Background: Irritable bowel syndrome (IBS) is a chronic intestinal disorder characterized by abdominal discomfort, stool characteristics, and changes in bowel habits. Among them, diarrhea-type (diarrhea-predominant irritable bowel syndrome, abbreviated as IBS-D) is the most common. Because its pathogenesis is not understood, symptomatic treatment is currently used in clinical practice, and its long-term effect is still unclear. Decoction of Angelica sinensis, Zingiberis Rhizoma Recens, and Mutton (DAZM) is a famous traditional Chinese medicine recipe created by Zhang Zhongjing, a famous doctor in the Eastern Han Dynasty 2000 years ago, and is still in use today. Our research team has previously investigated the clinical study of DAZM in the treatment of IBS-D and conducted animal experiment research, indicating that DAZM has a significant effect on improving IBS-D. Yet, there are few reports on the specific mechanism of action of DAZM in improving the treatment of IBS and related types. Most studies discuss and verify its efficacy and protection from a clinical perspective. For this reason, this research will explore the constituent targets and mechanisms of DAZM to improve the treatment of IBS-D, provide relevant scientific evidence, and also provide reference evidence for the efficacy of food therapy decoction in improving the treatment of diseases and mechanism to open up new experimental research ideas.
Methods: Identification of drug ingredients and collection of targets for DAZM using ultra-performance liquid chromatography with linear ion trap-electrostatic field orbitrap mass spectrometry and the Bioinformatics Analysis Tool for Molecular Mechanisms of Traditional Chinese Medicine database, active ingredients were selected based on their oral bioavailability and drug-like properties. Obtained IBS-D targets using the GeneCards database, took the intersection of IBS-D targets and DAZM targets and obtained potential targets of DAZM for the treatment of IBS-D. Using Cytoscape software to draw a network diagram of "Food therapy decoction-ingredient-target-disease" and selected the ingredients with larger parameter values by topological analysis. Correlation analysis of the selected active and parametric ingredients with prominent symptoms of IBS-D using SymMap database, and selection of potential core ingredients. The construction of protein interaction networks from the String database and the selection of potential core targets. Gene Ontology functional and Kyoto Encyclopedia of Genes and Genomes signaling pathway enrichment analyses using the Metascape database, establishing the bioinformatic processes and signaling pathways involved. Molecular docking of core ingredients and potential core targets was performed using AutoDock Vina, and the results were visualized using Python molecule (PyMOL) and LigPlus+. Finally, based on the results of this research combined with previous literature reports, th
{"title":"Using ultra-performance liquid chromatography with linear ion trap-electrostatic field orbitrap mass spectrometry, network pharmacology, and molecular docking to explore the constituent targets and action mechanisms of decoction of Angelica sinensis, Zingiberis Rhizoma Recens, and Mutton in the treatment of diarrhea-predominant irritable bowel syndrome.","authors":"Zhiyong Liu, Zihong Zheng, Ting Wang, Zhiyong Liu, Zhengyun Zuo","doi":"10.1093/jpp/rgad076","DOIUrl":"10.1093/jpp/rgad076","url":null,"abstract":"<p><strong>Background: </strong>Irritable bowel syndrome (IBS) is a chronic intestinal disorder characterized by abdominal discomfort, stool characteristics, and changes in bowel habits. Among them, diarrhea-type (diarrhea-predominant irritable bowel syndrome, abbreviated as IBS-D) is the most common. Because its pathogenesis is not understood, symptomatic treatment is currently used in clinical practice, and its long-term effect is still unclear. Decoction of Angelica sinensis, Zingiberis Rhizoma Recens, and Mutton (DAZM) is a famous traditional Chinese medicine recipe created by Zhang Zhongjing, a famous doctor in the Eastern Han Dynasty 2000 years ago, and is still in use today. Our research team has previously investigated the clinical study of DAZM in the treatment of IBS-D and conducted animal experiment research, indicating that DAZM has a significant effect on improving IBS-D. Yet, there are few reports on the specific mechanism of action of DAZM in improving the treatment of IBS and related types. Most studies discuss and verify its efficacy and protection from a clinical perspective. For this reason, this research will explore the constituent targets and mechanisms of DAZM to improve the treatment of IBS-D, provide relevant scientific evidence, and also provide reference evidence for the efficacy of food therapy decoction in improving the treatment of diseases and mechanism to open up new experimental research ideas.