Journal of pharmacological sciences最新文献

{"title":"Combined antiallodynic effects of Neurotropin®–tramadol and Neurotropin®–mirogabalin in rats with L5-spinal nerve ligation","authors":"Yukihiro Yoshimoto,&nbsp;Hisashi Okai,&nbsp;Hiroyoshi Namba,&nbsp;Kazuki Taguchi,&nbsp;Yoshiya Yamauchi,&nbsp;Jun Wakita,&nbsp;Ryohei Okazaki","doi":"10.1016/j.jphs.2024.07.001","DOIUrl":"https://doi.org/10.1016/j.jphs.2024.07.001","url":null,"abstract":"<div><p>We aimed to examine the efficacy of combination therapies of Neurotropin® with tramadol and Neurotropin with mirogabalin for neuropathic pain management. A neuropathic pain model (L5 spinal nerve ligation model: L5-SNL) using male Wistar rats was generated through tight ligation of the left fifth lumbar nerve using silk sutures. Mechanical allodynia was assessed using the 50% paw withdrawal threshold. The combined antiallodynic effects were evaluated using isobolographic analyses. Small intestinal transit was evaluated using the charcoal meal test, and motor coordination using the rota-rod test. Neurotropin (50–200 NU/kg, p.o.), tramadol (7.5–60 mg/kg, p.o.), and mirogabalin (3–30 mg/kg, p.o.) showed a dose-dependent antiallodynic effect in L5-SNL rats. The combined antiallodynic effects of Neurotropin and tramadol were additive or synergistic, whereas those of Neurotropin and mirogabalin were additive. Neurotropin (100–400 NU/kg, p.o.) did not affect the small intestinal transit, whereas tramadol (30–100 mg/kg, p.o.) significantly inhibited it. Neurotropin (100–400 NU/kg, p.o.) did not affect the walking time, whereas mirogabalin (10–100 mg/kg, p.o.) significantly decreased it. Neurotropin dose-dependently ameliorated mechanical allodynia in rats, and combination therapy with Neurotropin–tramadol or Neurotropin–mirogabalin may alleviate neuropathic pain without aggravating the adverse effects of tramadol and mirogabalin.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"156 1","pages":"Pages 30-37"},"PeriodicalIF":3.0,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S134786132400046X/pdfft?md5=1f42974a74708cb6655b49c70f8527d9&pid=1-s2.0-S134786132400046X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141542596","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":"Alteration of reactivity in isolated mesenteric artery from Zucker fatty diabetes mellitus rats","authors":"Kosuke Otani,&nbsp;Naofumi Uemura,&nbsp;Hiroshi Funada,&nbsp;Tomoko Kodama,&nbsp;Muneyoshi Okada,&nbsp;Hideyuki Yamawaki","doi":"10.1016/j.jphs.2024.06.006","DOIUrl":"https://doi.org/10.1016/j.jphs.2024.06.006","url":null,"abstract":"<div><p>Obesity and diabetes are major risk factors for cardiovascular diseases. Zucker fatty diabetes mellitus (ZFDM) rats are novel animal model of obesity and type 2 diabetes. We have recently reported that blood pressure in ZFDM-<em>Lepr</em>^fa/fa (Homo) rats was normal, while blood adrenaline level and heart rate were lower than those in control ZFDM-<em>Lepr</em>^fa/+ (Hetero) rats. Here, we compared the reactivity in isolated mesenteric artery between Hetero and Homo rats. Contraction induced by phenylephrine was increased, while relaxation induced by isoprenaline was decreased in Homo rats at 21–23 weeks old compared with those in Hetero rats. The mRNA expression for α_1A but not β₂ adrenoreceptor in Homo rats was increased. Nitric oxide (NO)-mediated relaxation induced by acetylcholine was decreased, while the mRNA expression for endothelial NO synthase (eNOS) was rather increased in mesenteric artery from Homo rats. These findings for the first time revealed that in Homo rats with reduced plasma adrenaline, blood pressure could be maintained by enhancing vascular contractility induced by adrenaline through the increased α₁ adrenoceptor expression and the attenuated β₂ adrenoceptor signaling. Additionally, NO-mediated endothelium-dependent relaxation is impaired perhaps due to eNOS dysfunction, which might also contribute to maintain the blood pressure in Homo rats.