Current molecular pharmacology最新文献

{"title":"Network Pharmacology and Bioinformatics of Flavonoids from <i>Scutellaria baicalensis stems</i>: Mitigating Aβ-Induced Cognitive Impairment in Rats <i>via</i> the MEK-ERK-CREB Pathway.","authors":"Yan Chen, Shuai Ma, Jing Huo, Shengkai Ding, Qianqian Liu, Chen Li, Yinhui Yao, Yazhen Shang","doi":"10.2174/0118761429381010250512060455","DOIUrl":"10.2174/0118761429381010250512060455","url":null,"abstract":"<p><strong>Introduction: </strong>This study investigates the effects and mechanisms of <i>Scutellaria baicalensis flavonoids</i> (SSF) on passive avoidance learning and memory deficits induced by composite amyloid-β proteins (Aβ) via the MEK-ERK-CREB signaling pathway in rats based on network pharmacology and bioinformatics.</p><p><strong>Methods: </strong>Network pharmacology and bioinformatics identified target pathways. An Alzheimer's disease model was induced in male wistar rats using Aβ_25-35, AlCl₃, and RHTGF-β₁(referred to as compound Aβ). Memory impairment was confirmed with the Morris water maze. Modeled rats were assigned to a control group and three SSF-treated groups for 33 days. Passive avoidance learning abilities were assessed with a step-down test, and p-crebser133 expression in the hippocampus was detected via immunohistochemistry. Real-time qPCR and western blotting measured mRNA and protein levels of c-Raf, MEKs, Rsk, and zif268 in the hippocampus and cortex.</p><p><strong>Results: </strong>Pathways such as the calcium signaling pathway, Apelin signaling pathway and cAMP signaling pathway were highlighted by KEGG analysis. The model had an 83.30% success rate. Model rats showed dry coats and unresponsiveness, while SSF treatment improved appearance and behavior. In passive avoidance tests, model rats made more errors and had shorter latencies (P < 0.01). They also showed decreased p-CREBSer133 and increased c-Raf, Rsk, and P-MEKs levels (P < 0.01), with reduced Zif268 (P < 0.01). SSF reversed these effects, enhancing p-CREBSer133 and Zif268 while regulating c-Raf, Rsk, and P-MEKs (P < 0.01).</p><p><strong>Conclusion: </strong>SSF ameliorates learning and memory impairments induced by composite Aβ, acting through the MEK-ERK-CREB pathway in rats.</p>","PeriodicalId":93964,"journal":{"name":"Current molecular pharmacology","volume":" ","pages":"e18761429381010"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144113131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracts from Artemisia annua Alleviates Myocardial Remodeling through TGF-β1/Smad2/3 Pathway and NLRP3 Inflammasome","authors":"Zizhe Ma, Zhenzhou Bai, Bohan Li, Yue Zhang, Wei Liu","doi":"10.2174/0118761429304142240528093541","DOIUrl":"10.2174/0118761429304142240528093541","url":null,"abstract":"<p><strong>Background and objectives: </strong>Artemisinin and its derivatives, the well-known anti-malarial drugs extracted from traditional Chinese medicine, Artemisia annua, have been implicated in treating fibrotic diseases. However, whether artemisinin affects cardiac fibrosis in the pathogenesis of heart failure is still unknown. This study aimed to evaluate the possible effects of artemisinin on cardiac function and myocardial fibrosis in the heart failure model and to explore the underlying mechanisms.</p><p><strong>Methods: </strong>Isoproterenol was injected subcutaneously for induction of the cardiac fibrosis model. Proteomic analysis was performed after 4 four weeks of artemisinin treatment. Echocardiography was used to evaluate cardiac function and structure. Hematoxylin and eosin (H&E) staining, as well as Masson trichrome staining, were performed for histopathology. The α-SMA, collagen I, and III expression in the myocardium was detected by immunohistochemical staining. The ratio of heart weight to body weight (HW/BW, mg/kg) and the ratio of heart weight to tibia length (HW/TL, mg/mm) were calculated as indicators for cardiac remodeling. Brain natriuretic peptide (BNP) levels were quantified in rat plasma using enzymelinked immunosorbent assay (ELISA). In contrast, the protein levels of TGF-β1, p-Smad2/3, and Smad2/3 were assessed in the myocardium and\u0000fibroblasts via western blot analysis. RT-qPCR was performed to analysis the expression of Col-I, Col-III, α-SMA, NLRP3, Caspase-1, IL-1β, and\u0000IL-18.