Biomolecules & Therapeutics最新文献_第5页

Coadministration of 6-Shogaol and Levodopa Alleviates Parkinson's Disease-Related Pathology in Mice. 6-Shogaol 和左旋多巴联合用药可缓解小鼠帕金森病相关病理变化

IF 3 3区医学

Biomolecules & Therapeutics Pub Date : 2024-09-01 Epub Date: 2024-08-02 DOI: 10.4062/biomolther.2024.075

Jin Hee Kim, Jin Se Kim, In Gyoung Ju, Eugene Huh, Yujin Choi, Seungmin Lee, Jun-Young Cho, Boyoung Y Park, Myung Sook Oh

{"title":"Coadministration of 6-Shogaol and Levodopa Alleviates Parkinson's Disease-Related Pathology in Mice.","authors":"Jin Hee Kim, Jin Se Kim, In Gyoung Ju, Eugene Huh, Yujin Choi, Seungmin Lee, Jun-Young Cho, Boyoung Y Park, Myung Sook Oh","doi":"10.4062/biomolther.2024.075","DOIUrl":"10.4062/biomolther.2024.075","url":null,"abstract":"Parkinson's disease (PD) is a neurodegenerative disease caused by the death of dopaminergic neurons in the nigrostriatal pathway, leading to motor and non-motor dysfunctions, such as depression, olfactory dysfunction, and memory impairment. Although levodopa (L-dopa) has been the gold standard PD treatment for decades, it only relieves motor symptoms and has no effect on non-motor symptoms or disease progression. Prior studies have reported that 6-shogaol, the active ingredient in ginger, exerts a protective effect on dopaminergic neurons by suppressing neuroinflammation in PD mice. This study investigated whether cotreatment with 6-shogaol and L-dopa could attenuate both motor and non-motor symptoms and dopaminergic neuronal damage. Both 6-shogaol (20 mg/kg) and L-dopa (80 mg/kg) were orally administered to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/probenecid- induced PD model mice for 26 days. The experimental results showed that L-dopa alleviated motor symptoms, but had no significant effect on non-motor symptoms, loss of dopaminergic neuron, or neuroinflammation. However, when mice were treated with 6-shogaol alone or in combination L-dopa, an amelioration in both motor and non-motor symptoms such as depression-like behavior, olfactory dysfunction and memory impairment was observed. Moreover, 6-shogaol-only or co-treatment with 6-shogaol and L-dopa protected dopaminergic neurons in the striatum and reduced neuroinflammation in the striatum and substantia nigra. Overall, these results suggest that 6-shogaol can effectively complement L-dopa by improving non-motor dysfunction and restoring dopaminergic neurons via suppressing neuroinflammation.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"523-530"},"PeriodicalIF":3.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11392672/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141874110","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: 0

Aromadendrin Inhibits Lipopolysaccharide-Induced Inflammation in BEAS-2B Cells and Lungs of Mice. 芳香树突素抑制脂多糖诱导的 BEAS-2B 细胞和小鼠肺部炎症

IF 3 3区医学

Biomolecules & Therapeutics Pub Date : 2024-09-01 Epub Date: 2024-08-02 DOI: 10.4062/biomolther.2024.022

Juhyun Lee, Ji-Won Park, Jinseon Choi, Seok Han Yun, Bong Hyo Rhee, Hyeon Jeong Jeong, Hyueyun Kim, Kihoon Lee, Kyung-Seop Ahn, Hye-Gwang Jeong, Jae-Won Lee

