Journal of Pharmacy and Pharmacology最新文献_第3页

Renoprotective effect of liraglutide on diabetic nephropathy by modulation of Krüppel-like transcription factor 5 expression in rats. 利拉鲁肽通过调节大鼠 Krüppel 样转录因子 5 的表达对糖尿病肾病的肾保护作用

IF 2.8 4区医学

Journal of Pharmacy and Pharmacology Pub Date : 2024-10-14 DOI: 10.1093/jpp/rgae127

Anfal F Bin Dayel, Nouf M Alrasheed, Asma S Alonazi, Maha A Alamin, Nawal M Al-Mutairi, Raghad A Alateeq

{"title":"Renoprotective effect of liraglutide on diabetic nephropathy by modulation of Krüppel-like transcription factor 5 expression in rats.","authors":"Anfal F Bin Dayel, Nouf M Alrasheed, Asma S Alonazi, Maha A Alamin, Nawal M Al-Mutairi, Raghad A Alateeq","doi":"10.1093/jpp/rgae127","DOIUrl":"https://doi.org/10.1093/jpp/rgae127","url":null,"abstract":"Objectives: Diabetic nephropathy (DN) is a serious consequence of diabetes that can develop through the lysophosphatidic acid axis. The purpose of this study was to determine whether the antidiabetic drug liraglutide can slow the development of diabetic kidney damage by altering the lysophosphatidic acid axis via KLF5.Methods: Wistar albino rats were divided into nondiabetic and diabetic rats (resulting from an intraperitoneal streptozotocin dose of 30 mg/kg and a high-fat diet). These rats were further divided into four groups: nondiabetic control, liraglutide-treated nondiabetic, diabetic control, and liraglutide-treated diabetic. The nondiabetic and diabetic control groups received normal saline for 42 days, while the liraglutide-treated nondiabetic and diabetic groups received normal saline for 21 days, followed by a subcutaneous dose of liraglutide (200 μg/kg/day) for 21 days. Subsequently, serum levels of DN biomarkers were evaluated, and kidney tissues were histologically examined. The protein expression of PCNA, autotaxin, and KLF5 was detected.Key findings: Liraglutide treatment in diabetic rats decreased DN biomarkers, histological abnormalities in kidney tissues, and the protein expression of PCNA, autotaxin, and KLF5.Conclusion: Liraglutide can slow the progression of DN by modulating KLF5-related lysophosphatidic acid axis. Thus, liraglutide may be an effective treatment for preventing or mitigating diabetes-related kidney damage.","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468371","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}

引用次数: 0

In vitro and in vivo performance of amorphous solid dispersions of ursolic acid as a function of polymer type and excipient addition. 熊果酸无定形固体分散体的体外和体内性能与聚合物类型和辅料添加量的关系。

IF 2.8 4区医学

Journal of Pharmacy and Pharmacology Pub Date : 2024-10-11 DOI: 10.1093/jpp/rgae125

Tingting Zhao, Chenming Gu, Jianbo Qi, Jingwen Liu, Yajun Wang, Xiaojing Chen, Fujiang Guo, Yiming Li

{"title":"In vitro and in vivo performance of amorphous solid dispersions of ursolic acid as a function of polymer type and excipient addition.","authors":"Tingting Zhao, Chenming Gu, Jianbo Qi, Jingwen Liu, Yajun Wang, Xiaojing Chen, Fujiang Guo, Yiming Li","doi":"10.1093/jpp/rgae125","DOIUrl":"https://doi.org/10.1093/jpp/rgae125","url":null,"abstract":"Objectives: The objective of this research was to enhance the bioavailability of ursolic acid (UA) by preparing multielement amorphous solid dispersion (ASD) systems comprising excipients.Methods: The ASDs were prepared via the solvent evaporation method, characterized by a range of techniques, and investigated with respect to permeability of human colorectal adenocarcinoma cell line (Caco-2) cells monolayers and pharmacokinetics, with comparisons made to the physical mixture and the pure drug.Key findings: The (UA-choline)-Polyethylcaprolactam-polyvinyl acetate-polyethylene glycol grafted copolymer (Soluplus)-Vitamin E polyethylene glycol succinate (TPGS) ASD demonstrated superior dissolution properties compared to the corresponding binary solid dispersions and ternary solid dispersions (P < .05). The permeability studies of Caco-2 cell monolayers revealed that the ASD exhibited moderate permeability, with an efflux rate that was significantly lower than that of the UA raw material (P < .05). Pharmacokinetic studies in rats demonstrated that the oral bioavailability of the ASD was 19.0 times higher than that of UA (P < .01).Conclusions: The research indicated that the multielement ASD could be employed as an efficacious drug delivery system for UA. Furthermore, the Soluplus/TPGS/choline combination represents a promising candidate for the fabrication of ASDs that can load weakly acidic and poorly soluble drugs.","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406533","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}

