Journal of pharmacological sciences最新文献

{"title":"Involvement of Cav3.2 T-type Ca2+ channels and cystathionine-β-synthase in colitis-related visceral hypersensitivity in mice","authors":"Maho Tsubota ,&nbsp;Yuriko Iba ,&nbsp;Tsukasa Hatakeyama ,&nbsp;Myu Honda ,&nbsp;Yoshihito Kasanami ,&nbsp;Fumiko Sekiguchi ,&nbsp;Atsushi Kawase ,&nbsp;Takuya Okada ,&nbsp;Naoki Toyooka ,&nbsp;Atsufumi Kawabata","doi":"10.1016/j.jphs.2024.09.003","DOIUrl":"10.1016/j.jphs.2024.09.003","url":null,"abstract":"<div><div>We tested the hypothesis that Ca_v3.2 T-type Ca²⁺ channels, which can be rebooted by sulfides from Zn²⁺ inhibition under physiological conditions, and sulfide-generating enzymes including cystathionine-β-synthase (CBS) would participate in the colitis-related visceral pain in mice treated with 2,4,6-trinitrobenzene sulfonic acid (TNBS). The visceral hypersensitivity following TNBS-induced colitis was abolished by an inhibitor or genetic deletion of Ca_v3.2 and by a CBS inhibitor, and accompanied by CBS upregulation in the colon. Our data thus suggest that the enhanced activity of Ca_v3.2 brought about by sulfides generated by upregulated CBS is involved in the colitis-related visceral hypersensitivity.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"156 4","pages":"Pages 209-213"},"PeriodicalIF":3.0,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861324000665/pdfft?md5=6b4df60c74f8375ac528d0445f540a97&pid=1-s2.0-S1347861324000665-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142314430","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}

{"title":"Role of CD34 in calcification of human aortic valve interstitial cells from patients with aortic valve stenosis","authors":"Shihu Men ,&nbsp;Zaiqiang Yu ,&nbsp;Xu Liu ,&nbsp;Kazuyuki Daitoku ,&nbsp;Mayuki Tachizaki ,&nbsp;Shogo Kawaguchi ,&nbsp;Tadaatsu Imaizumi ,&nbsp;Masahito Minakawa ,&nbsp;Kazuhiko Seya","doi":"10.1016/j.jphs.2024.09.002","DOIUrl":"10.1016/j.jphs.2024.09.002","url":null,"abstract":"<div><p>Various osteogenic factors are involved in ectopic human aortic valve calcification; however, the key cell species involved in calcification remains unclear. In a previous study, we reported that mesenchymal stem (CD73, 90, 105) and endothelial (VEGFR2) cell markers are positive in almost all human aortic valve interstitial cells (HAVICs) obtained from a patient with calcified aortic valve stenosis (CAVS). Further, CD34-negative HAVICs are highly sensitive to calcification stimulations. Here, we aimed to pathophysiologically clarify the role of CD34 in HAVICs obtained from individual patients with severe CAVS. A DNA microarray between CD34-positive and CD34-negative HAVICs, separated by fluorescence-activated cell sorting, indicated that tenascin X (TNX) mRNA expression significantly decreased in CD34-negative cells. Furthermore, the inflammatory cytokines, tumor necrosis factor (TNF)-α and interleukin (IL)-1β significantly downregulated CD34 expression in HAVICs. TGF-β, a key cytokine of endothelial-mesenchymal transition, did not affect HAVIC calcification. CD34 overexpression strongly inhibited TNF-α- and IL-1β-induced calcification and maintained TNX mRNA expression. These results suggest one possibility that CD34 is an inhibitory regulator of valve calcification. Furthermore, TNF-α- and IL-1β-induced CD34 downregulation in HAVICs contributes to HAVIC calcification by downregulating TNX protein expression.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"156 3","pages":"Pages 198-207"},"PeriodicalIF":3.0,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861324000653/pdfft?md5=b79f6f3c23bb64cde0cdbebb1b3c1e17&pid=1-s2.0-S1347861324000653-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142233063","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}

