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Volume 16· Issue 3 · March 2026
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Review papers
Promising TNF-α inhibitors: Targeting pathogenic TNF-α/TNFR signaling to restore Th17/Treg balance in rheumatoid arthritis
Jiajie Kuai, Zhuo Chen, Ju He, Fengling Wang, Wei Wei
J. Pharm. Anal. 2026. 16(3) 101382
https://doi.org/10.1016/j.jpha.2025.101382
类风湿关节炎(RA)中,Th17/Treg细胞失衡是疾病进展的关键。TNF-α通过TNFR1和TNFR2信号通路调控T细胞功能,其中TNFR1主要促进Th17介导的炎症反应,而TNFR2则有助于维持Treg的免疫抑制功能。现有的TNF-α抑制剂虽疗效显著,但其非选择性阻断的作用机制易导致感染等药物不良反应,且难以有效恢复Th17/Treg平衡。本文综述了TNF-α/TNFR信号诱导RA中Th17/Treg失衡的机制,并介绍了新型精准干预策略,包括TNFR1拮抗剂、TNFR2激动剂、下游信号分子抑制剂及双靶向融合蛋白等。这些策略旨在在保留免疫保护功能的同时恢复T细胞稳态,为优化RA治疗提供了新思路。
Highlights
TNF-α/TNFR cooperate with TCR signaling to maintain CD4+ T cell homeostasis.
TNF-α/TNFR signaling leads to Th17/Treg imbalance in rheumatoid arthritis.
The restoration of Th17/Treg balance by existing TNF inhibitors has limitations.
Precise targeting of TNF-α/TNFR proinflammatory signaling is a potential idea for the development of TNF-α inhibitors.
Antimicrobial sonodynamic therapy: Recent advances and challenges in new therapeutic approaches to antimicrobials
Linyu Xue, Shidian Ran, Jindie Huang, Xiaorui Wei, Xingrui Yan, Tongchuan He, Hongmei Zhang, Mengqin Gu
J. Pharm. Anal. 2026. 16(3) 101375
https://doi.org/10.1016/j.jpha.2025.101375
病原菌的出现对全球健康构成了严重威胁,并且值得注意的是,传统的抗生素疗法面临着加强细菌耐药性的风险。抗菌声动力疗法(aSDT)结合了声敏剂和低强度超声波(US),为治疗耐药细菌开辟了新的途径。该疗法的优势在于能将超声能量聚焦于深部组织中的细菌感染部位,局部激活声敏剂,产生具有细胞毒性的活性氧物种(ROS),从而诱导细菌死亡。近十年来,aSDT因其良好的组织穿透性、生物相容性及靶向性而迅速发展。本文重点介绍aSDT在抗菌领域的最新研究进展,系统总结了其作用机制与常用声敏剂的类型,并从改善缺氧环境、联合其他治疗方式等方面探讨了提升aSDT效果的相关策略。此外,本文还总结了aSDT发展过程中面临的挑战与未来前景,旨在深化对声动力疗法(SDT)在抗菌治疗中应用的理解,推动该技术的持续创新与临床转化。
Highlights
Reviews aSDT mechanisms and emerging sonosensitizer designs.
Proposes hypoxia-targeting and multimodal therapy strategies.
Identifies challenges and opportunities for clinical translation.
Advances aSDT innovation in antibacterial treatment applications.
A comprehensive narrative review of Epimedium and its bioactive compounds in respiratory diseases
Lanlan Song, Changyu Lei, Cheng Zheng, Yichen Liu, Jian Liu, Dan Yao, Xiaoying Huang
J. Pharm. Anal. 2026. 16(3) 101374
https://doi.org/10.1016/j.jpha.2025.101374
该文系统总结了淫羊藿及其活性成分治疗呼吸系统疾病的潜力与机制。通过文献检索及网络药理学分析,研究评估了淫羊藿中八种主要活性成分(包括朝藿定A、B、C,淫羊藿苷,淫羊藿次苷I、淫羊藿次苷II,淫羊藿素等)对非小细胞肺癌、哮喘、慢性阻塞性肺疾病、肺纤维化、肺动脉高压、急性肺损伤、新型冠状病毒感染和结核病等八种呼吸系统疾病的治疗作用。研究发现,淫羊藿活性成分主要通过抗炎、抗氧化和免疫调节等途径发挥保护作用。网络药理学分析识别出多个在多种疾病中均被富集的核心靶点,提示淫羊藿具有多靶点、多通路的系统调控潜力。尽管现有证据令人鼓舞,未来仍需聚焦提升活性成分生物利用度并推动临床转化。
Highlights
Broad-spectrum efficacy of Epimedium and its bioactive compounds in managing respiratory diseases.
Mechanistic insights into the respiratory therapeutics of Epimedium and its bioactive compounds.
Targeted delivery systems to enhance the bioavailability of Epimedium and its bioactive compounds.