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"156 1","pages":"Pages 38-44"},"PeriodicalIF":3.0,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861324000458/pdfft?md5=540649ac368aa19ed70b6770807da17e&pid=1-s2.0-S1347861324000458-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141542563","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":"Characterization of remodeling processes in the atria of atrioventricular block dogs: Utility as an early-stage atrial fibrillation model","authors":"Ryuichi Kambayashi ,&nbsp;Ai Goto ,&nbsp;Akira Takahara ,&nbsp;Hiroyuki Saito ,&nbsp;Hiroko Izumi-Nakaseko ,&nbsp;Yoshinori Takei ,&nbsp;Yasuki Akie ,&nbsp;Masaaki Hori ,&nbsp;Atsushi Sugiyama","doi":"10.1016/j.jphs.2024.06.004","DOIUrl":"https://doi.org/10.1016/j.jphs.2024.06.004","url":null,"abstract":"<div><p>To characterize utility of atrioventricular block (AVB) dogs as atrial fibrillation (AF) model, we studied remodeling processes occurring in their atria in acute (&lt;2 weeks) and chronic (&gt;4 weeks) phases. Fifty beagle dogs were used. Holter electrocardiogram demonstrated that paroxysmal AF occurred immediately after the production of AVB, of which duration tended to be prolonged in chronic phase. Electrophysiological analysis showed that inter-atrial conduction time and duration of burst pacing-induced AF increased in the chronic phase compared with those in the acute phase, but that atrial effective refractory period was hardly altered. Echocardiographic study revealed that diameters of left atrium, right pulmonary vein and inferior vena cava increased similarly in the acute and chronic phases. Histological evaluation indicated that hypertrophy and fibrosis in atrial tissue increased in the chronic phase. Electropharmacological characterization showed that i.v. pilsicainide effectively suppressed burst pacing-induced AF with increasing atrial conduction time and refractoriness of AVB dogs in chronic phase, but that i.v. amiodarone did not exert such electrophysiological effects. Taken together, AVB dogs in chronic phase appear to possess such pathophysiology as developed in the atria of early-stage AF patients, and therefore they can be used to evaluate drug candidates against early-stage AF.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"156 1","pages":"Pages 19-29"},"PeriodicalIF":3.0,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861324000434/pdfft?md5=8c223283ccc67452e3221247a8a58908&pid=1-s2.0-S1347861324000434-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141542565","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":"Contribution of MLKL to the development of doxorubicin-induced cardiomyopathy and its amelioration by rapamycin","authors":"Masaki Shimizu ,&nbsp;Wataru Ohwada ,&nbsp;Toshiyuki Yano ,&nbsp;Hidemichi Kouzu ,&nbsp;Tatsuya Sato ,&nbsp;Toshifumi Ogawa ,&nbsp;Arata Osanami ,&nbsp;Yuki Toda ,&nbsp;Hiroshi Nagahama ,&nbsp;Masaya Tanno ,&nbsp;Tetsuji Miura ,&nbsp;Atsushi Kuno ,&nbsp;Masato Furuhashi","doi":"10.1016/j.jphs.2024.06.005","DOIUrl":"https://doi.org/10.1016/j.jphs.2024.06.005","url":null,"abstract":"<div><p>Necroptosis, necrosis characterized by RIPK3-MLKL activation, has been proposed as a mechanism of doxorubicin (DOX)-induced cardiomyopathy. We showed that rapamycin, an mTORC1 inhibitor, attenuates cardiomyocyte necroptosis. Here we examined role of MLKL in DOX-induced myocardial damage and protective effects of rapamycin. Cardiomyopathy was induced in mice by intraperitoneal injections of DOX (10 mg/kg, every other day) and followed for 7 days. DOX-treated mice showed a significant decline in LVEF assessed by cardiac MRI (45.5 ± 5.1% vs. 65.4 ± 4.2%), reduction in overall survival rates, and increases in myocardial RIPK3 and MLKL expression compared with those in vehicle-treated mice, and those changes were prevented by administration of rapamycin (0.25 mg/kg) before DOX injection. In immunohistochemical analyses, p-MLKL signals were detected in the cardiomyocytes of DOX-treated mice, and the signals were reduced by rapamycin. <em>Mlkl</em>^<em>+/-</em> and <em>Mlkl</em>^<em>-/-</em> mice were similarly resistant to DOX-induced cardiac dysfunction, indicating that a modest reduction in MLKL level is sufficient to prevent the development of DOX-induced cardiomyopathy. However, evidence of cardiomyocyte necrosis assessed by C9 immunostaining, presence of replacement fibrosis, and electron microscopic analyses was negligible in the myocardium of DOX-treated mice. Thus, MLKL-mediated signaling contributes to DOX-induced cardiac dysfunction primarily by a necrosis-independent mechanism, which is inhibitable by rapamycin.