Chemical Biology & Drug Design最新文献

{"title":"The Development of Selective Chemical Probes for Serine Arginine Protein Kinase 3","authors":"Danielle Hanke,&nbsp;Conall McCutcheon,&nbsp;Brent D. G. Page","doi":"10.1111/cbdd.70101","DOIUrl":"https://doi.org/10.1111/cbdd.70101","url":null,"abstract":"<p>The serine arginine protein kinases (SRPKs) are a family of kinases whose irregular function is implicated in cancer and viral infections. While the roles of SRPK1 and SRPK2 in disease are well established, much less is known about SRPK3. There are several studies implicating SRPK3 in breast cancer, but the mechanism is still unknown. This work describes the first-reported SRPK3 chemical probes that show excellent selectivity over the other SRPKs. 1-(4-cyanophenyl)-3-phenylurea was identified as an initial hit for SRPK3 through a kinase screen. Subsequent rounds of in silico docking, medicinal chemistry optimization, and biochemical assays were performed to increase its potency and selectivity for SRPK3. Six top compounds were identified that displayed single digit micromolar IC₅₀ values in SRPK3 activity assays and negligible inhibition of SRPK1 or SRPK2. These six compounds demonstrated impairment of breast cancer cell viability that correlated with their biochemical IC₅₀ values, suggesting that they can be used as tools to study the biological functions of SRPK3 in breast cancer. With an enhanced understanding of SRPK3's biological function, it may emerge as a meaningful drug target, wherein our top inhibitors could be further optimized to produce novel cancer therapeutics.</p>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 4","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cbdd.70101","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762052","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}

{"title":"Tanshinone IIA Ameliorates Myocardial Ischemia–Reperfusion Injury via Activating HDAC1-Repressed Nrf2-xCT/Gpx4/HO-1 Axis","authors":"Ke Yan,&nbsp;Shenghui Yu,&nbsp;Xiang Gao,&nbsp;Lei Li,&nbsp;Li Ding","doi":"10.1111/cbdd.70095","DOIUrl":"https://doi.org/10.1111/cbdd.70095","url":null,"abstract":"<div>\u0000 \u0000 <p>Myocardial ischemia/reperfusion injury (MIRI) brings secondary injury to heart tissues and involves complicated pathophysiological activities, such as cell death, oxidative stress, and inflammation. HDAC1 (Histone Deacetylase 1) has been documented to strengthen MIRI; our study intended to investigate the concrete regulatory mechanisms and functions of tanshinone IIA on HDAC1 in MIRI, which might provide experimental proofs for the adjuvant application of tanshinone IIA in the treatment of MIRI. Genecards and SwissTargetPrediction websites were utilized to download the myocardial infarction-related and tanshinone IIA-targeted genes respectively, and then the String website was applied to display protein–protein interaction (PPI) network. The Cytoscape software was subsequently used to select and display the PPI network of hub genes. AutoDockTools and PyMOL software were utilized to operate molecular docking and visualize the docking results between tanshinone IIA and HDAC1, and Oxygen–glucose deprivation/reoxygenation (OGD/R)-treated myocardiocytes were used as the cell model of MIRI. The protein levels of HDAC1 and nuclear factor erythroid 2-related factor 2 (Nrf2)-regulated pathway were examined by western blot, and cell viability and apoptosis were evaluated by CCK8, Tunnel, and flow cytometry assays. The levels of lactate dehydrogenase, creatine kinase-MB, malondialdehyde, reduced glutathione, and Fe²⁺ were assessed by corresponding kit, and MIRI rat models were constructed to verify the therapeutic effects of tanshinone IIA in vivo. Finally, hematoxylin and eosin staining and immunohistochemistry were used to display the pathological changes of MIRI heart tissues and the levels of 4-hydroxynonenal respectively. HDAC1 was the possible target of tanshinone IIA and was involved in the myocardial infarction process. Tanshinone IIA could bind to amino acid residues of HDAC1 with high affinity. Besides, HDAC1 was elevated in OGD/R-treated myocardiocytes, and tanshinone IIA pretreatment ameliorated myocardiocyte apoptosis, the release of inflammatory mediators, and ferroptosis under the following OGD/R treatment, which were abolished by HDAC1 upregulation. Besides, tanshinone IIA pretreatment suppressed HDAC1 expression and further activated the Nrf2-xCT/Gpx4/HO-1 axis in myocardiocytes with OGD/R operation. Functionally, tanshinone IIA pre-injection ameliorated myocardial infarcted areas via activating the HDAC1-suppressed Nrf2-xCT/Gpx4/HO-1 pathway in vivo. Tanshinone IIA could attenuate myocardial apoptosis, inflammatory response, and ferroptosis via activating the HDAC1-repressed Nrf2-xCT/Gpx4/HO-1 axis, which promoted myocardial salvage in the MIRI process.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 4","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762161","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}

