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The multifaceted role of agents counteracting metabolic syndrome: A new hope for gastrointestinal cancer therapy 抗代谢综合征药物的多方面作用:胃肠道肿瘤治疗的新希望
IF 12 1区 医学
Pharmacology & Therapeutics Pub Date : 2025-04-10 DOI: 10.1016/j.pharmthera.2025.108847
Elena Crecca , Gianfranco Di Giuseppe , Claudia Camplone , Virginia Vigiano Benedetti , Ombretta Melaiu , Teresa Mezza , Chiara Cencioni , Francesco Spallotta
{"title":"The multifaceted role of agents counteracting metabolic syndrome: A new hope for gastrointestinal cancer therapy","authors":"Elena Crecca ,&nbsp;Gianfranco Di Giuseppe ,&nbsp;Claudia Camplone ,&nbsp;Virginia Vigiano Benedetti ,&nbsp;Ombretta Melaiu ,&nbsp;Teresa Mezza ,&nbsp;Chiara Cencioni ,&nbsp;Francesco Spallotta","doi":"10.1016/j.pharmthera.2025.108847","DOIUrl":"10.1016/j.pharmthera.2025.108847","url":null,"abstract":"<div><div>Metabolic syndrome (MetS) is defined by the presence of at least three of five clinical parameters including abdominal obesity, insulin resistance, elevated triglycerides, reduced high-density lipoprotein (HDL) and hypertension. Major features describing MetS have been recognized risk factors for cancer onset, with an alarming impact on gastrointestinal (GI) tumors. Intriguingly, therapeutic administration of drugs to improve glycemic control and dyslipidemia (including metformin, statins) has been shown to have a preventive role in the development and in prognosis improvement of several cancer types. Overall, these observations highlight the key role of altered metabolism prevalently in cancer risk development and unveil anti-MetS agent repurposing potential beyond their conventional pharmacological action. The objective of this review is to summarize the current knowledge about the antitumor activity of anti-diabetic and anti-lipemic agents in GI cancer onset and progression. Here, pre-clinical evidence of their therapeutic potential and of their integration in novel compelling therapeutic strategies will be discussed. Possible clinical outcomes of these novel therapeutic combined protocols specifically dedicated to GI cancer patients will be put under the spotlight. In the future, these novel therapeutic options should be considered to improve conventional chemotherapy response and prognosis of this group of patients.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"270 ","pages":"Article 108847"},"PeriodicalIF":12.0,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143855172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Where are we now? Biased signalling of Class B G protein-coupled receptor-targeted therapeutics 我们现在在哪里?B类G蛋白偶联受体靶向治疗的偏导信号
IF 12 1区 医学
Pharmacology & Therapeutics Pub Date : 2025-04-09 DOI: 10.1016/j.pharmthera.2025.108846
Zoe Tasma , Michael L. Garelja , Aqfan Jamaluddin , Tyla I. Alexander , Tayla A. Rees
{"title":"Where are we now? Biased signalling of Class B G protein-coupled receptor-targeted therapeutics","authors":"Zoe Tasma ,&nbsp;Michael L. Garelja ,&nbsp;Aqfan Jamaluddin ,&nbsp;Tyla I. Alexander ,&nbsp;Tayla A. Rees","doi":"10.1016/j.pharmthera.2025.108846","DOIUrl":"10.1016/j.pharmthera.2025.108846","url":null,"abstract":"<div><div>Class B G protein-coupled receptors (GPCRs) are a subfamily of 15 peptide hormone receptors with diverse roles in physiological functions and disease pathogenesis. Over the past decade, several novel therapeutics targeting these receptors have been approved for conditions like migraine, diabetes, and obesity, many of which are ground-breaking and first-in-class. Most of these therapeutics are agonist analogues with modified endogenous peptide sequences to enhance receptor activation or stability. Several small molecule and monoclonal antibody antagonists have also been approved or are in late-stage development. Differences in the sequence and structure of these therapeutic ligands lead to distinct signalling profiles, including biased behaviour or inhibition of specific pathways. Understanding this biased pharmacology offers unique development opportunities for improving therapeutic efficacy and reducing adverse effects. This review summarises current knowledge on the ligand bias of approved class B GPCR drugs, highlights strategies to refine and exploit their pharmacological profiles, and discusses key considerations related to receptor structure, localisation, and regulation for developing new therapies.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"270 ","pages":"Article 108846"},"PeriodicalIF":12.0,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143838373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