</p><p><strong>Methods: </strong>Identification of drug ingredients and collection of targets for DAZM using ultra-performance liquid chromatography with linear ion trap-electrostatic field orbitrap mass spectrometry and the Bioinformatics Analysis Tool for Molecular Mechanisms of Traditional Chinese Medicine database, active ingredients were selected based on their oral bioavailability and drug-like properties. Obtained IBS-D targets using the GeneCards database, took the intersection of IBS-D targets and DAZM targets and obtained potential targets of DAZM for the treatment of IBS-D. Using Cytoscape software to draw a network diagram of \"Food therapy decoction-ingredient-target-disease\" and selected the ingredients with larger parameter values by topological analysis. Correlation analysis of the selected active and parametric ingredients with prominent symptoms of IBS-D using SymMap database, and selection of potential core ingredients. The construction of protein interaction networks from the String database and the selection of potential core targets. Gene Ontology functional and Kyoto Encyclopedia of Genes and Genomes signaling pathway enrichment analyses using the Metascape database, establishing the bioinformatic processes and signaling pathways involved. Molecular docking of core ingredients and potential core targets was performed using AutoDock Vina, and the results were visualized using Python molecule (PyMOL) and LigPlus+. Finally, based on the results of this research combined with previous literature reports, th","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41203867","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}
Alaa A El-Banna, Eman Shawky, Ismail Celik, Doaa A Ghareeb, Shaymaa A Abdulmalek, Reham S Darwish
Objectives: To investigate the chemical composition of the alcoholic extract from creeping juniper leaves using HPLC-MS/MS and to elucidate its potential anti-inflammatory mechanism through network-based pharmacology analysis to collectively enable a systematic exploration of the chemical composition, mechanism of action, and therapeutic potential of the alcoholic extract from creeping juniper leaves, providing valuable insights into its suitability as an anti-inflammatory agent.
Methods: Chemical profiling of the alcoholic extract of creeping juniper leaves using HPLC-MS/MS and revealing its anti-inflammatory mechanism using network-based pharmacology. Further, isolation of some of the identified biomarkers, assessment of their ex-vivo anti-inflammatory activity, and determination of their binding to pro-inflammatory cytokines using molecular docking and dynamics.
Key findings: Thirty-seven compounds were annotated and forwarded to network pharmacology analysis which revealed that the highest interactions were exhibited by quercetin, cosmosiin, myricetin, amentoflavone, hyperoside, isorhamnetin, and quercitrin whereas the most enriched inflammatory targets were IL-2, PGF, VEGFA, and TNFs. PI3K-Akt signaling pathway, arachidonic acid metabolism, and MAPK signaling pathway were found to be the most enriched ones. Six hit compounds were isolated and identified as hyperoside, quercetrin, cupressuflavone, hinokiflavone, amentoflavone, and quercetin. The isolated compounds showed strong anti-inflammatory activity against TNF-α, IL-6, and IL-1β, and molecular docking and dynamics simulation showed that quercetin, quercitrin, and hyperoside had the least binding energy with TNF-α, IL-6, and IL-1B, respectively.
Conclusions: Creeping juniper may reduce inflammation based on the suggested multi-compounds and multi-pathways, and that provided the basis for creeping juniper use as a potential anti-inflammatory drug.
