Basic & Clinical Pharmacology & Toxicology最新文献_第3页

Eriocitrin Attenuates Diabetic Cardiomyopathy by Regulating Copper Homeostasis and Cuproptosis-Associated Pathways via SIRT7/YAP/ATP7A Signalling ericitrin通过SIRT7/YAP/ATP7A信号通路调节铜稳态和铜中毒相关通路，减轻糖尿病心肌病

IF 3.6 4区医学

Basic & Clinical Pharmacology & Toxicology Pub Date : 2026-09-15 DOI: 10.1111/bcpt.70301

Lin Chen, Sixin Mao, Yan Yu, Dingyong Zhang, Zixia Fan

{"title":"Eriocitrin Attenuates Diabetic Cardiomyopathy by Regulating Copper Homeostasis and Cuproptosis-Associated Pathways via SIRT7/YAP/ATP7A Signalling","authors":"Lin Chen, Sixin Mao, Yan Yu, Dingyong Zhang, Zixia Fan","doi":"10.1111/bcpt.70301","DOIUrl":"10.1111/bcpt.70301","url":null,"abstract":"<div>\u0000 \u0000 Diabetic cardiomyopathy (DCM) is a major complication of diabetes mellitus, with limited therapeutic strategies available. Cuproptosis, a novel form of copper-dependent cell death, has been implicated in cardiac dysfunction but remains unexplored in DCM. Here, we investigated the effects of Eriocitrin, a natural flavonoid, on DCM and examined the potential involvement of copper homeostasis, cuproptosis-associated molecular alterations and SIRT7/YAP/ATP7A signalling. Using high-fat diet and streptozotocin-induced diabetic mice, along with high-glucose-treated cardiomyocytes, we demonstrated that Eriocitrin improved cardiac function, attenuated myocardial remodelling and corrected glucose and lipid metabolism. Mechanistically, Eriocitrin improved myocardial copper homeostasis by enhancing ATP7A and ATP7B expression and reducing copper accumulation and cuproptosis-associated molecular alterations. Loss of SIRT7 impaired these effects, suggesting that SIRT7-associated YAP/ATP7A signalling contributes to Eriocitrin-mediated cardioprotection. The therapeutic efficacy of Eriocitrin showed similar protective trends to tetrathiomolybdate, a copper chelator. These findings suggest that Eriocitrin alleviates experimental DCM in association with improved myocardial copper homeostasis and attenuation of cuproptosis-associated molecular alterations, with SIRT7-associated YAP/ATP7A signalling potentially contributing to these effects.\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"139 4","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148966334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Evasins: Biology and Therapeutic Potential of Broad-Spectrum Chemokine Inhibitors 广谱趋化因子抑制剂的生物学和治疗潜力。

IF 3.6 4区医学

Basic & Clinical Pharmacology & Toxicology Pub Date : 2026-09-10 DOI: 10.1111/bcpt.70281

Emilia L. Bialek, Roos Buds, Ingrid Dijkgraaf, Pedro E. Marques

引用次数: 0

Abstracts for Nordic Conference on Future Health 2026 2026年北欧未来健康会议（NCFH 2026）， 2026年9月14-16日，丹麦哥本哈根。

IF 3.6 4区医学

Basic & Clinical Pharmacology & Toxicology Pub Date : 2026-09-10 DOI: 10.1111/bcpt.70280

引用次数: 0

Fluoride as a Modifier of Metallome Homeostasis: A Systematic Review of Animal Studies 氟化物作为金属组内平衡调节剂：动物研究的系统综述。

IF 3.6 4区医学

Basic & Clinical Pharmacology & Toxicology Pub Date : 2026-09-04 DOI: 10.1111/bcpt.70295

Natalia Macedo-Ribeiro, Jonas Tostes-Figueiredo, Davi da Silva Barbirato, Isabel Maria Porto, Eliude Barbosa Gomes, Erico Marlon Moraes Flores, Marília Afonso Rabelo Buzalaf, Fernando Barbosa Jr, Raquel Fernanda Gerlach

