Journal of Pharmacy and Pharmacology最新文献_第2页

Natural product Pulsatilla saponin D sensitizes BRCA-proficient ovarian cancers to PARP inhibitors through inhibiting homologous recombination repair.

IF 2.8 4区医学

Journal of Pharmacy and Pharmacology Pub Date : 2025-02-27 DOI: 10.1093/jpp/rgaf006

Shengbin Lin, Binghe Sun, Yin Zhu, Yi Huang, Yu Qin, Nan Yao, Yongzhu Liu, Guo Chen

{"title":"Natural product Pulsatilla saponin D sensitizes BRCA-proficient ovarian cancers to PARP inhibitors through inhibiting homologous recombination repair.","authors":"Shengbin Lin, Binghe Sun, Yin Zhu, Yi Huang, Yu Qin, Nan Yao, Yongzhu Liu, Guo Chen","doi":"10.1093/jpp/rgaf006","DOIUrl":"https://doi.org/10.1093/jpp/rgaf006","url":null,"abstract":"Background: As a strategy in the development of effective cancer therapeutics, synthetic lethality has been used in clinical practice. Poly adenosine diphosphate (ADP)-ribose polymerase inhibitors are the first approved drug utilized synthetic lethality and achieved promising therapeutic efficacy in cancer cells with BRCA1/2 mutation. Nonetheless, most cancer patients with wild-type BRCA1/2 gene are not qualified for PARPi therapy. To induce BRCAness phenotype in cancer cells with normal BRCA1/2 status, we identified Pulsatilla Saponin D (SB365), which efficiently inhibited recruitment of BRCA1 at DNA double-strand breaks, leading to homologous recombination repair deficiency.Methods: We utilized the HR repair reporter system. The reporter cells were treated with a natural compounds library to identify the agent that significantly decreased HR activity. Then, we detected the expression of HR related proteins using immunofluorescence and western blot. Colony formation and CCK8 was used to detect the inhibitory effect of Pulsatilla Saponin D on cell proliferation. Apoptosis was measured using Annexin V/PI staining. Comet assay kits were used to carry out the comet assay. Ovarian cancer xenograft model, immunohistochemical staining and Hematoxylin-Eosin staining was used to detect the antitumor efficacy and toxicity of Pulsatilla Saponin D.Key findings: Pulsatilla Saponin D greatly increased PARPi-induced DNA DSBs, growth inhibition and apoptosis in ovarian cancer cells. Combined administration of PARPi and Pulsatilla Saponin D induced synergistic anti-tumor effects in ovarian cancer cells and xenograft mouse model without obvious toxicity.Conclusions: In summary, our study found Pulsatilla Saponin D is a novel HR repair inhibitor and would optimize clinical application of PARP inhibitors on cancer patients with WT BRCA1/2.","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143557048","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

The effects of Calophyllum brasiliense leaves extract and isolated compound amentoflavone: implications in the resolution of inflammation.

IF 2.8 4区医学

Journal of Pharmacy and Pharmacology Pub Date : 2025-02-27 DOI: 10.1093/jpp/rgaf009

Larissa Benvenutti, Guilherme Moreschi Gerhardt, Ruth Meri Lucinda, Otto Maurício Santos Gerlach, Valdir Cechinel-Filho, Luiz Carlos Klein-Júnior, Nara Lins Meira Quintão, José Roberto Santin