{"title":"Deciphering the putative bioactive metabolites and the underlying mechanism of Juniperus horizontalis Moench (Creeping juniper) in the treatment of inflammation using network pharmacology and molecular docking.","authors":"Alaa A El-Banna, Eman Shawky, Ismail Celik, Doaa A Ghareeb, Shaymaa A Abdulmalek, Reham S Darwish","doi":"10.1093/jpp/rgad101","DOIUrl":"10.1093/jpp/rgad101","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the chemical composition of the alcoholic extract from creeping juniper leaves using HPLC-MS/MS and to elucidate its potential anti-inflammatory mechanism through network-based pharmacology analysis to collectively enable a systematic exploration of the chemical composition, mechanism of action, and therapeutic potential of the alcoholic extract from creeping juniper leaves, providing valuable insights into its suitability as an anti-inflammatory agent.</p><p><strong>Methods: </strong>Chemical profiling of the alcoholic extract of creeping juniper leaves using HPLC-MS/MS and revealing its anti-inflammatory mechanism using network-based pharmacology. Further, isolation of some of the identified biomarkers, assessment of their ex-vivo anti-inflammatory activity, and determination of their binding to pro-inflammatory cytokines using molecular docking and dynamics.</p><p><strong>Key findings: </strong>Thirty-seven compounds were annotated and forwarded to network pharmacology analysis which revealed that the highest interactions were exhibited by quercetin, cosmosiin, myricetin, amentoflavone, hyperoside, isorhamnetin, and quercitrin whereas the most enriched inflammatory targets were IL-2, PGF, VEGFA, and TNFs. PI3K-Akt signaling pathway, arachidonic acid metabolism, and MAPK signaling pathway were found to be the most enriched ones. Six hit compounds were isolated and identified as hyperoside, quercetrin, cupressuflavone, hinokiflavone, amentoflavone, and quercetin. The isolated compounds showed strong anti-inflammatory activity against TNF-α, IL-6, and IL-1β, and molecular docking and dynamics simulation showed that quercetin, quercitrin, and hyperoside had the least binding energy with TNF-α, IL-6, and IL-1B, respectively.</p><p><strong>Conclusions: </strong>Creeping juniper may reduce inflammation based on the suggested multi-compounds and multi-pathways, and that provided the basis for creeping juniper use as a potential anti-inflammatory drug.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138295457","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}
Jiahui Yue, Wenxin Xia, Yushu Wang, Yuanyuan Zhang, Yan Zhang, Yuxin Li, Lulu Wang, Cunbing Li, Tingting Li, Xueyan Fu
Morinda officinalis How oligosaccharide (MOO) stands as one of the principal active constituents of M. officinalis How, widely employed in traditional Chinese medicine. The methods for MOO extraction predominantly encompass hot water extraction, ethanol extraction, ultrasonic-assisted extraction, and microwave-assisted extraction. Distinct extraction techniques yield varying MOO quantities. MOO encompasses a diversity of oligosaccharides, including bajijiasu, sucrose, 1-kestose, nystose, mannose, 1F-fructofuranosylnystose, 1,1,1,1-kestohexose, fructoheptasaccharide, inulin-type hexasaccharide, inulin-type heptasaccharide, inulotriose, inulotetraose, inulopentaose, and mannose. MOO exhibits a wide spectrum of biological activities, exerting specific effects on the nervous system, cardiovascular system, motor system, reproductive system, and immune system. It demonstrates antidepressant properties, offers potential in mitigating Alzheimer's disease, stimulates angiogenesis, and possesses anti-osteoporotic and other pharmacological effects. Clinically, when combined with various antidepressants, MOO exhibits specific therapeutic efficacy across multiple forms of depression. As a naturally occurring plant oligosaccharide, MOO holds diverse pharmaceutical applications. This article conducts a review of the latest extraction and purification methodologies, structural characterization analysis, biological activity assessment, and clinical applications of MOO. Such a comprehensive analysis yields innovative insights for advancing the research and application of MOO in the future.