{"title":"Aromadendrin Inhibits Lipopolysaccharide-Induced Inflammation in BEAS-2B Cells and Lungs of Mice.","authors":"Juhyun Lee, Ji-Won Park, Jinseon Choi, Seok Han Yun, Bong Hyo Rhee, Hyeon Jeong Jeong, Hyueyun Kim, Kihoon Lee, Kyung-Seop Ahn, Hye-Gwang Jeong, Jae-Won Lee","doi":"10.4062/biomolther.2024.022","DOIUrl":"10.4062/biomolther.2024.022","url":null,"abstract":"Aromadendrin is a phenolic compound with various biological effects such as anti-inflammatory properties. However, its protective effects against acute lung injury (ALI) remain unclear. Therefore, this study aimed to explore the ameliorative effects of aromadendrin in an experimental model of lipopolysaccharide (LPS)-induced ALI. In vitro analysis revealed a notable increase in the levels of cytokine/chemokine formation, nuclear factor kappa B (NF-κB) activation, and myeloid differentiation primary response 88 (MyD88)/toll-like receptor (TLR4) expression in LPS-stimulated BEAS-2B lung epithelial cell lines that was ameliorated by aromadendrin pretreatment. In LPS-induced ALI mice, the remarkable upregulation of immune cells (ICs) and IL-1β/IL-6/TNF-α levels in the bronchoalveolar lavage fluid (BALF) and inducible nitric oxide synthase (iNOS)/cyclooxygenase-2 (COX-2)/CD68 expression in lung was decreased by the oral administration of aromadendrin. Histological analysis revealed the presence of cells in the lungs of acute lung injury (ALI) mice, which was alleviated by aromadendrin. In addition, aromadendrin ameliorated lung edema. This in vivo effect of aromadendrin was accompanied by its inhibitory effect on LPS-induced NF-κB activation, MyD88/TLR4 expression, and signal transducer and activator of transcription 3 (STAT3) activation. Furthermore, aromadendrin increased the expression of heme oxygenase-1 (HO-1)/ NAD(P)H quinone dehydrogenase 1 (NQO1) in the lungs of ALI mice. In summary, the in vitro and in vivo studies demonstrated that aromadendrin ameliorated endotoxin-induced pulmonary inflammation by suppressing cytokine formation and NF-κB activation, suggesting that aromadendrin could be a useful adjuvant in the treatment of ALI.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"546-555"},"PeriodicalIF":3.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11392671/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141874108","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: 0

Inhibition of Tumoral VISTA to Overcome TKI Resistance via Downregulation of the AKT/mTOR and JAK2/STAT5 Pathways in Chronic Myeloid Leukemia. 通过抑制 CML 中的 AKT/mTOR 和 JAK2/STAT5 通路抑制肿瘤 VISTA 以克服 TKI 抗性

IF 3 3区医学

Biomolecules & Therapeutics Pub Date : 2024-09-01 Epub Date: 2024-08-06 DOI: 10.4062/biomolther.2024.017

Kexin Ai, Mu Chen, Zhao Liang, Xiangyang Ding, Yang Gao, Honghao Zhang, Suwan Wu, Yanjie He, Yuhua Li

{"title":"Inhibition of Tumoral VISTA to Overcome TKI Resistance via Downregulation of the AKT/mTOR and JAK2/STAT5 Pathways in Chronic Myeloid Leukemia.","authors":"Kexin Ai, Mu Chen, Zhao Liang, Xiangyang Ding, Yang Gao, Honghao Zhang, Suwan Wu, Yanjie He, Yuhua Li","doi":"10.4062/biomolther.2024.017","DOIUrl":"10.4062/biomolther.2024.017","url":null,"abstract":"Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment landscape for chronic myeloid leukemia (CML). However, TKI resistance poses a significant challenge, leading to treatment failure and disease progression. Resistance mechanisms include both BCR::ABL1-dependent and BCR::ABL1-independent pathways. The mechanisms underlying BCR::ABL1 independence remain incompletely understood, with CML cells potentially activating alternative signaling pathways, including the AKT/mTOR and JAK2/STAT5 pathways, to compensate for the loss of BCR::ABL1 kinase activity. This study explored tumoral VISTA (encoded by VSIR) as a contributing factor to TKI resistance in CML patients and identified elevated tumoral VISTA levels as a marker of resistance and poor survival. Through in vitro and in vivo analyses, we demonstrated that VSIR knockdown and the application of NSC-622608, a novel VISTA inhibitor, significantly impeded CML cell proliferation and induced apoptosis by attenuating the AKT/ mTOR and JAK2/STAT5 pathways, which are crucial for CML cell survival independent of BCR::ABL1 kinase activity. Moreover, VSIR overexpression promoted TKI resistance in CML cells. Importantly, the synergistic effect of NSC-622608 with TKIs offers a potent therapeutic avenue against both imatinib-sensitive and imatinib-resistant CML cells, including those harboring the challenging T315I mutation. Our findings highlight the role of tumoral VISTA in mediating TKI resistance in CML, suggesting that inhibition of VISTA, particularly in combination with TKIs, is an innovative approach to enhancing treatment outcomes in CML patients, irrespective of BCR::ABL1 mutation status. This study not only identified a new pathway contributing to TKI resistance but also revealed the possibility of targeting tumoral VISTA as a means of overcoming this significant clinical challenge.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"582-600"},"PeriodicalIF":3.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11392669/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141892805","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: 0