{"title":"Evaluation of inhibitory actions of antidepressants on muscarinic receptors assessed by a binding assay in the mouse cerebral neocortex","authors":"Keisuke Obara,&nbsp;Yuki Usami,&nbsp;Risa Okamoto,&nbsp;Kento Yoshioka,&nbsp;Yoshio Tanaka","doi":"10.1016/j.jphs.2024.09.001","DOIUrl":"10.1016/j.jphs.2024.09.001","url":null,"abstract":"<div><div>We investigated the inhibitory effects of 32 antidepressants on [³H]<em>N</em>-methylscopolamine ([³H]NMS)-specific binding in the mouse cerebral neocortex to determine which antidepressants should be recommended for patients with Alzheimer's disease (AD). Of those tested, nine antidepressants (10⁻⁴ M) exhibited less inhibitory effect on [³H]NMS-specific binding (&lt;35%): tianeptine (a tricyclic); trazodone (a serotonin 5-HT_2A blocker); sulpiride (a dopamine D₂ blocker); fluvoxamine (a selective serotonin reuptake inhibitor (RI)); milnacipran, levomilnacipran, venlafaxine, and desvenlafaxine (serotonin and noradrenaline RIs); and bupropion (a noradrenaline and dopamine RI). Therefore, these antidepressants show little anticholinergic effect in the brain and are recommended for use in patients with AD.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"156 4","pages":"Pages 214-217"},"PeriodicalIF":3.0,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142425178","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}

{"title":"Emodin alleviates lung injury via the miR-217-5p/Sirt1 axis in rats with severe acute pancreatitis","authors":"Zhihang Zhang ,&nbsp;Yalan Luo ,&nbsp;Xijing Zhuang ,&nbsp;Haifeng Gao ,&nbsp;Qi Yang ,&nbsp;Hailong Chen","doi":"10.1016/j.jphs.2024.08.007","DOIUrl":"10.1016/j.jphs.2024.08.007","url":null,"abstract":"<div><p>Acute lung injury (ALI) is closely related to high mortality in severe acute pancreatitis (SAP). This study unveils the therapeutic effect and mechanism of miR-217-5p on SAP-associated ALI. The miR-217-5p RNA expression was significantly up-regulated in lipopolysaccharide (LPS)-stimulated primary rat alveolar epithelial type II cells (AEC II) and sodium taurocholate-treated pancreas and lung in SAP rats. miR-217 inhibition protected AEC II from LPS-induced damage by inhibiting apoptosis and reducing the TNF-α, IL-6, and ROS levels. miR-217 inhibition suppressed apoptosis and alleviated mitochondrial damage through mitochondria-mediated apoptotic pathway <em>in vitro</em>. Sirt1 is a direct target of miR-217-5p. Dual-luciferase reporter assay confirmed the binding of miR-217-5p to Sirt1 mRNA 3′-UTR. The rescue experiment identified that the anti-apoptotic, anti-inflammatory, and anti-oxidative effects of miR-217 inhibition were mediated by Sirt1 <em>in vitro</em>. Emodin (EMO) protected AEC II from LPS-induced damage and alleviated pancreatic and lung tissue injuries. EMO exerted similar effects as miR-217 inhibition <em>in vitro</em> and <em>in vivo</em>. The effects of EMO were abolished by miR-217 overexpression. In conclusion, miR-217-5p inhibition exerts protective effects on SAP-ALI <em>in vitro</em> and <em>in vivo</em> by repressing apoptosis, inflammation, and oxidative stress through Sirt1 activation. EMO protects against lung injuries in SAP-associated ALI rats through miR-217-5p/Sirt1 axis.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"156 3","pages":"Pages 188-197"},"PeriodicalIF":3.0,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S134786132400063X/pdfft?md5=3d53035ef4c6f969c6fe0d4f04792bd1&pid=1-s2.0-S134786132400063X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142167512","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}

