Pharmacological research最新文献

{"title":"Questions and comments on “ALKBH5 attenuates mitochondrial fission and ameliorates liver fibrosis by reducing Drp1 methylation,” published in Pharmacological Research (2023)","authors":"Bing Bai, Wenming Bao, Ling Wang, Ningling Kang","doi":"10.1016/j.phrs.2026.108101","DOIUrl":"10.1016/j.phrs.2026.108101","url":null,"abstract":"","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"224 ","pages":"Article 108101"},"PeriodicalIF":10.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146003605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Benefits and risks of herbal medicine use during pregnancy on offspring outcomes: A systematic review and meta-analysis of randomized controlled trials and observational studies","authors":"Chen Chen ,&nbsp;Yuezhen Li ,&nbsp;Wenling Wang ,&nbsp;Chunrong Liu ,&nbsp;Qiumei Luo ,&nbsp;Yan Ren ,&nbsp;Yiquan Xiong ,&nbsp;Xin Sun ,&nbsp;Jing Tan","doi":"10.1016/j.phrs.2026.108092","DOIUrl":"10.1016/j.phrs.2026.108092","url":null,"abstract":"<div><h3>Purpose</h3><div>Herbal medicines are widely used during pregnancy, yet their potential effects on offspring remain uncertain. This systematic review aimed to comprehensively evaluate both the potential benefits and risks of prenatal herbal medicine use on offspring outcomes by synthesizing evidence from randomized controlled trials (RCTs) and observational studies.</div></div><div><h3>Methods</h3><div>We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials from inception to November 9, 2024. Eligible studies reported maternal use of herbal medicines during pregnancy and assessed offspring-related outcomes.</div></div><div><h3>Results</h3><div>A total of 111 studies met the inclusion criteria, comprising 39 RCTs, 36 cohort studies, 18 case–control studies, and 18 cross-sectional surveys. In RCTs, prenatal use of certain herbal medicines was associated the live birth rate (RR=1.14, 95 % CI: 1.05–1.24) and a lower risk of birth defects (RR=0.46, 95 % CI: 0.22–0.94), primarily among women undergoing assisted reproduction; reductions in miscarriage were observed among those with threatened or recurrent miscarriage. At the overall level, observational studies adjusted for confounding did not show significant associations between prenatal herbal medicine use and major adverse offspring outcomes (including birth defects, miscarriage, stillbirth, or preterm birth). Exploratory analyses of individual herbal products suggested that some specific herbs—such as almond oil and <em>Glycyrrhiza</em> (with preterm birth), betel quid (with low birth weight), An-Tai-Yin (with musculoskeletal malformations), khat (with nervous system malformations), and <em>Coptidis Rhizoma</em> (with nervous system and genital organ malformations)—may be linked to increased risks. However, these signals were based on a limited number of studies and should be interpreted with caution given variability in exposure definitions, study quality, and potential residual confounding.</div></div><div><h3>Conclusions</h3><div>For women undergoing assisted reproduction or those at increased risk of miscarriage, certain herbal medicines may offer potential benefits during pregnancy. Overall, evidence from RCTs and adjusted observational studies does not indicate a clear increase in adverse offspring outcomes associated with prenatal herbal medicine use. Nonetheless, a few herbs have been linked to potential safety concerns, although the supporting evidence remains limited and heterogeneous. Cautious use is advised, particularly for products without robust data on fetal and long-term postnatal safety.</div></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"224 ","pages":"Article 108092"},"PeriodicalIF":10.