巴戟天寡糖(Morinda officinalis How oligosaccharide, MOO)是巴戟天的主要活性成分之一,在中药中应用广泛。MOO的提取方法主要包括热水提取、乙醇提取、超声辅助提取和微波辅助提取。不同的提取技术产生不同的MOO量。MOO包含多种低聚糖,包括巴吉加素、蔗糖、1-酮糖、甘露糖、f -果糖呋喃糖、1,1,1,1-酮己糖、果糖七糖、菊糖型六糖、菊糖型七糖、菊糖四糖、菊糖五糖和甘露糖。MOO具有广泛的生物活性,对神经系统、心血管系统、运动系统、生殖系统和免疫系统有特殊作用。它具有抗抑郁的特性,有可能减轻阿尔茨海默病,刺激血管生成,并具有抗骨质疏松症和其他药理作用。临床上,当与各种抗抑郁药联合使用时,MOO对多种形式的抑郁症表现出特定的治疗效果。作为一种天然存在的植物寡糖,MOO具有多种制药应用。本文就MOO的最新提取纯化方法、结构表征分析、生物活性评价及临床应用等方面进行综述。这种全面的分析为未来推进mooo的研究和应用提供了创新的见解。
{"title":"Isolation, phytochemistry, characterization, biological activity, and application of Morinda officinalis How oligosaccharide: a review.","authors":"Jiahui Yue, Wenxin Xia, Yushu Wang, Yuanyuan Zhang, Yan Zhang, Yuxin Li, Lulu Wang, Cunbing Li, Tingting Li, Xueyan Fu","doi":"10.1093/jpp/rgad096","DOIUrl":"10.1093/jpp/rgad096","url":null,"abstract":"<p><p>Morinda officinalis How oligosaccharide (MOO) stands as one of the principal active constituents of M. officinalis How, widely employed in traditional Chinese medicine. The methods for MOO extraction predominantly encompass hot water extraction, ethanol extraction, ultrasonic-assisted extraction, and microwave-assisted extraction. Distinct extraction techniques yield varying MOO quantities. MOO encompasses a diversity of oligosaccharides, including bajijiasu, sucrose, 1-kestose, nystose, mannose, 1F-fructofuranosylnystose, 1,1,1,1-kestohexose, fructoheptasaccharide, inulin-type hexasaccharide, inulin-type heptasaccharide, inulotriose, inulotetraose, inulopentaose, and mannose. MOO exhibits a wide spectrum of biological activities, exerting specific effects on the nervous system, cardiovascular system, motor system, reproductive system, and immune system. It demonstrates antidepressant properties, offers potential in mitigating Alzheimer's disease, stimulates angiogenesis, and possesses anti-osteoporotic and other pharmacological effects. Clinically, when combined with various antidepressants, MOO exhibits specific therapeutic efficacy across multiple forms of depression. As a naturally occurring plant oligosaccharide, MOO holds diverse pharmaceutical applications. This article conducts a review of the latest extraction and purification methodologies, structural characterization analysis, biological activity assessment, and clinical applications of MOO. Such a comprehensive analysis yields innovative insights for advancing the research and application of MOO in the future.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138291255","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}
Mariane Minussi Baptistella, Raphaela Rebeca Silveira Assunção, Carolina Sales de Oliveira, Aléxia Polo Siqueira, Elda Gonçalves Dos Santos, Matheus de Freitas Silva, Ellen Tardelli Faleiros Lima, Ester Siqueira Caixeta, Rômulo Dias Novaes, Eric Batista Ferreira, Marisa Ionta, Claudio Viegas, Pollyanna Francielli de Oliveira
Based on the effectiveness of resveratrol and curcumin in carcinogenesis, (E)-3-(4-hydroxy-3-methoxyphenyl)-N'-((E)-4-methoxybenzylidene) acrylohydrazide (PQM-162), curcumin-resveratrol hybrid derivative, was designed by molecular hybridization using a hydrazone functionality as a spacer moiety between pharmacophoric fragments inspired by the parent compounds.
Objectives: The present study aimed to evaluate the chemopreventive effects of the hybrid against pre-neoplastic lesions induced in the colon of rodents.
Methods: The doses were determined based on the reduction in DNA damage induced by doxorubicin [15 mg/kg body weight (b.w.)] in peripheral blood of Swiss mice. Doses of 8, 16, 32, and 64 mg/kg b.w. were antimutagenic. For the evaluation of pre-neoplastic lesions in the colon, Wistar rats were treated with PQM-162 at doses of 0.5, 1, and 2 mg/kg b.w. for 6 weeks using three approaches: simultaneous treatment, pre-treatment, and post-treatment. Pre-neoplastic lesions were induced with 1,2 dimethylhydrazine (160 mg/kg b.w.).
Key findings: PQM-162 reduced the formation of aberrant crypt foci in the simultaneous treatment and post-treatment. TNF-α and COX-2 mRNA levels decreased, while Nrf2 mRNA levels increased. PQM-162 also reduced the expression of COX-2, PCNA, and β-catenin protein markers and increased Nrf2 expression.
Conclusion: Our findings suggest a chemopreventive potential of PQM-162 in colorectal carcinogenesis, which acts on anti-inflammatory, antioxidant, and cell proliferation pathways.