{"title":"Effect of antiemetics on zolbetuximab-induced gastric injury and emesis in ferrets","authors":"Fumitaka Kinugasa ,&nbsp;Satoru Kajikawa ,&nbsp;Jane Weng ,&nbsp;Tohru Ugawa ,&nbsp;Hiroshi Fushiki ,&nbsp;Yosuke Yamanaka ,&nbsp;Masanori Nagata ,&nbsp;Gillian Haggerty ,&nbsp;Shinobu Akuzawa ,&nbsp;Taisuke Nakazawa ,&nbsp;Hiroshi Suzuki ,&nbsp;Taiji Sawamoto","doi":"10.1016/j.jphs.2024.08.005","DOIUrl":"10.1016/j.jphs.2024.08.005","url":null,"abstract":"<div><p>Claudin-18 splice variant 2 (CLDN18.2), a tight junction protein, is a highly cell type–specific antigen that is expressed by differentiated gastric mucosa cells. The expression of CLDN18.2 in gastric mucosa cells may be retained upon malignant transformation and is displayed on the surface of several tumors, including gastric/gastroesophageal junction adenocarcinoma. Zolbetuximab is a genetically engineered, highly purified chimeric (mouse/human IgG1) antibody directed against CLDN18.2. Nausea and vomiting were observed as adverse events of zolbetuximab. To investigate the mechanism of nausea and vomiting in humans, we evaluated emesis (retching and vomiting) and conducted histopathologic assessment in ferrets after the administration of zolbetuximab. Emesis was frequently observed in all ferrets treated with zolbetuximab in the first hour after administration. Histopathologic assessment revealed the surface of the gastric mucosa was the primary site of emesis-associated tissue damage. The effect of antiemetics (dexamethasone, ondansetron, fosaprepitant, and olanzapine) on emesis induced by zolbetuximab was investigated. Fosaprepitant showed suppressive effects on emesis, and use of dexamethasone or concomitant use of fosaprepitant with other antiemetics tended to alleviate gastric tissue damage. The onset of emesis in humans receiving zolbetuximab may be associated with damage in the gastric mucosa, and antiemetics may mitigate gastrointestinal adverse events.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"156 3","pages":"Pages 161-170"},"PeriodicalIF":3.0,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861324000616/pdfft?md5=9b59c0d1648aac137bdf955240f12ad2&pid=1-s2.0-S1347861324000616-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142076865","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}

{"title":"Amitriptyline and duloxetine attenuate activities of superficial dorsal horn neurons in a rat reserpine-induced fibromyalgia model","authors":"Daisuke Uta ,&nbsp;Katsuyuki Tsuboshima ,&nbsp;Kazue Mizumura ,&nbsp;Hisao Nishijo ,&nbsp;Toru Taguchi","doi":"10.1016/j.jphs.2024.08.006","DOIUrl":"10.1016/j.jphs.2024.08.006","url":null,"abstract":"<div><p>Fibromyalgia (FM) is an intractable disease with a chief complaint of chronic widespread pain. Amitriptyline (AMI) and duloxetine (DLX), which are antidepressant drugs, have been reported to ameliorate pain in patients with FM and pain-related behaviors in several rodent models of FM. However, the mechanisms of action of AMI and DLX are not yet fully understood. Here, we examined the effects of these drugs on the responsiveness of superficial dorsal horn (SDH) neurons in the spinal cord, using a rat FM model developed by injecting a biogenic amine depleter (reserpine). Extracellular recordings of SDH neurons <em>in vivo</em> demonstrated that bath application of AMI and DLX at concentrations of 0.1–1.0 mM on the dorsal surface of the spinal cord markedly suppressed spontaneous discharge and von Frey filament-evoked mechanical firing in SDH neurons. The suppression induced by the drugs was noted in a concentration-dependent manner and the suppressive effects resolved after washing the spinal cord surface. These results show that SDH neurons are the site of action for AMI and DLX in a rat reserpine-induced FM model. Spinal mechanisms may underlie the therapeutic effects of these drugs in patients with FM.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"156 3","pages":"Pages 180-187"},"PeriodicalIF":3.0,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861324000628/pdfft?md5=9e053b739e9dddd2bd8d1a990fd5cd41&pid=1-s2.0-S1347861324000628-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142096895","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}