Unraveling Stereochemical Structure-Activity Relationships of Sesquiterpene Lactones for Inhibitory Effects on STAT3 Activation. 揭示抑制 STAT3 激活作用的倍半萜内酯的立体化学结构-活性关系

IF 3 3区医学

Biomolecules & Therapeutics Pub Date : 2024-09-01 Epub Date: 2024-08-02 DOI: 10.4062/biomolther.2023.210

Seungchan An, Jaemoo Chun, Joohee Lee, Yeong Shik Kim, Minsoo Noh, Hyejin Ko

{"title":"Unraveling Stereochemical Structure-Activity Relationships of Sesquiterpene Lactones for Inhibitory Effects on STAT3 Activation.","authors":"Seungchan An, Jaemoo Chun, Joohee Lee, Yeong Shik Kim, Minsoo Noh, Hyejin Ko","doi":"10.4062/biomolther.2023.210","DOIUrl":"10.4062/biomolther.2023.210","url":null,"abstract":"Sesquiterpene lactones, a class of natural compounds abundant in the Asteraceae family, have gained attention owing to their diverse biological activities, and particularly their anti-proliferative effects on human cancer cells. In this study, we systematically investigated the structure-activity relationship of ten sesquiterpene lactones with the aim of elucidating the structural determinants for the STAT3 inhibition governing their anti-proliferative effects. Our findings revealed a significant correlation between the STAT3 inhibitory activity and the anti-proliferative effects of sesquiterpene lactones in MDA-MB-231 breast cancer cell lines. Among the compounds tested, alantolactone and isoalantolactone emerged as the most potent STAT3 inhibitors, highlighting their potential as candidates for anticancer drug development. Through protein-ligand docking studies, we revealed the structural basis of STAT3 inhibition by sesquiterpene lactones, emphasizing the critical role of hydrogen-bonding interactions with key residues, including Arg609, Ser611, Glu612, and Ser613, in the SH2 domain of STAT3. Furthermore, our conformational analysis revealed the decisive role of the torsion angle within the geometry-optimized structures of sesquiterpene lactones in their STAT3 inhibitory activity (R=0.80, p<0.01). These findings not only provide preclinical evidence for sesquiterpene lactones as promising phytomedicines against diseases associated with abnormal STAT3 activation, but also highlight the importance of stereochemical aspects in their activity.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"627-634"},"PeriodicalIF":3.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11392665/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141874075","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: 0

Carnosine and Retinol Synergistically Inhibit UVB-Induced PGE₂ Synthesis in Human Keratinocytes through the Up-Regulation of Hyaluronan Synthase 2. 卡诺辛和视黄醇通过上调透明质酸合成酶 2 协同抑制 UVB 诱导的人角质形成细胞中 PGE2 的合成

IF 3 3区医学

Biomolecules & Therapeutics Pub Date : 2024-09-01 Epub Date: 2024-08-02 DOI: 10.4062/biomolther.2023.226

In Guk Park, Sun Hee Jin, Seungchan An, Min Won Ki, Won Seok Park, Hyoung-June Kim, Yongjoo Na, Minsoo Noh

引用次数: 0

Loganin Ameliorates Acute Kidney Injury and Restores Tofacitinib Metabolism in Rats: Implications for Renal Protection and Drug Interaction. 洛加尼改善大鼠急性肾损伤并恢复托法替尼代谢：对肾脏保护和药物相互作用的影响。

IF 3 3区医学

Biomolecules & Therapeutics Pub Date : 2024-09-01 Epub Date: 2024-08-02 DOI: 10.4062/biomolther.2024.008

