Archives of Pharmacal Research最新文献_第10页

MEKs/ERKs-mediated FBXO1/E2Fs interaction interference modulates G1/S cell cycle transition and cancer cell proliferation MEKs/ erks介导的FBXO1/E2Fs相互作用干扰调节G1/S细胞周期转变和癌细胞增殖

IF 6.7 3区医学

Archives of Pharmacal Research Pub Date : 2023-01-06 DOI: 10.1007/s12272-023-01426-5

Ga-Eun Lee, Dohyun Jeung, Weidong Chen, Jiin Byun, Joo Young Lee, Han Chang Kang, Hye Suk Lee, Dae Joon Kim, Jin-Sung Choi, Cheol-Jung Lee, Hyun-Jung An, Yong-Yeon Cho

{"title":"MEKs/ERKs-mediated FBXO1/E2Fs interaction interference modulates G1/S cell cycle transition and cancer cell proliferation","authors":"Ga-Eun Lee, Dohyun Jeung, Weidong Chen, Jiin Byun, Joo Young Lee, Han Chang Kang, Hye Suk Lee, Dae Joon Kim, Jin-Sung Choi, Cheol-Jung Lee, Hyun-Jung An, Yong-Yeon Cho","doi":"10.1007/s12272-023-01426-5","DOIUrl":"10.1007/s12272-023-01426-5","url":null,"abstract":"<div><p>E2F 1, 2, and 3a, (refer to as E2Fs) are a subfamily of E2F transcription factor family that play essential roles in cell-cycle progression, DNA replication, DNA repair, apoptosis, and differentiation. Although the transcriptional regulation of E2Fs has focused on pocket protein retinoblastoma protein complex, recent studies indicate that post-translational modification and stability regulation of E2Fs play key roles in diverse cellular processes. In this study, we found that FBXO1, a component of S-phase kinase-associated protein 1 (SKP1)-cullin 1-F-box protein (SCF) complex, is an E2Fs binding partner. Furthermore, FBXO1 to E2Fs binding induced K48 ubiquitination and subsequent proteasomal degradation of E2Fs. Binding domain analysis indicated that the Arg (R)/Ile (I) and R/Val (V) motifs, which are located in the dimerization domain of E2Fs, of E2F 1 and 3a and E2F2, respectively, acted as degron motifs (DMs) for FBXO1. Notably, RI/AA or RV/AA mutation in the DMs reduced FBXO1-mediated ubiquitination and prolonged the half-lives of E2Fs. Importantly, the stabilities of E2Fs were affected by phosphorylation of threonine residues located near RI and RV residues of DMs. Phosphorylation prediction database analysis and specific inhibitor analysis revealed that MEK/ERK signaling molecules play key roles in FBXO1/E2Fs’ interaction and modulate E2F protein turnover. Moreover, both elevated E2Fs protein levels by knockdown of FBXO1 and decreased E2Fs protein levels by sh-E2F3a delayed G<sub>1</sub>/S cell cycle transition, resulting in inhibition of cancer cell proliferation. These results demonstrated that FBXO1-E2Fs axis-mediated precise E2Fs stability regulation plays a key role in cell proliferation via G<sub>1</sub>/S cell cycle transition.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2023-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50020123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Recent advances in selective and targeted drug/gene delivery systems using cell-penetrating peptides 利用细胞穿透肽的选择性和靶向药物/基因传递系统的最新进展

IF 6.7 3区医学

Archives of Pharmacal Research Pub Date : 2023-01-03 DOI: 10.1007/s12272-022-01425-y