Exploring TGFBR3 in disease pathogenesis: Mechanisms, clinical implications, and pharmacological modulation
Hui Song, Jinjiang Chou, Peng Zhao, Meijun Chen, Jue Yang, Xiaojiang Hao
J. Pharm. Anal. 2026. 16(3) 101372
https://doi.org/10.1016/j.jpha.2025.101372
转化生长因子-β受体3(TGFBR3)是转化生长因子-β(TGF-β)信号通路的重要辅助受体,以膜结合型和可溶型两种形式存在,在多种生理和病理过程中发挥关键调控作用。本文系统综述了TGFBR3的结构特征及其在疾病发生发展中的分子机制,重点阐述了其在肿瘤、神经系统疾病、心血管疾病、糖尿病及感染性疾病中的异常表达与功能“双相性”。TGFBR3在多数实体瘤中发挥抑癌作用,但在特定肿瘤中亦表现出促癌特性。可溶性TGFBR3可作为“配体陷阱”抑制 TGF-β信号,是潜在的生物标志物与治疗靶点。文章还总结了表观遗传调控及药理干预策略,并指出当前研究局限与未来方向,为靶向TGFBR3的治疗策略开发提供理论参考。
Highlights
TGFBR3 modulates TGF-β signaling and exhibits dual functions in various diseases.
Soluble TGFBR3 suppresses TGF-β signaling by ligand sequestration.
Dysregulated TGFBR3 expression is linked to prognosis in cancer and fibrosis.
Epigenetic and pharmacological interventions significantly impact TGFBR3 function.
TGFBR3 emerges as a promising target for cancer and metabolic disorder therapies.
Mechanisms and therapeutic potential of YTHDF readers: Linking epitranscriptomics to cancer
Na Deng, Qiang Sun, Shuying Wang, Shiheng Jia, Chen Zheng, Fanglin Wang, Shuang Ma, Heng Zhou, Weiwei Liu
J. Pharm. Anal. 2026. 16(3) 101371
https://doi.org/10.1016/j.jpha.2025.101371
本文系统综述了YTHDF家族蛋白(YTHDF1/2/3)作为 m⁶A、m¹A、m⁵C 等RNA 甲基化修饰的识别蛋白在肿瘤发生发展中的核心作用与临床转化潜力。YTHDFs 通过保守YTH结构域结合修饰RNA,调控mRNA翻译、稳定性与代谢,参与上皮间质转化、肿瘤干细胞干性维持、代谢重编程、免疫逃逸等多种癌症特征进程,同时介导化疗、放疗、靶向及免疫治疗耐药,在多种肿瘤中异常表达并发挥促癌或抑癌双重作用。YTHDF1/2/3的表达与活性受非编码 RNA、转录因子、泛素化、磷酸化等多层级调控。目前针对YTHDFs的干预策略已取得重要进展,包括 siRNA/shRNA、CRISPR基因编辑、小分子抑制剂、PROTAC等,在临床前研究中展现出抑制肿瘤、逆转耐药及增强免疫治疗效果的潜力。尽管仍面临功能冗余、亚型选择性差、脱靶效应等难题,但依托蛋白结构开展精准药物设计,结合纳米颗粒、抗体偶联等靶向递送技术,可为解决上述瓶颈提供可行路径。YTHDFs作为表观转录组核心效应分子,有望成为肿瘤新型治疗靶点,为攻克肿瘤耐药、实现精准治疗开辟全新路径。
Highlights
YTHDFs orchestrate critical molecular processes in tumor cells through m6A, m1A, and m5C modifications.
YTHDFs participate in the maintenance of malignancy phenotypes in multiple tumors, such as tumor invasion and metastasis.
The expression and activity of YTHDFs are manipulated by transcription factors, posttranslational modifications, etc.
YTHDFs are implicated in antitumor resistance. Targeting YTHDFs provides a promising therapeutic strategy.
Astrocytes: Unveiling their role in the molecular mechanism of natural antidepressants
Shimeng Lv, Ruirui Shang, Xia Zhong, Yitong Lu, Haonan Gao, Guangheng Zhang, Linghui Kong, Yunhao Yi, Yufei Huang, Yuexiang Ma, Jing Teng, Sheng Wei
J. Pharm. Anal. 2026. 16(3) 101370
https://doi.org/10.1016/j.jpha.2025.101370
抑郁症是以持续情绪低落、快感缺失为核心特征的情绪障碍,临床主流药物可缓解症状,但仍存在起效延迟、个体差异显著、不良反应突出等问题。天然产物凭借多成分协同效应及多靶点、多通路调控的特点,在抑郁症干预中展现出独特潜力。星形胶质细胞作为中枢神经系统中含量最丰富的胶质细胞,深度参与抑郁症病理进程,已成为天然产物发挥抗抑郁作用的重要靶点。现有研究虽已揭示天然产物对星形胶质细胞功能的调控作用,但仍缺乏系统分类与机制整合。本综述通过系统文献梳理,总结了天然产物调控星形胶质细胞功能的分子机制,客观分析了当前转化研究的关键瓶颈,旨在为优化抑郁症治疗方案、推动天然产物研究的临床转化提供理论基础与技术路径。
Highlights
Astrocytes regulate CNS homeostasis via diverse physiological roles.
