Acta Pharmaceutica Sinica. B最新文献

{"title":"Reprogramming gut microbiota and targeting CXCL1: The multifaceted mechanism of PLP1 in ameliorating alcohol-induced liver disease","authors":"Zhu Yang,&nbsp;Qiuyue Lv,&nbsp;Qiangbao Xu,&nbsp;Yan Chen,&nbsp;Yiping Yang,&nbsp;Zihan Li,&nbsp;Hui Che,&nbsp;Guodong Wang,&nbsp;Wei Wei,&nbsp;Jiangping Wu,&nbsp;Jun Han","doi":"10.1016/j.apsb.2026.06.057","DOIUrl":"10.1016/j.apsb.2026.06.057","url":null,"abstract":"<div><div>Hepatic inflammation and gut barrier dysfunction are core pathologies of alcohol-associated liver disease (ALD), yet effective therapies remain limited. <em>Pueraria lobata</em> polysaccharide (PLP1), a key active constituent of <em>P</em>. <em>lobata</em> Radix, has demonstrated hepatoprotective potential; however, its underlying mechanisms remain poorly understood. In this study, we sought to elucidate the therapeutic mechanism of PLP1 against experimental ALD by integrating proteomics, metabolomics, and gut microbiota analyses. We demonstrated that PLP1 initially functions through a microbiota-dependent pathway, transferable by fecal microbiota transplantation (FMT), to restore gut barrier integrity and suppress the gut‒LPS‒TLR4 inflammatory axis. Furthermore, PLP1 exerted a direct, microbiota-independent effect, maintaining its therapeutic efficacy in antibiotic-depleted mice. Mechanistically, PLP1 directly and specifically targets CXCL1, promoting its ubiquitin-mediated proteasomal degradation as confirmed by biophysical assays. The functional necessity of this interaction was definitively established <em>via</em> comprehensive genetic manipulation of CXCL1 <em>in vitro</em> and <em>in vivo</em>. Specifically, CXCL1 overexpression reversed PLP1's benefits, whereas CXCL1 knockdown mimicked its effects and occluded any additional benefit from PLP1. Overall, PLP1 ameliorates ALD by independently targeting both extrinsic and intrinsic inflammatory triggers. This study reveals the multifaceted pharmacology of a natural polysaccharide and validates a dual-pronged therapeutic strategy for ALD.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 10","pages":"Pages 6686-6704"},"PeriodicalIF":14.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149204667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between the use of traditional Chinese medicine patterns as an inclusion criterion and statistical significance in primary outcomes of randomized placebo-controlled trials of Chinese herbal formulas","authors":"Zhijun Bu,&nbsp;Meirong Song,&nbsp;Chen Chen,&nbsp;Xinyi Shi,&nbsp;Xuefeng Wang,&nbsp;Yao Li,&nbsp;Jinchen Chong,&nbsp;Yijia Zhu,&nbsp;Feng Jiang,&nbsp;Yugen Chen","doi":"10.1016/j.apsb.2026.07.033","DOIUrl":"10.1016/j.apsb.2026.07.033","url":null,"abstract":"<div><div>Randomized, placebo-controlled trials of Chinese herbal formulas (CHFs) are commonly used to evaluate efficacy, but a proportion of such trials fail to demonstrate statistically significant effects on primary outcomes. Some researchers have pointed out that excluding traditional Chinese medicine (TCM) pattern differentiation from inclusion criteria may reduce the alignment between treatment and enrolled patient characteristics, which could, in turn, affect observed efficacy. This study analyzed 378 randomized, placebo-controlled trials of CHFs with clearly defined primary outcomes that were published between January 1, 2020, and October 21, 2025, and identified through searches of eight databases. A total of 92,691 participants were included in the primary outcome analyses. Of these, 324 trials (85.7%) reported statistically significant results on primary outcomes, and 197 (52.1%) used TCM patterns as an inclusion criterion. Multivariable Poisson regression revealed that trials using TCM patterns were more likely to report statistically significant results (adjusted risk ratio [aRR] = 1.14; 95% CI: 1.06–1.23; <em>P</em> = 0.001). The association was generally consistent across prespecified subgroups and sensitivity analyses; however, only 52 studies (13.8%) were evaluated as low risk of bias according to the Cochrane Risk of Bias 2.0 tool. Because this study included only published trials and few published pattern-based trials reported statistically nonsignificant primary outcomes, the observed association should be interpreted cautiously and may be influenced by publication bias, selective outcome reporting, and contextual differences in research and reporting practices. Further high-quality, prospectively registered, methodologically rigorous, and better-standardized trials are needed to evaluate this association.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 10","pages":"Pages 6664-6675"},"PeriodicalIF":14.