So Hee Nam, Joonhyuck Park, Heebeom Koo

{"title":"Recent advances in selective and targeted drug/gene delivery systems using cell-penetrating peptides","authors":"So Hee Nam, Joonhyuck Park, Heebeom Koo","doi":"10.1007/s12272-022-01425-y","DOIUrl":"10.1007/s12272-022-01425-y","url":null,"abstract":"<div><p>Biological cell membranes are a natural barrier for living cells. In the last few decades, the cell membrane has been the main hurdle in the efficient delivery of bioactive and therapeutic agents. To increase the drug efficacy of these agents, additional mediators have been considered. Cell-penetrating peptides (CPPs), a series of oligopeptides composed of mostly hydrophobic and/or positively charged side chains, can increase the interaction with the cell membrane. CPP-based delivery platforms have shown great potential for the efficient and direct cytosol delivery of various cargos, including genes, proteins, and small molecule drugs. Bypassing endocytosis allows the CPP-based delivery systems greater defense against the degradation of protein-based drugs than other drug delivery systems. However, the delivery of CPPs exhibits intrinsically non-specific targeting, which limits their medical applications. To endow CPPs with specific targeting ability, the conjugation of pH-sensitive, enzyme-specific cleavable, and multiple targeting ligands has been reported. Optimization of the length and sequence of CPPs is still needed for various drugs of different sizes and surface charges. Toxicity issues in CPP-based delivery systems should be addressed carefully before clinical use.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2023-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12272-022-01425-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10635928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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: 15

Effects of CYP2C19 genetic polymorphism on the pharmacokinetics of tolperisone in healthy subjects CYP2C19基因多态性对健康受试者托培里松药代动力学的影响

IF 6.7 3区医学

Archives of Pharmacal Research Pub Date : 2022-12-23 DOI: 10.1007/s12272-022-01423-0

Chang‑Keun Cho, Ji-Young Byeon, Pureum Kang, Hye-Jung Park, Eunvin Ko, Chou Yen Mu, Choon-Gon Jang, Seok-Yong Lee, Yun Jeong Lee

{"title":"Effects of CYP2C19 genetic polymorphism on the pharmacokinetics of tolperisone in healthy subjects","authors":"Chang‑Keun Cho, Ji-Young Byeon, Pureum Kang, Hye-Jung Park, Eunvin Ko, Chou Yen Mu, Choon-Gon Jang, Seok-Yong Lee, Yun Jeong Lee","doi":"10.1007/s12272-022-01423-0","DOIUrl":"10.1007/s12272-022-01423-0","url":null,"abstract":"<div><p>Tolperisone hydrochloride is a centrally-acting muscle relaxant used for relieving spasticities of neurological origin and muscle spasms associated with painful locomotor diseases. It is metabolized to the inactive metabolite mainly by CYP2D6 and, to a lesser extent, by CYP2C19 and CYP1A2. In our previous study, the pharmacokinetics of tolperisone was significantly affected by the genetic polymorphism of <i>CYP2D6</i>, but the wide interindividual variation of tolperisone pharmacokinetics was not explained by genetic polymorphism of <i>CYP2D6</i> alone. Thus, we studied the effects of <i>CYP2C19</i> genetic polymorphism on tolperisone pharmacokinetics. Eighty-one subjects with different <i>CYP2C19</i> genotypes received a single oral dose of 150 mg tolperisone with 240 mL of water, and blood samples were collected up to 12 h after dosing. The plasma concentration of tolperisone was measured by a liquid chromatography-tandem mass spectrometry system. The CYP2C19PM group had significantly higher C<sub>max</sub> and lower CL/F values than the CYP2C19EM and CYP2C19IM groups. The AUC<sub>inf</sub> of the CYP2C19PM group was 2.86-fold and 3.00-fold higher than the CYP2C19EM and CYP2C19IM groups, respectively. In conclusion, the genetic polymorphism of <i>CYP2C19</i> significantly affected tolperisone pharmacokinetics.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2022-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10762271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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: 3

Effects of CYP2D6*10 allele on the pharmacokinetics of tolperisone CYP2D6*10等位基因对托培里松药动学的影响

IF 6.7 3区医学

Archives of Pharmacal Research Pub Date : 2022-12-21 DOI: 10.1007/s12272-022-01422-1

Chang‑Keun Cho, Ji-Young Byeon, Pureum Kang, Jung-In Park, Choon-Gon Jang, Seok-Yong Lee, Chang-Ik Choi, Jung‑Woo Bae, Yun Jeong Lee