引用次数: 0

Rhein induces apoptosis of AGS and MGC803 cells by regulating the Ras/PI3K/AKT and p38/MAPK signaling pathway. Rhein 通过调节 Ras/PI3K/AKT 和 p38/MAPK 信号通路诱导 AGS 和 MGC803 细胞凋亡。

IF 2.8 4区医学

Journal of Pharmacy and Pharmacology Pub Date : 2024-10-11 DOI: 10.1093/jpp/rgae115

Meiqi Wan, Anna Gan, Jun Dai, Fei Lin, Ruixuan Wang, Bo Wu, Tingxu Yan, Ying Jia

{"title":"Rhein induces apoptosis of AGS and MGC803 cells by regulating the Ras/PI3K/AKT and p38/MAPK signaling pathway.","authors":"Meiqi Wan, Anna Gan, Jun Dai, Fei Lin, Ruixuan Wang, Bo Wu, Tingxu Yan, Ying Jia","doi":"10.1093/jpp/rgae115","DOIUrl":"https://doi.org/10.1093/jpp/rgae115","url":null,"abstract":"Objectives: Rhein is one of the main bioactive compounds in the Polygonaceae plant, and has been proven to have anti-cancer activity in some reports. But the mechanism of Rhein in the treatment of gastric cancer (GC) is limited reported. In this research, network pharmacology combined with in vitro experiments was used for systematically studying the mechanism of Rhein.Methods: Network pharmacology confirmed the major effect signaling pathway and key targets of Rhein in the treatment of GC. Cell viability assay, colony formation assay, fluorescence probe assay, apoptosis assay, western blot and qRT-PCR verified the mechanism of Rhein in the treatment of GC cells (AGS and MGC803 cells).Key findings: The results showed that Rhein significantly induced the apoptosis process of AGS and MGC803 cells by regulating the Ras/phosphoinositide-3 kinase (PI3K)/protein kinase B (AKT) and the p38/mitogen-activated protein kinase signaling pathways. The AKT activator (SC79) and p38 inhibitor (SB202190) inhibited Rhein-induced apoptosis.Conclusions: All results proved that Rhein could be recognized as a potential natural drug for the treatment of GC.","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406534","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}

引用次数: 0

Production of mRNA lipid nanoparticles using advanced crossflow micromixing. 利用先进的横流微混合技术生产 mRNA 脂质纳米颗粒。

IF 2.8 4区医学

Journal of Pharmacy and Pharmacology Pub Date : 2024-10-09 DOI: 10.1093/jpp/rgae122

Muattaz Hussain, Burcu Binici, Liam O'Connor, Yvonne Perrie

{"title":"Production of mRNA lipid nanoparticles using advanced crossflow micromixing.","authors":"Muattaz Hussain, Burcu Binici, Liam O'Connor, Yvonne Perrie","doi":"10.1093/jpp/rgae122","DOIUrl":"https://doi.org/10.1093/jpp/rgae122","url":null,"abstract":"Objectives: Lipid nanoparticles (LNPs) play a crucial role in RNA-based therapies, and their production is generally based on nanoprecipitation and coalescence of lipids around an RNA core. This study investigated crossflow micromixing to prepare LNPs across various mixing ratios and production speeds.Methods: A range of LNPs were prepared using crossflow micromixing across production speeds of 10-500 ml/min, and their physico-chemical characteristics (size, polydispersity index (PDI), zeta potential, and mRNA encapsulation), in vitro mRNA expression and in vitro efficacy (protein expression and antibody and cytokine responses).Key findings: Our results demonstrate the reproducible production of mRNA-LNPs with controlled critical quality attributes, including high mRNA encapsulation from the initial screening scale through to GMP-scale production, where the same mixing ratio can be adopted across all product speeds from 30 to 500 ml/min used.Conclusions: We confirm the applicability of stainless-steel crossflow membrane micromixing for the entire spectrum of mRNA-LNP production, ranging from initial discovery volumes to GMP-production scale.","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468356","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}