Hyeon Gyeom Choi, So Yeon Park, Sung Hun Bae, Sun-Young Chang, So Hee Kim

{"title":"Loganin Ameliorates Acute Kidney Injury and Restores Tofacitinib Metabolism in Rats: Implications for Renal Protection and Drug Interaction.","authors":"Hyeon Gyeom Choi, So Yeon Park, Sung Hun Bae, Sun-Young Chang, So Hee Kim","doi":"10.4062/biomolther.2024.008","DOIUrl":"10.4062/biomolther.2024.008","url":null,"abstract":"Tofacitinib, a Janus kinase (JAK) inhibitor used to treat rheumatoid arthritis, is metabolized through hepatic cytochrome P450 (CYP), specifically CYP3A1/2 and CYP2C11. Prolonged administration of rheumatoid arthritis medications is generally associated with an increased risk of renal toxicity. Loganin (LGN), an iridoid glycoside, has hepatorenal regenerative properties. This study investigates the potential of LGN to mitigate acute kidney injury (AKI) and its effects on the pharmacokinetics of tofacitinib in rats with cisplatin-induced AKI. Both intravenous and oral administration of tofacitinib to AKI rats significantly increased the area under the plasma concentration-time curve from time 0 to infinity (AUC) compared with control (CON) rats, an increase attributed to the decelerated non-renal clearance (CLNR) and renal clearance (CLR) of tofacitinib. Administration of LGN to AKI rats, however, protected kidneys from severe impairment, restoring the pharmacokinetic parameters (AUC, CLNR, and CLR) of tofacitinib to those observed in untreated CON rats, with partial recovery of kidney function, as evidenced by an increase in creatinine clearance (CLCR). Possible interactions between drugs and natural components should be considered, especially when co-administering both a drug and a natural extract containing LGN or iridoid glycosides to patients with kidney injury.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"601-610"},"PeriodicalIF":3.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11392661/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141874073","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: 0

Analysis of SARS-CoV-2 Mutations after Nirmatrelvir Treatment in a Lung Cancer Xenograft Mouse Model. 在肺癌异种移植小鼠模型中进行 Nirmatrelvir 治疗后的 SARS-CoV-2 变异分析

IF 3 3区医学

Biomolecules & Therapeutics Pub Date : 2024-07-01 Epub Date: 2024-06-05 DOI: 10.4062/biomolther.2023.195

Bo Min Kang, Dongbum Kim, Jinsoo Kim, Kyeongbin Baek, Sangkyu Park, Ha-Eun Shin, Myeong-Heon Lee, Minyoung Kim, Suyeon Kim, Younghee Lee, Hyung-Joo Kwon

{"title":"Analysis of SARS-CoV-2 Mutations after Nirmatrelvir Treatment in a Lung Cancer Xenograft Mouse Model.","authors":"Bo Min Kang, Dongbum Kim, Jinsoo Kim, Kyeongbin Baek, Sangkyu Park, Ha-Eun Shin, Myeong-Heon Lee, Minyoung Kim, Suyeon Kim, Younghee Lee, Hyung-Joo Kwon","doi":"10.4062/biomolther.2023.195","DOIUrl":"10.4062/biomolther.2023.195","url":null,"abstract":"Paxlovid is the first approved oral treatment for coronavirus disease 2019 and includes nirmatrelvir, a protease inhibitor targeting the main protease (Mpro) of SARS-CoV-2, as one of the key components. While some specific mutations emerged in Mpro were revealed to significantly reduce viral susceptibility to nirmatrelvir in vitro, there is no report regarding resistance to nirmatrelvir in patients and animal models for SARS-CoV-2 infection yet. We recently developed xenograft tumors derived from Calu-3 cells in immunodeficient mice and demonstrated extended replication of SARS-CoV-2 in the tumors. In this study, we investigated the effect of nirmatrelvir administration on SARS-CoV-2 replication. Treatment with nirmatrelvir after virus infection significantly reduced the replication of the parental SARS-CoV-2 and SARS-CoV-2 Omicron at 5 days post-infection (dpi). However, the virus titers were completely recovered at the time points of 15 and 30 dpi. The virus genomes in the tumors at 30 dpi were analyzed to investigate whether nirmatrelvir-resistant mutant viruses had emerged during the extended replication of SARS-CoV-2. Various mutations in several genes including ORF1ab, ORF3a, ORF7a, ORF7b, ORF8, and N occurred in the SARS-CoV-2 genome; however, no mutations were induced in the Mpro sequence by a single round of nirmatrelvir treatment, and none were observed even after two rounds of treatment. The parental SARS-CoV-2 and its sublineage isolates showed similar IC50 values of nirmatrelvir in Vero E6 cells. Therefore, it is probable that inducing viral resistance to nirmatrelvir in vivo is challenging differently from in vitro passage.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"481-491"},"PeriodicalIF":3.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11214963/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141247251","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: 0

Elafibranor PPARα/δ Dual Agonist Ameliorates Ovalbumin-Induced Allergic Asthma. Elafibranor PPARα/δ 双激动剂可改善卵清蛋白诱发的过敏性哮喘