{"title":"Effects of CYP2D6*10 allele on the pharmacokinetics of tolperisone","authors":"Chang‑Keun Cho, Ji-Young Byeon, Pureum Kang, Jung-In Park, Choon-Gon Jang, Seok-Yong Lee, Chang-Ik Choi, Jung‑Woo Bae, Yun Jeong Lee","doi":"10.1007/s12272-022-01422-1","DOIUrl":"10.1007/s12272-022-01422-1","url":null,"abstract":"<div><p>Tolperisone, a muscle relaxant used for post-stroke spasticity, has been reported to have a very wide interindividual pharmacokinetic variability. It is metabolized mainly by CYP2D6 and, to a lesser extent, by CYP2C19 and CYP1A2. CYP2D6 is a highly polymorphic enzyme, and <i>CYP2D6*wt</i>/<i>*wt</i>, <i>CYP2D6*wt/*10</i> and <i>CYP2D6*10/*10</i> genotypes constitute more than 90% of the <i>CYP2D6</i> genotypes in the Korean population. Thus, effects of the <i>CYP2D6*10</i> on tolperisone pharmacokinetics were investigated in this study to elucidate the reasons for the wide interindividual variability. Oral tolperisone 150 mg was given to sixty-four healthy Koreans, and plasma concentrations of tolperisone were measured by liquid chromatography-tandem mass spectrometry (LC–MS/MS). The <i>CYP2D6*10/*10</i> and <i>CYP2D6*wt/*10</i> groups had significantly higher C<sub>max</sub> and lower CL/F values than the <i>CYP2D6*wt/*wt</i> group. The AUC<sub>inf</sub> of <i>CYP2D6*10/*10</i> and <i>CYP2D6*wt/*10</i> groups were 5.18-fold and 2.25-fold higher than the <i>CYP2D6*wt/*wt</i> group, respectively. There were considerable variations in the C<sub>max</sub> and AUC values within each genotype group, and the variations were greater as the activity of CYP2D6 decreased. These results suggest that the genetic polymorphism of <i>CYP2D6</i> significantly affected tolperisone pharmacokinetics and factor(s) other than CYP2D6 may also have significant effects on the pharmacokinetics of tolperisone.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2022-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12272-022-01422-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10657760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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: 3

Targeting cytokines and signaling molecules related to immune pathways in atopic dermatitis: therapeutic implications and challenges 靶向细胞因子和信号分子相关的免疫途径在特应性皮炎:治疗意义和挑战

IF 6.7 3区医学

Archives of Pharmacal Research Pub Date : 2022-12-03 DOI: 10.1007/s12272-022-01421-2

Hyung-Ook Kim

{"title":"Targeting cytokines and signaling molecules related to immune pathways in atopic dermatitis: therapeutic implications and challenges","authors":"Hyung-Ook Kim","doi":"10.1007/s12272-022-01421-2","DOIUrl":"10.1007/s12272-022-01421-2","url":null,"abstract":"<div><p>Although atopic dermatitis (AD) is primarily a Th2-driven disease, it shows high heterogeneity with additional variable contributions of the Th22, Th17, and Th1 pathways, depending on the subtype of the disease. Expanding knowledge and understanding of AD pathogenesis has promoted the development of numerous novel therapeutics that target cytokines and their signaling molecules, representatively, Janus kinases, involved in the underlying immune pathways, resulting in therapeutic success and failure. The first FDA approval was for the targeted biologic dupilumab. Although this proved the therapeutic relevance of targeting Th2 cytokines in moderate-to-severe forms of AD, it did not treat all patients, necessitating additional targeted therapeutics that modulate other cytokine pathways to resolve AD in all subtypes. Three more recently FDA-approved targeted therapeutics and several others that have been developed represent different targeted approaches directed to the Th2, Th22, Th17, or Th1 pathways. This review summarizes the main features and clinical outcomes of various approaches targeting cytokines and signaling molecules in these different pathways in view of both successful and failed cases, with a discussion of their therapeutic implications. In future, AD should be treated with more specific treatments reflecting the disease heterogeneity, but the current development of targeted therapeutics has faced some challenges in this context, which is also discussed.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2022-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10374383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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: 2

Non-alcoholic fatty liver disease and liver secretome 非酒精性脂肪性肝病与肝脏分泌组

IF 6.7 3区医学

Archives of Pharmacal Research Pub Date : 2022-11-28 DOI: 10.1007/s12272-022-01419-w