{"title":"SAIAME: Semi-Parameter Adaptation Information-Assisted Multi-Objective Evolutionary for Protein-Ligand Docking","authors":"Wei Xiao,&nbsp;Haichuan Shu,&nbsp;Chen Xu,&nbsp;Wangyan Li,&nbsp;Juhui Ren","doi":"10.1111/cbdd.70094","DOIUrl":"https://doi.org/10.1111/cbdd.70094","url":null,"abstract":"<div>\u0000 \u0000 <p>Molecular docking, which simulates the binding pose of a drug molecule to target proteins and predicts the binding affinity, is an important computational tool in structure-based drug discovery. However, the difficulties of high ligand connectivity and dimensionality reduce the search ability of the conformational sampling. To this end, a semi-parameter adaptation information-assisted multi-objective evolution method named SAIAME is proposed for protein-ligand docking optimization. SAIAME employs a staged and dynamic semi-parameter adaptive updating strategy, in which the crossover rate is updated by a weighted arithmetic average algorithm in the exploration phase, as well as the scaling factor is updated by the Lehmer mean in the exploitation phase. It integrates a gradient enhancement based on infinity norms to smooth the decay of the weights of the learning rate during gradient descent to enhance the handling of outliers. It introduces a population size reduction strategy that combines linear and bilateral symmetric sawtooth functions to enhance its execution efficiency. The experimental results demonstrate that SAIAME not only achieves the accuracies of 87.02% for the best poses and 72.98% for the top-score poses within an RMSD of 2 Å, but also has certain advantages in execution efficiency.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 4","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762001","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}

{"title":"Selective Antiproliferative and Apoptotic Effects of 2,6-Diketopiperazines on MDA-MB-231 Triple-Negative Breast Cancer","authors":"Flor Paulina Garrido González,&nbsp;Martha Edith Macías Pérez,&nbsp;Octavio Rodríguez Cortés,&nbsp;Elvia Mera Jiménez,&nbsp;Teresa Mancilla Percino","doi":"10.1111/cbdd.70098","DOIUrl":"https://doi.org/10.1111/cbdd.70098","url":null,"abstract":"<p>Diketopiperazines (DKPs) have emerged as promising candidates for treating diverse diseases, particularly cancer. In this context, 2,5-diketopiperazines have been extensively investigated in comparison with 2,6-diketopiperazines. This work explores the selectivity and impact of 2,6-diketopiperazine enantiomers derived from α-amino acids on MDA-MB-231 triple-negative breast cancer cells (TNBC). This subtype of cancer is recognized for its aggressiveness and the lack of effective therapeutic options. The evaluation utilized MTT and flow cytometry assays to examine the impact of 2,6-DPKs on the MDA-MB-231 breast cancer cell line. The obtained IC₅₀ values for compounds <b>1</b> and (<i>S</i>)-enantiomers ranged from 4.6 μM to 4.944 mM, where <b>1</b> and (<i>S</i>)-<b>2a</b> exhibited the lowest values. The IC₅₀ values for (<i>R</i>) enantiomers ranged from 0.021 to 3.639 mM, whereas (<i>R</i>)-<b>2b</b> was the lowest. Flow cytometry results revealed that compounds increase in apoptosis at 48 h compared to 24 h, ranging from 54.1% to 76.2%; however, (<i>S</i>)-<b>12a</b> exhibited a 3% decrease in apoptotic induction at 48 h. All investigated 2,6-diketopiperazines derived from α-amino acids showed potential as anticancer agents against MDA-MB-231 cancer cells. In particular, compounds <b>1</b>, (<i>S</i>)-<b>2a</b>, -4a, and -<b>5a</b> showed remarkable inhibitory effects on proliferation, viability, and apoptosis. The MTT results in the culture of healthy cells of the kidney line Vero did not display cytotoxicity at the tested concentrations up to 12.0 mM. Hence, these 2,6-DPKs are suitable for in vivo testing shortly.</p>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 4","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cbdd.70098","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762009","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}