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145948872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"YBX1-LDHB axis orchestrates pyruvate production from lactate to promote ICC initiation and development","authors":"Yong Liu ,&nbsp;Fei Wang ,&nbsp;Mi Zhang ,&nbsp;Xiabing Shi ,&nbsp;Lei Li ,&nbsp;Tingjie Wang ,&nbsp;Haifeng Zhang ,&nbsp;Zhongyu Cheng ,&nbsp;Xiangpan Li ,&nbsp;Juan Chen ,&nbsp;Chuanrui Xu","doi":"10.1016/j.phrs.2026.108110","DOIUrl":"10.1016/j.phrs.2026.108110","url":null,"abstract":"<div><div>Previous work from our group established that Y-box binding protein 1 (YBX1) plays a pivotal role in the initiation and progression of intrahepatic cholangiocarcinoma (ICC); however, its specific biological functions and underlying regulatory mechanisms remain unclear. The current study demonstrates that YBX1 is highly expressed in ICC tissues, and its highly expression correlates significantly with a poor prognosis in patients with ICC. <em>In vitro</em> experiments revealed that YBX1 overexpression significantly enhanced the proliferation of ICC cells. Conversely, YBX1 knockout robustly inhibited tumor growth in both <em>in vitro</em> and <em>in viv</em>o models. Mechanistically, YBX1 upregulated the expression of lactate dehydrogenase B (LDHB) by increasing its transcriptional activity and stabilizing LDHB mRNA. Elevated LDHB expression drives the conversion of lactate to pyruvate, which is further metabolized to acetyl coenzyme A. This metabolic reprogramming enhances the activity of tricarboxylic acid (TCA) cycle and production of adenosine triphosphate, thereby providing essential energy support for the proliferation of ICC cells. Corroboratively, inhibiting LDHB <em>via</em> CRISPR-Cas9-mediated knockout suppressed ICC cell proliferation, whereas LDHB overexpression accelerated the ICC tumor progression. Lactate induces YBX1 nuclear translocation, which in turn activates LDHB transcription. Collectively, our findings demonstrate the oncogenic roles of YBX1 and LDHB in ICC progression, identify lactate as a key energy source sustaining the activity of TCA cycle and oxidative phosphorylation, and highlight the YBX1-LDHB axis as a potential therapeutic target.</div></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"224 ","pages":"Article 108110"},"PeriodicalIF":10.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146038222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply to letter to the editor questions and comments on “ALKBH5 attenuates mitochondrial fission and ameliorates liver fibrosis by reducing Drp1 methylation”","authors":"Juan Wang,&nbsp;Hui Tao,&nbsp;Chao Lu,&nbsp;Jingjing Yang","doi":"10.1016/j.phrs.2026.108102","DOIUrl":"10.1016/j.phrs.2026.108102","url":null,"abstract":"","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"224 ","pages":"Article 108102"},"PeriodicalIF":10.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146019228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-target neuroprotective effects of notoginsenoside R1 in neurodegenerative diseases: From pharmacokinetics to translational prospects","authors":"Hao-wen Lin ,&nbsp;Shi-pian Li ,&nbsp;Jia-xin Wen ,&nbsp;Jia-xuan Zhang ,&nbsp;Bi-meng Zhang ,&nbsp;Yong-jun Wang ,&nbsp;Xue-jun Cui ,&nbsp;Min Yao","doi":"10.1016/j.phrs.2025.108074","DOIUrl":"10.1016/j.phrs.2025.108074","url":null,"abstract":"<div><div>Neurodegenerative diseases impose a heavy social and economic burden, and effective therapeutic strategies are essential for slowing disease progression and improving patient quality of life. Notoginsenoside R1 (NGR1), a key saponin derived from <em>Panax notoginseng</em> (Burk. F.H. Chen), has been widely studied in experimental models of neurodegenerative diseases, such as stroke and Alzheimer’s disease (AD). Based on a rigorous literature screening and a meta-analysis of animal studies, we confirmed that NGR1 significantly reduces infarct volumes in cerebral ischemia-reperfusion models and improves escape latency in AD mice. Mechanistically, NGR1 confers neuroprotection by attenuating oxidative stress, suppressing neuroinflammation, inhibiting apoptosis, and preserving the neurovascular unit. Furthermore, using network pharmacology, reverse virtual screening, and molecular docking, we preliminarily identified potential targets and signaling pathways, providing a theoretical basis for future studies. However, clinical translation of NGR1 remains limited due to poor oral bioavailability and restricted permeability across the blood-brain and blood-spinal cord barriers. To address these challenges, we summarized delivery strategies, including nanoparticle-based carriers, intranasal administration, and permeability enhancers, to facilitate NGR1 entry into the central nervous system. We also discussed additional potential approaches, such as structural modification and targeted delivery, analyzing their respective advantages and limitations. Collectively, these findings highlight NGR1 as a promising candidate for the prevention and treatment of neurodegenerative diseases.