引用次数: 0

Puerarin improves Dioscorea bulbifera L.-induced liver injury by regulating drug transporters and the Nrf2/NF-κB/Bcl-2 signaling pathway. 葛根素通过调节药物转运体和Nrf2/NF-κB/Bcl-2信号通路改善薯蓣皂苷诱导的肝损伤

IF 2.8 4区医学

Journal of Pharmacy and Pharmacology Pub Date : 2024-10-07 DOI: 10.1093/jpp/rgae123

Xin Wang, Yuhan Zhang, Hongzhe Zhu, Leilei Shi, Yong Shi, Shanshan Cao, Jiping Liu, Yundong Xie

{"title":"Puerarin improves Dioscorea bulbifera L.-induced liver injury by regulating drug transporters and the Nrf2/NF-κB/Bcl-2 signaling pathway.","authors":"Xin Wang, Yuhan Zhang, Hongzhe Zhu, Leilei Shi, Yong Shi, Shanshan Cao, Jiping Liu, Yundong Xie","doi":"10.1093/jpp/rgae123","DOIUrl":"https://doi.org/10.1093/jpp/rgae123","url":null,"abstract":"Purpose: Investigate the protective effect and mechanism of Puerarin (PU) against Dioscorea bulbifera L. (DB)-induced liver injury.Materials and methods: The protective effect of PU against DB-induced liver injury was evaluated by the present animal experiment, which assessed the pathological changes in the liver of mice and detected Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Alkaline phosphatase (AKP), as well as inflammation and oxidative stress-related indexes. Finally, the transcription and expression of related proteins were detected using western blot and quantitative reverse transcription (PCR) techniques.Results: PU significantly increased body weight, reduced liver index, and attenuated pathological changes in the liver compared to the DB group. It also decreased levels of AST, ALT, AKP, tumor necrosis factor-α, interleukin-1β, and malondialdehyde while increasing interleukin-10 levels and superoxide dismutase activity. Additionally, it upregulated inhibitor of NF-κB (IκB-α), B-cell lymphoma-2 (Bcl-2), Nuclear respiratory factor 2 (Nrf2), and Heme oxygenase 1 (HO-1) expression while down-regulating p-NF-κB p65 and bcl2-associated x (Bax) expression in the liver. Furthermore, PU upregulated protein and gene expression levels of Multidrug resistance-associated protein2, bile salt export pump, p-glycoprotein, and UDP-glucuronyltransferase 1A1 (UGT1A1) as well.Conclusion: PU mitigates DB-induced liver injury by regulating the expression of drug transporters and modulating the Nrf2/NF-κB/Bcl-2 signaling pathway.","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142391388","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}

引用次数: 0

Tilianin obtained from Agastache mexicana inhibits monoamine oxidase and modifies depressive behavior in rats. 从 Agastache mexicana 中提取的 Tilianin 可抑制单胺氧化酶并改变大鼠的抑郁行为。

IF 2.8 4区医学

Journal of Pharmacy and Pharmacology Pub Date : 2024-10-07 DOI: 10.1093/jpp/rgae117

Edgar Rodríguez-Wilson, Samuel Estrada-Soto, Moisés Rubio-Osornio, Luis Tristán-López, Gabriel Navarrete-Vázquez, Abraham Gutiérrez-Hernández, Sergio Montes