G-protein coupled receptors in metabolic reprogramming and cancer 代谢重编程和癌症中的g蛋白偶联受体
IF 12 1区 医学
Pharmacology & Therapeutics Pub Date : 2025-04-07 DOI: 10.1016/j.pharmthera.2025.108849
Songyeon Ahn , Benny Abraham Kaipparettu
{"title":"G-protein coupled receptors in metabolic reprogramming and cancer","authors":"Songyeon Ahn ,&nbsp;Benny Abraham Kaipparettu","doi":"10.1016/j.pharmthera.2025.108849","DOIUrl":"10.1016/j.pharmthera.2025.108849","url":null,"abstract":"<div><div>G-protein coupled receptors (GPCR) are one of the frequently investigated drug targets. GPCRs are involved in many human pathophysiologies that lead to various disease conditions, such as cancer, diabetes, and obesity. GPCR receptor activates multiple signaling pathways depending on the ligand and tissue type. However, this review will be limited to the GPCR-mediated metabolic modulations and the activation of relevant signaling pathways in cancer therapy. Cancer cells often have reprogrammed cell metabolism to support tumor growth and metastatic plasticity. Many aggressive cancer cells maintain a hybrid metabolic status, using both glycolysis and mitochondrial metabolism for better metabolic plasticity. In addition to glucose and glutamine pathways, fatty acid is a key mitochondrial energy source in some cancer subtypes. Recently, targeting alternative energy pathways like fatty acid beta-oxidation (FAO) has attracted great interest in cancer therapy. Several <em>in vitro</em> and <em>in vivo</em> experiments in different cancer models reported encouraging responses to FAO inhibitors. However, due to the potential liver toxicity of FAO inhibitors in clinical trials, new approaches to indirectly target metabolic reprogramming are necessary for <em>in vivo</em> targeting of cancer cells. This review specifically focused on free fatty acid receptors (FFAR) and β-adrenergic receptors (β-AR) because of their reported significance in mitochondrial metabolism and cancer. Further understanding the pharmacology of GPCRs and their role in cancer metabolism will help repurpose GPCR-targeting drugs for cancer therapy and develop novel drug discovery strategies to combine them with standard cancer therapy to increase anticancer potential and overcome drug resistance.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"270 ","pages":"Article 108849"},"PeriodicalIF":12.0,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143820425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Investigation into biased signaling, glycosylation, and drug vulnerability of acute myeloid leukemia 急性髓性白血病的偏倚信号、糖基化和药物易感性的研究。
IF 12 1区 医学
Pharmacology & Therapeutics Pub Date : 2025-04-05 DOI: 10.1016/j.pharmthera.2025.108848
Tomasz Pienkowski , Aleksandra Golonko , Lukasz Bolkun , Katarzyna Wawrzak-Pienkowska , Lukasz Szczerbinski , Adam Kretowski , Michal Ciborowski , Wlodzimierz Lewandowski , Waldemar Priebe , Renata Swislocka
{"title":"Investigation into biased signaling, glycosylation, and drug vulnerability of acute myeloid leukemia","authors":"Tomasz Pienkowski ,&nbsp;Aleksandra Golonko ,&nbsp;Lukasz Bolkun ,&nbsp;Katarzyna Wawrzak-Pienkowska ,&nbsp;Lukasz Szczerbinski ,&nbsp;Adam Kretowski ,&nbsp;Michal Ciborowski ,&nbsp;Wlodzimierz Lewandowski ,&nbsp;Waldemar Priebe ,&nbsp;Renata Swislocka","doi":"10.1016/j.pharmthera.2025.108848","DOIUrl":"10.1016/j.pharmthera.2025.108848","url":null,"abstract":"<div><div>Understanding and harnessing biased signaling offers significant potential for developing novel therapeutic strategies or enhancing existing treatments. By managing biased signaling, it is possible to minimize adverse effects, including toxicity, and to optimize therapeutic outcomes by selectively targeting beneficial pathways. In