</div></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"224 ","pages":"Article 108074"},"PeriodicalIF":10.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145800202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response letter to Chi-Tung Lu et al.’s Comment on “Efficacy and safety of Gutong Patch compared with NSAIDs for knee osteoarthritis: A real-world multicenter, prospective cohort study in China”","authors":"Yu Zhang,&nbsp;Yingjie Wang","doi":"10.1016/j.phrs.2026.108086","DOIUrl":"10.1016/j.phrs.2026.108086","url":null,"abstract":"","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"224 ","pages":"Article 108086"},"PeriodicalIF":10.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145918201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Study on epigenetic regulatory mechanism of MBD4 with a germline loss-of-function mutation (rs140693) responsible for retinoblastoma chemoresistance via the cell cycle and apoptotic pathways","authors":"Li Zhang ,&nbsp;Wenping Song ,&nbsp;Junting Wang ,&nbsp;Yelin Zhao ,&nbsp;Chenyu Yuan ,&nbsp;Zhilong Ruan ,&nbsp;Jiaqi Chen ,&nbsp;Junyang Zhao ,&nbsp;Hongjuan Yao ,&nbsp;Hebing Chen ,&nbsp;Chengyue Zhang ,&nbsp;Liang Li","doi":"10.1016/j.phrs.2026.108098","DOIUrl":"10.1016/j.phrs.2026.108098","url":null,"abstract":"<div><div>Recurrence of high-risk advanced retinoblastoma (RB) is still a major obstacle even after enucleation due to resistance to adjuvant chemotherapy, especially in China. To identify any germline alterations or candidate genes associated with RB prognosis, we obtained whole-exome sequencing (WES) and reduced-representation bisulfite sequencing (RRBS) profiles by using patient peripheral blood samples, followed by clinical validation and functional characterization. For follow-up studies, we selected 17 candidate genes from the WES and RRBS analyses. Among them, <em>MBD4</em>, which carries a germline loss-of-function mutation (rs140693), was identified for further clinical replication. MBD4 downregulation significantly impaired carboplatin or etoposide efficacy in vitro and in vivo, respectively. There were marked decreases in the expression of 5 related genes plus increased DNA methylation in their promoters in Y79 (MBD4^-/-) cells, along with even more significant effects after carboplatin treatment. MBD4 affected the transcription and expression of its downstream genes, such as FADD and P21, via MBDCap-PCR, ChIP<img>qPCR, and reporter gene assays. Moreover, the germline mutation was responsible for MBD4 instability with attenuated binding to USP7, thereby leading to impaired drug sensitivity. It was confirmed by the reinstated susceptibility of Y79 (MBD4^-/-) cells after MBD4-WT was restored. In the present study, our findings indicate that depletion or mutation of MBD4 interferes with the activation of the cell cycle and apoptosis via epigenetic regulation, thereby reducing drug susceptibility. It provides new insights into the role in RB chemoresistance of MBD4 as an epigenetic regulator, which might fuel the development of new RB-targeted strategies.</div></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"224 ","pages":"Article 108098"},"PeriodicalIF":10.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145980180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “TREX1 activators: A novel therapeutic strategy for rheumatoid arthritis management via cfDNA clearance” [Pharmacol. Res. 218 (2025) 107817]","authors":"Yuping Wang ,&nbsp;Weidan Luo ,&nbsp;Wanyu Wu ,&nbsp;Chang Chen ,&nbsp;Bo Qin ,&nbsp;Xiongfei Xu ,&nbsp;Yulin Xu ,&nbsp;Jianghuiyi Zeng ,&nbsp;Linna Wang ,&nbsp;Jiujie Yang ,&nbsp;Jerome P.L. Ng ,&nbsp;Wuyan Zheng ,&nbsp;Xiaoyun Yun ,&nbsp;Jie Zhou ,&nbsp;Baixiong Huang ,&nbsp;Betty Yuen-Kwan Law ,&nbsp;Vincent Kam-Wai Wong","doi":"10.1016/j.phrs.2026.108093","DOIUrl":"10.1016/j.phrs.2026.108093","url":null,"abstract":"","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"224 ","pages":"Article 108093"},"PeriodicalIF":10.