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149204734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting the nervous system: Mechanistic insights into neuro–tumor communication and therapeutic opportunities","authors":"Tong Wu,&nbsp;Yaguang Zhang,&nbsp;Junhong Han","doi":"10.1016/j.apsb.2026.07.011","DOIUrl":"10.1016/j.apsb.2026.07.011","url":null,"abstract":"<div><div>The nervous system has emerged as an active regulator of the tumor ecosystem. Neural inputs from the central, peripheral, and enteric nervous systems influence tumor initiation, progression, metastasis, and therapeutic response through innervation and signal transmission. In addition to regulating tumor cell states, neural signaling reshapes stromal and immune compartments, promoting stemness, invasion, angiogenesis, metabolic adaptation, and immune evasion. Tumors, in turn, actively remodel their neural niche through neurogenesis, axonal remodeling, and tumor–nerve feedforward circuits. The biological effects of neuro–tumor crosstalk are highly context-dependent and are jointly determined by neural origin, receptor distribution, tumor state, and the local microenvironment. Accordingly, neural signaling has become a promising axis for therapeutic intervention. In this review, we summarize key advances in the molecular mechanisms of neuro–tumor communication over the past five years. We also highlight neurotransmitter and neuropeptide receptor axes with pharmacological and translational relevance, related targeted agents, and therapeutic strategies for targeting these pathways, as well as recent progress in neuro-immune combination therapy and clinical studies. Together, these advances provide an updated framework for understanding the role of neural signaling in tumor biology and its therapeutic potential.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 9","pages":"Pages 5592-5621"},"PeriodicalIF":14.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148949550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quercetin's antitumor effect in bladder cancer: Synergistic regulation of gut microbiota and l-serine metabolic pathway","authors":"Zhao Zhai,&nbsp;Feiya Yang,&nbsp;Ru Feng,&nbsp;Haojian Zhang,&nbsp;Jingyue Wang,&nbsp;Hengtong Zuo,&nbsp;Xinyu Yang,&nbsp;Mengliang Ye,&nbsp;Hui Xu,&nbsp;Jiachun Hu,&nbsp;Jinyue Lu,&nbsp;Yi Zhao,&nbsp;Jianye Song,&nbsp;Yong Zhang,&nbsp;Yan Wang,&nbsp;Nianzeng Xing","doi":"10.1016/j.apsb.2026.03.034","DOIUrl":"10.1016/j.apsb.2026.03.034","url":null,"abstract":"<div><div>Quercetin is a bioflavonoid that is abundant and easy to extract, and has beneficial effects such as anti-cancer, anti-inflammatory, and antioxidant properties. We have demonstrated that oral administration of quercetin in an animal model inhibits bladder cancer (BCa), with inhibition rates of 48.5% (100 mg/kg) and 51.41% (200 mg/kg), respectively. Additionally, quercetin treatment reverses gut microbiota dysbiosis in the model mice. Metabolomics results showed that <span>l</span>-serine had the highest correlation coefficient with tumor weight in model mice (<em>r</em> = 0.935), and oral quercetin reduced <span>l</span>-serine levels by modulating the abundance of <em>Escherichia-Shigella</em> in the gut microbiota. Transcriptomic sequencing results revealed that quercetin treatment downregulates the expression of phosphoserine phosphatase (PSPH), inhibiting the serine synthesis pathway (SSP) and reducing <span>l</span>-serine levels in the body, thus exerting anti-tumor effects. Fecal microbiota transplantation (FMT) experiments reproduced the pharmacological results of oral quercetin treatment for BCa and identified <em>Escherichia coli</em> Nissle 1917 as capable of inhibiting BCa growth by metabolizing <span>l</span>-serine. In conclusion, quercetin effectively inhibits the progression of BCa by comprehensively regulating <span>l</span>-serine levels in the body at both endogenous and exogenous levels.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 9","pages":"Pages 5961-5979"},"PeriodicalIF":14.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148940127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel intervention strategy for bladder cancer targeting dual metabolic pathways—Unraveling the pleiotropic mechanisms of quercetin","authors":"Elaine Lai-Han Leung","doi":"10.1016/j.apsb.2026.08.015","DOIUrl":"10.1016/j.apsb.2026.08.015","url":null,"abstract":"","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 9","pages":"Pages 6299-6300"},"PeriodicalIF":14.