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"156 1","pages":"Pages 9-18"},"PeriodicalIF":3.0,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861324000446/pdfft?md5=96d1d026ca9fff759593a72f659ebe9a&pid=1-s2.0-S1347861324000446-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141542564","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":"Cinnamaldehyde protects SH-SY5Y cells against advanced glycation end-products induced ectopic cell cycle re-entry","authors":"Yijing Wu ,&nbsp;Jing Zhong ,&nbsp;Jiaqi Wang ,&nbsp;Hemei Li ,&nbsp;Xiuting Chen ,&nbsp;Xing Xia ,&nbsp;Jinling Zhou","doi":"10.1016/j.jphs.2024.06.003","DOIUrl":"10.1016/j.jphs.2024.06.003","url":null,"abstract":"<div><p>Accumulation of advanced glycation end-products (AGEs) in the brain contributes significantly to cognitive impairment in patients with diabetes by disrupting the post-mitotic state of neuronal cells, thereby triggering ectopic cell cycle re-entry (CCR) and subsequent neuronal apoptosis. Cinnamaldehyde (CINA), a potential mitigator of cognitive impairment due to its blood glucose-lowering properties, warrants exploration for its role in counteracting diabetes-related neurological damage. In this study, we examined the neuroprotective effect of CINA on AGE-damaged SH-SY5Y human neuroblastoma cells differentiated in vitro. We investigated the impact of CINA on AGE-induced neuronal CCR and apoptosis, finding that it substantially suppressed aberrant DNA replication, precluded cells from entering the mitotic preparatory phase, and diminished apoptosis. Additionally, CINA inhibited the expression of eIF4E without altering S6K1 phosphorylation. These findings indicate that CINA safeguards neuronal cells from AGE-related damage by preventing abnormal CCR, preserving the post-mitotic state of neuronal cells, and reducing AGE-induced apoptosis, potentially through the inhibition of eIF4E-controlled cell proliferation. Our results highlight the prospective utility of CINA in managing diabetic neuropathy.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"156 1","pages":"Pages 1-8"},"PeriodicalIF":3.0,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861324000422/pdfft?md5=fa47db25c51ebc234aef8acd7c1c29c7&pid=1-s2.0-S1347861324000422-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141501114","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":"Alpha-linolenic acid selectively inhibits the contraction of pig coronary arteries mediated through prostanoid TP receptors","authors":"Kento Yoshioka ,&nbsp;Keisuke Obara ,&nbsp;Mikoto Ozawa,&nbsp;Mayu Kiguchi,&nbsp;Yuri Nakao,&nbsp;Hinako Miyaji,&nbsp;Toma Yamashita,&nbsp;Noboru Saitoh,&nbsp;Yutaka Nakagome,&nbsp;Yoshio Tanaka","doi":"10.1016/j.jphs.2024.06.001","DOIUrl":"10.1016/j.jphs.2024.06.001","url":null,"abstract":"<div><p>We examined the inhibitory effects of α-linolenic acid (ALA) on the contractions of pig coronary arteries. ALA concentration-dependently inhibited the contractions elicited by U46619 and prostaglandin F_2α without affecting those elicited by 80 mM KCl, histamine, acetylcholine, and serotonin. ALA rightward shifted the concentration-response curve of U46619, and Schild plot analysis revealed that ALA competitively antagonized U46619. Furthermore, ALA inhibited the increase in intracellular Ca²⁺ concentration caused by TP receptor stimulation but not that caused by FP receptor stimulation. These results suggest that ALA behaves as a selective antagonist of TP receptors in coronary arteries.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"155 4","pages":"Pages 148-151"},"PeriodicalIF":3.5,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861324000409/pdfft?md5=784818b35f35232c1de03608f1c7c542&pid=1-s2.0-S1347861324000409-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141279741","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":"Structure-activity relationship studies of pyrogallol as a calcineurin/NFAT signaling suppressor","authors":"Hiroyuki Mizuguchi ,&nbsp;Tomohira Ito ,&nbsp;Kohei Nishida ,&nbsp;Tomoharu Wakugawa ,&nbsp;Tomohiro Nakano ,&nbsp;Akie Tanabe ,&nbsp;Tomokazu Watano ,&nbsp;Noriko Kitamura ,&nbsp;Osamu Kaminuma ,&nbsp;Katsunori Kimura ,&nbsp;Tatsuya Ishida ,&nbsp;Atsushi Matsunaga ,&nbsp;Kazumi Ohta ,&nbsp;Rina Shimono ,&nbsp;Haruo Kutsuna ,&nbsp;Taiei Yasuda ,&nbsp;Masami Yabumoto ,&nbsp;Yoshiaki Kitamura ,&nbsp;Noriaki Takeda ,&nbsp;Hiroyuki