Journal of Pharmacy and Pharmacology最新文献

{"title":"Unravelling the role of dipeptidyl peptidases-8/9 (DPP-8/9) in inflammatory osteoporosis: a comprehensive study investigating chrysin as a potential anti-osteoporotic agent.","authors":"Syed Sufian Ahmad, Faraha Ahmed, Mohd Mumtaz Alam, Sayeed Ahmad, Mohammad Ahmed Khan","doi":"10.1093/jpp/rgae109","DOIUrl":"https://doi.org/10.1093/jpp/rgae109","url":null,"abstract":"<p><strong>Objectives: </strong>This study aimed to investigate the role of dipeptidyl peptidase-8 and 9 (DPP-8/9) enzymes in inflammatory bone loss using a 4-vinylcyclohexene diepoxide (VCD)-induced model in Wistar rats. Additionally, we evaluated the therapeutic potential of inhibiting these enzymes with the flavonoid chrysin.</p><p><strong>Methods: </strong>Inflammatory osteoporosis was induced by administering VCD that elevated interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α) levels. DPP-8/9 enzyme expression and various bone markers were assayed using serum. Further analysis included bone microarchitecture, histology, and immunohistochemistry. Additionally, chrysin's potential to inhibit DPP-8/9 and mitigate VCD-induced inflammatory bone loss was also evaluated.</p><p><strong>Key findings: </strong>VCD administration in rats caused ovotoxicity that increased IL-6 and TNF-α levels, resulting in significant bone loss. Serum analysis revealed elevated bone resorption markers and DPP-8/9 enzyme levels. Inhibiting DPP-8/9 with 1G244 reversed these effects, confirmed by histology, immunohistochemistry, and micro-CT scans. Moreover, chrysin significantly reduced DPP-8/9 levels compared with the untreated group, improved bone markers, and lower inflammatory cytokines, indicating reduced osteoclastogenesis.</p><p><strong>Conclusion: </strong>This study highlights the role of DPP-8/9 in inflammation-induced osteoporosis. Following inhibition of DPP-8/9, we observed improved bone markers with preservation of trabecular bone mineral density in rats. Additionally, chrysin demonstrated potential as an anti-DPP-8/9 agent, suggesting its viability for future therapeutic interventions in DPP-8/9-related inflammatory diseases.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142133055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preparation, characteristic, biological activities, and application of polysaccharide from Lilii Bulbus: a review.","authors":"Xueqin Duan, Huicong Li, Zhenwei Sheng, Weimin Zhang, Yingqiu Liu, Wuren Ma, Dezhang Lu, Lin Ma, Yunpeng Fan","doi":"10.1093/jpp/rgae078","DOIUrl":"10.1093/jpp/rgae078","url":null,"abstract":"<p><strong>Objectives: </strong>This review highlights the current knowledge of polysaccharide from Lilii Bulbus, including the extraction, purification, structure, structure modification, biological activities and application, which will hopefully provide reference for further research and development of polysaccharide from Lilii Bulbus.</p><p><strong>Materials and methods: </strong>Literature searches were conducted on the following databases: Pubmed, ACS website, Elsevier, Google Scholar, Web of Science and CNKI database. Keywords such as \"Lilii Bulbus\", \"polysaccharide\", \"preparation\", \"biological activities\" and \"application\" were used to search relevant journals and contents, and some irrelevant contents were excluded.</p><p><strong>Results: </strong>In general, the study of Lilium Bulbus polysaccharide extraction and purification, structure characterization and biological activity has made substantial progress, these findings highlight the lilium brownii polysaccharide enormous potential in biomedical applications, of lilium brownii polysaccharide laid a solid foundation for further research.</p><p><strong>Discussion and conclusions: </strong>However, it should be noted that the relevant mechanism of the effective effect of lily bulb polysaccharide still needs to be worked on by researchers. These findings highlight the great potential of lily polysaccharides in biomedical applications, and lay a solid foundation for further research on lily polysaccharides.