{"title":"Breviscapine Attenuates Lipopolysaccharide-Induced Airway Dysfunction in Normal Human Bronchial Epithelial Cells by Suppressing the TLR4/MyD88 Signaling Pathway","authors":"Shaocong Zhao,&nbsp;Wanwan Li,&nbsp;Yanfeng Zhao,&nbsp;Xiaomin Sun","doi":"10.1111/cbdd.70096","DOIUrl":"https://doi.org/10.1111/cbdd.70096","url":null,"abstract":"<div>\u0000 \u0000 <p>Pediatric asthma is a common chronic respiratory disorder characterized by airway inflammation and hyperresponsiveness. Breviscapine (Bre) is a natural flavonoid with a broad spectrum of pharmacological activities. Previous studies have found that Bre exerts a protective effect on inflammation in airway and lung tissues. However, the effect of Bre on asthma has not yet been reported. The effects of Bre on asthmatic airway dysfunction were investigated in lipopolysaccharide (LPS)-induced normal human bronchial epithelial cells (NHBEs). Cell viability was determined by CCK-8 assay. Secretion levels of cytokines (IL-1β and IL-6) and chemokine (MCP-1) in the supernatant of NHBEs were measured by using ELISA. Whether Bre could influence LPS-caused oxidative stress in NHBEs was evaluated by detecting malondialdehyde (MDA) production and activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). RT-PCR was applied to determine the mRNA levels of mucin 5 AC (MUC5AC), collagen I (Col-I), and fibronectin (FN). Western blotting was performed to assess the expression levels of toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), and TNF receptor associated factor 6 (TRAF6). To further confirm the role of TLR4/MyD88 signaling pathway, TLR4-overexpressing cells were constructed. Results showed that Bre attenuated LPS-induced inflammatory responses with decreased release of IL-1β, IL-6, and MCP-1 in NHBEs. The oxidative status in LPS-stimulated NHBEs was suppressed by Bre treatment, as shown by reduced MDA production and increased activities of SOD and GSH-Px. Bre also attenuated LPS-induced expression of MUC5AC, Col-I, and FN. LPS induced the activation of the TLR4/MyD88 signaling pathway in NHBEs, which could be reversed by Bre treatment. Additionally, overexpression of TLR4 lessened the protective effects of Bre on LPS-stimulated NHBEs. Overall, the foregoing results suggested that the TLR4/MyD88 signaling pathway mediated a critical protective effect of Bre on LPS-induced asthmatic airway dysfunction, which provided evidence for the potential usage of Bre for the treatment of asthma.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 4","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143741442","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}

{"title":"1,2,3-Triazole Tethered Spiro[Indoline-Oxirane] Derivatives Induce Anticancer Effects in Human Hepatoma Cells","authors":"Shashikala Mariswamy Rajesh,&nbsp;Prasanna Doddakunche Shivaramu,&nbsp;Chandra Sekhar Bhol,&nbsp;Toreshettahally R. Swaroop,&nbsp;Habbanakuppe D. Preetham,&nbsp;Rajaghatta N. Suresh,&nbsp;Arunachalam Chinnathambi,&nbsp;Chandramohan Govindasamy,&nbsp;Sulaiman Ali Alharbi,&nbsp;Veeresha Gowda Shalini,&nbsp;Kwang Seok Ahn,&nbsp;Shobith Rangappa,&nbsp;Kanchugarakoppal S. Rangappa","doi":"10.1111/cbdd.70091","DOIUrl":"https://doi.org/10.1111/cbdd.70091","url":null,"abstract":"<div>\u0000 \u0000 <p>Epoxides are well-known compounds as anticancer agents. In this article, we present the synthesis of novel 3′-phenyl-1-((1-aryl-1<i>H</i>-1,2,3-triazol-5-yl)methyl)spiro[indoline-3,2′-oxiran]-2-one derivatives by the regioselective reaction of sulfur ylides with 1,2,3-triazole-tethered isatins and their anticancer effects on hepatocellular carcinoma (HCC) cells HepG2 and HCCLM3. The cell viability assays indicated that <b>RR-01</b> and <b>RR-07</b> had emerged as the most potent cytotoxic agents on the tested cell lines. Colony formation and migration assay results confirmed the anticancer effects of these compounds by inhibiting the formation of colonies and migration. Further, nuclear fragmentation staining assay showed that the compounds induce apoptosis. Acridine orange staining assays showed that our lead candidates (<b>RR-01</b> and <b>RR-07</b>) induced autophagy in liver cancer cells.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 4","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143698858","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}