Fukui","doi":"10.1016/j.jphs.2024.06.002","DOIUrl":"https://doi.org/10.1016/j.jphs.2024.06.002","url":null,"abstract":"<div><p>Previously, we have shown that pyrogallol alleviated nasal symptoms and suppressed IL-9 gene up-regulation in allergy model rats by inhibiting calcineurin/NFAT signaling. As pyrogallol has antioxidative activity, it may be responsible for inhibiting calcineurin/NFAT signaling-mediated IL-9 gene expression. However, the relationship between antioxidative activity and suppression of IL-9 gene expression has not been elucidated yet. Here, we conducted the structure-activity relationship studies of pyrogallol and its structurally related compounds to understand the mechanism of IL-9 gene suppression by pyrogallol. 2, 2-Diphenyl-1-picrylhydrazyl radical scavenging assay showed that the antioxidative activity of catechol, resorcinol, phloroglucinol, and gallic acid is 60.1%, 10.4%, 18.8%, and 113.5% of pyrogallol, respectively. Catechol, resorcinol, and phloroglucinol did not suppress NFAT dephosphorylation. Gallic acid suppressed dephosphorylation of NFAT. Gallic acid also suppressed ionomycin-induced up-regulation of IL-9 gene expression with the IC₅₀ value of 82.6 μM. However, catechol, resorcinol and phloroglucinol showed no suppressive activity. In addition, using gallic acid-immobilized beads, we isolated and identified Poly(U)-binding-splicing factor 60 (PUF60) as a pyrogallol binding protein. These results suggest that the antioxidative activity of pyrogallol is not likely to be the mechanism of IL-9 gene suppression. Data also suggest that PUF60 is one of its target molecules responsible for the suppression of calcineurin/NFAT signaling by pyrogallol.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"155 4","pages":"Pages 140-147"},"PeriodicalIF":3.5,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861324000410/pdfft?md5=987182f899d3f70e134d5521c0594ef1&pid=1-s2.0-S1347861324000410-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141289637","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":"H2S prevents the disruption of the blood-brain barrier in rats with prenatal hyperhomocysteinemia","authors":"A.V. Yakovlev ,&nbsp;A.S. Detterer ,&nbsp;O.V. Yakovleva ,&nbsp;A. Hermann ,&nbsp;G.F. Sitdikova","doi":"10.1016/j.jphs.2024.05.001","DOIUrl":"10.1016/j.jphs.2024.05.001","url":null,"abstract":"<div><p>Elevation of the homocysteine concentration in the plasma called hyperhomocysteinemia (hHCY) during pregnancy causes a number of pre- and postnatal developmental disorders. The aim of our study was to analyze the effects of H₂S donors –NaHS and N-acetylcysteine (NAC) on blood-brain barrier (BBB) permeability in rats with prenatal hHCY. In rats with mild hHCY BBB permeability assessed by Evans Blue extravasation in brain increased markedly throughout life. Administration of NaHS or NAC during pregnancy attenuated hHCY-associated damage and increased endogenous concentrations of sulfides in brain tissues. Acute application of <span>dl</span>-homocysteine thiolactone induced BBB leakage, which was prevented by the NMDA receptor antagonist MK-801 or H₂S donors. Rats with hHCY demonstrated high levels of NO metabolite – nitrites and proinflammatory cytokines (IL-1β, TNF-α, IL-6) in brain. Lactate dehydrogenase (LDH) activity in the serum was higher in rats with hHCY. Mitochondrial complex-I activity was lower in brain of hHCY rats. NaHS treatment during pregnancy restored levels of proinflammatory cytokines, nitrites and activity of the respiratory chain complex in brain as well as the LDH activity in serum. Our data suggest that H₂S has neuroprotective effects against prenatal hHCY-associated BBB disturbance providing a potential strategy for the prevention of developmental impairments in newborns.