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"1132-1148"},"PeriodicalIF":2.8,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141419560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anoectochilus roxburghii polysaccharide reduces D-GalN/LPS-induced acute liver injury by regulating the activation of multiple inflammasomes.","authors":"Yulu Yan, Xiqi Ye, Chunqing Huang, Junjun Wu, Yunbiao Liu, Pingping Zheng, Congqi Shen, Zhaofang Bai, Shen Tingming","doi":"10.1093/jpp/rgae077","DOIUrl":"10.1093/jpp/rgae077","url":null,"abstract":"<p><strong>Background: </strong>Acute liver injury (ALI) is a serious syndrome with a high mortality rate due to viral infection, toxic exposure, and autoimmunity, and its severity can range from mildly elevated liver enzymes to severe liver failure. Activation of the nod-like receptor pyrin domain-containing 3 (NLRP3) inflammasome is closely associated with the development of ALI, and the search for an inhibitor targeting this pathway may be a novel therapeutic option. Anoectochilus roxburghii polysaccharide (ARP) is a biologically active ingredient extracted from Anoectochilus roxburghii with immunomodulatory, antioxidant, and anti-inflammatory bioactivities and pharmacological effects. In this study, we focused on D-galactosamine (D-GalN)/lipopolysaccharide (LPS)-induced acute liver injury by ARP through inhibition of NLRP3 inflammasome.</p><p><strong>Methods: </strong>An inflammasome activation model was established in bone marrow-derived macrophages (BMDMs) to investigate the effects of ARP on caspase-1 cleavage, IL-1β secretion, and ASC oligomerization in inflammasomes under different agonists. We used the D-GalN/LPS-induced acute liver injury model in mice, intraperitoneally injected ARP or MCC950, and collected liver tissues, serum, and intraperitoneal lavage fluid for pathological and biochemical indexes.</p><p><strong>Results: </strong>ARP effectively inhibited the activation of the NLRP3 inflammasome and had an inhibitory effect on non-classical NLRP3, AIM2, and NLRC4 inflammasomes. It also effectively inhibited the oligomerization of apoptosis-associated speck-like protein (ASC) from a variety of inflammatory vesicles. Meanwhile, ARP has good therapeutic effects on acute liver injury induced by D-GaIN/LPS.</p><p><strong>Conclusion: </strong>The inhibitory effect of ARP on a wide range of inflammasomes, as well as its excellent protection against acute liver injury, suggests that ARP may be a candidate for acute liver injury.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"1212-1224"},"PeriodicalIF":2.8,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141580018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Shengqing Jiangzhuo capsule ameliorates diabetic nephropathy by improving Keap1/Nrf2 signaling pathway.","authors":"Yanna Yu, Min Li, Weijie Lai, Xin Dong, Shu Zhang, Liangyou Zhang, Gangyi Chen","doi":"10.1093/jpp/rgae095","DOIUrl":"10.1093/jpp/rgae095","url":null,"abstract":"<p><strong>Background: </strong>Diabetic nephropathy (DN) is a major contributor to end-stage renal failure, and lacking effective treatment options. Shengqing Jiangzhuo capsule (SQJZJN), a traditional Chinese medicine prescription with known efficacy in chronic kidney disease, has not been thoroughly investigated for its potential in DN protection.</p><p><strong>Methods: </strong>Eight-week-old male C57BLKS/J db/db, C57BLKS/J db/m mice, and human glomerular mesangial cell (HMC) cells cultured with high glucose were used as experimental models in this study.</p><p><strong>Results: </strong>The in vivo investigation showed that SQJZJN can significantly ameliorate renal pathological damage, reduce serum creatinine, and lower urinary microalbumin levels in db/db mice. In vitro, SQJZJN treatment mitigated advanced glycation end products (AGEs) and reactive oxygen species (ROS), leading to a reduction in renal cell apoptosis. Mechanistically, SQJZJN activated the Keap1/Nrf2/ARE pathway by promoting nuclear factor erythroid-derived 2-related factor 2 (Nrf2), γ-glutamylcysteine synthetase heavy subunit (γ-GCS), and Heme oxygenase-1 (HO-1) expressions, while decreasing Kelch-like ECH-associated protein 1 (KEAP1) expressions.</p><p><strong>Conclusion: </strong>These findings suggest that SQJZJN exerts a protective effect on DN, potentially through the activation of the Keap1/Nrf2/ARE pathway.