the context of acute myeloid leukemia (AML), a highly aggressive blood cancer characterized by the rapid proliferation of abnormal myeloid cells in the bone marrow and blood, the dysregulation of these signaling pathways, particularly those involving G protein-coupled receptors (GPCRs) and receptor tyrosine kinases (RTKs), significantly contributes to disease progression and therapeutic resistance. Traditional therapies for AML often struggle with resistance and toxicity, leading to poor patient outcomes. However, by exploiting the concept of biased signaling, researchers may be able to design drugs that selectively activate pathways that inhibit cancer cell growth while avoiding those that contribute to resistance or toxicity. Glycosylation, a key post-translational modification (PTM), plays a crucial role in biased signaling by altering receptor conformation and ligand-binding affinity, thereby affecting the outcome of biased signaling. Chemokine receptors like CXCR4, which are often overexpressed and heavily glycosylated in AML, serve as targets for therapeutic intervention. By externally inducing or inhibiting specific PTMs, it may be possible to further refine therapeutic strategies, unlocking new possibilities for developing more effective and less toxic treatments. This review highlights the importance of understanding the dynamic relationship between glycosylation and biased signaling in AML, which is essential for the development of more effective treatments and overcoming drug resistance, ultimately leading to better patient outcomes.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"270 ","pages":"Article 108848"},"PeriodicalIF":12.0,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Fibroblast growth factor receptor signaling in metabolic dysfunction-associated fatty liver disease: Pathogenesis and therapeutic targets 代谢功能障碍相关脂肪肝的成纤维细胞生长因子受体信号:发病机制和治疗靶点
IF 12 1区 医学
Pharmacology & Therapeutics Pub Date : 2025-03-18 DOI: 10.1016/j.pharmthera.2025.108844
Yi Chu, Su Yang, Xiaodong Chen
{"title":"Fibroblast growth factor receptor signaling in metabolic dysfunction-associated fatty liver disease: Pathogenesis and therapeutic targets","authors":"Yi Chu,&nbsp;Su Yang,&nbsp;Xiaodong Chen","doi":"10.1016/j.pharmthera.2025.108844","DOIUrl":"10.1016/j.pharmthera.2025.108844","url":null,"abstract":"<div><div>Metabolic dysfunction-associated fatty liver disease (MAFLD) has emerged as a significant hepatic manifestation of metabolic syndrome, with its prevalence increasing globally alongside the epidemics of obesity and diabetes. MAFLD represents a continuum of liver damage, spanning from uncomplicated steatosis to metabolic dysfunction-associated steatohepatitis (MASH). This condition can advance to more severe outcomes, including fibrosis and cirrhosis. Fibroblast growth factor receptors (FGFRs) are a family of four receptor tyrosine kinases (FGFR1–4) that interact with both paracrine and endocrine fibroblast growth factors (FGFs). This interaction activates the phosphorylation of tyrosine kinase residues, thereby triggering downstream signaling pathways, including RAS-MAPK, JAK-STAT, PI3K-AKT, and PLCγ. In the context of MAFLD, paracrine FGF-FGFR signaling is predominantly biased toward the development of liver fibrosis and carcinogenesis. In contrast, endocrine FGF-FGFR signaling is primarily biased toward regulating the metabolism of bile acids, carbohydrates, lipids, and phosphate, as well as maintaining the overall balance of energy metabolism in the body. The interplay between these biased signaling pathways significantly influences the progression of MAFLD. This review explores the critical functions of FGFR signaling in MAFLD from three perspectives: first, it examines the primary roles of FGFRs relative to their structure; second, it summarizes FGFR signaling in hepatic lipid metabolism, elucidating mechanisms underlying the occurrence and progression of MAFLD; finally, it highlights recent advancements in drug development aimed at targeting FGFR signaling for the treatment of MAFLD and its associated diseases.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"269 ","pages":"Article 108844"},"PeriodicalIF":12.0,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143668685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Plant-derived nanovesicles and therapeutic application 植物源性纳米囊泡及其治疗应用。