Muhammad Sohaib Khan, Choongho Lee, Sang Geon Kim

{"title":"Non-alcoholic fatty liver disease and liver secretome","authors":"Muhammad Sohaib Khan, Choongho Lee, Sang Geon Kim","doi":"10.1007/s12272-022-01419-w","DOIUrl":"10.1007/s12272-022-01419-w","url":null,"abstract":"<div><p>Metabolism of carbohydrates and lipids and protein degradation occurs in the liver and contributes to the body's homeostasis by secreting a variety of mediators. Any imbalance in this homeostasis due to excess fat consumption and the pathologic events accompanying lipotoxicity, autophagy dysregulation, endoplasmic reticulum stress, and insulin resistance may cause disturbances in the secretion of the proteins from the liver and their physiologic modifications and interactions with others. Since the liver secretome plays a role in the regulation of fuel metabolism and inflammation not only in the liver per se but also in other organs, the proteins belong to the utmost targets for treating metabolic and inflammatory diseases (e.g., COVID-19), depending on the available and feasible approaches to controlling their biological effects. However, in this era, we still come across new liver-derived proteins but are yet unable to entirely understand the pathologic basis underlying disease progression. This review aims to provide an updated overview of liver secretome biology with explanatory mechanisms with regard to the progression of metabolic and inflammatory liver diseases.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2022-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12272-022-01419-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10747603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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: 3

Neurological disorders of COVID-19: insights to applications of natural products from plants and microorganisms 2019冠状病毒病神经系统疾病:植物和微生物天然产物应用的见解

IF 6.7 3区医学

Archives of Pharmacal Research Pub Date : 2022-11-28 DOI: 10.1007/s12272-022-01420-3

Faezeh Almasi, Wen Dang, Fatemeh Mohammadipanah, Ning Li

{"title":"Neurological disorders of COVID-19: insights to applications of natural products from plants and microorganisms","authors":"Faezeh Almasi, Wen Dang, Fatemeh Mohammadipanah, Ning Li","doi":"10.1007/s12272-022-01420-3","DOIUrl":"10.1007/s12272-022-01420-3","url":null,"abstract":"<div><p>In addition to the typical respiratory manifestations, various disorders including involvement of the nerve system have been detected in COVID-19 ranging from 22 to 36%. Although growing records are focusing on neurological aspects of COVID-19, the pathophysiological mechanisms and related therapeutic methods remain obscure. Considering the increased concerns of SARS-CoV-2 potential for more serious neuroinvasion conditions, the present review attempts to focus on the neuroprotective effects of natural compounds as the principle source of therapeutics inhibiting multiple steps of the SARS-CoV-2 infection cycle. The great majority of the natural products with anti-SARS-CoV-2 activity mainly inhibit the attachment, entry and gene expression rather than the replication, assembly, or release. Although microbial-derived natural products comprise 38.5% of the known natural products with neuroprotective effects following viral infection, the neuroprotective potential of the majority of microorganisms is still undiscovered. Among natural products, chrysin, huperzine A, ginsenoside Rg1, pterostilbene, and terrein have shown potent in vitro neuroprotective activity and can be promising for new or repurpose drugs for neurological complications of SARS-CoV-2.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2022-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12272-022-01420-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10747604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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: 2

Effects of phytoestrogens on reproductive organ health 植物雌激素对生殖器官健康的影响

IF 6.7 3区医学

Archives of Pharmacal Research Pub Date : 2022-11-28 DOI: 10.1007/s12272-022-01417-y

S. Swathi Krishna, Beena Briget Kuriakose, P. K. Lakshmi

引用次数: 8

Scope and challenges of nanoparticle-based mRNA delivery in cancer treatment 基于纳米颗粒的mRNA递送在癌症治疗中的范围和挑战

IF 6.7 3区医学

Archives of Pharmacal Research Pub Date : 2022-11-24 DOI: 10.1007/s12272-022-01418-x

Md. Emranul Karim, Sheikh Tanzina Haque, Hamed Al-Busaidi, Athirah Bakhtiar, Kyi Kyi Tha, Mark M. Banaszak Holl, Ezharul Hoque Chowdhury