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"1149-1159"},"PeriodicalIF":2.8,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141603724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: FoxO1 as the critical target of puerarin to inhibit osteoclastogenesis and bone resorption.","authors":"","doi":"10.1093/jpp/rgae052","DOIUrl":"10.1093/jpp/rgae052","url":null,"abstract":"","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"1238"},"PeriodicalIF":2.8,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140856857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunotherapy in Alzheimer's disease: focusing on the efficacy of gantenerumab on amyloid-β clearance and cognitive decline.","authors":"Ali Azargoonjahromi","doi":"10.1093/jpp/rgae066","DOIUrl":"10.1093/jpp/rgae066","url":null,"abstract":"<p><p>Gantenerumab, a human monoclonal antibody (mAb), has been thought of as a potential agent to treat Alzheimer's disease (AD) by specifically targeting regions of the amyloid-β (Aβ) peptide sequence. Aβ protein accumulation in the brain leads to amyloid plaques, causing neuroinflammation, oxidative stress, neuronal damage, and neurotransmitter dysfunction, thereby causing cognitive decline in AD. Gantenerumab involves disrupting Aβ aggregation and promoting the breakdown of larger Aβ aggregates into smaller fragments, which facilitates the action of Aβ-degrading enzymes in the brain, thus slowing down the progression of AD. Moreover, Gantenerumab acts as an opsonin, coating Aβ plaques and enhancing their recognition by immune cells, which, combined with its ability to improve the activity of microglia, makes it an intriguing candidate for promoting Aβ plaque clearance. Indeed, the multifaceted effects of Gantenerumab, including Aβ disaggregation, enhanced immune recognition, and improved microglia activity, may position it as a promising therapeutic approach for AD. Of note, reports suggest that Gantenerumab, albeit its capacity to reduce or eliminate Aβ, has not demonstrated effectiveness in reducing cognitive decline. This review, after providing an overview of immunotherapy approaches that target Aβ in AD, explores the efficacy of Gantenerumab in reducing Aβ levels and cognitive decline.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"1115-1131"},"PeriodicalIF":2.8,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141071355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: 1H-NMR-based metabolomics to dissect the traditional Chinese medicine promotes mesenchymal stem cell homing as intervention in liver fibrosis in mouse model of Wilson's disease.","authors":"","doi":"10.1093/jpp/rgae036","DOIUrl":"10.1093/jpp/rgae036","url":null,"abstract":"","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"1236"},"PeriodicalIF":2.8,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140288407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative pharmacokinetics of five primary constituents in Huai-hua powder: a study on normal rats and rats with ulcerative colitis.","authors":"Yiwei Shi, Guoyue Zhong, Huilian Huang, Nazhi Li, Jinxiang Zeng, Jixiao Zhu, Jinbin Yuan, Jian Liang","doi":"10.1093/jpp/rgae062","DOIUrl":"10.1093/jpp/rgae062","url":null,"abstract":"<p><strong>Objectives: </strong>The goal of this research was to develop a fast, reliable, and sensitive method to simultaneously quantify five key components of Huai-hua Powder (HHP) in rat plasma with genistein served as the internal standard. Furthermore, the established method was used to perform a comparative evaluation of the pharmacokinetic properties of HHP in normal rats and rats with ulcerative colitis (UC).</p><p><strong>Methods: </strong>Chromatographic separation was conducted using an ACQUITY HSS T3 column held at a constant temperature of 35°C, with acetonitrile and a 0.1% formic acid solution in water employed as the mobile phases. Multiple-reaction monitoring facilitated MS operation in positive-negative-ion-switching mode. The method's validation demonstrated exceptional linearity (with a correlation coefficient of r ≥ 0.9970), and the validation tests, encompassing precision within and between days, accuracy, recovery, matrix effect, and stability; all met the predefined acceptable criteria.</p><p><strong>Key findings: </strong>The results revealed significant variations in the pharmacokinetic characteristics of the five components between normal and UC rats, suggesting altered drug metabolism rates and extents in the latter group.</p><p><strong>Conclusions: </strong>These findings offer crucial scientific insights into the potential clinical application of HHP, particularly in the context of treating UC.