{"title":"The effects of Calophyllum brasiliense leaves extract and isolated compound amentoflavone: implications in the resolution of inflammation.","authors":"Larissa Benvenutti, Guilherme Moreschi Gerhardt, Ruth Meri Lucinda, Otto Maurício Santos Gerlach, Valdir Cechinel-Filho, Luiz Carlos Klein-Júnior, Nara Lins Meira Quintão, José Roberto Santin","doi":"10.1093/jpp/rgaf009","DOIUrl":"https://doi.org/10.1093/jpp/rgaf009","url":null,"abstract":"Calophyllum brasiliense is employed in folk medicine as an analgesic and to treat inflammation. This study aimed to evaluate the anti-inflammatory effect of C. brasiliense leaves' methanol extract, fractions, and the isolated compound amentoflavone. In vitro fMLP-induced neutrophil chemotaxis and LPS-induced inflammatory mediator levels were assessed in neutrophils or macrophages treated or not with different concentrations of C. brasiliense extract, its fractions or amentoflavone. Their effects on inflammation resolution was assessed by evaluating the efferocytosis. The extract and its fractions (DFCB, AFCB, and MFCB) impaired neutrophil migration stimulated by the chemotactic mediator fMLP and its ability to produce and/or to release cytokines (TNF and IL-6) and NO. The increase of the apoptotic neutrophil efferocytosis was observed for cells treated with the ethyl acetate and methanol fractions, accompanied by the enhanced IL-10 levels in the supernatant and the decrease of TNF, as well. Amentoflavone, present in high concentration in ethyl acetate fraction, reduced the inflammatory mediators levels in LPS-stimulated macrophages, impaired the neutrophil chemotaxis, and enhanced the efferocytosis. The obtained data demonstrate that C. brasiliense extract presented anti-inflammatory effects by modulating neutrophil migration/activation, macrophage-dependent efferocytosis, and inflammatory mediator release, effects at least partly addressed to amentoflavone content.","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143557049","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

Tiaogan Jiejiu Tongluo formula alleviates hepatic steatosis in NAFLD mice by regulating AMPK signaling pathway.

IF 2.8 4区医学

Journal of Pharmacy and Pharmacology Pub Date : 2025-02-14 DOI: 10.1093/jpp/rgaf005

Yuting Lei, Lianping Wang, Linze Song, Jiajun Han, He Ma, Haoming Luo, Yan Ma, Dong Han

{"title":"Tiaogan Jiejiu Tongluo formula alleviates hepatic steatosis in NAFLD mice by regulating AMPK signaling pathway.","authors":"Yuting Lei, Lianping Wang, Linze Song, Jiajun Han, He Ma, Haoming Luo, Yan Ma, Dong Han","doi":"10.1093/jpp/rgaf005","DOIUrl":"https://doi.org/10.1093/jpp/rgaf005","url":null,"abstract":"Objectives: Tiaogan Jiejiu Tongluo formula (TJTF) is a traditional Chinese medicine formula for liver disease. The purpose of this study was to explore the protective effects and mechanisms of TJTF on nonalcoholic fatty liver disease (NAFLD) mice.Methods: A NAFLD model of mice was established by a combination of a high-fat diet and CCL4 and then treated with TJTF. The damage to liver tissue was observed through histopathology, and the levels of AST, ALT, TG, TC, LDL-C, and HDL-C in the serum, as well as SOD, GSH, and MDA in the liver tissue were determined using biochemistry or ELISA kit. The expression of proteins related to the AMPK pathway was detected by western blotting.Results: Biochemical indicators and pathological examination showed that TJTF could enhance the antioxidant capacity of liver tissue and significantly reduce liver lipid deposition. In addition, TJTF significantly increased levels of LKB1 and p-AMPK, and decreased the levels of HMGCR, SREBP-1c, FAS, and ACC.Conclusion: TJTF can alleviate hepatic steatosis and effectively improve NAFLD by regulating AMPK signaling pathway in NAFLD mice.","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414475","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 antidiabetic activity of Treculia africana leaf extracts: identification of chlorogenic acid and α-mangostin.

IF 2.8 4区医学

Journal of Pharmacy and Pharmacology Pub Date : 2025-02-14 DOI: 10.1093/jpp/rgaf003

Victorine Lorette Yimgang, Elisa Pangrazzi, Francine Medjiofack Djeujo, Yanick Kevin Dongmo Melogmo, Franklin Loïc Tchinda Taghu, Rufin Marie Toghueo Kouipou, Fabrice Fekam Boyom, Guglielmina Froldi