Abnormal astrocyte activity drives MDD pathogenesis via multifaceted mechanisms.
Natural products modulate astrocytes to induce antidepressant effects via multimodal pathways.
Certain natural products pose toxicity/adverse effects and struggle with BBB penetration.
Future studies must explore astrocyte-MDD and natural product modulation to advance clinical translation.
Phytomedicine-mediated time-dependent inactivation of CYP3A4 by chemical modification
Xu Mao
J. Pharm. Anal. 2026. 16(3) 101352
https://doi.org/10.1016/j.jpha.2025.101352
由于细胞色素P450(Cytochromes P450,CYP)3A4作为人体内最丰富的P450酶参与约50%的药物代谢,故药物强烈抑制CYP3A4可能引发药物-药物相互作用。亲电性失活剂(药物)或亲电性中间体(药物经代谢活化生成)对宿主酶的化学修饰可诱导时间依赖性失活(TDI),其通常比可逆性抑制产生更严重的不良后果。许多植物药已被鉴定为CYP3A4时间依赖性失活剂,其结构中具有化学反应性的特定官能团是诱导TDI的关键。本综述系统总结了这些官能团诱导TDI的化学机制,为理解此类失活剂与宿主酶的构效关系提供科学依据;文章还对已报道的天然CYP3A4时间依赖性失活剂进行了分类归纳,为临床合理联合用药,避免由TDI导致的药物-药物相互作用提供理论指导。
Highlights
TDI of CYP3A4 mainly includes MBI, quasi-irreversible inactivation, and affinity-labeling inactivation.
Increasing phytomedicines have been identified as time-dependent inactivators of CYP3A4.
Phytomedicine-mediated TDI of CYP3A4 results from chemical modification to the host enzyme.
MDP- and furan-containing phytomedicines mostly contribute to TDI of CYP3A4.
The correlation between characteristics and pharmacological effects of monoterpene glycosides and tannins in Radix Paeoniae Alba
Qitong Zheng, Mengyao Chen, Jialiang Ying, Zhichao Wang, Qiyuan Shan, Xia-Nan Sang, Gang Cao
J. Pharm. Anal. 2026. 16(3) 101471
https://doi.org/10.1016/j.jpha.2025.101471
白芍为毛茛科芍药属植物芍药的干燥根,是中医药临床常用中药材,历史悠久且临床应用广泛。其主要活性成分为单萜苷类与鞣酸类两大类,但当前相关研究多聚焦于单萜苷类成分,鞣酸类成分在白芍中的作用机制关注相对不足。本研究系统梳理白芍中单萜苷类与鞣酸类成分的生物利用度、药理活性及作用机制,深入阐明白芍的化学成分与药材药效之间的内在关联。研究总结发现白芍的单萜苷类成分主要在免疫调节、抗炎、肝保护及抗抑郁等方面发挥治疗效果;而鞣酸类成分则主要聚焦于抗病毒(体外)、抗癌(腹膜给药)及胃肠道疾病防治的成分药效作用规律。本研究揭示了白芍化学成分与其药效作用的内在关联,为白芍的研究与应用奠定基础。
Highlights
Monoterpene glycosides and tannins are the two main compounds of Radix Paeoniae Alba, which all have poor bioavailability.
A key intestinal carboxylesterase transformed monoterpene glycosides and tannins.
Monoterpene glycosides exert anti-inflammatory, immunomodulatory, and neuromodulatory pharmacological effects.
Tannins have limited bioavailability due to hydrophobicity, focusing their effects on the digestive system.
Glycosides and tannins' activity are related to Radix Paeoniae Alba's pharmacological effects.
Recent advances in the analysis of unsaturated fatty acids in biological samples based on chemical derivatization and mass spectrometry techniques
Yuanyuan Lin, Ningbo Chen, Wenda Chen, Fan Yin, Ling Yang, Xuan Chen, Jian-Liang Zhou, Tian Xie
J. Pharm. Anal. 2026. 16(3) 101491
https://doi.org/10.1016/j.jpha.2025.101491
脂肪酸(FAs)在人体多种生理过程中发挥着重要作用。对脂肪酸异构体进行准确分析有助于深入理解多种疾病的发生发展机制以及脂肪酸的代谢途径。近年来,研究发现,通过化学衍生化对脂肪酸结构进行修饰,可以有效提高其在质谱(MS)分析中的离子化效率,从而显著提升检测灵敏度。同时,一些化学衍生化方法还能够实现碳碳双键(C=C)位置的准确解析,甚至区分顺式和反式异构体。因此,基于化学衍生化的脂肪酸质谱分析方法逐渐成为研究热点。本综述总结了基于化学衍生化策略的质谱检测技术在不饱和脂肪酸(UFAs)分析中的研究进展,重点介绍了两类常用方法:羧基衍生化和C=C键衍生化。同时,还概述了这些方法在不同研究领域中的应用情况,分析了目前存在的挑战,并对未来的发展方向进行了展望。总体而言,本文从化学衍生化的角度,对脂肪酸质谱检测方法的设计思路及其发展趋势进行了系统综述。
Highlights
Derivatization of carboxyl groups improves the detection sensitivity of fatty acids in mass spectrometry.