</p><p><strong>Results: </strong>Proteomic analysis identified 227 differentially expressed proteins (DEPs), including 119 upregulated and 108 downregulated proteins. These proteins were identified as the core proteins targeted by artemisinin for improving myocardial remodeling. GO annotation of the DEPs indicated that the DEPs were mainly associated with biological processes such as inflammation regulation. In the in vivo study of an isoproterenol-induced\u0000rat cardiac remodeling model, we found that artemisinin administration significantly ameliorated cardiac dysfunction and reduced collagen production by suppressing TGFβ-1/Smads signaling and inhibiting NLRP3 inflammasome activation. As manifested by downregulating the expression of α-SMA, Col-I, and Col-III, NLRP3, IL-1β, IL-18, Caspase-1 mRNA, and TGF-β1, p-SMAD 2/3 protein in the myocardium. Similar beneficial effects of artemisinin were consistently observed in TGF-β1 treated primary cardiac fibroblasts.</p><p><strong>Conclusions: </strong>Extracts from Artemisia annua relieves myocardial remodeling through TGF-β1/Smad2/3 pathway and NLRP3 inflammasome</p>","PeriodicalId":93964,"journal":{"name":"Current molecular pharmacology","volume":" ","pages":"e18761429304142"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141461314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Pharmacological Mechanisms of P-hydroxylcinnamaldehyde for Treating Gastric Cancer: A Pharmacological Perspective with Experimental Confirmation.","authors":"Sumaya Fatima, Yanru Song, Zhe Zhang, Yuhui Fu, Ruinian Zhao, Khansa Malik, Lianmei Zhao","doi":"10.2174/0118761429322420241112051105","DOIUrl":"10.2174/0118761429322420241112051105","url":null,"abstract":"<p><strong>Background: </strong>Momordica cochinchinensis is a dried and mature seed of Cucurbitaceae plants, which has the effect of dispersing nodules, detumescence, attacking poison, and treating sores, and is used in the treatment of tumors in the clinic. P-hydroxylcinnamaldehyde (CMSP) is an ethanol extract of cochinchina momordica seed (CMS). Our previous studies have found that CMSP is an effective anti-tumor component with good anti-tumor effects on melanoma and esophageal tumors. However, the inhibitory effect of CMSP on gastric cancer (GC) and its potential mechanism remain to be further elucidated.</p><p><strong>Methods: </strong>First, we utilized network pharmacology to predict potential targets and mechanisms of action for the treatment of GC. Subsequently, a series of biological function experiments were conducted to assess the effects of CMSP on the proliferation and apoptosis of GC cells in vitro. To elucidate the molecular mechanism of CMSP, bioinformatics and high-efficiency liquid chromatography tandem mass spectrometry (HPLC-MS/MS) were employed for analysis. Additionally, a resistant cell line of the chemotherapy drug paclitaxel for GC was established, and the impact of 10μg/mL CMSP on the sensitivity of GC-resistant cells was examined.</p><p><strong>Results: </strong>The network pharmacology results demonstrated that the active components of CMS exert an anti-GC effect through multi-target and multipathway mechanisms. The main pathways involved included the PI3K/Akt pathway, p53 signaling pathway, multi-species apoptosis pathway, as well as ADRB2 and CAV1 genes. Cell experiments revealed that CMSP can effectively inhibit the proliferation and induce apoptosis of GC cells in vitro. However, it did not show any sensitizing effect on paclitaxel-resistant cells. Importantly, CMSP exhibited no toxic or side effects on normal gastric epithelial cells. Furthermore, differential protein expression patterns following CMSP treatment were elucidated using HPLCMS/ MS and western blot analysis, highlighting its role in regulating apoptosis signaling pathways.