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145966740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PHGDH as a therapeutic node: Natural modulators from TCM, degradation pathways, and emerging TPD strategies","authors":"Song-Song Shi ,&nbsp;Yu-Dan Du ,&nbsp;Si-Yi Chen ,&nbsp;Wen Zhang ,&nbsp;Guo-Wu Rao ,&nbsp;Quan Zheng","doi":"10.1016/j.phrs.2025.108079","DOIUrl":"10.1016/j.phrs.2025.108079","url":null,"abstract":"<div><div>Phosphoglycerate dehydrogenase (PHGDH) has emerged as a promising therapeutic target due to its critical roles in the pathogenesis of cancer and neurological disorders. Targeting PHGDH holds significant theoretical and translational potential for cancer therapy and the amelioration of cognitive impairments. However, currently available PHGDH inhibitors are limited in number and primarily function through inhibition of the enzyme's catalytic activity. This review systematically summarizes PHGDH modulators identified from traditional Chinese medicine, including both inhibitors and activators, and presents a detailed analysis of their structure–activity relationships (SAR) and mechanisms of action. It also comprehensively outlines the signaling pathways that regulate PHGDH degradation through the ubiquitin–proteasome system and autophagy–lysosome pathway. Importantly, it also discusses emerging targeted protein degradation (TPD) technologies, including PROTACs, LYTACs, AUTACs, and ATTECs. The development of these frontier technologies has opened new pathways for mitigating the limitations of existing inhibitors.</div></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"224 ","pages":"Article 108079"},"PeriodicalIF":10.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145834543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IUPHAR review: From foe to friend: Repurposing glucagon to treat obesity and type 2 diabetes","authors":"Andrew J. Elmendorf ,&nbsp;Mostafa Yousefian ,&nbsp;Il-Man Kim ,&nbsp;J. Andrew Hardaway ,&nbsp;Kirk Habegger ,&nbsp;Jonathan N. Flak","doi":"10.1016/j.phrs.2025.108077","DOIUrl":"10.1016/j.phrs.2025.108077","url":null,"abstract":"<div><div>The epidemics of metabolic disease, in the form of obesity and type 2 diabetes, are a growing public health concern. However, incretin-based therapeutics have transformed our ability to address these diseases. While this current generation of incretin analogues show weight regain upon cessation of treatment, the amount of which can depend on the treatment and patient, iterative advancements may improve weight loss durability in the long term. In this review, we discuss the development of glucagon like peptide-1 receptor (GLP-1R) agonists and GLP-1R/ glucose-dependent insulinotropic polypeptide receptor (GIPR) co-agonists, and how future generations will leverage this strategy. We focus our review on glucagon receptor (GCGR) agonism, which has recently been combined with both GLP-1R and GLP-1R/GIPR agonism to generate dual (e.g. survodutide, cotatutide, mazdutide, etc) and triple agonists (e.g. retatrutide, etc) for improved body weight loss via energy expenditure stimulation. We rely on largely pre-clinical evidence for action because clinical data is extremely limited for GCGR agonism. Herein, we review mechanisms by which glucagon receptor agonists act to increase energy expenditure. Finally, we discuss future improvements to incretin-based therapeutics, and how they can include strategies that target the GCGR. The purpose of this review is to discuss mechanisms by which GCGR agonism can reduce body weight and put them in the context of the combination with incretin receptor agonists. Mechanistic data has only currently been evaluated in preclinical rodent models and evidence for similar processes in humans is limited. We also provide perspectives about how treatments can improve for future advancement of obesity treatment.</div></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"223 ","pages":"Article 108077"},"PeriodicalIF":10.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145889625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}