{"title":"Oridonin Alleviates Doxorubicin-Induced Cardiotoxicity by Inhibiting p38 MAPK/MMP3 Signaling Pathway","authors":"Xingyuan Hou,&nbsp;Suifen Xie,&nbsp;Ni Zhou,&nbsp;Shanshan Wei,&nbsp;Yuanying Yang,&nbsp;Ziheng Luo,&nbsp;Sa Liu,&nbsp;Jian Liu,&nbsp;Ning Xie,&nbsp;Wenqun Li,&nbsp;Bikui Zhang","doi":"10.1111/cbdd.70093","DOIUrl":"https://doi.org/10.1111/cbdd.70093","url":null,"abstract":"<div>\u0000 \u0000 <p>Although doxorubicin (DOX) is an efficient chemotherapeutic drug for human tumors, severe cardiotoxicity restricts its clinical use. Oridonin (Ori), a bioactive component isolated from <i>Isodon rubescens</i> (Hemsl.) H. Hara, possesses potent anti-inflammatory and anticancer potentials. Therefore, our study aimed to evaluate the protective effects of Ori against DOX-induced cardiotoxicity. DIC models were established in vivo and in vitro. The action targets and pharmaceutical mechanism of Ori against DIC were comprehensively examined by network pharmacology, RNA-sequencing, and experimental validation. Ori relieved Dox-induced cell apoptosis in vitro and in vivo. A total of 7084 DEGs, 196 Ori, and 8172 DIC targets were screened by transcriptomics and network pharmacology, respectively. The three sets contained 11 intersection genes, including Ccl2, Myc, Mmp3, Egfr, p38 MAPK (MAPK14), Esr1, Tnf, Jun, Cdk1, Alb, and Ccnd1. The experimental results showed that Ori significantly decreased MMP-3 activity and the expression of p38 MAPK, thereby attenuating myocardial apoptosis and inflammatory infiltration. This study suggests that Ori is a potential therapeutic agent for DOX-induced cardiotoxicity that exerts its effects by inhibiting the p38 MAPK/MMP-3 signaling pathway.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143690101","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}

{"title":"Pyrazoles: A Master Key to Tackle Multidrug-Resistant Acinetobacter baumannii and Its Structure Activity Relationship Studies","authors":"Saraswati Sharma,&nbsp;Sahana Raju,&nbsp;Santosh Kumar Verma,&nbsp; Kamal,&nbsp;Rameshwari Verma,&nbsp;Piyush Kumar Thakur,&nbsp;Kothanahally S. Sharath Kumar","doi":"10.1111/cbdd.70092","DOIUrl":"https://doi.org/10.1111/cbdd.70092","url":null,"abstract":"<div>\u0000 \u0000 <p>Infections caused by Gram-negative bacteria within the ESKAPE group pose significant treatment challenges. These bacteria feature effective efflux pumps and possess lipopolysaccharides in their outer membranes, as well as a thin peptidoglycan layer measuring 5–10 nm in thickness. <i>Acinetobacter baumannii</i> (<i>A. baumannii</i>), a Gram-negative bacterium, is a significant contributor to serious infections acquired in hospitals and communities, representing a substantial risk to human health. This bacterium has developed resistance to nearly all existing antibiotics, and in the past 50 years, no new antibacterial class has been introduced for treating <i>A. baumannii</i> infections, highlighting an urgent necessity for the development of new antibacterials. The unique structural framework and adaptable features of the pyrazole ring attract researchers to develop new antibiotics. The present study outlines the advancements made over the last decade in pyrazole-containing derivatives that exhibit a wide range of antibacterial activity against various bacterial strains. Specifically, we discuss the effectiveness of diverse pyrazole derivatives against multidrug-resistant <i>A. baumannii</i> strains and explore various aspects of the structure–activity relationship (SAR). This compilation of data could serve as an excellent platform for designing and developing new pyrazole-based small molecules to target the growth of <i>A. baumannii</i>.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143690103","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}