</p><p><strong>Conclusion: </strong>Our study presents novel evidence regarding pertinent potential target genes and signaling pathways through which CMSP mediates its anti-GC effects, with a particular emphasis on its role in modulating apoptotic signaling pathways. Collectively, these findings underscore the promising candidacy of CMSP as a therapeutic agent for GC that merits further investigation in clinical contexts.</p>","PeriodicalId":93964,"journal":{"name":"Current molecular pharmacology","volume":"17 1","pages":"e18761429322420"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142808842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating the Anti-inflammatory Efficacy of a Novel Bipyrazole Derivative in Alleviating Symptoms of Experimental Colitis.","authors":"Yousra Bseiso, Omar Gammoh, Mohammad Alqudah, Sara Altaber, Esam Qnais, Mohammed Wedyan, Abdelrahim Alqudah, Badriyah S Alotaibi","doi":"10.2174/0118761429333261241021034043","DOIUrl":"10.2174/0118761429333261241021034043","url":null,"abstract":"<p><strong>Aims: </strong>This aims to assess the efficacy of 2', 3, 3, 5'-Tetramethyl-4'-nitro-2'H-1, 3'-bipyrazole (TMNB), a novel compound, in colitis treatment.</p><p><strong>Background: </strong>Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract with limited effective treatments available. The exploration of new therapeutic agents is critical for advancing treatment options.</p><p><strong>Objective: </strong>To assess the effect of TMNB in alleviating symptoms of experimental colitis in mice and to compare its effectiveness with that of sulfasalazine, a standard treatment.</p><p><strong>Methods: </strong>Experimental colitis was induced in mice, which were subsequently treated with TMNB at dosages of 50, 100, and 150 mg/kg. The outcomes were evaluated based on colitis symptoms, Colon damage, Disease Activity Index (DAI) scores, and inflammation markers, including nitric oxide (NO) and myeloperoxidase (MPO) levels. Additional assessments included spleen cell proliferation, pro-inflammatory cytokine production (TNF-&#945;, IL-6, IL-1&#946;), and inflammatory genes expression (IL-1&#946;, IL-6, TNF-&#945;, COX2, and iNOS).</p><p><strong>Results: </strong>TMNB treatment significantly alleviated colitis symptoms (100 and 150 mg/kg). These higher doses notably reduced colonic damage, inflammation, hyperemia, edema, and ulceration (p&#60;0.01). The treatment also effectively decreased Disease Activity Index (DAI) scores, demonstrating a marked improvement in clinical signs of colitis (100 mg/kg, p&#60;0.05; 150 mg/kg, p&#60;0.01). Additionally, TMNB substantially lowered myeloperoxidase (MPO) levels, indicating reduced neutrophil activity and inflammation (100 mg/kg, p&#60;0.05; 150 mg/kg, p&#60;0.01), and nitric oxide (NO) levels, suggesting diminished oxidative stress (100 mg/kg, p&#60;0.05; 150 mg/kg, p&#60;0.01). The treatment also led to a significant reduction in spleen cell proliferation (100 mg/kg, p&#60;0.05; 150 mg/kg, p&#60;0.01) and pro-inflammatory cytokine levels, with TNF-&#945;, IL-1&#946;, and IL-6 all showing decreases comparable to those observed with sulfasalazine (p&#60;0.01). Moreover, TMNB effectively downregulated IL-1&#946;, IL-6, TNF-&#945;, COX2, and iNOS (p&#60;0.01), affirming its broad-spectrum anti-inflammatory and immunomodulatory effects.</p><p><strong>Conclusion: </strong>TMNB exhibits potent anti-inflammatory and immunomodulatory activities, suggesting that TMNB could be a new therapeutic agent for managing inflammatory bowel disease. This study supports the need for further clinical trials to explore TMNB's efficacy and safety in human subjects.</p>","PeriodicalId":93964,"journal":{"name":"Current molecular pharmacology","volume":"17 1","pages":"e18761429333261"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142741652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aloperine Alleviates Atherosclerosis by Inhibiting NLRP3 Inflammasome Activation in Macrophages and ApoE^-/- Mice.","authors":"Zengxu Wang, Yuchuan Wang, Faisal Raza, Hajra Zafar, Chunling Guo, Weihua Sui, Yongchao Yang, Ran Li, Yifen Fang, Bao Li","doi":"10.2174/0118761429342447241214044859","DOIUrl":"10.2174/0118761429342447241214044859","url":null,"abstract":"<p><strong>Background and aims: </strong>Atherosclerosis is a chronic cardiovascular disease which is regarded as one of the most common causes of death in the elderly. Recent evidence has shown that atherosclerotic patients can benefit by targeting interleukin-1 beta (IL-1β). Aloperine (ALO) is an alkaloid which is mainly isolated from <i>Sophora alopecuroides</i> L. and has been recognized as an anti-inflammatory disease. Herein, the effect of ALO on atherosclerosis was investigated.