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148949545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Supramolecular strategy in traditional Chinese medicine processing: Mechanistic insights mediated by self-assembly","authors":"Wenqi Song,&nbsp;Huan Gong,&nbsp;Huijun Wang,&nbsp;Doudou Huang,&nbsp;Lianna Sun","doi":"10.1016/j.apsb.2026.06.048","DOIUrl":"10.1016/j.apsb.2026.06.048","url":null,"abstract":"<div><div>The processing of traditional Chinese medicine (TCM) is a critical process that upholds tradition and determines medicinal efficacy. The mechanisms underlying changes in TCM efficacy resulting from processing are currently a key focus of TCM research. Advances in supramolecular chemistry have significantly advanced the understanding of the mechanisms governing the efficacy of TCM complex chemical systems. Both the active ingredient basis and the adjuvant materials used in processing can be regarded as supramolecular units. Processing guides the TCM supermolecules to change structure through covalent forces and self-assemble non-covalently, forming soft matter aggregates that enable selective recognition, transformation, and assembly of components. These aggregates autonomously steer the entire system toward enhanced efficacy and reduced toxicity, thereby revealing the TCM's true active substance foundation. This paper highlights that the dynamic chemical system formed <em>via</em> supramolecular self-assembly during TCM processing can be likened to an “imprinting template” with memory function, which underlies the TCM “holistic” effects—characterized by multiple components, pathways, and targets. This study aims to provide valuable insights into TCM processing based on supramolecular development, bridging the gap between supramolecular science and TCM. Consequently, it offers profound inspiration for designing next-generation smart drug delivery systems, responsive biomaterials, and adaptive chemical systems.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 9","pages":"Pages 5709-5729"},"PeriodicalIF":14.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148961155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut microbiota-derived 5-HTP penetrates the host blood–brain barrier and ameliorates autism symptoms","authors":"Bei Li,&nbsp;Qianqian Yang,&nbsp;Min Li,&nbsp;Junqing He,&nbsp;Zhiqi Zhang,&nbsp;Xuchun Wan,&nbsp;Zihao Mo,&nbsp;Ruizhen Li,&nbsp;Shihan Li,&nbsp;Weirong Xu,&nbsp;Man Gu,&nbsp;Hanning Huang,&nbsp;Wei Li,&nbsp;Ziming Huang,&nbsp;Hongju Yang,&nbsp;Wei-Hua Chen,&nbsp;Zhi Liu","doi":"10.1016/j.apsb.2026.06.025","DOIUrl":"10.1016/j.apsb.2026.06.025","url":null,"abstract":"<div><div>Autism spectrum disorder (ASD), a highly prevalent neurodevelopmental condition, is increasingly recognized for its strong association with the intestinal microbiome. However, the development of gut microbiota-targeted therapies has been impeded by a limited understanding of the molecular mechanisms underlying interactions between commensal bacteria and the host nervous system. In this study, shotgun metagenomic sequencing and UPLC–MS/MS targeted metabolic analyses identified altered tryptophan metabolites in the gut microbiota of both human ASD patients and ASD mouse models. Notably, we demonstrate that commensal bacteria-derived 5-hydroxytryptophan (5-HTP), metabolite of tryptophan, ameliorates anxiety, stereotypical and repetitive behaviors, as well as social deficits in these mouse models. Furthermore, 5-HTP is capable of crossing the blood–brain barrier and inhibits the overexpression of receptor tyrosine kinase (RTK) ligands, thereby suppressing the downstream RTK/MAPK/ERK signaling cascade. This inhibition subsequently normalizes the excessive stabilization of dendritic spines in the hippocampus in MeCP2 mouse. Our research demonstrates that gut microbiota producing 5-HTP improves ASD symptoms in various ASD animal models, elucidates the molecular mechanisms between gut microbiota and the onset and treatment of ASD, and provides a promising therapeutic approach for ameliorating ASD through the expression of neuron-regulated small molecules by gut indigenous bacteria.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 9","pages":"Pages 6168-6184"},"PeriodicalIF":14.