{"title":"Fluoride as a Modifier of Metallome Homeostasis: A Systematic Review of Animal Studies","authors":"Natalia Macedo-Ribeiro, Jonas Tostes-Figueiredo, Davi da Silva Barbirato, Isabel Maria Porto, Eliude Barbosa Gomes, Erico Marlon Moraes Flores, Marília Afonso Rabelo Buzalaf, Fernando Barbosa Jr, Raquel Fernanda Gerlach","doi":"10.1111/bcpt.70295","DOIUrl":"10.1111/bcpt.70295","url":null,"abstract":"Fluoride is widely used for caries prevention due to its effects on mineralized tissues, yet its potential role as a modifier of systemic metal homeostasis remains insufficiently explored. This systematic review synthesizes preclinical evidence on the association between fluoride exposure and changes in metal and semi-metal concentrations across biological matrices. A comprehensive search strategy was conducted across major databases without language or date restrictions, following SyRF, CAMARADES and PRISMA 2020 guidelines. Thirty-one animal studies were included, encompassing multiple species, exposure conditions and analytical approaches. Despite substantial methodological heterogeneity, consistent patterns emerged. Fluoride exposure was associated with element-specific redistribution of the metallome rather than uniform change. Essential elements were predominantly depleted, most consistently zinc, copper and manganese, whereas the toxic metals lead and cadmium tended to be retained. This contrast between homeostatically regulated essential elements that are lost and non-regulated toxic metals that accumulate supports the hypothesis that fluoride differentially modifies the distribution and retention of co-existing elements. The novelty of this review lies in integrating metallomic outcomes across experimental models, highlighting fluoride as a potential systemic modulator rather than a tissue-specific agent. Although variability in study design and risk of bias limits causal inference, the consistent directionality of findings across models reinforces their biological plausibility and translational relevance.","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"139 4","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13543053/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148890854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Effects of Trazodone on Testicular Morphology, Sperm Parameters and Contractility of the Distal Cauda Epididymal Duct in Rats 曲唑酮对大鼠睾丸形态、精子参数及附睾远尾管收缩性的影响。

IF 3.6 4区医学

Basic & Clinical Pharmacology & Toxicology Pub Date : 2026-09-04 DOI: 10.1111/bcpt.70302

Maria Santana da Silva, Vitória Barros Marques, Fernanda Karoline Oliveira da Silva, Maele Oliveira de Sena, Yanka do Vale Carvalho, Bruna da Silva Figueiredo, Luana Talinne da Costa Gomes, Samia Ellen Alves Fernandes, Edherlayne Bezerra dos Santos Silva, Jackson Nazareno Gomes de Lima, Anna Karynna Alves de Alencar Rocha, Expedito Silva do Nascimento Junior, Elaine Cristina Gavioli, Edilson Dantas da Silva Junior

{"title":"Effects of Trazodone on Testicular Morphology, Sperm Parameters and Contractility of the Distal Cauda Epididymal Duct in Rats","authors":"Maria Santana da Silva, Vitória Barros Marques, Fernanda Karoline Oliveira da Silva, Maele Oliveira de Sena, Yanka do Vale Carvalho, Bruna da Silva Figueiredo, Luana Talinne da Costa Gomes, Samia Ellen Alves Fernandes, Edherlayne Bezerra dos Santos Silva, Jackson Nazareno Gomes de Lima, Anna Karynna Alves de Alencar Rocha, Expedito Silva do Nascimento Junior, Elaine Cristina Gavioli, Edilson Dantas da Silva Junior","doi":"10.1111/bcpt.70302","DOIUrl":"10.1111/bcpt.70302","url":null,"abstract":"Trazodone is an antidepressant approved for the treatment of major depressive disorder and is associated with a low incidence of sexual dysfunction. However, its effects on male reproductive health are not yet fully understood. Therefore, this study aimed to evaluate the effects of repeated trazodone administration on reproductive parameters and the distal cauda epididymal duct contractions in rats. Adult male Wistar rats were orally treated by gavage for 21 days with saline (control) or trazodone at 10 and 20 mg/kg. After treatment, the blood and reproductive organs were collected for the experimental analysis. Trazodone induced adverse reproductive effects in rats, evidenced by testicular tissue damage, increased intratesticular lipid peroxidation and reduced sperm production and sperm count in different epididymal regions. Additionally, trazodone treatment reduced progressive sperm motility, the number of viable and morphologically normal sperm, indicating decreased sperm quality. The contraction of the isolated distal cauda epididymal duct was also impaired by trazodone treatment, suggesting possible alterations during the emission phase of ejaculation. In conclusion, trazodone exhibited significant reproductive effects that may impair male fertility. These findings provide, to our knowledge, the first integrated assessment of trazodone-induced changes in testicular morphology, sperm parameters and epididymal duct contractility.","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"139 4","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13543052/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148890910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