{"title":"A synthetic resveratrol-curcumin hybrid derivative exhibits chemopreventive effects on colon pre-neoplastic lesions by targeting Wnt/β-catenin signaling, anti-inflammatory and antioxidant pathways.","authors":"Mariane Minussi Baptistella, Raphaela Rebeca Silveira Assunção, Carolina Sales de Oliveira, Aléxia Polo Siqueira, Elda Gonçalves Dos Santos, Matheus de Freitas Silva, Ellen Tardelli Faleiros Lima, Ester Siqueira Caixeta, Rômulo Dias Novaes, Eric Batista Ferreira, Marisa Ionta, Claudio Viegas, Pollyanna Francielli de Oliveira","doi":"10.1093/jpp/rgad077","DOIUrl":"10.1093/jpp/rgad077","url":null,"abstract":"<p><p>Based on the effectiveness of resveratrol and curcumin in carcinogenesis, (E)-3-(4-hydroxy-3-methoxyphenyl)-N'-((E)-4-methoxybenzylidene) acrylohydrazide (PQM-162), curcumin-resveratrol hybrid derivative, was designed by molecular hybridization using a hydrazone functionality as a spacer moiety between pharmacophoric fragments inspired by the parent compounds.</p><p><strong>Objectives: </strong>The present study aimed to evaluate the chemopreventive effects of the hybrid against pre-neoplastic lesions induced in the colon of rodents.</p><p><strong>Methods: </strong>The doses were determined based on the reduction in DNA damage induced by doxorubicin [15 mg/kg body weight (b.w.)] in peripheral blood of Swiss mice. Doses of 8, 16, 32, and 64 mg/kg b.w. were antimutagenic. For the evaluation of pre-neoplastic lesions in the colon, Wistar rats were treated with PQM-162 at doses of 0.5, 1, and 2 mg/kg b.w. for 6 weeks using three approaches: simultaneous treatment, pre-treatment, and post-treatment. Pre-neoplastic lesions were induced with 1,2 dimethylhydrazine (160 mg/kg b.w.).</p><p><strong>Key findings: </strong>PQM-162 reduced the formation of aberrant crypt foci in the simultaneous treatment and post-treatment. TNF-α and COX-2 mRNA levels decreased, while Nrf2 mRNA levels increased. PQM-162 also reduced the expression of COX-2, PCNA, and β-catenin protein markers and increased Nrf2 expression.</p><p><strong>Conclusion: </strong>Our findings suggest a chemopreventive potential of PQM-162 in colorectal carcinogenesis, which acts on anti-inflammatory, antioxidant, and cell proliferation pathways.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50158222","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}
Yi Xu, Qiuxia Xu, Zhirui Zheng, Xin Jiang, Yuansen Shi, Yipu Huang, Yun Liu
Objectives: Accumulating evidence demonstrates that copper deficiency (CuD) is a risk factor for cardiovascular diseases, besides, fructose has been strongly linked to the development of cardiovascular diseases. However, how CuD or fructose causes cardiovascular diseases is not clearly delineated. The present study aims to investigate the mechanism of CuD or fructose on cardiac remodeling.
Methods: We established a model of CuD- or fructose-induced cardiac hypertrophy in 3-week-old male Sprague-Dawley (SD) rats by CuD diet supplemented with or without 30% fructose for 4 weeks. In vitro study was performed by treating cardiomyocytes with tetrathiomolydbate (TM) and fructose. Echocardiography, histology analysis, immunofluorescence, western blotting, and qPCR were performed.
Key findings: Our findings revealed that CuD caused noticeable cardiac hypertrophy either in the presence or absence of fructose supplement. Fructose exacerbated CuD-induced cardiac remodeling and intramyocardial lipid accumulation. Furthermore, we presented that the inhibition of autophagic flux caused by Ca2+ disturbance is the key mechanism by which CuD- or fructose-induced cardiac remodeling. The reduced expression of sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2a (SERCA2a) in cardiomyocytes accounts for the elevated cytoplasmic Ca2+ concentration.
Conclusions: Collectively, our study suggested that fructose aggravated CuD-induced cardiac remodeling through the blockade of autophagic flux via SERCA2a decreasing-induced Ca2+ imbalance.
{"title":"Fructose aggravates copper-deficiency-induced cardiac remodeling by inhibiting SERCA2a.","authors":"Yi Xu, Qiuxia Xu, Zhirui Zheng, Xin Jiang, Yuansen Shi, Yipu Huang, Yun Liu","doi":"10.1093/jpp/rgae002","DOIUrl":"10.1093/jpp/rgae002","url":null,"abstract":"<p><strong>Objectives: </strong>Accumulating evidence demonstrates that copper deficiency (CuD) is a risk factor for cardiovascular diseases, besides, fructose has been strongly linked to the development of cardiovascular diseases. However, how CuD or fructose causes cardiovascular diseases is not clearly delineated. The present study aims to investigate the mechanism of CuD or fructose on cardiac remodeling.</p><p><strong>Methods: </strong>We established a model of CuD- or fructose-induced cardiac hypertrophy in 3-week-old male Sprague-Dawley (SD) rats by CuD diet supplemented with or without 30% fructose for 4 weeks. In vitro study was performed by treating cardiomyocytes with tetrathiomolydbate (TM) and fructose. Echocardiography, histology analysis, immunofluorescence, western blotting, and qPCR were performed.