IF 12 1区 医学
Pharmacology & Therapeutics Pub Date : 2025-02-27 DOI: 10.1016/j.pharmthera.2025.108832
Dokyung Jung , Na-Eun Kim , Sua Kim , Ju-Hyun Bae , Il-Young Jung , Kyung-Won Doh , Byungheon Lee , Do-Kyun Kim , Young-Eun Cho , Moon-Chang Baek
{"title":"Plant-derived nanovesicles and therapeutic application","authors":"Dokyung Jung ,&nbsp;Na-Eun Kim ,&nbsp;Sua Kim ,&nbsp;Ju-Hyun Bae ,&nbsp;Il-Young Jung ,&nbsp;Kyung-Won Doh ,&nbsp;Byungheon Lee ,&nbsp;Do-Kyun Kim ,&nbsp;Young-Eun Cho ,&nbsp;Moon-Chang Baek","doi":"10.1016/j.pharmthera.2025.108832","DOIUrl":"10.1016/j.pharmthera.2025.108832","url":null,"abstract":"<div><div>Plant-derived nanovesicles (PDNVs) are becoming more popular as promising therapeutic tools owing to their diversity, cost-effectiveness, and biocompatibility with very low toxicity. Therefore, this review aims to discuss the methods for isolating and characterizing PDNVs and emphasize their versatile roles in direct therapeutic applications and drug delivery systems. Their ability to effectively encapsulate and deliver large nucleic acids, proteins, and small-molecule drugs was highlighted. Moreover, advanced engineering strategies, such as surface modification and fusion with other vesicles, have been developed to enhance the therapeutic effects of PDNVs. Additionally, we describe key challenges related to this field, encouraging further research to optimize PDNVs for various clinical applications for prevention and therapeutic purposes. The distinctive properties and diverse applications of PDNVs could play a crucial role in the future of personalized medicine, fostering the development of innovative therapeutic strategies.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"269 ","pages":"Article 108832"},"PeriodicalIF":12.0,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536358","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}
引用次数: 0
Understanding the regulatory landscape of protein phosphatase 2A (PP2A): Pharmacological modulators and potential therapeutics 了解蛋白磷酸酶2A (PP2A)的调控景观:药理学调节剂和潜在的治疗方法。
IF 12 1区 医学
Pharmacology & Therapeutics Pub Date : 2025-02-27 DOI: 10.1016/j.pharmthera.2025.108834
David A. Neale , Jonathan C. Morris , Nicole M. Verrills , Alaina J. Ammit
{"title":"Understanding the regulatory landscape of protein phosphatase 2A (PP2A): Pharmacological modulators and potential therapeutics","authors":"David A. Neale ,&nbsp;Jonathan C. Morris ,&nbsp;Nicole M. Verrills ,&nbsp;Alaina J. Ammit","doi":"10.1016/j.pharmthera.2025.108834","DOIUrl":"10.1016/j.pharmthera.2025.108834","url":null,"abstract":"<div><div>Protein phosphatase 2A (PP2A) is a ubiquitously expressed serine/threonine phosphatase with a diverse and integral role in cellular signalling pathways. Consequently, its dysfunction is frequently observed in disease states such as cancer, inflammation and Alzheimer’s disease. A growing understanding of both PP2A and its endogenous regulatory proteins has presented numerous targets for therapeutic intervention. This provides important context for the dynamic control and dysregulation of PP2A function in disease states. Understanding the intricate regulation of PP2A signalling in disease has resulted in the development of novel pharmacological agents aimed at restoring cellular homeostasis. Herein we review the structure and function of PP2A together with pharmacological modulators, both endogenous (proteins) and exogenous (small molecules and peptides), with relevance to targeting PP2A as a future pharmacotherapeutic strategy.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"269 ","pages":"Article 108834"},"PeriodicalIF":12.0,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Receptor dimers and biased ligands: Novel strategies for targeting G protein-coupled receptors 受体二聚体和偏置配体:靶向G蛋白偶联受体的新策略。
IF 12 1区 医学
Pharmacology & Therapeutics Pub Date : 2025-02-27 DOI: 10.1016/j.pharmthera.2025.108829
Wenkai Liu , Dexiu Wang , Luoqi Wang , Shujuan Hu , Yunlu Jiang , Yixiang Wang , Xin Cai , Jing Chen