{"title":"In vivo cardiovascular profile of ryanodine receptor 2 inhibitor M201-A: Utility as an anti-atrial fibrillatory drug for patients suffering from heart failure with preserved ejection fraction","authors":"Ryuichi Kambayashi ,&nbsp;Ai Goto ,&nbsp;Makoto Shinozaki ,&nbsp;Hiroko Izumi-Nakaseko ,&nbsp;Yoshinori Takei ,&nbsp;Kunio Iwata ,&nbsp;Noboru Kaneko ,&nbsp;Atsushi Sugiyama","doi":"10.1016/j.jphs.2024.08.004","DOIUrl":"10.1016/j.jphs.2024.08.004","url":null,"abstract":"<div><p>Atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF) often coexist; however, clinically available anti-AF drugs can exacerbate symptoms of HFpEF. M201-A suppressed ryanodine receptor-mediated diastolic Ca²⁺ leakage, possibly inhibiting common pathological processes toward AF and HFpEF. To bridge the basic information to clinical practice, we assessed its cardiohemodynamic, anti-AF and ventricular proarrhythmic profile using halothane-anesthetized dogs (n = 4). M201-A hydrochloride in doses of 0.03, 0.3 and 3 mg/kg/10 min was intravenously administered, providing peak plasma concentrations of 0.09, 0.81 and 5.70 μg/mL, respectively. The high dose of M201-A showed various cardiovascular actions. Namely, M201-A increased mean blood pressure and tended to enhance isovolumetric ventricular relaxation without suppressing ventricular contraction or decreasing cardiac output. M201-A enhanced atrioventricular conduction, but hardy affected intra-atrial/ventricular conduction. Importantly, M201-A prolonged effective refractory period more potently in the atrium than in the ventricle, indicating that it may become an atrial-selective antiarrhythmic drug. Meanwhile, M201-A prolonged QT interval/QTcV, and showed reverse frequency-dependent delay of ventricular repolarization. M201-A prolonged J-T_peakc without prolonging T_peak-T_end or terminal repolarization period, indicating the risk of causing torsade de pointes is negligible. Thus, M201-A is expected to become a hopeful therapeutic strategy for patients having pathology of both AF and HFpEF.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"156 3","pages":"Pages 171-179"},"PeriodicalIF":3.0,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861324000604/pdfft?md5=3db6b114f7405a63b252c17bce83b376&pid=1-s2.0-S1347861324000604-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142096847","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}

{"title":"Oxymatrine alleviates NSAID-associated small bowel mucosal injury by regulating MIP-1/CCR1 signalling and gut microbiota","authors":"Ming Chen ,&nbsp;Haixia Zhou ,&nbsp;Jie Shen ,&nbsp;Miaomiao Wei ,&nbsp;Zhaoyu Chen ,&nbsp;Xiaoyu Chen ,&nbsp;Huining Fan ,&nbsp;Jing Zhang ,&nbsp;Jinshui Zhu","doi":"10.1016/j.jphs.2024.08.003","DOIUrl":"10.1016/j.jphs.2024.08.003","url":null,"abstract":"<div><p>Oxymatrine (OMT) as a quinazine alkaloid extracted from matrine has been shown to exhibit anti-inflammatory and anti-tumour effects. However, the protective mechanism of OMT on NSAID-associated small bowel mucosal injury remains unreported. We found that OMT could improve the clinical symptoms and pathological inflammation scoring, reduce the secretion of proinflammatory cytokines IL-1β, IL-6 and TNF-α and cell apoptosis, promote cell proliferation and protect intestinal mucosal barrier as compared with the Diclofenac Sodium (DS) group. Further RNA-seq and KEGG analysis uncovered that the differentially expressed genes between DS and control groups were mainly enriched in immune regulation, of which MIP-1γ and its receptor CCR1 expression were validated to be repressed by OMTH. MAPK/NF-κB as the MIP-1 upstream signalling was also inactivated by OMT treatment. In this study, OMT regulated gut microbiota. Venn diagrams visualized and identified 1163 shared OTUs between DS group and OMTH group. The results showed that the α diversity index in the DS group was lower than that in the OMTH group, indicating that the complexity of the flora was reduced in the intestinal inflammatory state. β diversity mainly includes Principal Component Analysis (PCA) and Principal Co-ordinates Analysis (PCoA). The differences between groups can be observed through PCA. The more similar the composition of the flora, the closer the samples are. We found that the difference was smaller in the DS group than in the OMTH group. The results of PcoA showed that the sample similarity between OMTH groups was the highest. Moreover, gut microbiota analysis unveiled that the abundances of <em>Ruminococcus 1</em>, <em>Oscillibacter</em> and <em>Prevotellaceae</em> at the genus level as well as <em>Lactobacillus</em> SP-L-Yj at the species level were increased in OMTH group as compared with the DS group but the abundance of <em>Allobaculum</em>, <em>Ruminococceos-UCG-005</em>, <em>Ruminococceos-NK4A214</em> and <em>Clostridium</em> associated with DS-induced small bowel mucosal injury could be decreased by OMTH. MIP-1α and CCR1 were upregulated in human small bowel injury samples as compared with the normal ileal mucosa tissues. In conclusion, our findings demonstrated that OMT could alleviate NSAID-associated small bowel mucosal injury by inhibiting MIP-1γ/CCR1 signalling and regulating gut microbiota.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"156 3","pages":"Pages 149-160"},"PeriodicalIF":3.0,"publicationDate":"2024-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861324000598/pdfft?md5=22d206d463d278866864a0310e23b1a7&pid=1-s2.0-S1347861324000598-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142002159","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}