IF 3 3区医学

Biomolecules & Therapeutics Pub Date : 2024-07-01 Epub Date: 2024-06-05 DOI: 10.4062/biomolther.2023.194

Ye-Eul Lee, Dong-Soon Im

{"title":"Elafibranor PPARα/δ Dual Agonist Ameliorates Ovalbumin-Induced Allergic Asthma.","authors":"Ye-Eul Lee, Dong-Soon Im","doi":"10.4062/biomolther.2023.194","DOIUrl":"10.4062/biomolther.2023.194","url":null,"abstract":"Asthma is characterized by chronic inflammation and respiratory tract remodeling. Peroxisome proliferator-activated receptors (PPARs) play important roles in the pathogenesis and regulation of chronic inflammatory processes in asthma. The role of PPARγ has been studied using synthetic PPARγ agonists in patients with asthma. However, involvement of PPARα/δ has not been studied in asthma. In the present study, we investigated if elafibranor, a PPARα/δ dual agonist, can modulate ovalbumin (OVA)-induced allergic asthma, which is a potential drug candidate for non-alcoholic fatty liver in obese patients. Elafibranor suppresses antigen-induced degranulation in RBL-2H3 mast cells without inducing cytotoxicity in vitro. In mice with OVA-induced allergic asthma, the administration of elafibranor suppressed OVA-induced airway hyper-responsiveness at a dose of 10 mg/kg. Elafibranor also suppressed the OVA-induced increase in immune cells and pro-inflammatory cytokine production in the bronchoalveolar lavage fluid (BALF). Histological studies suggested that elafibranor suppressed OVA-induced lung inflammation and mucin hyper-production in the bronchial airways. In addition, elafibranor suppressed OVA-induced increases in serum immunoglobulin E and IL-13 levels in BALF. Conversely, the present study suggests that elafibranor has the potential for use in patients with allergic asthma.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"460-466"},"PeriodicalIF":3.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11214965/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141247257","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: 0

Engineered T Cell Receptor for Cancer Immunotherapy. 用于癌症免疫疗法的工程 T 细胞受体。

IF 3 3区医学

Biomolecules & Therapeutics Pub Date : 2024-07-01 Epub Date: 2024-06-07 DOI: 10.4062/biomolther.2023.197

So Won Lee, Hyang-Mi Lee

引用次数: 0

Selonsertib, an ASK1 Inhibitor, Ameliorates Ovalbumin-Induced Allergic Asthma during Challenge and Sensitization Periods. ASK1抑制剂Selonsertib能改善卵清蛋白诱发的过敏性哮喘的挑战期和致敏期症状。

IF 3 3区医学

Biomolecules & Therapeutics Pub Date : 2024-07-01 Epub Date: 2024-06-07 DOI: 10.4062/biomolther.2023.203

So-Young Han, Dong-Soon Im

{"title":"Selonsertib, an ASK1 Inhibitor, Ameliorates Ovalbumin-Induced Allergic Asthma during Challenge and Sensitization Periods.","authors":"So-Young Han, Dong-Soon Im","doi":"10.4062/biomolther.2023.203","DOIUrl":"10.4062/biomolther.2023.203","url":null,"abstract":"Apoptosis signal-regulating kinase 1 (ASK1) is an upstream signaling molecule in oxidative stress-induced responses. Because oxidative stress is involved in asthma pathogenesis, ASK1 gene deficiency was investigated in animal models of allergic asthma. However, there is no study to investigate whether ASK1 inhibitors could be applied for asthma to date. Selonsertib, a potent and selective ASK1 inhibitor, was applied to BALB/c mice of an ovalbumin (OVA)-induced allergic asthma model. Selonsertib suppressed antigen-induced degranulation of RBL-2H3 mast cells in a concentration-dependent manner. The administration of selonsertib both before OVA sensitization and OVA challenge significantly reduced airway hyperresponsiveness, and suppressed eosinophil numbers and inflammatory cytokine levels in the bronchoalveolar lavage fluid. Histopathologic examination elucidated less inflammatory responses and reduced mucin-producing cells around the peribronchial regions of the lungs. Selonsertib also suppressed the IgE levels in serum and the protein levels of IL-13 in the bronchoalveolar lavage fluid. These results suggest that selonsertib may ameliorate allergic asthma by suppressing immune responses and be applicable to allergic asthma.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"451-459"},"PeriodicalIF":3.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11214966/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141282899","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: 0