{"title":"In vitro antidiabetic activity of Treculia africana leaf extracts: identification of chlorogenic acid and α-mangostin.","authors":"Victorine Lorette Yimgang, Elisa Pangrazzi, Francine Medjiofack Djeujo, Yanick Kevin Dongmo Melogmo, Franklin Loïc Tchinda Taghu, Rufin Marie Toghueo Kouipou, Fabrice Fekam Boyom, Guglielmina Froldi","doi":"10.1093/jpp/rgaf003","DOIUrl":"https://doi.org/10.1093/jpp/rgaf003","url":null,"abstract":"Objective: This research studied two extracts from Treculia africana leaves for their potential against hyperglycaemia-related disorders.Methods: The influence of the extracts on α-glucosidase activity and albumin glycation was investigated, and cell viability was estimated in HT-29 human colorectal cells. Phenolic and flavonoid contents and antiradical activity were also detected. The extracts were examined using HPLC-DAD analysis.Key findings: The methanol and dichloromethane leaf extracts showed a significant concentration-dependent inhibition of α-glucosidase activity (IC50= 3.73 and 21.28 µg/ml, respectively). Both extracts also inhibited ribose-induced glycation of bovine serum albumin from 250 µg/ml. Phytochemical analysis revealed the presence of chlorogenic acid and α-mangostin in the extracts. The extracts did not change HT-29 cell viability up to 250 µg/ml, thus showing very low cytotoxicity.Conclusions: The methanol leaf extract of T. africana inhibited α-glucosidase activity in a concentration-dependent manner, supporting the use of the leaves in traditional medicine to control hyperglycaemia. Chlorogenic acid and α-mangostin, the latter identified for the first time in this species, were found in the T. africana leaves. Further, in vivo studies and pilot clinical trials should be conducted using standardized T. africana leaf extracts to evaluate their potential effectiveness in diabetes mellitus.","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414466","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

Integrated metabolomics and network pharmacology analysis to reveal the mechanisms of naringin against atherosclerosis.

IF 2.8 4区医学

Journal of Pharmacy and Pharmacology Pub Date : 2025-02-13 DOI: 10.1093/jpp/rgae156

Gaoning Zhang, Xiaoyi Yin, Xiao Tang, Kexin Wang, Yifan Liu, Lili Gong, Zhenhua Tian

{"title":"Integrated metabolomics and network pharmacology analysis to reveal the mechanisms of naringin against atherosclerosis.","authors":"Gaoning Zhang, Xiaoyi Yin, Xiao Tang, Kexin Wang, Yifan Liu, Lili Gong, Zhenhua Tian","doi":"10.1093/jpp/rgae156","DOIUrl":"https://doi.org/10.1093/jpp/rgae156","url":null,"abstract":"Objectives: The purpose of this study was to explore the mechanism of naringin in atherosclerotic mice from the perspective of network pharmacology and non-targeted metabolomics.Methods: ApoE-/- mice were induced to establish an atherosclerotic model to explore the pharmacodynamics and potential mechanism of naringin in atherosclerosis (AS). Pathological section and blood lipid levels were used to evaluate the intervention effects. The core targets, metabolites, and related pathways of naringin alleviating atherosclerotic were predicted through network pharmacology and metabolomics analysis. Furthermore, the inflammatory factors and pathway-related protein expression were detected using ELISA and Western blot methods.Key findings: It turned out that compared with the model group, the naringin could reduce the development degree in atherosclerotic mice. The network pharmacology suggested that PI3K-AKT pathway was an important mechanism for naringin to interfere with AS. Serum metabolic data were collected and analyzed, and a total of 27 potential biomarkers were identified, involving vitamin B6 metabolism, arginine metabolism, and retinol metabolism. The experiment verified that naringin inhibited inflammation in AS through the PI3K-AKT/TLR4/NF-κB pathway.Conclusions: This study provides a strategy combining metabolomics and network pharmacology to explore the alleviation of AS by naringin and offers a new idea for its application.","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414470","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

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. 揭示二肽基肽酶-8/9（DPP-8/9）在炎症性骨质疏松症中的作用：一项将菊黄素作为潜在抗骨质疏松症药物的综合研究。

IF 2.8 4区医学

Journal of Pharmacy and Pharmacology Pub Date : 2025-02-03 DOI: 10.1093/jpp/rgae109

Syed Sufian Ahmad, Faraha Ahmed, Mohd Mumtaz Alam, Sayeed Ahmad, Mohammad Ahmed Khan