{"title":"Scope and challenges of nanoparticle-based mRNA delivery in cancer treatment","authors":"Md. Emranul Karim, Sheikh Tanzina Haque, Hamed Al-Busaidi, Athirah Bakhtiar, Kyi Kyi Tha, Mark M. Banaszak Holl, Ezharul Hoque Chowdhury","doi":"10.1007/s12272-022-01418-x","DOIUrl":"10.1007/s12272-022-01418-x","url":null,"abstract":"<div><p>Messenger RNA (mRNA) recently emerged as an appealing alternative to treat and prevent diseases ranging from cancer and Alzheimer’s disease to COVID-19 with significant clinical outputs. The in vitro-transcribed mRNA has been engineered to mimic the structure of natural mRNA for vaccination, cancer immunotherapy and protein replacement therapy. In past decades, significant progress has been noticed in unveiling the molecular pathways of mRNA, controlling its translatability and stability, and its evolutionary defense mechanism. However, numerous unsolved structural, biological, and technical difficulties hamper the successful implementation of systemic delivery of mRNA for safer human consumption. Advances in designing and manufacturing mRNA and selecting innovative delivery vehicles are mandatory to address the unresolved issues and achieve the full potential of mRNA drugs. Despite the substantial efforts made to improve the intracellular delivery of mRNA drugs, challenges associated with diverse applications in different routes still exist. This study examines the current progress of mRNA therapeutics and advancements in designing biomaterials and delivery strategies, the existing translational challenges of clinical tractability and the prospects of overcoming any challenges related to mRNA.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2022-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12272-022-01418-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10402808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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: 8

6′-Sialylactose abolished lipopolysaccharide-induced inflammation and hyper-permeability in endothelial cells 6′-唾液酰基乳糖可消除脂多糖诱导的内皮细胞炎症和高通透性

IF 6.7 3区医学

Archives of Pharmacal Research Pub Date : 2022-11-19 DOI: 10.1007/s12272-022-01415-0

Dung Van Nguyen, Thuy Le Lam Nguyen, Yujin Jin, Lila Kim, Chang-Seon Myung, Kyung-Sun Heo

{"title":"6′-Sialylactose abolished lipopolysaccharide-induced inflammation and hyper-permeability in endothelial cells","authors":"Dung Van Nguyen, Thuy Le Lam Nguyen, Yujin Jin, Lila Kim, Chang-Seon Myung, Kyung-Sun Heo","doi":"10.1007/s12272-022-01415-0","DOIUrl":"10.1007/s12272-022-01415-0","url":null,"abstract":"<div><p>\u0000Disruption of the endothelial barrier function and reduction in cell migration leads to endothelial dysfunction. One of the most abundant human milk oligosaccharides, 6′-sialylactose (6′-SL), is reported to exert various biological functions related to inflammatory responses. In this study, we evaluated the effects of 6′-SL on lipopolysaccharide (LPS)-induced inflammation caused by endothelial barrier damage. Our results showed that LPS at 500 ng/mL strongly not only abolished cell migration but also hyperactivated MAPK and NF-κB pathways. 6′-SL suppressed LPS-induced endothelial inflammation via ERK1/2, p38, and JNK MAPK pathways. 6′-SL supported endothelial junctions by upregulating PECAM-1 expression and mRNA levels of tight junctions, such as ZO-1 and occludin, which were downregulated by LPS stimulation. It significantly inhibited the nuclear translocation of NF-κB, along with the downregulation of inflammatory cytokines, including TNF-α, IL-1β, MCP-1, VCAM-1, and ICAM-1. Furthermore, 6′-SL abolished NF-κB-mediated STAT3 in controlling endothelial migration and hyperpermeability via downregulating STAT3 activation and nuclear translocation. Finally, LPS induced over-expression of VCAM-1 and ZO-1 disassembly in both atheroprone and atheroprotective areas of mouse aorta, which were reversed by 6′-SL treatment. Altogether, our findings suggest that 6′-SL is a potent therapeutic agent for modulating inflammatory responses and endothelial hyperpermeability.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2022-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40695784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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: 3