{"title":"Discovery of New 4-Aminoquinoline–Thiazolidinone Hybrid Analogs as Antiproliferative Agents Inhibiting TLR4–LPS-Mediated Migration in Triple-Negative Breast Cancer Cells","authors":"S. K. Batin Rahaman,&nbsp;Satyajit Halder,&nbsp;Kuldeep K. Roy,&nbsp;Pallab K. Halder,&nbsp;Utsab Debnath,&nbsp;Kuladip Jana","doi":"10.1111/cbdd.70089","DOIUrl":"https://doi.org/10.1111/cbdd.70089","url":null,"abstract":"<div>\u0000 \u0000 <p>The Toll-like receptor 4 (TLR4) signaling pathway plays a leading role in triggering proinflammatory responses by targeting lipopolysaccharide (LPS) molecules from different bacteria. Meanwhile, it is also expressed at higher levels in breast cancer cells than in normal breast tissue. After LPS binding, it initiates downstream signaling pathways that promote inflammation and cell apoptosis. Thus, targeting TLR4–LPS presents a promising dual therapeutic strategy for breast cancer treatment by not only inhibiting tumor growth but also reducing inflammation within the tumor microenvironment. To achieve this, the discovery of a new antiinflammatory agent is needed to reduce LPS-mediated cancer cell proliferation and migration. In this study, a series of 4-aminoquinoline–thiazolidinone hybrid analogs (4a-m) have been synthesized to explore their antiinflammatory as well as anticancer activity to find a new lead. Among them, 4e revealed the most promising antiinflammatory (IC50 = 2.38 ± 0.77 μM) as well as anticancer activity (IC50 = 3.26 ± 1.06 μM) in RAW 267.7 cell line and triple-negative breast cancer (TNBC) cell line, respectively. Further structure–activity relationship study followed by MD simulation analysis was carried out to identify probable binding residues of TLR4 which may play a significant role in developing antiinflammatory activity for promoting cell apoptosis in cancer cells.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143690158","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}

{"title":"Potential Role of Hesperidin in Improving Experimental Pulmonary Arterial Hypertension in Rats via Modulation of the NF-κB Pathway","authors":"Jun He,&nbsp;Jun-hua Liao","doi":"10.1111/cbdd.70068","DOIUrl":"10.1111/cbdd.70068","url":null,"abstract":"<div>\u0000 \u0000 <p>This study was designed to evaluate the therapeutic effects of hesperidin, an anti-inflammatory compound, on pulmonary arterial hypertension (PAH). A PAH rat model was established using monocrotaline (MCT, 60 mg/kg). Next, the experimental animals were assigned into the following four groups (<i>n</i> = 6 per group): Control group, MCT group, MCT + H20 group (20 mg/kg hesperidin), and MCT + H40 group (40 mg/kg hesperidin). According to the experimental outcomes, the PAH rat model was built successfully. In PAH animals, hesperidin significantly reduced right ventricular systolic pressure, Fulton index, and mean pulmonary arterial pressure. Concurrently, it improved pulmonary artery velocity-time integral and acceleration time, as well as alleviated pulmonary artery and right ventricular remodeling. On a molecular level, hesperidin inhibited the expression of vascular endothelial-cadherin, alpha-smooth muscle actin, matrix metalloproteinase-9, and transforming growth factor beta. Also, hesperidin downregulated pro-inflammatory cytokines such as interleukin (IL)-6, IL-1β, IL-18, chemokine C-C motif ligand 2, and C-X-C motif chemokine ligand 1 levels, and reduced the number of CD68+ cells in tissue samples. Further analysis revealed that hesperidin could inhibit the activation of p-IκB-α and p-p65 in samples induced by MCT. Collectively, these findings suggest that hesperidin may inhibit inflammation through the NF-κB pathway, thereby improving experimental PAH in rats induced by MCT.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143665745","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}