{"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":"10.1093/jpp/rgae109","url":null,"abstract":"Objectives: 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.Methods: 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.Key findings: 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.Conclusion: 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.","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"249-263"},"PeriodicalIF":2.8,"publicationDate":"2025-02-03","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}

引用次数: 0

Roflumilast mitigates cisplatin-induced nephrotoxicity by regulating TNF-α/TNFR1/TNFR2/Fas/Caspase mediated apoptosis and inflammatory signals. 罗氟司特通过调节TNF-α/TNFR1/TNFR2/Fas/Caspase介导的细胞凋亡和炎症信号，减轻顺铂诱导的肾毒性。

IF 2.8 4区医学

Journal of Pharmacy and Pharmacology Pub Date : 2025-02-03 DOI: 10.1093/jpp/rgae142

Priyal Patel, Sandip Patel, Yash Patel, Piyush Chudasama, Shailesh Soni, Samir Patel, Manan Raval

{"title":"Roflumilast mitigates cisplatin-induced nephrotoxicity by regulating TNF-α/TNFR1/TNFR2/Fas/Caspase mediated apoptosis and inflammatory signals.","authors":"Priyal Patel, Sandip Patel, Yash Patel, Piyush Chudasama, Shailesh Soni, Samir Patel, Manan Raval","doi":"10.1093/jpp/rgae142","DOIUrl":"10.1093/jpp/rgae142","url":null,"abstract":"Purpose: The study aimed to evaluate the effect of roflumilast on modulating TNF-α/Caspase mediated cellular signals in cisplatin-induced nephrotoxicity in rats.Methods: The rats (Male Wistar) were divided into five groups: normal control, disease control (cisplatin: 7 mg/kg i.p.), and cisplatin + roflumilast (0.25, 0.5, and 1 mg/kg b.w., p.o.). Cisplatin was administrated to rats on 0 day, and roflumilast treatment was started from the 6th-15th days. Blood and tissue were collected. Tissue was used to measure oxidative stress, such as malondialdehyde, superoxide dismutase, and catalase. Gene expression study involved real-time PCR of key genes linked with inflammation and apoptosis, i.e. Tnf-α, Tnfr1, Tnfr2, Fas, Nfkb, Casp3, Casp8, and Nrf2.Findings: Cisplatin showed decreased serum creatinine and urea, high albumin, and total protein. Cisplatin elevated the malondialdehyde and reduced superoxide dismutase and catalase activity. Cisplatin also attributed an overexpression of Tnf-α, Tnfr1, Tnfr2, Nfkb, Fas, Casp3, and Casp8, and a decrease in the Nrf2 gene. Roflumilast decreased creatinine and urea and increased albumin and total protein levels. Roflumilast also downregulated the expression of Tnf-α, Tnfr1, Tnfr2, Nfkb, Fas, Casp3, and Casp8 and upregulated the Nrf2 gene expression.Conclusion: Roflumilast manifested as a potential reno-protective agent against cisplatin-induced nephrotoxicity.","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"308-320"},"PeriodicalIF":2.8,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142682177","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

Mechanism of traditional drug treatment of cancer-related ascites: through the regulation of IL-6/JAK-STAT3 pathway. 传统药物治疗癌症相关腹水的机制：通过调节 IL-6/JAK-STAT3 通路。

IF 2.8 4区医学

Journal of Pharmacy and Pharmacology Pub Date : 2025-02-03 DOI: 10.1093/jpp/rgae111

Yehan Sun, Pengcheng Zhang, Jia Ma, Youmou Chen, Xingxing Huo, Hang Song, Yongfu Zhu