</p><p><strong>Key findings: </strong>Our findings revealed that CuD caused noticeable cardiac hypertrophy either in the presence or absence of fructose supplement. Fructose exacerbated CuD-induced cardiac remodeling and intramyocardial lipid accumulation. Furthermore, we presented that the inhibition of autophagic flux caused by Ca2+ disturbance is the key mechanism by which CuD- or fructose-induced cardiac remodeling. The reduced expression of sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2a (SERCA2a) in cardiomyocytes accounts for the elevated cytoplasmic Ca2+ concentration.</p><p><strong>Conclusions: </strong>Collectively, our study suggested that fructose aggravated CuD-induced cardiac remodeling through the blockade of autophagic flux via SERCA2a decreasing-induced Ca2+ imbalance.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139563744","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}
Hui-Ju Lee, Yae-Ji Kim, Kyung-Hyun Kim, Sung-Pil Cho, Geum-Lan Hong, Ju-Young Jung
Cisplatin-induced acute kidney injury (AKI) is a clinical disease characterized by a sudden loss of renal function within a few hours or days, due to cisplatin uptake. Fulvestrant is an oestrogen receptor alpha (ERα) antagonist used for endocrine therapy. However, the role of fulvestrant in cisplatin-induced AKI remains unclear. In this study, we investigated the effects of fulvestrant on the regulation of apoptotic cell death and autophagic response in cisplatin-induced AKI. The human kidney proximal tubule epithelial cell line (HK-2) was co-treated with fulvestrant and cisplatin. C57BL/6 mice were subcutaneously injected with fulvestrant and cisplatin was administered via intraperitoneal injection. First, cisplatin treatment increased ERα expression, apoptosis, and autophagy in HK-2 cells. Fulvestrant treatment decreased apoptosis and autophagy, which were accompanied by cisplatin treatment in HK-2 cells. Consistent with in vitro results, cisplatin treatment significantly increased ERα expression in vivo. Additionally, cisplatin treatment increased renal injury, apoptosis, and autophagy. Surprisingly, compared to that in the cisplatin-treated mice group, reduced cisplatin-induced renal injury, apoptosis, and autophagy was observed in the cisplatin+fulvestrant-treated mice group. In summary, these results suggest that fulvestrant plays an important role in cisplatin-induced AKI by decreasing apoptosis and autophagy.
{"title":"Fulvestrant alleviates cisplatin-induced acute kidney injury via repression of BNIP3-mediated apoptosis and autophagy.","authors":"Hui-Ju Lee, Yae-Ji Kim, Kyung-Hyun Kim, Sung-Pil Cho, Geum-Lan Hong, Ju-Young Jung","doi":"10.1093/jpp/rgad094","DOIUrl":"10.1093/jpp/rgad094","url":null,"abstract":"<p><p>Cisplatin-induced acute kidney injury (AKI) is a clinical disease characterized by a sudden loss of renal function within a few hours or days, due to cisplatin uptake. Fulvestrant is an oestrogen receptor alpha (ERα) antagonist used for endocrine therapy. However, the role of fulvestrant in cisplatin-induced AKI remains unclear. In this study, we investigated the effects of fulvestrant on the regulation of apoptotic cell death and autophagic response in cisplatin-induced AKI. The human kidney proximal tubule epithelial cell line (HK-2) was co-treated with fulvestrant and cisplatin. C57BL/6 mice were subcutaneously injected with fulvestrant and cisplatin was administered via intraperitoneal injection. First, cisplatin treatment increased ERα expression, apoptosis, and autophagy in HK-2 cells. Fulvestrant treatment decreased apoptosis and autophagy, which were accompanied by cisplatin treatment in HK-2 cells. Consistent with in vitro results, cisplatin treatment significantly increased ERα expression in vivo. Additionally, cisplatin treatment increased renal injury, apoptosis, and autophagy. Surprisingly, compared to that in the cisplatin-treated mice group, reduced cisplatin-induced renal injury, apoptosis, and autophagy was observed in the cisplatin+fulvestrant-treated mice group. In summary, these results suggest that fulvestrant plays an important role in cisplatin-induced AKI by decreasing apoptosis and autophagy.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71521906","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}
Mahdieh Raeeszadeh, Borhan Shokrollahi, Abolfazl Akbari, Sima Masumi, Ali Akbar Amiri
Objectives: Oxidative stress and disruption of energy metabolism in the reproductive system, especially sperm, play a significant role in diabetes-related infertility. Zataria multiflora Boissis (ZMB), a medicinal plant containing various bioactive compounds, may have efficacy in treating metabolic diseases and reproductive disorders. Therefore, the aim of this study was to investigate the effects of different doses of ZMB extract on diabetes-induced reproductive dysfunction by assessing oxidative damage and the gene expression of insulin receptor substrate (IRS) and pyruvate kinase (PK) in male rats' sperm.