</p><p><strong>Methods: </strong>ApoE^-/- mice fed with western diet received ALO once daily. Plaques in the aortas were evaluated using oil red O and hematoxylin & eosin (H&E) staining. Inflammation, lipids and kinases phosphorylation levels were evaluated using ELISA assay and western blot. Pyroptosis was examined by THP-1 cells treated with oxidized low-density lipoprotein (ox-LDL).</p><p><strong>Results: </strong>Plaque development in aortic sinus and <i>en face</i> aortas were reduced after ALO treatment in ApoE^-/- miceTreatment with ALO ameliorated inflammation and profile of blood lipid. Western blot assay showed that ALO treatment substantially inhibited phosphorylation of p38 and Jun Nterminal kinase (JNK) in aorta of ApoE^-/- mice. Meanwhile, ALO significantly inhibited levels of IL-1β and IL-18 in serum and cleaved caspase-1 and IL-1β expression in aorta of ApoE^-/- mice. Interestingly, ALO mildly increased pro-caspase-1 expression in ApoE^-/- aorta in comparison with saline group. In a dose dependent fashion, ALO treatment markedly inhibited ox-LDL-induced IL-1β and IL-18 levels in THP-1 cells and reduced cleaved caspase-1 and IL-1β expression and caspase-1 activity, while ALO had little effect on nod-like receptor protein containing pyrin-3 (NLRP3), apoptosis associated speck-like protein containing a caspase-1 recruitment domain (ASC).</p><p><strong>Conclusion: </strong>It is of great practical significance to find the natural product to regulate macrophage pyroptosis, which are key drivers to accelerate the progression of atherosclerosis. ALO could inhibit NLRP3 inflammasome activation in macrophages during atherogenesis, which may serve as a potential candidate for the treatment of atherosclerosis.</p>","PeriodicalId":93964,"journal":{"name":"Current molecular pharmacology","volume":"17 ","pages":"e18761429342447"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143018215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to: Progress of Angiogenesis Signal Pathway and Antiangiogenic Drugs in Nasopharyngeal Carcinoma.","authors":"Yunzhi Zhu, Yi Hu, Chengsheng Yang, Shipu Huang, Jianping Wen, Weiguo Huang, Shengjun Xiao","doi":"10.2174/187446721701240918095836","DOIUrl":"https://doi.org/10.2174/187446721701240918095836","url":null,"abstract":"<p><p>In the online version of the article titled 'Progress of Angiogenesis Signal Pathway and Antiangiogenic Drugs in Nasopharyngeal Carcinoma' published in Current Molecular Pharmacology (2024; 2: e18761429290933), a change was made in the author position. [1]. The original article can be found online at: https://www.eurekaselect.com/article/139869 Original: Yunzhi Zhu1,3,#, Yi Hu2,#, Chengsheng Yang1, Shipu Huang1, Jianping Wen4,#, Weiguo Huang1,3,# and Shengjun Xiao1,3,* Corrected: Yunzhi Zhu1,3,#, Yi Hu2,#, Chengsheng Yang1, Shipu Huang1, Jianping Wen4,*, Weiguo Huang1,3,* and Shengjun Xiao1,3,.</p>","PeriodicalId":93964,"journal":{"name":"Current molecular pharmacology","volume":"17 ","pages":"e180924234131"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144259695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tangeretin in the Treatment of Pulmonary Fibrosis: Current Advances and Future Perspectives","authors":"Ling-Jie Wang, Peng-Fei Guo, Yi-Zhao Chen, Hong-Wang Yan, Xue-Lin Zhang","doi":"10.2174/0118761429385520250508041438","DOIUrl":"10.2174/0118761429385520250508041438","url":null,"abstract":"<p><p>Pulmonary fibrosis seriously endangers human health, with its incidence and mortality rates steadily increasing. Current treatment methods have limitations. This review