{"title":"Receptor dimers and biased ligands: Novel strategies for targeting G protein-coupled receptors","authors":"Wenkai Liu ,&nbsp;Dexiu Wang ,&nbsp;Luoqi Wang ,&nbsp;Shujuan Hu ,&nbsp;Yunlu Jiang ,&nbsp;Yixiang Wang ,&nbsp;Xin Cai ,&nbsp;Jing Chen","doi":"10.1016/j.pharmthera.2025.108829","DOIUrl":"10.1016/j.pharmthera.2025.108829","url":null,"abstract":"<div><div>G protein-coupled receptors (GPCRs) are the largest superfamily of membrane receptors. They regulate physiological and pathological processes such as metabolic homeostasis, cell proliferation and differentiation, and the immune response, and are one of the most important classes of drug targets, being targeted by 30–40 % of marketed drugs. A growing number of studies continue to reveal the complexity of GPCRs, especially their ability to interact with each other to form higher-order structures such as homodimers and heterodimers, which have different functions than monomers, and are involved in disease development and progression. The existence of GPCR homodimers and heterodimers is opening up new directions in drug discovery and development to harness their therapeutic potential. Particularly striking is the ability of GPCR dimers to trigger unique biased signalling pathways, which exquisitely balance the relationship between therapeutic effects and side effects. By suppressing adverse reactions and enhancing beneficial drug effects, GPCR dimers provide an unprecedented opportunity to minimise side effects, maximise therapeutic efficacy and enhance safety. This review aims to highlight the latest research advances in GPCR dimerization and GPCR-biased signalling, focusing on the development of dimer-targeting and biased ligands as innovative drugs that will likely provide new strategies for treating GPCR-related diseases as well as a better understanding of drug design for compounds that target GPCRs. GPCRs will play an increasingly important role in precision medicine and personalised therapy, leading us towards a safer, more efficient and smarter pharmaceutical future.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"269 ","pages":"Article 108829"},"PeriodicalIF":12.0,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Inflammatory bowel disease and neuropsychiatric disorders: Mechanisms and emerging therapeutics targeting the microbiota-gut-brain axis 炎症性肠病和神经精神疾病:针对微生物-肠-脑轴的机制和新兴治疗方法。
IF 12 1区 医学
Pharmacology & Therapeutics Pub Date : 2025-02-27 DOI: 10.1016/j.pharmthera.2025.108831
Giulia Petracco , Isabella Faimann , Florian Reichmann
{"title":"Inflammatory bowel disease and neuropsychiatric disorders: Mechanisms and emerging therapeutics targeting the microbiota-gut-brain axis","authors":"Giulia Petracco ,&nbsp;Isabella Faimann ,&nbsp;Florian Reichmann","doi":"10.1016/j.pharmthera.2025.108831","DOIUrl":"10.1016/j.pharmthera.2025.108831","url":null,"abstract":"<div><div>Crohn's disease (CD) and ulcerative colitis (UC) are the two major entities of inflammatory bowel disease (IBD). These disorders are known for their relapsing disease course and severe gastrointestinal symptoms including pain, diarrhoea and bloody stool. Accumulating evidence suggests that IBD is not only restricted to the gastrointestinal tract and that disease processes are able to reach distant organs including the brain. In fact, up to 35 % of IBD patients also suffer from neuropsychiatric disorders such as generalized anxiety disorder and major depressive disorder. Emerging research in this area indicates that in many cases these neuropsychiatric disorders are a secondary condition as a consequence of the disturbed communication between the gut and the brain via the microbiota-gut-brain axis. In this review, we summarise the current knowledge on IBD-associated neuropsychiatric disorders. We examine the role of different pathways of the microbiota-gut-brain axis in the development of CNS disorders highlighting altered neural, immunological, humoral and microbial communication. Finally, we discuss emerging therapies targeting the microbiota-gut-brain axis to alleviate IBD and neuropsychiatric symptoms including faecal microbiota transplantation, psychobiotics, microbial metabolites and vagus nerve stimulation.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"269 ","pages":"Article 108831"},"PeriodicalIF":12.0,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536356","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}