{"title":"Tilianin obtained from Agastache mexicana inhibits monoamine oxidase and modifies depressive behavior in rats.","authors":"Edgar Rodríguez-Wilson, Samuel Estrada-Soto, Moisés Rubio-Osornio, Luis Tristán-López, Gabriel Navarrete-Vázquez, Abraham Gutiérrez-Hernández, Sergio Montes","doi":"10.1093/jpp/rgae117","DOIUrl":"https://doi.org/10.1093/jpp/rgae117","url":null,"abstract":"Background: Agastache mexicana is used in traditional medicine to treat anxiety, insomnia, pain, among others. In a previous study, the methanolic extract exerted anxiolytic and sedative effects, as observed behaviorally, associated with one of its major components, tilianin.Objective: To assess the effect produced by the extracts and tilianin obtained from Agastache mexicana on depressive-induced behavior model and on the activity of monoamine oxidases (MAOs).Methods: The depression experimental model consisted of the forced swimming test in rats. MAOs activity was evaluated in cortex and hippocampus from the tilianin and Agastache extracts treated rats using specific inhibitors for each isoform. The quantification of monoamines was carried out using an High Performance Liquid Chromatography method.Results: An increase in the swimming time was observed in rodents treated with doses of 16 (226.6 ± 5.5 seconds) and 50 mg/kg (237.8 ± 5.7 seconds) of tilianin, methanolic (260.4 ± 3 seconds), and hydroalcoholic extracts (249.6 ± 2.6 seconds) at 100 mg/kg. MAOs activity was significantly decreased in brain tissue from animals treated with 16 and 50 mg/kg of tilianin, methanolic, and hydroalcoholic extracts at 100 mg/kg.Conclusions: The tilianin effect on monoamine oxidases inhibition is confirmed, suggesting its potential use in the treatment of certain neurological disorders.","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142391389","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}

引用次数: 0

Deciphering farnesol's anti-arthritic and immunomodulatory potential by targeting multiple pathways: a combination of network pharmacology guided exploration and experimental verification. 通过靶向多种途径破解法尼醇的抗关节炎和免疫调节潜力：网络药理学指导下的探索与实验验证相结合。

IF 2.8 4区医学

Journal of Pharmacy and Pharmacology Pub Date : 2024-10-07 DOI: 10.1093/jpp/rgae126

Shaimaa R Ahmed, Ambreen Malik Uttra, Muhammad Usman, Sumera Qasim, Shah Jahan, Muhammad Roman, Hanan Khojah, Omnia Hendawy, Eman K Rashwan

{"title":"Deciphering farnesol's anti-arthritic and immunomodulatory potential by targeting multiple pathways: a combination of network pharmacology guided exploration and experimental verification.","authors":"Shaimaa R Ahmed, Ambreen Malik Uttra, Muhammad Usman, Sumera Qasim, Shah Jahan, Muhammad Roman, Hanan Khojah, Omnia Hendawy, Eman K Rashwan","doi":"10.1093/jpp/rgae126","DOIUrl":"https://doi.org/10.1093/jpp/rgae126","url":null,"abstract":"Objective: Farnesol (FAR), a sesquiterpene alcohol, has documented FAR's anti-inflammatory and antioxidant activities. Current study was undertaken to assess the efficacy and mechanism of FAR in arthritis by employing network pharmacology and experimental models.Methods: Two experimental models comprising formaldehyde- and complete Freund's adjuvant (CFA)-induced arthritis evaluated the efficacy of FAR in treating arthritis. Various parameters were assessed. Then, a network pharmacology approach was applied to gain further insight into the potential mechanism and signaling pathways.Key findings: FAR significantly reduced paw volume and the arthritic score and improved the hematological and biochemical changes. Radiographic and histological examination showed the anti-arthritic efficacy of FAR, which was associated with down-regulation of pro-inflammatory mediators and upregulation of anti-inflammatory mediators. Network pharmacology analysis revealed that FAR may exert its anti-arthritic effects by targeting specific genes associated with arthritis. Pathway analysis revealed the involvement of three key signaling pathways (IL-17 signaling, TNF signaling, and toll-like receptor signaling) in the development and progression of arthritis.Conclusions: The results pointed out the protective attributes of farnesol against formaldehyde and CFA-induced arthritis via modulation of multiple targets. This study provides a valuable reference for the development of a new treatment or complementary therapy for arthritis.","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142391387","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}

引用次数: 0

Hydroalcoholic extract of Araucaria sp. brown propolis alleviates ulcerative colitis induced by TNBS in rats by reducing inflammatory cell infiltration and oxidative damage. 褐蜂胶水醇提取物通过减少炎症细胞浸润和氧化损伤，缓解了 TNBS 诱导的大鼠溃疡性结肠炎。