Methods: Sixty adult male Wistar rats were randomly divided into six groups; control (C), diabetes (D), and diabetic animals treated with glibenclamide (G, 50 mg/kg) and thyme extract (T100, T200, and T400). Diabetes was induced by intraperitoneal injection of Streptozotocin (STZ) (50 mg/kg). Insulin, glucose, oxidative and pro-inflammatory markers in the serum, and gene expressions of IRS, and PK were measured in the stored sperms in the epididymis. Changes in the process of spermatogenesis were assessed through the histological evaluation of the testis. Gas chromatography-mass spectrometry (GC-MS) was used to analyze the quantity and quality of thyme extract.
Key findings: The study results indicated that body weight, food intake, and sperm parameters significantly improved in a dose-dependent manner in the T200 group compared to the other groups. Additionally, in the same group, pro-inflammatory biomarkers, DNA fragmentation, and MDA levels decreased, while the levels of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) enzymes in the stored epididymal sperm significantly improved compared to the other groups. The expression of IRS and PK, along with the mean counts of spermatogenesis cell lines (especially Sertoli cells), significantly increased in the T200 group.
Summary: In conclusion, thymol appears to alleviate diabetes-induced reproductive dysfunction by inhibiting oxidative damage, improving the metabolic state, and upregulating the expression of IRS and PK genes in the sperm of male rats.
{"title":"Thyme extract could overcome diabetes-induced reproductive dysfunction by inhibiting oxidative damage and increasing the expression of insulin receptor substrate and pyruvate kinase in the rat sperm.","authors":"Mahdieh Raeeszadeh, Borhan Shokrollahi, Abolfazl Akbari, Sima Masumi, Ali Akbar Amiri","doi":"10.1093/jpp/rgad099","DOIUrl":"10.1093/jpp/rgad099","url":null,"abstract":"<p><strong>Objectives: </strong>Oxidative stress and disruption of energy metabolism in the reproductive system, especially sperm, play a significant role in diabetes-related infertility. Zataria multiflora Boissis (ZMB), a medicinal plant containing various bioactive compounds, may have efficacy in treating metabolic diseases and reproductive disorders. Therefore, the aim of this study was to investigate the effects of different doses of ZMB extract on diabetes-induced reproductive dysfunction by assessing oxidative damage and the gene expression of insulin receptor substrate (IRS) and pyruvate kinase (PK) in male rats' sperm.</p><p><strong>Methods: </strong>Sixty adult male Wistar rats were randomly divided into six groups; control (C), diabetes (D), and diabetic animals treated with glibenclamide (G, 50 mg/kg) and thyme extract (T100, T200, and T400). Diabetes was induced by intraperitoneal injection of Streptozotocin (STZ) (50 mg/kg). Insulin, glucose, oxidative and pro-inflammatory markers in the serum, and gene expressions of IRS, and PK were measured in the stored sperms in the epididymis. Changes in the process of spermatogenesis were assessed through the histological evaluation of the testis. Gas chromatography-mass spectrometry (GC-MS) was used to analyze the quantity and quality of thyme extract.</p><p><strong>Key findings: </strong>The study results indicated that body weight, food intake, and sperm parameters significantly improved in a dose-dependent manner in the T200 group compared to the other groups. Additionally, in the same group, pro-inflammatory biomarkers, DNA fragmentation, and MDA levels decreased, while the levels of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) enzymes in the stored epididymal sperm significantly improved compared to the other groups. The expression of IRS and PK, along with the mean counts of spermatogenesis cell lines (especially Sertoli cells), significantly increased in the T200 group.</p><p><strong>Summary: </strong>In conclusion, thymol appears to alleviate diabetes-induced reproductive dysfunction by inhibiting oxidative damage, improving the metabolic state, and upregulating the expression of IRS and PK genes in the sperm of male rats.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138440900","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}
Wenjing Ta, Jie Wang, Jihong Song, Xingyue Li, Jianxiang Wang, Wen Lu
Imperatorin (IMP) is the main bioactive furanocoumarin of Angelicae dahuricae radix, which is a well-known traditional Chinese medicine. The purpose of this study was to elucidate the role of IMP in promoting absorption and the possible mechanism on the compatible drugs of Angelicae dahuricae radix. The influence of IMP on drugs' intestinal absorption was conducted by the Caco-2 cell model. The mechanism was studied by investigating the transcellular transport mode of IMP and its influence on P-glycoprotein (P-gp)-mediated efflux, protein expression of P-gp and tight junction, and cell membrane potential. The result showed IMP promoted the uptake of osthole, daidzein, ferulic acid, and puerarin and improved the transport of ferulic acid and puerarin in Caco-2 cells. The absorption-promoting mechanism of IMP might involve the reduction of the cell membrane potential, decrease of P-gp-mediated drug efflux and inhibition of the P-gp expression level in the cellular pathway, and the loosening of the tight junction protein by the downregulation of the expression levels of occludin and claudin-1 in the paracellular pathway. This study provides new insights into the understanding of the improved bioavailability of Angelicae dahuricae radix with its compatible drugs.