focused on the research progress and future prospects of tangeretin in the treatment of pulmonary fibrosis. Tangeretin, a compound derived from the peel of citrus fruits, has garnered attention in pulmonary fibrosis research due to its unique chemical structure and its background in traditional medical applications. This paper discussed the pathological mechanisms of pulmonary fibrosis, including the initiation and persistent inflammation, abnormal activation and proliferation of fibroblasts, imbalance in extracellular matrix (ECM) metabolism, and the cycle of oxidative stress injury. Tangeretin has shown potential therapeutic effects, including anti-inflammation, regulation of ECM metabolism, and antioxidative stress activities. This paper reviewed the current research progress and possible therapeutic effects of tangeretin on pulmonary fibrosis and proposed future research directions for its application</p>","PeriodicalId":93964,"journal":{"name":"Current molecular pharmacology","volume":" ","pages":"e18761429385520"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144082852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alnustone: A Review of its Sources, Pharmacology, and Pharmacokinetics","authors":"Zahra Salari, Maryam Alavi, Hojjat Rezaii-Zadeh, Abdelhakim Bouyahya, Ammar Alfergah, Sahar Afsari Sardari, Ehsan Amiri-Ardekani","doi":"10.2174/0118761429252459231115060139","DOIUrl":"10.2174/0118761429252459231115060139","url":null,"abstract":"<p><p>Alnustone (4(E)-,6(E)-1,7-Diphenyl-hepta-4,6-dien-3-one) is a non-phenolic natural diarylheptanoid, which was first isolated and identified from the male flower of Alnus pendula (Betulaceae). It can also be isolated from Curcuma xanthorrhiza Roxb (Zingiberaceae) rhizomes and Alpinia katsumadai Hayata (Zingiberaceae) seeds. It was first synthesized through a five-step process from β-phenyl propionyl chloride. In later years, new methods for synthesizing Alnustone were designed and performed with different yields. Due to the various therapeutic effects exhibited by alnustone like other diarylheptanoids, its biological activities such as antioxidant, antibacterial, and anti-inflammatory properties have been the subject of many studies.\u0000\u0000This article has reviewed different aspects of this valuable natural compound, including its natural and synthetic sources, therapeutic effects, and pharmacokinetics as a potential future therapeutic agent.</p>","PeriodicalId":93964,"journal":{"name":"Current molecular pharmacology","volume":" ","pages":"e18761429252459"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139572447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Dapagliflozin in the Modulation of Hypothermia and Renal Injury Caused by Septic Shock in Euglycemic and Hyperglycemic Rat Models.","authors":"Wael A Alanazi, Turki Alharbi, Khalid M Bin Anzan, Musab K Alyahiya, Doaa M El-Nagar, Mohammed M Alanazi, Mohammed M Almutairi, Hussain N Alhamami, Abdullah M Albogami, Mohamed Mohany","doi":"10.2174/0118761429329635241016054513","DOIUrl":"10.2174/0118761429329635241016054513","url":null,"abstract":"<p><strong>Background: </strong>Recent research has validated the efficacy of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in reducing glucose levels and exerting a nephroprotective role.</p><p><strong>Objective: </strong>This study aimed to examine the impact of dapagliflozin in preventing sepsis-induced acute kidney injury (AKI) and related consequences. The study used both normal and diabetic rat models to investigate whether the effectiveness of dapagliflozin is influenced by glycemia levels.</p><p><strong>Methods: </strong>Normal and diabetic Wistar albino rats were treated with dapagliflozin for two weeks and then received a single dose of lipopolysaccharide (LPS). After sepsis induction, skin and deep body temperatures were recorded every two hours. Blood and kidneys were collected for analysis using histological examination and biochemical assays.