)的释放有关。方法 在大鼠背部和尾根部多点皮内注射完全弗氏佐剂(complete Freund’s adjuvant,CFA)与鸡Ⅱ型胶原蛋白(chicken typeⅡcollagen,CCⅡ)等体积混合物,构建CIA模型,在此基础上,给予风湿热刺激,建立风湿热痹证CIA大鼠(CIA rats with moist heat arthralgia spasm syndrome,CIA-S)模型。造模成功后随机分组,给药组分别用GE(60、120 mg·kg-1·d-1)、MTX (0.5 mg·kg-1·3d-1)灌胃两周,取材。观察大鼠体质量、关节炎指数(arthritis index,AI)等评价模型情况,关节表面温度和血流变指标评价热痹模型热属性,HE染色观察大鼠滑膜病理,多普勒彩超检测血流信号,免疫组化和Westren blot法检测滑膜组织HSP70、CD31、VEGF含量,ELISA法检测大鼠血清HSP70含量。EdU染色、细胞划痕和Transwell迁移实验以及成管实验探究HSP70对人脐静脉血管内皮细胞(human umbilic vein endothelial cells,HUVECs)的增殖、迁移、成管能力的影响。结果 与空白组相比,CIA-S组关节肿胀,热属性明显,血管新生强烈,滑膜组织异常增生,炎性细胞浸润,可见微血管形成;CIA-S组与CIA组比较,关节红肿程度加重,炎症峰值提前、持续时间延长,消退缓慢,血管新生与HSP70表达更为强烈。GE给药组呈剂量依赖性,有效改善关节炎症状,减少HSP70含量。细胞实验结果表明,GE抑制HSP70的表达和释放,进而抑制HSP70诱导的HUVECs增殖、迁移和成管能力增强。结论 GE有可能通过抑制HSP70的释放改善风湿热痹证CIA大鼠血管新生,进而改善关节炎。

细胞在炎性微环境影响下发生糖代谢重编程， 使其主要供能方式由氧化磷酸化转变为有氧糖酵解， 该过程参与炎症相关疾病发生发展的各个阶段。糖代谢重编程不仅改变单个细胞的代谢模式， 而且打破了机体微环境的代谢稳态， 进一步促进细胞有氧糖酵解， 为炎症相关疾病的恶性进展提供有利条件。有氧糖酵解的相关代谢酶、转运蛋白、代谢产物等均为关键信号分子， 药物通过靶向这些特异性强的关键分子， 抑制有氧糖酵解从而发挥治疗作用。本文围绕糖代谢重编程对炎症相关肿瘤、类风湿关节炎、阿尔茨海默病等炎症相关疾病发生发展的影响以及药物靶向糖代谢重编程对疾病的治疗作用展开综述。