IF 2.8 4区医学

Journal of Pharmacy and Pharmacology Pub Date : 2024-10-03 DOI: 10.1093/jpp/rgae083

Benhur Judah Cury, Daniele Teixeira Jerônimo, Levy Mota da Silva, Thiago Farias de Queiroz E Silva, Tauani Caroline Santos França, Ana Caroline Dos Santos, Ian Richard Lucena Andriolo, José Roberto Santin, Larissa Benvenutti, Carlos Rafael Vaz, Mario Ferreira Conceição Santos, Jairo Bastos Kenupp, Luisa Mota da Silva

{"title":"Hydroalcoholic extract of Araucaria sp. brown propolis alleviates ulcerative colitis induced by TNBS in rats by reducing inflammatory cell infiltration and oxidative damage.","authors":"Benhur Judah Cury, Daniele Teixeira Jerônimo, Levy Mota da Silva, Thiago Farias de Queiroz E Silva, Tauani Caroline Santos França, Ana Caroline Dos Santos, Ian Richard Lucena Andriolo, José Roberto Santin, Larissa Benvenutti, Carlos Rafael Vaz, Mario Ferreira Conceição Santos, Jairo Bastos Kenupp, Luisa Mota da Silva","doi":"10.1093/jpp/rgae083","DOIUrl":"10.1093/jpp/rgae083","url":null,"abstract":"Objective: To investigate the effects of Araucaria sp. brown propolis (ABP) against trinitrobenzenesulfonic acid (TNBS)-induced colitis in rats.Methods: Animals received vehicle (1% DMSO, 1 ml/kg) or hydroalcoholic extract of ABP (hydroalcoholic extract of Araucaria sp. brown propolis (HEABP), 30, 100, and 300 mg/kg) orally, or dexamethasone (25 mg/kg, s.c.) for 5 days. On day 4, the animals received intracolonic TNBS (150 mg/kg), on day 6 they were euthanized. The weight of the animals, the macroscopic and microscopic colonic damage, reduced glutathione (GSH) and malondialdehyde (MDA) levels, and the activity of glutathione S-transferase (GST), catalase (CAT), superoxide dismutase (SOD), and myeloperoxidase (MPO) were measured in colon homogenate. The action of HEABP and two isolated compounds in neutrophil migration was recorded.Key findings: HEABP (100 and 300 mg/kg), but not dexamethasone, decreased colonic lesion, and increased colonic mucin staining. In parallel, HEABP decreased MDA and restored GSH levels and the activity of SOD, CAT, and GST in the colon. A dose-dependent inhibition of MPO activity was observed (LogIC50 = 1.9). Moreover, HEBPA and the junicedric and abietic acids inhibited the neutrophil chemotaxis in vitro and HEBPA reduced neutrophil migration in vivo.Conclusion: HEABP may be promising in the therapies for inflammatory bowel diseases, reducing oxidative and inflammatory damage, especially mediated by neutrophils.","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141759412","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}

引用次数: 0

Osteogenic effect of alogliptin in chemical-induced bone loss: a tri-modal in silico, in vitro, and in vivo analysis. 阿格列汀在化学物质诱导的骨质流失中的成骨作用：硅学、体外和体内三模式分析。

IF 2.8 4区医学

Journal of Pharmacy and Pharmacology Pub Date : 2024-10-03 DOI: 10.1093/jpp/rgae112

Faraha Ahmed, Syed Sufian Ahmad, Mohammad Mumtaz Alam, Mohammad Shaquiquzzaman, Mohammad Altamish, Anuja Krishnan, Divya Vohora, Abul Kalam Najmi, Mohammad Ahmed Khan