Derivatization targeting C=C bonds allows for the analysis of fatty acid positional isomers.
Comprehensive fatty acid characterization enables both high sensitivity and precise double bond localization.
Original articles
Development and validation of a static multiple light scattering (SMLS) method for real-time colloidal stability assessment in nanoparticle formulations
Haiyang Shen, Shiqi Huang, Renjie Li, Hongliang Wang, Yanfang Yang, Yuling Liu, Jun Ye, Xiaohai Ma
J. Pharm. Anal. 2026. 16(3) 101396
https://doi.org/10.1016/j.jpha.2025.101396
纳米药物的临床转化成功与否,高度依赖于其胶体稳定性——这不仅决定了药物在体内的行为与安全性,也是满足监管要求的关键指标。针对这一核心问题,本研究建立并系统验证了一种基于静态多重光散射技术(SMLS)的纳米颗粒胶体稳定性实时监测方法。该方法克服了传统动态光散射需稀释样品、无法实时监测动态失稳过程的局限性,可在不稀释、高浓度条件下实时追踪颗粒的聚集、沉降等不稳定行为。研究以不同粒径的标准颗粒及四种已上市纳米药物为模型,验证了SMLS方法的准确性与适用性。结果表明,SMLS可灵敏捕捉动态光散射难以识别的早期失稳变化,并通过稳定性指数提供定量评估指标。该方法的建立为纳米制剂的合理设计、质量控制及符合监管要求的稳定性评价提供了新工具,具有广阔的应用前景。
Highlights
An SMLS method was established and validated for monitoring the colloidal stability of nanoparticle formulations.
SMLS overcomes DLS limitations and enables real-time, non-diluted monitoring.
This method facilitates nanoparticle formulations design optimization and clinical translation.
Metabolic heterogeneity, networks, and biomarkers of drug-induced liver injury
Xian Ding, Hongchuan Liu, Qingrong Qiu, Kongcai Zhu, Xiaohong Zhu, Rui Zhao, Ting Hu, Yuan Sun, Zhuoling An
J. Pharm. Anal. 2026. 16(3) 101496
https://doi.org/10.1016/j.jpha.2025.101496
本研究纳入了来自北京朝阳医院与北京佑安医院的200名药物性肝损伤(DILI)患者和221名健康对照者,收集其治疗前(基线期)和恢复期的516份血清样本,进行了靶向代谢组学研究。研究表征了谷胱甘肽、脂肪酸和肉碱代谢随DILI严重程度进展的代谢动力学;比较了抗生素、中药、非甾体抗炎药和他汀类药物诱导型DILI的代谢谱差异,并基于此构建了药物特异性的DILI代谢相关性协调网络。重要的是,研究揭示了长链酰基肉碱(如C18:1肉碱和C16:2肉碱)水平升高可特异性影响中药诱导型DILI的病理进展与恢复。孟德尔随机化分析验证了C18:1肉碱与总胆红素水平之间的因果关系;百合碱诱导的中药型DILI小鼠模型的肝脏Cpt2 mRNA表达受到抑制,进一步验证了该结论。最后,研究利用机器学习算法开发了一个包含10种代谢物的DILI分类器,可判别区分不同药物诱导的DILI亚型,在两个独立测试集上分别获得了0.915和0.904的准确率。本研究加深了对DILI代谢异质性的理解,并从代谢角度为DILI的临床诊断和治疗提供了科学证据。
Highlights
Metabolites' change trajectory and dynamics throughout DILI's disease progress were illustrated.
Metabolic networks of antibiotics-, herbs-, NSAIDS-, and statins-DILI were constructed based on metabolic coordination.
Elevated long-chain acylcarnitines potentially contribute to progression of herbs-DILI via Cpt2.
Mendelian randomization revealed the casual effect between C18:1 Car and TBIL.
A 10-metabolite model for DILI identification was developed with accuracies of 0.915 and 0.904.