{"title":"Mechanism of traditional drug treatment of cancer-related ascites: through the regulation of IL-6/JAK-STAT3 pathway.","authors":"Yehan Sun, Pengcheng Zhang, Jia Ma, Youmou Chen, Xingxing Huo, Hang Song, Yongfu Zhu","doi":"10.1093/jpp/rgae111","DOIUrl":"10.1093/jpp/rgae111","url":null,"abstract":"Context: Our clinical observation found that JiJiaoLiHuang Pill (JJLH), a classic traditional Chinese medicine (TCM) formulation, can significantly reduce the abdominal circumference of patients with malignant ascites, increase urine output, and improve the quality of life of patients, with preliminary efficacy. But, the exact mechanism is not yet clear.Objective: Based on the above observations, the potential mechanism of action of the treatment was preliminarily explored.Methods: We identified active ingredients by constructing a \"Chinese medicine ingredient-key target-target\" network, and verified them by molecular docking using AutoDock tools and PyMOL. Finally, we conducted preliminary verification of the validated pathways and targets using a mouse model of liver cancer ascites.Results: Network pharmacology analysis obtained the top five active ingredients were quercetin, EUPATIN, kaempferol, Obtucarbamate B, and isorhamnetin and the top five key genes were SRC, HSP90AA1, MAPK1, STAT3, and PIK3CA. Molecular docking showed that all 5 active compounds were closely bound to key target genes (binding energy <-6). The animal experiment results showed that JJLH can significantly reduce abdominal circumference, increase urine output, and exhibit dose-dependent inhibition of the AQP-3/JAK-STAT-3 signaling pathway and the expression of related inflammatory factors.Conclusions: The JJLH potentially inhibits the recurrence of liver cancer malignant ascites through the AQP-3/JAK-STAT-3 pathway and affects the prognosis of MA patients.","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"264-274"},"PeriodicalIF":2.8,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142622678","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

The natural polyphenol fisetin in atherosclerosis prevention: a mechanistic review. 天然多酚菲赛汀在动脉粥样硬化预防中的作用：机理综述。

IF 2.8 4区医学

Journal of Pharmacy and Pharmacology Pub Date : 2025-02-03 DOI: 10.1093/jpp/rgae053

Wei Yu, Yaping Zhao, Iqra Ilyas, Li Wang, Peter J Little, Suowen Xu

引用次数: 0

Systems pharmacology-based drug discovery from Amaryllidaceae alkaloids and investigation of mechanisms of action in treatment of Alzheimer's disease. 从金盏花科生物碱中发现基于系统药理学的药物，并研究治疗阿尔茨海默病的作用机制。

IF 2.8 4区医学

Journal of Pharmacy and Pharmacology Pub Date : 2025-02-03 DOI: 10.1093/jpp/rgae113

Jianing Li, Jialiang Chen, Dan Qu, Lin Zhu, Shuhong Ye, Ming Li, Wei Li, Yan Ding

{"title":"Systems pharmacology-based drug discovery from Amaryllidaceae alkaloids and investigation of mechanisms of action in treatment of Alzheimer's disease.","authors":"Jianing Li, Jialiang Chen, Dan Qu, Lin Zhu, Shuhong Ye, Ming Li, Wei Li, Yan Ding","doi":"10.1093/jpp/rgae113","DOIUrl":"10.1093/jpp/rgae113","url":null,"abstract":"Objectives: Given the success of galanthamine in treating Alzheimer's disease, this study aims to establish an effective method to find drugs from Amaryllidaceae alkaloids and to clarify its mechanism in treating Alzheimer's disease.Methods: The pharmacodynamic basis and mechanism of action between Amaryllidaceae alkaloids and Alzheimer's disease were explored by constructing a compound-target-disease network, targets protein-protein interaction, gene ontology, Kyoto Encyclopedia of Genes and Genomes pathway enrichment, and molecular docking verification.Key findings: In total, a chemical library of 357 potential alkaloids was constructed. A total of 100 active alkaloid components were identified. Thirty-nine associated targets were yielded based on network construction, and the key targets were defined as HSP90AA1, ESR1, NOS3, PTGS2, and PPARG using protein-protein interaction network. Gene ontology items (490) and 68 Kyoto Encyclopedia of Genes and Genomes pathways were selected through the enrichment of target functions, including neuroactive ligand-receptor interaction, calcium signaling pathway, cAMP signaling pathway, Alzheimer disease, and serotonergic synapse that were related to Alzheimer's disease. Lastly, molecular docking demonstrated good stability in combining selected alkaloids with targets.Conclusions: This study explained the mechanisms of Amaryllidaceae alkaloids in preventing and treating Alzheimer's disease and established a novel strategy to discover new drugs from biological chemical sources.","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"222-235"},"PeriodicalIF":2.8,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289725","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