The Crosstalk Between Diabetes and Alzheimer's Disease: A Molecular Perspective 糖尿病和阿尔茨海默病之间的串扰：分子视角。

IF 3.6 4区医学

Basic & Clinical Pharmacology & Toxicology Pub Date : 2026-09-03 DOI: 10.1111/bcpt.70294

Deniz Catakli, Ozlem Ozen-Basoglu, Ebru Busra Tuncgovde, Gonen Ozsarlak-Sozer

{"title":"The Crosstalk Between Diabetes and Alzheimer's Disease: A Molecular Perspective","authors":"Deniz Catakli, Ozlem Ozen-Basoglu, Ebru Busra Tuncgovde, Gonen Ozsarlak-Sozer","doi":"10.1111/bcpt.70294","DOIUrl":"10.1111/bcpt.70294","url":null,"abstract":"The global prevalence of type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) is increasing significantly in an age-dependent manner. Growing evidence supports the conceptualization of AD as ‘type 3 diabetes,’ a term proposed to describe a metabolic disease primarily driven by impaired insulin signalling and insulin resistance within the brain. This review explores the shared molecular mechanisms underlying both T2DM and AD, including chronic neuroinflammation, oxidative stress, mitochondrial dysfunction and impaired glucose metabolism. Specifically, the crosstalk involves the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway, where insulin resistance leads to increased glycogen synthase kinase 3β (GSK-3β) activity, promoting tau hyperphosphorylation and amyloid-β (Aβ) accumulation. Furthermore, the article examines the roles of the NOD-like receptor protein 3 (NLRP3) inflammasome, O-linked β-N-acetylglucosamine modification (O-GlcNAcylation), and the gut–brain axis as critical mediators linking metabolic dysfunction to neurodegeneration. Unlike previous reviews that predominantly address individual pathways in isolation, this review provides an integrated molecular framework that connects insulin resistance to neurodegeneration through converging signalling cascades and highlights emerging therapeutic targets including the NLRP3 inflammasome and O-GlcNAcylation as potential mechanistic bridges between T2DM and AD. Finally, the therapeutic potential of various antidiabetic agents such as glucagon-like peptide-1 (GLP-1) receptor agonists, sodium-glucose cotransporter-2 (SGLT-2) inhibitors and thiazolidinediones is discussed, as these drugs offer promising opportunities for the treatment and prevention of AD by targeting these common molecular pathways.","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"139 4","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13542629/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148885993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Macrophage FOXO1 Inhibition Protects Against Hyperglycaemia-Associated Kidney Injury 巨噬细胞FOXO1抑制对高血糖相关性肾损伤的保护作用

IF 3.6 4区医学

Basic & Clinical Pharmacology & Toxicology Pub Date : 2026-09-03 DOI: 10.1111/bcpt.70296

Hejie Zhu, Qian Liu, Lunqiang Yang, Chenyu Zhang, Ying Zhang, Ruiqi Zhao, Zhongyuan Zheng, Xi Wang, Linlin Li, Long Zhang, Lu Tie