Dual regulation of antiviral IFN response by Scutellariae Radix: Therapeutic implications for influenza
Li Li, Manjing Jiang, Hong Wei, Linpan Liang, Yunlong Song, Dongni Xia, Qiang Luo, Huimin Huang, Xu Li, Haisheng Yang, Lijun Ning, Ying Wu
J. Pharm. Anal. 2026. 16(3) 101399
https://doi.org/10.1016/j.jpha.2025.101399
I型及III型干扰素(IFN-I/IFN-III)是抗流感病毒的重要防线。本研究探究基于IFN-I/IFN-III的中药黄芩干预甲型流感病毒(IAV)感染的作用及机制。结果显示,黄芩可改善IAV感染小鼠的症状,促进IFN-I/IFN-III产生及干扰素刺激基因(ISGs)表达。体外人肺腺癌(A549)细胞、人单核细胞白血病(THP-1)细胞及中性粒细胞实验证明黄芩通过调控核因子κB(NF-κB)、干扰素调节因子3/7(IRF3/7)等分子促进IFN-I/IFN-III产生,经酪氨酸激酶2(TYK2)上调ISGs表达,其作用具有细胞特异性;调控NF-κB、FOS原癌基因(c-FOS)及丝裂原活化蛋白激酶p38等分子抑制炎性细胞因子转录;抑制IFN-I刺激的中性粒细胞活性氧(ROS)及中性粒细胞外陷阱(NETs)。此外,通过IAV感染IFN-α/β受体1(Ifnar1)-/-、IFN-λ受体1(Ifnlr1)-/-小鼠模型,证明黄芩的抗流感效应依赖于IFN-I/IFN-III系统,提示IFN-I/IFN-III是黄芩治疗IAV感染的主要靶点;黄芩对IFN系统有双向调控作用,促进IFN-I/IFN-III产生及抗病毒效应,同时抑制IFN-I诱导的中性粒细胞炎症。在感染后不同时相给药证明黄芩在感染早期给药的效果优于极期。本研究为黄芩治疗流感的临床应用提供实验依据。
Highlights
SR acted during the early stages of virus infection.
SRboosted the antiviral IFN activity while reducing IFN-I-induced inflammation.
Early intervention was crucial for successful treatment of IAV infection with SR.
IFN-I/III pathways were indispensable for the therapeutic effects of SR against influenza.
Equivariant graph neural network-based accurate and ultra-fast virtual screening of small molecules targeting miRNA-protein complex
Huabei Wang, Zhimin Zhang, Guangyang Zhang, Ming Wen, Hongmei Lu
J. Pharm. Anal. 2026. 16(3) 101339
https://doi.org/10.1016/j.jpha.2025.101339
Highlights
miRPVS enables ultra-fast virtual screening of small molecules targeting miRNA-protein complexes.
miRPVS achievs accurate docking score prediction compared to the traditional molecular docking method.
miRPVS enables tens of thousands of times acceleration compared to the traditional molecular docking method.
To our knowledge, this is the first study to use miRNA-protein complexes as targets for large-scale virtual screening.
A novel proteolysis-targeting chimera strategy targeting multiple immune checkpoints containing ITIMs enhances antitumor immunity
Yue-Yuan Qiu, Zhao-Wei Wang, Lei He, Ge-Ge Shi, Zhao-Zhao Li, Shuang-Xin Ma, Duo Yu, Hai-Chen Du, Fei Xie, Cun Zhang, Ying-Qi Zhang, Meng Li, Wei-Na Li
J. Pharm. Anal. 2026. 16(3) 101511
https://doi.org/10.1016/j.jpha.2025.101511
免疫检查点抑制剂的问世重塑了肿瘤治疗格局,然而低应答率与耐药性问题仍是制约其临床获益的主要瓶颈。目前临床多采用联合用药策略,但难以从根本上克服上述难题。针对这一问题,本研究提出了一种基于共同结构靶点的通用型干预策略。多种免疫检查点(如PD-1、BTLA、NKG2A等)的胞内区均包含免疫受体酪氨酸抑制基序(ITIM),当受体激活时,ITIM通过招募含SHP2在内的磷酸酶传递抑制信号。本研究模拟SHP2的C-SH2结构域,设计了一种能广谱结合ITIM的多肽并进一步以该多肽为靶蛋白配体,与VHL配体连接,构建了PROTAC分子PITIP。该分子可在T细胞、NK细胞及巨噬细胞等多种免疫细胞中诱导多种免疫抑制受体发生蛋白酶体依赖性降解,从而同时阻断多条抑制信号通路。体内实验表明,PITIP在移植瘤模型(包括抗PD-1耐药模型)中激发了强劲的抗肿瘤免疫应答。将其封装于抗CD45抗体偶联的脂质体后,免疫细胞靶向性与治疗效果进一步提升。本研究首次报道了一种靶向免疫检查点共有ITIM结构域的通用PROTAC策略,实现了多种免疫细胞中多个免疫检查点的同步降解,为提升免疫治疗响应率、克服耐药性提供了新思路。
Highlights
PITIP increased CD8+ T cell and NK cell activation and cytotoxicity.
PITIP reprogrammed macrophages to polarize towards an antitumor phenotype.
PITIP elicited antitumor immune response in various mouse xenograft tumor models.
PITIP induced antitumor immune responses in anti-PD-1-resistant tumor models.
PITIP offered a new strategy for overcoming the limitations of current ICI therapies.