{"title":"Effects of D-Allose on experimental cardiac hypertrophy","authors":"Steeve Akumwami ,&nbsp;Asadur Rahman ,&nbsp;Masafumi Funamoto ,&nbsp;Akram Hossain ,&nbsp;Asahiro Morishita ,&nbsp;Yasumasa Ikeda ,&nbsp;Hiroaki Kitamura ,&nbsp;Kento Kitada ,&nbsp;Takahisa Noma ,&nbsp;Yuichi Ogino ,&nbsp;Akira Nishiyama","doi":"10.1016/j.jphs.2024.08.002","DOIUrl":"10.1016/j.jphs.2024.08.002","url":null,"abstract":"<div><p>The hallmark of pathological cardiac hypertrophy is the decline in myocardial contractility caused by an energy deficit resulting from metabolic abnormalities, particularly those related to glucose metabolism. Here, we aim to explore whether D-Allose, a rare sugar that utilizes the same transporters as glucose, may restore metabolic equilibrium and reverse cardiac hypertrophy. Isolated neonatal rat cardiomyocytes were stimulated with phenylephrine and treated with D-Allose simultaneously for 48 h. D-Allose treatment resulted in a pronounced reduction in cardiomyocyte size and cardiac remodelling markers accompanied with a dramatic reduction in the level of intracellular glucose in phenylephrine-stimulated cells. The metabolic flux analysis provided further insights revealing that D-Allose exerted a remarkable inhibition of glycolysis as well as glycolytic capacity. Furthermore, in mice subjected to a 14-day continuous infusion of isoproterenol (ISO) to induce cardiac hypertrophy, D-Allose treatment via drinking water notably reduced ISO-induced cardiac hypertrophy and remodelling markers, with minimal effects on ventricular wall thickness observed in echocardiographic analyses. These findings indicate that D-Allose has the ability to attenuate the progression of cardiomyocyte hypertrophy by decreasing intracellular glucose flux and inhibiting glycolysis.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"156 2","pages":"Pages 142-148"},"PeriodicalIF":3.0,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861324000586/pdfft?md5=01718de9705446a18a3cda333ebff15e&pid=1-s2.0-S1347861324000586-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141963380","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}

{"title":"Benproperine reduces IL-6 levels via Akt signaling in monocyte/macrophage-lineage cells and reduces the mortality of mouse sepsis model induced by lipopolysaccharide","authors":"Ayumi Kawamura,&nbsp;Akane Ito,&nbsp;Ayaka Takahashi,&nbsp;Atsushi Sawamoto,&nbsp;Satoshi Okuyama,&nbsp;Mitsunari Nakajima","doi":"10.1016/j.jphs.2024.08.001","DOIUrl":"10.1016/j.jphs.2024.08.001","url":null,"abstract":"<div><p>Benproperine (BNP) is a nonnarcotic antitussive drug that is used to treat bronchitis. In the present study, we examined the anti-inflammatory effects of BNP <em>in vitro</em> and <em>in vivo</em>. BNP was found to reduce the secretion of pro-inflammatory cytokines, such as interleukin (IL)-6, in lipopolysaccharide (LPS)-treated RAW264.7 monocyte/macrophage-lineage cells <em>in vitro</em>. As IL-6 is a biomarker for sepsis and has been suggested to exacerbate symptoms, we used an animal model to determine whether BNP reduces IL-6 levels <em>in vivo</em> and improves sepsis symptoms. Notably, BNP reduced IL-6 levels in the lungs of LPS-treated mice and improved LPS-induced hypothermia, one of the symptoms of sepsis. BNP reduced the mortality of septic mice administered a lethal dose of LPS. To reveal the mechanisms underlying the anti-inflammatory function of BNP, we assessed intracellular signaling in LPS-treated RAW264.7 cells. BNP induced the phosphorylation of protein kinase B (Akt) in RAW264.7 cells with/without LPS treatment. Wortmannin, an inhibitor of phosphoinositide 3-kinase reduced the phosphorylation levels of Akt. Wortmannin also obstructed the reduction of IL-6 secretion caused by BNP. Altogether, BNP was found to exhibit an anti-inflammatory function via Akt signaling. Therefore, BNP could be a drug candidate for inflammatory diseases, including sepsis.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"156 2","pages":"Pages 125-133"},"PeriodicalIF":3.0,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861324000574/pdfft?md5=3c27f63ec96a7dd694bab1cfe047e3f1&pid=1-s2.0-S1347861324000574-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141944361","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}