Current molecular pharmacology最新文献

{"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":2.9,"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":"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":"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":"(R)-STU104 and Brefeldin-A Synergistically Enhance the Therapeutic Effect On IBD By Inhibiting the TAK1-MKK3-P38 Signaling Pathway.","authors":"Haidong Li, Xiaoyan Shen, Xiaogang Qin, Yongxia Liu","doi":"10.2174/0118761429377081250508081722","DOIUrl":"10.2174/0118761429377081250508081722","url":null,"abstract":"<p><strong>Introduction: </strong>Inflammatory Bowel Disease (IBD) imposes a huge burden on both patients and the society. Standard treatments are often ineffective and can lead to adverse effects. Biological Tumor Necrosis Factor (TNF-α) inhibitors, though effective, have issues with immunogenicity and high costs. Our study investigates the potential of Brefeldin A (BFA) and (R)-STU104 in treating IBD by targeting the Transforming Growth Factor-β-Activated Kinase 1 (TAK1) - Mitogen-Activated Protein Kinase Kinase 3 (MKK3)-p38 pathway.</p><p><strong>Methods: </strong>RAW264.7 cells (Murine Leukemia macrophage cell line) were treated with (R)-STU104 and BFA to evaluate their impact on the TAK1-MKK3- p38 pathway using Western blotting and RT-qPCR. <i>In vivo</i>, C57BL/6 mice were given Dextran Sulfate Sodium (DSS) to induce IBD, and the effects of BFA and (R)-STU104 were assessed by monitoring Disease Activity Index (DAI), colon length, and cytokine levels.</p><p><strong>Results: </strong>Both compounds inhibited the MKK3-p38 pathway and reduced TNF-α mRNA expression levels in a dose-dependent manner. Combination therapy showed an enhanced inhibitory effect, reducing mRNA levels of TNF-α, Interleukin (IL)-1β, and IL-6. In the DSS-induced IBD model, this combination alleviated symptoms, improved DAI scores, increased colon length, and reduced inflammatory cell infiltration.</p><p><strong>Discussion: </strong>This study delved into the synergistic effect of BFA combined with (R)-STU104 on IBD treatment, and revealed that this combination can more effectively inhibit inflammatory responses, as well as enhance disease condition improvement. (R)-STU104selectively suppresses TNF-α production by targeting the p38 signaling pathway, and this suppressive effect is further strengthened when used in tandem with BFA. While,the combination therapy shows potential as an effective IBD treatment strategy,additional research is necessary to confirm its clinical applicability.</p><p><strong>Conclusion: </strong>BFA and (R)-STU104 exert synergistic anti-inflammatory effects by inhibiting the TAK1-MKK3-p38 pathway, suggesting a new therapeutic approach for IBD. Further studies are required to determine the clinical potential of this combination therapy.</p>","PeriodicalId":93964,"journal":{"name":"Current molecular pharmacology","volume":" ","pages":"e18761429377081"},"PeriodicalIF":2.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144818878","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":"Empagliflozin Mitigates High Glucose-Disrupted Mitochondrial Respiratory Function in H9c2 Cardiomyoblasts: A Comparative Study with NHE-1 and ROCK Inhibition.","authors":"Cheng-I Cheng, Ming-Huei Chou, I-Ling Shih, Po-Han Chen, Ying-Hsien Kao","doi":"10.2174/0118761429360640250227054103","DOIUrl":"10.2174/0118761429360640250227054103","url":null,"abstract":"<p><strong>Background: </strong>Hyperglycemia in patients with Diabetes Mellitus (DM) increases the risk of developing cardiomyopathy and heart failure. Elevation of sodium/proton exchanger-1 (NHE-1) expression and activity in cardiomyocytes leads to greater sensitivity to neurohormonal stimulation and cardiomyopathy, whereas inhibition of Sodium-Glucose Cotransporter 2 (SGLT2) clinically benefits DM population in reducing heart failure risk.</p><p><strong>Aims: </strong>This study characterized the expression profiles of NHE-1 and SGLT2 in H9c2 cardiomyoblasts under High Glucose (HG) exposure and examined the effects of Empagliflozin (EMPA), an SGLT2 inhibitor, on the HG-induced cardiomyoblasts deterioration, in comparison with NHE-1 specific inhibitor cariporide and Rho/ROCK inhibitor hydroxy fasudil.</p><p><strong>Methods: </strong>Western blotting and immunofluorescent staining were used to monitor protein expression and subcellular location, respectively. Reactive Oxygen Species (ROS) production and mitochondrial membrane potential were measured by flow cytometry. Kinetic mitochondrial oxygen consumption rate and respiratory function were monitored by a real-time cell metabolic analyzer.</p><p><strong>Results: </strong>HG treatment upregulated SGLT2 and NHE-1 expression and RhoA/ROCK activity in H9c2 cardiomyoblasts. The HG-upregulated NHE-1 is localized in actin-rich cortical cytoplasm, implicating its involvement in cell shape and adhesion alterations. Treatment with NHE-1 and ROCK inhibitors, but not EMPA, significantly attenuated the HG-induced ROS overproduction and mitochondrial membrane potential elevation. However, EMPA treatment restored the HG-suppressed mitochondrial maximal respiration, spare respiratory capacity, and non-mitochondrial oxygen consumption rate.</p><p><strong>Conclusion: </strong>In comparison, Rho/ROCK and NHE-1 inhibitions effectively prevent ROS overproduction, while SGLT2 inhibition rescues the deteriorated mitochondrial respiratory function under diabetogenic conditions. Blockade of SGLT2, NHE-1, or Rho/ROCK activity is useful for the prevention of diabetic cardiomyopathy.</p>","PeriodicalId":93964,"journal":{"name":"Current molecular pharmacology","volume":" ","pages":"e18761429360640"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143545112","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":"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":2.9,"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}