引用次数: 0
Improvement of chronic metabolic inflammation and regulation of gut homeostasis: Tea as a potential therapy 改善慢性代谢性炎症和调节肠道稳态:茶是一种潜在的治疗方法。
IF 12 1区 医学
Pharmacology & Therapeutics Pub Date : 2025-02-26 DOI: 10.1016/j.pharmthera.2025.108828
Shiyi Yu , Xuan Zhu , Xiayu Zhao , Yan Li , Xinghe Niu , Yinghua Chen , Jian Ying
{"title":"Improvement of chronic metabolic inflammation and regulation of gut homeostasis: Tea as a potential therapy","authors":"Shiyi Yu ,&nbsp;Xuan Zhu ,&nbsp;Xiayu Zhao ,&nbsp;Yan Li ,&nbsp;Xinghe Niu ,&nbsp;Yinghua Chen ,&nbsp;Jian Ying","doi":"10.1016/j.pharmthera.2025.108828","DOIUrl":"10.1016/j.pharmthera.2025.108828","url":null,"abstract":"<div><div>Chronic metabolic inflammation is a common mechanism linked to the development of metabolic disorders such as obesity, diabetes, and cardiovascular disease (CVD). Chronic metabolic inflammation often related to alterations in gut homeostasis, and pathological processes involve the activation of endotoxin receptors, metabolic reprogramming, mitochondrial dysfunction, and disruption of intestinal nuclear receptor activity. Recent investigations into homeostasis and chronic metabolic inflammation have revealed a novel mechanism which is characterized by a timing interaction involving multiple components and targets. This article explores the positive impact of tea consumption on metabolic health of populations, with a special focus on the improvement of inflammatory indicators and the regulation of gut microbiota. Studies showed that tea consumption is related to the enrichment of gut microbiota. The relative proportion of Firmicutes/Bacteroidetes (F/B) is altered, while the abundance of <em>Lactobacillus</em>, <em>Bifidobacterium</em>, and <em>A. muciniphila</em> increased significantly in most of the studies. Thus, tea consumption could provide potential protection from the development of chronic diseases by improving gut homeostasis and reducing chronic metabolic inflammation. The direct impact of tea on intestinal homeostasis primarily targets lipopolysaccharide (LPS)-related pathways. This includes reducing the synthesis of intestinal LPS, inhibiting LPS translocation, and preventing the binding of LPS to TLR4 receptors to block downstream inflammatory pathways. The TLR4/MyD88/NF-κB p65 pathway is crucial for anti-metaflammatory responses. The antioxidant properties of tea are linked to enhancing mitochondrial function and mitigating mitochondria-related inflammation by eliminating free radicals, inhibiting NLRP3 inflammasomes, and modulating Nrf2/ARE activity. Tea also contributes to safeguarding the intestinal barrier through various mechanisms, such as promoting the synthesis of short-chain fatty acids in the intestine, activating intestinal aryl hydrocarbon receptor (AhR) and farnesoid X receptor (FXR), and improving enteritis. Functional components that improve chronic metabolic inflammation include tea polyphenols, tea pigments, TPS, etc. Tea metabolites such as 4-Hydroxyphenylacetic acid and 3,4-Dihydroxyflavan derivatives, etc., also contribute to anti-chronic metabolic inflammation effects of tea consumption. The raw materials and processing technologies affect the functional component compositions of tea; therefore, consuming different types of tea may result in varying action characteristics and mechanisms. However, there is currently limited elaboration on this aspect. Future research should conduct in-depth studies on the mechanism of tea and its functional components in improving chronic metabolic inflammation. Researchers should pay attention to whether there are interactions between tea and other foods or drugs, explor","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"269 ","pages":"Article 108828"},"PeriodicalIF":12.0,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143530825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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