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148940081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"L-cell-specific Abca1 deficiency impairs glucose homeostasis through defective GLP-1 production in mice","authors":"Luyang Gao,&nbsp;Yubi Lin,&nbsp;Qianqian Ye,&nbsp;Yuhang Zhao,&nbsp;Wenxin He,&nbsp;Shijie Lv,&nbsp;Ke Yang,&nbsp;Jia Chen,&nbsp;Zhen Zhang,&nbsp;Xinxin Xiang,&nbsp;Geyang Xu","doi":"10.1016/j.apsb.2026.07.018","DOIUrl":"10.1016/j.apsb.2026.07.018","url":null,"abstract":"<div><div>Evidence suggests dietary cholesterol intake associates with higher diabetes risk, but mechanisms need further study. Glucagon-like peptide-1 (GLP-1), a glucose-regulating hormone produced by intestinal L-cells, has served as the basis for widely used diabetes therapeutics. However, how dietary cholesterol and intracellular cholesterol in L-cells affects GLP-1 and glucose regulation remains unclear. We studied ABCA1 (a cholesterol efflux protein) in L-cells using L cell specific <em>Abca1</em> gene null nice (<em>IntL-Abca1</em>^{<em>−/−</em>}) mice and ABCA1-targeted interventions in STC-1 and GLUTag cells. A high-cholesterol diet induced mouse glucose intolerance and reduced GLP-1. <em>IntL-Abca1</em>^{<em>−/−</em>} mice showed worse hyperglycemia and GLP-1 impairment <em>via</em> disrupted caveolin-1–<em>β</em>-catenin signaling. <em>Abca1</em> overexpression and cholesterol depletion in STC-1 and GLUTag cells enhanced the CAV1—<em>β</em>-catenin pathway and GLP-1 secretion, whereas cholesterol loading, <em>Abca1</em> siRNA knockdown, and treatment with probucol (an ABCA1 inhibitor) produced opposite effects. The findings of this study confirm that ABCA1 is a key regulator in maintaining cholesterol homeostasis in intestinal L cells and in the synthesis and secretion of GLP-1. Moreover, the regulatory effect of ABCA1 on GLP-1 is mediated through the CAV1–<em>β</em>-catenin signaling pathway. These observations further uncover promising therapeutic targets for metabolic disorders linked to diabetes.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 9","pages":"Pages 5980-5994"},"PeriodicalIF":14.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148940129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural elucidation of the herpesvirus replication machinery: Cryo-EM insights into helicase–primase complex assembly and mechanisms of antiviral inhibition","authors":"Qiaomei Zhou,&nbsp;Baohu Li,&nbsp;Dazhou Shi,&nbsp;Shenghua Gao,&nbsp;Peng Zhan,&nbsp;Jinfei Yang","doi":"10.1016/j.apsb.2026.06.050","DOIUrl":"10.1016/j.apsb.2026.06.050","url":null,"abstract":"","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 9","pages":"Pages 6292-6295"},"PeriodicalIF":14.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148940585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanomaterial-mediated functional remodeling of antigen-presenting cells: A novel strategy to break tumor immune escape","authors":"Hongzhi Dong,&nbsp;Xueyi Song,&nbsp;Yao Li,&nbsp;Qian Wei,&nbsp;Mingyi Ju,&nbsp;Yunong Li,&nbsp;Qi Cui,&nbsp;Jia Bi,&nbsp;Minjie Wei,&nbsp;Heran Li,&nbsp;Lin Zhao","doi":"10.1016/j.apsb.2026.06.038","DOIUrl":"10.1016/j.apsb.2026.06.038","url":null,"abstract":"<div><div>With the cross-integration of nanotechnology and immunology, nanomaterials have shown great potential in tumor treatment. This review begins with the nanomaterials have unique advantages in reshaping the tumor immune microenvironment (TIME), including improving targeting, enhancing stability, increasing delivery efficiency, achieving controllable release, and endowing a multi-functional integrated platform. We then systematically reviews the recently research progress on the multi-mechanism regulation of antigen-presenting cells (APCs) by nanomaterials: (1) In the aspect of dendritic cell activation, we focus on the breakthrough achievements such as the activation of immune responses through the generation of immune signal complexes and the promotion of tumor neoantigen presentation; (2) In the field of macrophage reprogramming, we analyze the applications of nanomaterials in inducing macrophage polarization, improving the anti-tumor phagocytosis of macrophages, blocking macrophage autophagy, and enhancing the synergy of immune cells; (3) In the regulation of B cells, we explore the mechanism by which nanomaterials enhance the germinal center response and thereby exert anti-tumor immune effects. This article further discusses key challenges in clinical translation, including the dynamic fate of nanomaterials in complex TIME and the balance between immunogenicity and efficacy, and proposes future directions for accelerating clinical translation through computer-aided design (such as AI prediction of nanomaterial-immune cell interaction networks) and organ-on-a-chip evaluation systems. This review provides a theoretical framework and technical route for the development of next-generation tumor immunonanomedicines.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 9","pages":"Pages 5785-5813"},"PeriodicalIF":14.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148940643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}