Rational design of a novel specific fluorescent substrate for monitoring hUGT1A4 activity and its application in identification of selective inhibitors
Ning Mao, Shi-Qing Li, Xiang-Lu Zhou, Cong Hu, Wen-Chao Wu, Hua Wei, Li-Wei Zou, Ling Yang
J. Pharm. Anal. 2026. 16(3) 101415
https://doi.org/10.1016/j.jpha.2025.101415
尿苷二磷酸葡萄糖醛酸转移酶(UGTs)家族氨基酸序列高度相似,区分其各自的功能极具挑战性。开发选择性探针和抑制剂对于理解单一亚型酶的独特功能至关重要。本研究设计合成了四种新型萘酰亚胺类荧光探针,并鉴定出BAD3为UGT1A4的高选择性和高灵敏度底物。利用该探针建立的抑制剂筛选平台,本研究从天然产物库中筛选出熊果酸作为先导化合物,并对其进行了结构改造,获得了2种UGT1A4强效抑制剂T25和T26。构效关系(SAR)研究显示,3位羟基酯化能显著提升抑制活性,而28位羧基修饰则会导致活性下降。同时,T25能在动物体内显著改变BAD3的药代动力学特征,证实了其在体内的UGT1A4抑制效应。本研究开发的BAD3及选择性抑制剂T25/T26,为深入探索UGT1A4的生理与药理功能提供了有力的分子工具。
Highlights
Discovery of the first specific fluorescent substrate for UGT1A4.
Novel UGT1A4 inhibition screening system developed using a self-designed fluorescent substrate.
Identification of pentacyclic triterpenoids as the most promising natural inhibitors of UGT1A4.
28-carboxylic acid group in ursolic acid derivatives shown critical for UGT1A4 inhibition.
3-Acetylursolic acid and 3-Butyroylursolic acid confirmed as competitive inhibitors.
MST4 as a key driver of osteoclast activation in osteoporosis
Bin Zhang, Jiangjiang Zhang, Xuqiang Liu, Qiang Xu
J. Pharm. Anal. 2026. 16(3) 101401
https://doi.org/10.1016/j.jpha.2025.101401
本研究鉴定出哺乳动物sterile20样激酶(MST4)是骨质疏松症中破骨细胞活化与骨吸收的关键调控因子。研究显示,MST4在骨质疏松症患者中表达显著升高,并与骨密度呈负相关。功能实验表明,MST4在体外及体内均可促进破骨细胞分化及其骨吸收活性。机制上,MST4通过磷酸化TRAF6蛋白的第463位苏氨酸和第486位苏氨酸,增强其自身泛素化水平,进而激活NF-κB及MAPK信号通路。重要的是,沉默MST4可减轻去卵巢小鼠模型的骨量丢失。上述发现揭示了骨代谢中一条新的MST4–TRAF6信号轴,提示MST4是骨质疏松症潜在的治疗靶点。
Highlights
This study reveals a novel mechanism where MST4 promotes osteoclast differentiation through the phosphorylation modification of TRAF6 for the first time.
It delineates the pivotal role of TRAF6 autoubiquitination in osteoclast activity.
The study uncovers the significant impact of the MST4-TRAF6 interaction on the progression of osteoporosis.
It provides a theoretical basis for targeting MST4 and TRAF6 as novel therapeutic approaches for osteoporosis.
This research opens new directions for further understanding osteoclast regulation and osteoporosis treatment.
Covalent modification of Keap1 Cys489 by NU6300 activates Nrf2 signaling and suppresses NLRP3 inflammasome-mediated pyroptosis
Xueqin Jiang, Hongyu Zheng, Xinlu Zhang, Minghai Tang, Jing Peng, Xiaoying Cai, Kaiyue Su, Ruijia Zhang, Neng Ye, Lei Lin, Rupei Ma, Caiyun Shen, Wenshuang Wu, Haoyu Ye
J. Pharm. Anal. 2026. 16(3) 101458
https://doi.org/10.1016/j.jpha.2025.101458
Kelch样ECH相关蛋白1(Keap1)–核因子E2相关因子2(Nrf2)信号通路是调控氧化应激的重要枢纽,并在炎症反应与细胞焦亡中发挥关键作用。本研究发现,NU6300作为一种新型Nrf2激活剂,通过共价修饰Keap1半胱氨酸489位点,破坏Keap1与Nrf2相互作用,激活Nrf2信号,从而改善线粒体功能并降低氧化应激水平,进而抑制NOD样受体热蛋白结构域相关蛋白3(NLRP3)-Gasdermin D(GSDMD)信号介导的细胞焦亡。在对乙酰氨基酚诱导的急性肝损伤模型中,NU6300发挥抗氧化及抗炎作用,并改善肝组织损伤。本研究揭示了NU6300通过Keap1-Nrf2-NLRP3-GSDMD轴调控氧化应激与炎症反应的新机制,并为其作为潜在抗炎抗氧化先导化合物提供重要依据。
Highlights
NU6300 covalently modifies Keap1 at cysteine-489, disrupting Keap1-Nrf2 interaction.
NU6300 activates Nrf2 signaling to inhibit NLRP3 inflammasome-mediated pyroptosis.
NU6300 alleviates liver injury via antioxidant and anti-inflammatory mechanisms.
NU6300 is a novel therapeutic compound for oxidative stress-driven inflammatory disorders.