{"title":"Osteogenic effect of alogliptin in chemical-induced bone loss: a tri-modal in silico, in vitro, and in vivo analysis.","authors":"Faraha Ahmed, Syed Sufian Ahmad, Mohammad Mumtaz Alam, Mohammad Shaquiquzzaman, Mohammad Altamish, Anuja Krishnan, Divya Vohora, Abul Kalam Najmi, Mohammad Ahmed Khan","doi":"10.1093/jpp/rgae112","DOIUrl":"https://doi.org/10.1093/jpp/rgae112","url":null,"abstract":"Objective: To investigate the effects of Alogliptin in chemical-induced post-menopausal osteoporosis.Methodology: The binding affinity of alogliptin with osteogenic proteins was analysed in silico. The effect of alogliptin on osteogenic proteins and mineralization of osteoblastic cells was evaluated in UMR-106 cells. Further, in vivo anti-osteoporotic activity of alogliptin was evaluated in postmenopausal osteoporosis. Various bone turnover markers were assayed in serum. This followed the analysis of microarchitecture of bone, histology, and immunohistochemistry (IHC) of bone tissue.Results: Docking scores showed that alogliptin has binding affinity for bone alkaline phosphatase (BALP), osteocalcin, and bone morphogenic protein (BMP-2). Alogliptin also enhanced mineralization of osteoblast cells, evidenced with increased ALP, osteocalcin, and BMP-2. Animal studies revealed significant elevation of bone formation markers, bone ALP, osteocalcin and BMP-2, and decreased bone resorption markers, receptor activator of NF-κβ (RANKL), cathepsin K (CTSK), tartrate resistant acid phosphatase (TRAcP5b) in VCD-induced post-menopausal osteoporosis. Micro computed tomography (μCT) analysis and histology of femur bone and lumbar vertebrae demonstrated decrease in trabecular separation and improved bone density. IHC of femur showed reduced DPP4 enzyme.Conclusions: Alogliptin increased mineralization in osteoblast cells. It had beneficial effects also altered bone turnover markers, repaired the trabecular microstructure, improved bone mineral density, and exhibited bone forming capacity targeting DPP-4 enzyme in postmenopausal osteoporosis.","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142365642","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}

引用次数: 0

Exploring the anxiolytic mechanism of Fructus gardeniae based on metabolomics, network pharmacology, and molecular docking. 基于代谢组学、网络药理学和分子对接，探索栀子的抗焦虑机制。

IF 2.8 4区医学

Journal of Pharmacy and Pharmacology Pub Date : 2024-10-03 DOI: 10.1093/jpp/rgad102

Yue Tian, Fuli Yuan, Jiao Kong, Zhenshuang Yuan, Chunxue Jia, Hongqian Kui, Ziqiang Yin, Chuanxin Liu, Jianmei Huang

{"title":"Exploring the anxiolytic mechanism of Fructus gardeniae based on metabolomics, network pharmacology, and molecular docking.","authors":"Yue Tian, Fuli Yuan, Jiao Kong, Zhenshuang Yuan, Chunxue Jia, Hongqian Kui, Ziqiang Yin, Chuanxin Liu, Jianmei Huang","doi":"10.1093/jpp/rgad102","DOIUrl":"10.1093/jpp/rgad102","url":null,"abstract":"Objective: To explore the effect and anxiolytic mechanism of a natural remedy called Fructus gardeniae (FG).Methods: The elevated-plus maze (EPM) test was used to confirm the anxiolytic effect of FG. The potential and anxiolytic components, targets, and route processes of FG were investigated using the network pharmacology method in conjunction with metabolomics and molecular docking technologies.Results: FG could greatly enhance the proportion of time and times of opening arms, according to the EPM data. As to the metabolomics findings, a total of 61 distinct metabolites were found, mainly involved in glycine, serine, and threonine metabolism as well as alanine, aspartate, and glutamate metabolism. The primary active ingredients of FG, nicotiflorin, jasminodiol, and crocetin, demonstrated substantial binding affinities with monoamine oxidase A (MAOA), monoamine oxidase A (ACHE), malate dehydrogenase 2 (MDH2), glutamate decarboxylase 2 (GAD2), glutamate decarboxylase 1 (GAD1), and nitric oxide synthase (NOS1), according to the findings of network pharmacology and molecular docking.Conclusion: FG exerts an anxiolytic action via targeting MAOA, ACHE, MDH2, GAD2, GAD1, and NOS1, and regulating the metabolism of glycine, serine, and threonine as well as alanine, aspartic acid, and glutamic acid.","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141590596","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}

引用次数: 0