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"155 4","pages":"Pages 131-139"},"PeriodicalIF":3.5,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861324000380/pdfft?md5=f67d33bc8f485841c29607fa19a99e4e&pid=1-s2.0-S1347861324000380-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141134318","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":"Supersulfide catabolism participates in maladaptive remodeling of cardiac cells","authors":"Liuchenzi Zhou ,&nbsp;Akiyuki Nishimura ,&nbsp;Keitaro Umezawa ,&nbsp;Yuri Kato ,&nbsp;Xinya Mi ,&nbsp;Tomoya Ito ,&nbsp;Yasuteru Urano ,&nbsp;Takaaki Akaike ,&nbsp;Motohiro Nishida","doi":"10.1016/j.jphs.2024.05.002","DOIUrl":"https://doi.org/10.1016/j.jphs.2024.05.002","url":null,"abstract":"<div><p>The atrophic myocardium resulting from mechanical unloading and nutritional deprivation is considered crucial as maladaptive remodeling directly associated with heart failure, as well as interstitial fibrosis. Conversely, myocardial hypertrophy resulting from hemodynamic loading is perceived as compensatory stress adaptation. We previously reported the abundant presence of highly redox-active polysulfide molecules, termed supersulfide, with two or more sulfur atoms catenated in normal hearts, and the supersulfide catabolism in pathologic hearts after myocardial infarction correlated with worsened prognosis of heart failure. However, the impact of supersulfide on myocardial remodeling remains unclear. Here, we investigated the involvement of supersulfide metabolism in cardiomyocyte remodeling, using a model of adenosine 5′-triphosphate (ATP) receptor-stimulated atrophy and endothelin-1 receptor-stimulated hypertrophy in neonatal rat cardiomyocytes. Results revealed contrasting changes in intracellular supersulfide and its catabolite, hydrogen sulfide (H₂S), between cardiomyocyte atrophy and hypertrophy. Stimulation of cardiomyocytes with ATP decreased supersulfide activity, while H₂S accumulation itself did not affect cardiomyocyte atrophy. This supersulfide catabolism was also involved in myofibroblast formation of neonatal rat cardiac fibroblasts. Thus, unraveling supersulfide metabolism during myocardial remodeling may lead to the development of novel therapeutic strategies to improve heart failure.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"155 4","pages":"Pages 121-130"},"PeriodicalIF":3.5,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861324000392/pdfft?md5=a62f72057fa85a8a8ca86cdc6437f47b&pid=1-s2.0-S1347861324000392-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141091090","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":"Protective effects of paeonol against cognitive impairment in lung diseases","authors":"Yen-Chang Chen ,&nbsp;Jia-Hong Chen ,&nbsp;Cheng-Fang Tsai ,&nbsp;Chen-Yun Wu ,&nbsp;Chen-Ni Chang ,&nbsp;Chen-Teng Wu ,&nbsp;Wei-Lan Yeh","doi":"10.1016/j.jphs.2024.04.006","DOIUrl":"https://doi.org/10.1016/j.jphs.2024.04.006","url":null,"abstract":"<div><p>Pulmonary inflammation may lead to neuroinflammation resulting in neurological dysfunction, and it is associated with a variety of acute and chronic lung diseases. Paeonol is a herbal phenolic compound with anti-inflammatory and anti-oxidative properties. The aim of this study is to understand the beneficial effects of paeonol on cognitive impairment, pulmonary inflammation and its underlying mechanisms. Pulmonary inflammation-associated cognitive deficit was observed in TNFα-stimulated mice, and paeonol mitigated the cognitive impairment by reducing the expressions of interleukin (IL)-1β, IL-6, and NOD-like receptor family pyrin domain-containing 3 (NLRP3) in hippocampus. Moreover, elevated plasma miR-34c-5p in lung-inflamed mice was also reduced by paeonol. Pulmonary inflammation induced by intratracheal instillation of TNFα in mice resulted in immune cells infiltration in bronchoalveolar lavage fluid, pulmonary edema, and acute fibrosis, and these inflammatory responses were alleviated by paeonol orally. In MH-S alveolar macrophages, tumor necrosis factor (TNF) α- and phorbol myristate acetate (PMA)-induced inflammasome activation was ameliorated by paeonol. In addition, the expressions of antioxidants were elevated by paeonol, and reactive oxygen species production was reduced. In this study, paeonol demonstrates protective effects against cognitive deficits and pulmonary inflammation by exerting anti-inflammatory and anti-oxidative properties, suggesting a powerful benefit as a potential therapeutic agent.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"155 3","pages":"Pages 101-112"},"PeriodicalIF":3.5,"publicationDate":"2024-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861324000367/pdfft?md5=7b307097cfa192b42043d6d54d7040ec&pid=1-s2.0-S1347861324000367-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140880623","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}