Tranilast ameliorates experimental abdominal aortic aneurysm by inhibiting the NLRP3 inflammasome pathway
Haole Liu, Kangli Tian, Weilai Fu, Longlong Qin, Ruipu Tian, Panpan Wei, Jiawei Zou, Naqash Alam, Fizza Malik, Kexin Li, Meng Li, Boyu Xu, Jia Guo, Congcong Xia, Rong Wang, Weirong Wang, Liang Bai, Enqi Liu, Baohui Xu, Yankui Li, Sihai Zhao
J. Pharm. Anal. 2026. 16(3) 101453
https://doi.org/10.1016/j.jpha.2025.101453
腹主动脉瘤(AAA)通常伴随典型的炎症反应,但临床上尚无药物疗法,筛选安全性好的抗炎药物是防治AAA的可行途径。本研究证实,在猪胰弹性蛋白酶 (PPE)诱导的AAA小鼠模型,无论是曲尼司特预防性给药,还是对已经形成的AAA进行干预,均可显著抑制AAA的进展。病理学上,曲尼司特可减轻平滑肌细胞耗竭和弹性纤维降解,减少炎性细胞浸润。生物信息学分析及体内外实验表明NLRP3是曲尼司特抑制AAA的关键靶点,减少Caspase 1的切割和IL-1β的分泌是其关键机制。此外,Nlrp3敲除和曲尼司特处理均对AAA有抑制作用,但两者无协同作用,曲尼司特可能通过抑制NLRP3通路延缓动脉瘤的发生与发展。
Highlights
Tranilast suppressed AAA formation and progression by inhibiting the NLRP3 inflammasome pathway.
Tranilast treatment or Nlrp3 deficiency reduced leukocyte accumulation, neovessel density, and MMPs expression in vivo.
Tranilast treatment decreased NLRP3, cleaved caspase 1, and interleukin-1β levels in vitro.
Crebanine protects against ovariectomy-induced bone loss by targeting Sirt1 to interfere with NF-κB acetylation and ROS activity
Haojie Zhang, Xuan Zhao, Zheng Wang, Jiansen Miao, Xinli Hu, Peng Cui, Chen Jin, Xibin Zhao, Haibo Liang, Hantao Ye, Yining Xu, Xiaolong Chen, Wei Wang, Shibao Lu
J. Pharm. Anal. 2026. 16(3) 101426
https://doi.org/10.1016/j.jpha.2025.101426
骨质疏松是一种以骨量减少和骨结构破坏为特征的常见代谢性疾病,其核心机制与破骨细胞过度活化及骨重建失衡密切相关。本研究围绕天然生物碱克班宁(Cre)的抗骨质疏松作用展开,系统评估其在体内外的干预效果及分子机制。结果表明,Cre能够显著抑制核因子κB受体激活剂配体(RANKL)诱导的破骨细胞分化及骨吸收功能,同时促进成骨细胞分化与矿化,从而恢复骨代谢平衡。机制研究发现,Cre通过激活Sirt1,抑制NF-κB信号通路并降低氧化应激水平,进而下调NFATc1等关键转录因子的表达。此外,Cre还可干扰RANKL-核因子κB受体激活剂(RANK)相互作用,阻断下游Akt/MAPK信号通路。在卵巢切除小鼠模型中,Cre有效改善骨丢失且未见明显毒性。本研究为开发基于天然产物的骨质疏松干预策略提供了重要依据。
Highlights
Crebanine inhibits osteoclast formation via Sirt1-mediated suppression of NF-κB and ROS pathways while enhancing osteoblast activity, balancing bone remodeling.
Crebanine activates Sirt1 to deacetylate NF-κB (p65) and stabilize IκBα, blocking osteoclastogenesis and oxidative stress.
SPR and molecular docking confirm crebanine directly binds Sirt1, disrupting RANKL and downstream Akt/MAPK pathways.
Apatinib and silver nanoparticles synergize against gastric cancer through the PI3K/Akt signaling pathway-mediated ferroptosis
Zichang Lin, Zhenghao Deng, Jiahao Liang, Binlong Chen, Yanyan Huang, Bin Liu, Yanzhong Zhao
J. Pharm. Anal. 2026. 16(3) 101400
https://doi.org/10.1016/j.jpha.2025.101400
铁死亡是一种由脂质过氧化引起的受调控的细胞死亡形式。在本研究中,本研究检测到人胃癌组织中谷胱甘肽过氧化物酶 4(GPX4)和溶质载体家族 7 成员 11(SLC7A11)的表达水平高于癌旁组织,因此,研究者猜测,GPX4和SLC7A11表达的下调在一定程度上能抑制胃癌(GC)的发生发展。阿帕替尼(Apa)被发现能通过SLC7A11/ GPX4 途径诱导铁死亡。然而,长期高剂量使用会产生副作用及耐药性。为了解决这些局限性,本研究采用联合治疗策略并开发了一种纳米载药系统,即使用透明质酸(HA)修饰的(聚乳酸-乙酸)(PLGA)纳米颗粒靶向递送Apa和壳聚糖银纳米颗粒(Chi-Ag)。研究结果表明,该系统实现了胃癌的协同治疗。并通过调节磷脂酰肌醇-3-激酶/蛋白激酶 B(PI3K/Akt)信号通路有效诱导了铁死亡。
Highlights
HA-Ag-PLGA@Apa NPs exhibit synergistic tumor eradication, favorable targeting, and induce ferroptosis via PI3K/Akt pathway.