{"title":"Macrophage FOXO1 Inhibition Protects Against Hyperglycaemia-Associated Kidney Injury","authors":"Hejie Zhu, Qian Liu, Lunqiang Yang, Chenyu Zhang, Ying Zhang, Ruiqi Zhao, Zhongyuan Zheng, Xi Wang, Linlin Li, Long Zhang, Lu Tie","doi":"10.1111/bcpt.70296","DOIUrl":"10.1111/bcpt.70296","url":null,"abstract":"<div>\u0000 \u0000 Diabetic kidney disease (DKD) is one of the most significant microvascular complications of diabetes, characterized by high incidence and mortality; however, its pathogenesis remains unclear. Renal inflammation and macrophage infiltration play pivotal roles in driving DKD progression. The transcription factor forkhead box protein O1 (FOXO1) regulates the transcriptional expression of multiple pro-inflammatory molecules and modulates macrophage polarization. Nevertheless, its specific role in DKD macrophages remains unknown. In vivo, streptozotocin-induced DKD mice showed significantly higher FOXO1 expression in infiltrated kidney macrophages. Treatment with the FOXO1-selective inhibitor AS1842856 for 4 or 12 weeks reduced serum creatinine, blood urea nitrogen, renal matrix collagen deposition and the severity of macrophage infiltration in DKD mice. In vitro, using mouse bone marrow–derived macrophages and RAW264.7 cells cultured under high glucose, we found that high glucose promoted pro-inflammatory M1 macrophage polarization. This polarization process was effectively blocked by either AS1842856 treatment or FOXO1 small interfering RNA-mediated gene silencing. In summary, FOXO1 critically regulates macrophage infiltration and functional phenotype in DKD-affected renal tissue. Targeting FOXO1 therefore holds promise as a potential therapeutic strategy to delay DKD progression.\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"139 4","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148886066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Hypotonicity-Induced WNK1 Phosphorylation Prevents H2O2-Induced Apoptosis in Vascular Smooth Muscle Cells 低张力诱导的WNK1磷酸化阻止h2o2诱导的血管平滑肌细胞凋亡。

IF 3.6 4区医学

Basic & Clinical Pharmacology & Toxicology Pub Date : 2026-08-31 DOI: 10.1111/bcpt.70299

Yajuan Zhang, Wei Lin, Fengting Lu, Zhujun Liang, Chengcui Huang, Ma mingming, Liang Sijia, Pang Ruiping, Jiaguo Zhou, Yongyuan Guan, Guozheng Liang, Xiaofei Lv

{"title":"Hypotonicity-Induced WNK1 Phosphorylation Prevents H2O2-Induced Apoptosis in Vascular Smooth Muscle Cells","authors":"Yajuan Zhang, Wei Lin, Fengting Lu, Zhujun Liang, Chengcui Huang, Ma mingming, Liang Sijia, Pang Ruiping, Jiaguo Zhou, Yongyuan Guan, Guozheng Liang, Xiaofei Lv","doi":"10.1111/bcpt.70299","DOIUrl":"10.1111/bcpt.70299","url":null,"abstract":"<div>\u0000 \u0000 Vascular smooth muscle cells (VSMCs) are essential for maintaining arterial wall integrity, with their associated apoptosis critically involved in cardiovascular diseases. Intracellular chloride anion (Cl−) dysregulation is closely linked to apoptosis. However, the underlying mechanism via chloride-sensitive kinases remains unclear. Here, we show that hypotonic stimulation activates volume-regulated chloride channels (VRCCs) and induces the phosphorylation of the chloride-sensitive kinase WNK1. Activated WNK1 protects VSMCs against H2O2-induced apoptosis by maintaining the Bcl-2/Bax balance, preserving mitochondrial membrane potential and inhibiting caspase-9/3 activation. These findings uncover a novel protective role of WNK1 in VRCC-mediated Cl− signalling and provide new perspectives for targeting chloride-sensitive kinases in the treatment of hypertension and related cardiovascular diseases.\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"139 4","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Regional Variation in ADHD Treatment and Diagnosis Among Children and Adolescents in Denmark 丹麦儿童和青少年ADHD治疗和诊断的地区差异。

IF 3.6 4区医学

Basic & Clinical Pharmacology & Toxicology Pub Date : 2026-08-30 DOI: 10.1111/bcpt.70298

Heidi Sonne, Anton Pottegård, Anna Sofie Kjærgaard Hansen, Mickael Bech, Helene Kildegaard