</p><p><strong>Results: </strong>Dapagliflozin attenuated the consequences of sepsis through mitigation of LPS-induced hypothermia and AKI in the normal and diabetic septic groups. Dapagliflozin regulated the serum levels of AKI markers, including creatinine and blood urea nitrogen, as well as ion levels. Dapagliflozin attenuated LPS-induced AKI through modulation of renal inflammation and oxidative stress, which showed well-abundant glomeruli. These results indicated the protective effect of dapagliflozin against LPS-induced hypothermia and AKI, which was likely unrelated to its glucose-lowering properties, as evidenced in the non-diabetic septic group.</p><p><strong>Conclusion: </strong>The outcomes suggest that dapagliflozin has a potential impact in preventing sepsis-induced hypothermia and AKI via modulation of inflammation and oxidative stress, irrespective of glycemic levels.</p>","PeriodicalId":93964,"journal":{"name":"Current molecular pharmacology","volume":"17 1","pages":"e18761429329635"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142820394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stimulation of Soluble Guanylyl Cyclase (sGC) by Cinaciguat Attenuates Sepsisinduced Cardiac Injury","authors":"Wanqian Li, Cheng Zheng, Xijiang Zhang, Binhui Wang, Enjian Shen, Lingjun Wang, Guang Chen, Ronghai Lin","doi":"10.2174/0118761429387280250506114040","DOIUrl":"10.2174/0118761429387280250506114040","url":null,"abstract":"<p><strong>Background: </strong>Cinaciguat is a soluble Guanylyl Cyclase (sGC) activator that plays a crucial role in cardiovascular diseases. Previous research has shown that cinaciguat is involved in the progression of cardiomyopathy, which encompasses cardiac enlargement, heart dysfunction, and doxorubicin-induced heart damage. However, its therapeutic potential in sepsis-induced cardiomyopathy remains unknown.</p><p><strong>Objectives: </strong>This study examined the impact of cinaciguat on Lipopolysaccharide (LPS)-induced myocardial injury and the underlying molecular mechanisms.</p><p><strong>Methods: </strong>The mice model was established through intraperitoneal injection of LPS (10 mg/kg), and an <i>in vitro</i> model was generated by stimulating H9C2 cells with LPS (10 μg/ml) for 12 h. Subsequently, the sGC activator cinaciguat was used to assess its effects on LPS-induced cardiac injury. Additionally, echocardiography was conducted 12 hours after modeling to analyze cardiac function in mice. We used various methods to evaluate inflammation, and apoptosis, including Enzyme-Linked Immunosorbent Assay (ELISA), terminal deoxynucleotidyl transferase-mediated deoxyuridine Triphosphate Nick End Labeling (TUNEL) assay, Hematoxylin and Eosin (H&E) staining, western blotting and Real-Time Polymerase Chain Reaction (RT-PCR). Additionally, the protein kinase cGMP-dependent 1 (PRKG1)/cAMP-Response Element Binding protein (CREB) signaling pathway and Mitochondrial Ferritin (FtMt) in LPS-induced cardiac injury was assessed via Western blot analysis.</p><p><strong>Results: </strong>LPS-induced cardiac dysfunction and increased levels of cardiac injury markers Cardiac Troponin T (cTnT) <i>in vivo</i> . This change was accompanied by an increase in inflammatory cytokines through Interleu-1β (IL-1β), Tumor Necrosis Factor α (TNF-α), and Interleu-6 (IL-6). The expression of apoptosis, such as cleaved caspase-3, Bax, and Bcl-2, was also upregulated. However, these effects were reversed via treatment with cinaciguat. Additionally, cinaciguat alleviated LPS-induced cardiac inflammation and apoptosis by activating the PRKG1/CREB signaling pathway, and promoting FtMt expression. The same results were also obtained in H9C2 cardiomyocytes.</p><p><strong>Conclusion: </strong>We demonstrated that cinaciguat alleviated LPS-induced cardiac dysfunction, inflammation, and apoptosis through the PRKG1/CREB/FtMt pathway, thereby protecting against LPS-induced cardiac injury. This study identified a new strategy for treating cardiac injury caused by sepsis.</p>","PeriodicalId":93964,"journal":{"name":"Current molecular pharmacology","volume":" ","pages":"e18761429387280"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144113135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}