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"1160-1168"},"PeriodicalIF":2.8,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141442909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In silico evidence of bitopertin's broad interactions within the SLC6 transporter family.","authors":"Gustavo Almeida de Carvalho, Paul Magogo Tambwe, Lucas Rodrigues Couto Nascimento, Bruna Kelly Pedrosa Campos, Raphaela Almeida Chiareli, Guilhermino Pereira Nunes Junior, Ricardo Menegatti, Renato Santiago Gomez, Mauro Cunha Xavier Pinto","doi":"10.1093/jpp/rgae051","DOIUrl":"10.1093/jpp/rgae051","url":null,"abstract":"<p><p>The Glycine Transporter Type 1 (GlyT1) significantly impacts central nervous system functions, influencing glycinergic and glutamatergic neurotransmission. Bitopertin, the first GlyT1 inhibitor in clinical trials, was developed for schizophrenia treatment but showed limited efficacy. Despite this, bitopertin's repositioning could advance treating various pathologies. This study aims to understand bitopertin's mechanism of action using computational methods, exploring off-target effects, and providing a comprehensive pharmacological profile. Similarity Ensemble Approach (SEA) and SwissTargetPrediction initially predicted targets, followed by molecular modeling on SWISS-MODEL and GalaxyWeb servers. Binding sites were identified using PrankWeb, and molecular docking was performed with DockThor and GOLD software. Molecular dynamics analyses were conducted on the Visual Dynamics platform. Reverse screening on SEA and SwissTargetPrediction identified GlyT1 (SLC6A9), GlyT2 (SLC6A5), PROT (SLC6A7), and DAT (SLC6A3) as potential bitopertin targets. Homology modeling on SwissModel generated high-resolution models, optimized further on GalaxyWeb. PrankWeb identified similar binding sites in GlyT1, GlyT2, PROT, and DAT, indicating potential interaction. Docking studies suggested bitopertin's interaction with GlyT1 and proximity to GlyT2 and PROT. Molecular dynamics confirmed docking results, highlighting bitopertin's target stability beyond GlyT1. The study concludes that bitopertin potentially interacts with multiple SLC6 family targets, indicating a broader pharmacological property.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"1199-1211"},"PeriodicalIF":2.8,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141563587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vivo and in silico elucidation of possible potential and mechanisms involved in the analgesic action of ethanolic extract of Lavandula Stoechas.","authors":"Muhammad Muzammil Nazir, Sana Inam, Muhammad Umar Ijaz, Nimrah Zafar, Derya Karatas Yeni, Farkhanda Asad, Iqra Farzeen, Asma Ashraf","doi":"10.1093/jpp/rgae072","DOIUrl":"10.1093/jpp/rgae072","url":null,"abstract":"<p><strong>Objectives: </strong>Our research focused on plant's ethanolic extract Lavandula stoechas flower part to investigate the potential analgesic effects and possible pathways involvements.</p><p><strong>Methods: </strong>Four experimental tests were performed on Swiss albino mice with five animals in each group at different doses (50, 100, and 200mg/kg); formalin test, tail-flick test, acetic acid-induced writhing, and hot-plate test. The opioidergic, noradrenergic, cholinergic, and K channel blockers in the analgesic actions were also carried out for the potential route involvement.</p><p><strong>Key finding: </strong>The percentage inhibition for abdominal writhing's and formalin activity showed a dose-dependent manner for early and late phases reducing abdominal writhing's and time period of licking, respectively. Tail immersion and hot-plate test demonstrated a substantial and dose-dependent increase in the latency time and time period of paw liking and jumping response respectively. GC-MS showed the abundantly present compounds were octadecatrienoic acid (34.35%), n-hexadecanoic acid (12.98%). In silico analyses have revealed three compounds that had good interactions with 6y3c receptor proteins, demonstrating strong binding affinities and satisfying docking parameters.</p><p><strong>Conclusions: </strong>Overall, these studies showed that ethanolic extract of L. stoechas is an important medicinal plant, with both central and peripheral antinociceptive and analgesic activities supporting its traditional use for therapeutic purposes.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"1178-1198"},"PeriodicalIF":2.8,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141563588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}