{"title":"Regional Variation in ADHD Treatment and Diagnosis Among Children and Adolescents in Denmark","authors":"Heidi Sonne, Anton Pottegård, Anna Sofie Kjærgaard Hansen, Mickael Bech, Helene Kildegaard","doi":"10.1111/bcpt.70298","DOIUrl":"10.1111/bcpt.70298","url":null,"abstract":"Geographic variation in ADHD treatment and diagnosis among children and adolescents is well documented, yet the system-level factors driving such differences remain poorly understood. We examined nationwide patterns of ADHD medication use and diagnoses in Denmark in 2024 and assessed whether municipal socioeconomy, regional hospital waiting times or private child psychiatrist capacity contributed to geographic variation. In this register-based cross-sectional study, we included all Danish residents aged 4–17 years using data from national registers. Pharmacological treatment was defined as at least one redeemed prescription for ADHD drugs, and diagnosis was defined as at least one hospital contact with ICD-10 codes F90.x/F98.8. Prevalence was calculated overall and stratified by sex and age, with associations explored using Spearman's rank correlations and regression analyses. ADHD medication prevalence varied sixfold across municipalities (9.6–58 per 1000), with parallel variation in diagnoses (15–74 per 1000) and the largest differences observed among adolescents. Municipal socioeconomic status was weakly and inversely correlated with medication use (ρ = −0.20, p = 0.049), but not diagnoses. Neither waiting times nor specialist capacity was significantly associated with either outcome. Marked geographic variation in ADHD medication use and diagnoses persists in Denmark despite a uniform healthcare framework, and appears largely unexplained by the system-level factors examined.","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"139 4","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13526647/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148860371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Plant-Derived Heterocyclic Compounds: A Promising Review on Natural Remedies for Rheumatoid Arthritis Management and Their Mechanistic Insights in Inflammation and Joint Protection 植物衍生的杂环化合物：类风湿性关节炎治疗的自然疗法及其炎症和关节保护的机制综述

IF 3.6 4区医学

Basic & Clinical Pharmacology & Toxicology Pub Date : 2026-08-27 DOI: 10.1111/bcpt.70292

Jindong Dai, Xue Xia, Xincheng Hu, Thangamani Kanagaraj, Kanagaraj Rajalakshmi, Mangirish Deshpande, Natarajan Kiruthiga, Dongwei Zhu, Yisun Fan

{"title":"Plant-Derived Heterocyclic Compounds: A Promising Review on Natural Remedies for Rheumatoid Arthritis Management and Their Mechanistic Insights in Inflammation and Joint Protection","authors":"Jindong Dai, Xue Xia, Xincheng Hu, Thangamani Kanagaraj, Kanagaraj Rajalakshmi, Mangirish Deshpande, Natarajan Kiruthiga, Dongwei Zhu, Yisun Fan","doi":"10.1111/bcpt.70292","DOIUrl":"https://doi.org/10.1111/bcpt.70292","url":null,"abstract":"Rheumatoid arthritis (RA) represents a persistent autoimmune disease that causes continuous joint inflammation and results in synovial tissue overgrowth and worsening cartilage breakdown together with degeneration of bones. The existing pharmaceutical treatments provide symptom management although they create important adverse effects and raise ongoing security concerns. Plant-derived heterocyclic compounds present themselves as promising pharmaceutical substitution options because they demonstrate a wide spectrum of bioactivities that include anti-inflammatory protection together with immunomodulatory and antioxidative properties. This review investigates the therapeutic properties of natural heterocyclic compounds principally including flavonoids, alkaloids, coumarins and terpenoids for RA treatment. Medical plants contain these abundant compounds that adjust inflammatory pathways consisting of NF-κB, MAPK and JAK/STAT to decrease pro-inflammatory cytokines TNF-α, IL-1β and IL-6 and restrict synovial fibroblast proliferation. The heterocyclic compounds found in medicinal plants also protect joints through two mechanisms: by improving antioxidant defences and activating cartilage repair. In addition to laboratory and animal test results the study evaluates how these natural compounds work together when combined in treatment plans. Research into structure–activity interactions of heterocyclic compounds alongside their molecular targets enables better development of safe plant-derived drugs. The research review demonstrates that plant-derived heterocyclic compounds need to become essential components in treating RA while promoting clinical studies to determine their human subject action and mechanism of operation.","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"139 4","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70292","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148816628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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