NPs has high biosafety and also can improves the efficacy of Apatinib.
NPs exhibited tumor growth inhibition in BGC-823 heterotopic animal models by inducing ferroptosis and penetrating into tumor regions.
Short communications
An ultrasensitive and rapid immunoassay for the analysis of Helicobacter pylori in clinical samples based on hollow gold nanoparticles
Xiaorong Dai, Qingjie Zhang, Xianghui Yun, Yujuan Mao, Chuanjiang Ran, Zihan Ling, Yan Shen, Yongkang Chen, Liang Ge
J. Pharm. Anal. 2026. 16(3) 101425
https://doi.org/10.1016/j.jpha.2025.101425
Highlights
A sensitive and instrument-free detection platform was constructed.
Hollow gold nanoparticles were used as signal amplification probe.
A low detection limit of 1 ng/mL for the antigen was achieved with naked eyes.
The HGNPs-LFIA strip has good stability and performance in testing with clinical samples.
Feature-based molecular networking and building blocks identification advance novel natural products characterization: Sesquiterpene-chromone hybrids in agarwood as an application
Qian Wang, Han Li, Huiting Liu, Yujie Pei, Pengfei Tu, Huixia Huo, Jun Li, Yuelin Song
J. Pharm. Anal. 2026. 16(3) 101478
https://doi.org/10.1016/j.jpha.2025.101478
本研究提出了一种天然产物快速结构鉴定和靶向引导分离的策略。基于对照品总结的化学结构与质谱特征的基础上,通过质量亏损过滤(MDF)和基于特征的分子网络(FBMN)联合筛选得到25个倍半萜-色酮杂聚体(SCH),通过匹配全激发能三级质谱(FEER-MS3)图谱分别鉴定倍半萜和色酮结构单元,全碰撞能二级质谱(FCER-MS2)图谱用于二者连接方式的确认,最终纯化和鉴定了七个新的SCH用于结构验证。验证结果表明该策略通过拼接结构单元,可以实现倍半萜-色酮杂聚体结构的快速鉴定。
Highlights
Mass defect filtering and feature-based molecular networking accelerated capturing sesquiterpene-chromone hybrids (SCHs).
FEER-MS3 matching strategy facilitated fragment ion identification for SCHs.
Twenty-five SCHs were captured and structurally annotated by separately deciphering units A and B.
Seven new SCHs, including one bearing C–C linkage between substructures were purified for structural justification.
Two new SCHs showed cell-protective, and six exhibited anti-inflammatory activities.
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期刊简介
Journal of Pharmaceutical Analysis(JPA,《药物分析学报(英文)》)创刊于2011年,由教育部主管,西安交通大学主办,是国内第一本有关药物分析的专业英文学术期刊,JPA 始终秉承服务国家重大战略需求、建设世界一流科技期刊的办刊宗旨,重点报道药物发现与药品全生命周期质量控制的新理论、新技术、新方法,临床精准用药,以及药物与生物、人工智能等交叉领域的技术方法方面的最新研究成果,为全球药物研发和药品质量控制提供高水平的国际学术交流平台,持续推动药物分析学科以及药学领域的快速发展。
JPA目前已组建一支以主编贺浪冲教授为核心的国际化的学术团队和专业的编辑出版团队,已实现编委国际化、稿源国际化、同行评议国际化、读者国际化和出版国际化。已被SCIE、PubMed、Scopus、DOAJ、中国科学引文数据库(CSCD)及中国科技论文与引文数据库(中国科技核心期刊)等多种重要国际和国内数据库和评价体系定为刊源。JPA连续8年入选“中国最具国际影响力学术期刊”。2019年入选“中国科技期刊卓越行动计划”重点期刊,2024年入选“中国科技期刊卓越行动计划二期”英文领军期刊。2024年影响因子 8.9,位于全球药理学和药学类学术期刊第14位(14/352),进入药学与药理学前4%,继续稳居于Q1区前列。2025年中科院1区,Top期刊。
收稿范围
药物分析新技术、新方法,分析药理学,药物代谢与递送,中药与天然药物,生物传感,可视化分析,生物功能分析,生物技术药物,药物分析装备,人工智能应用
收稿栏目
原创论文、综述、快报、展望、观点、新闻、社评等
期刊官网
https://www.journals.elsevier.com/journal-of-pharmaceutical-analysis
投稿网址
https://www.editorialmanager.com/jpa/Default.aspx
编辑 | 李 蕾
校对 | 朱丹丹
审核 | 王梦杰、马维娜
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