{"title":"Elucidation the mechanism of the active ingredient imperatorin promoting drug absorption in cell model.","authors":"Wenjing Ta, Jie Wang, Jihong Song, Xingyue Li, Jianxiang Wang, Wen Lu","doi":"10.1093/jpp/rgad127","DOIUrl":"10.1093/jpp/rgad127","url":null,"abstract":"<p><p>Imperatorin (IMP) is the main bioactive furanocoumarin of Angelicae dahuricae radix, which is a well-known traditional Chinese medicine. The purpose of this study was to elucidate the role of IMP in promoting absorption and the possible mechanism on the compatible drugs of Angelicae dahuricae radix. The influence of IMP on drugs' intestinal absorption was conducted by the Caco-2 cell model. The mechanism was studied by investigating the transcellular transport mode of IMP and its influence on P-glycoprotein (P-gp)-mediated efflux, protein expression of P-gp and tight junction, and cell membrane potential. The result showed IMP promoted the uptake of osthole, daidzein, ferulic acid, and puerarin and improved the transport of ferulic acid and puerarin in Caco-2 cells. The absorption-promoting mechanism of IMP might involve the reduction of the cell membrane potential, decrease of P-gp-mediated drug efflux and inhibition of the P-gp expression level in the cellular pathway, and the loosening of the tight junction protein by the downregulation of the expression levels of occludin and claudin-1 in the paracellular pathway. This study provides new insights into the understanding of the improved bioavailability of Angelicae dahuricae radix with its compatible drugs.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139432573","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}
Objectives: Breast cancer is a common malignancy in women. More than 90% of breast cancer deaths are caused by metastasis. Epimedii Folium (EF) is a commonly used herb with anti-tumor benefits, but its underlying mechanisms and active components for breast cancer prevention are little understood. This study assessed the therapeutic role of Icariside I (ICS I) in Epimedium flavonoids (EF) on lung metastasis of breast cancer, including the underlying mechanism.
Methods: Western blot, RT-qPCR, wound healing assay, colony formation assay, and flow cytometry were used to investigate the inhibition of breast cancer cells growth and migration by EF and ICS I through disrupting the IL-6/STAT3 pathway. Combined with 4T1 breast cancer model in mice, Western blot, RT-qPCR, Hematoxylin and Eosin staining, immunohistochemistry were used to evaluate the therapeutic role of ICS I in proliferation, apoptosis, invasion, and metastasis of breast cancer.
Key findings: EF can inhibit STAT3 phosphorylation and reduce the colony formation and migration of breast cancer cells. Detecting the active ingredients in EF, we found ICS I can reduce the activation of STAT3 in 4T1 breast cancer cells, impair colony formation and migration. Moreover, ICS I induced cells G1 phase arrest and modulated Cyclin D1, CDK4, bcl-2, and bax to inhibit proliferation and survival of breast cancer cells. Similarly, the in vivo studies demonstrated that ICS I significantly suppressed tumor development and lung metastasis in the 4T1 mouse model. Tumor cells in vehicle group were arranged in a spoke-like pattern with obvious heterogeneity, and multinucleated tumor giant cells were seen. But, the tumor cells in the ICS I group were disorganized and necrotic lysis was seen in some areas. In ICS I-treated group, tumors' STAT3 phosphorylation level, IL-6, Cyclin D1, CDK4, bcl-2, and vimentin expression were downregulated, bax and cleaved caspase 3 expression were upregulated. In the lung tissue, we could find less metastasis of breast cancer cells and less lung injury in the ICS I group. Besides, the expression of metastasis-related genes MMP9 and vimentin was decreased in the lung tissue of ICS I group.
Conclusions: These findings suggest that ICS I can inhibit breast cancer proliferation, apoptosis, invasion and metastasis probably via targeting IL-6/STAT3 pathway. Therefore, ICS I has the potential to become an innovative therapeutic candidate to breast cancer prevention and treatment.
{"title":"Icariside I reduces breast cancer proliferation, apoptosis, invasion, and metastasis probably through inhibiting IL-6/STAT3 signaling pathway.","authors":"Manting Hou, Hui Li, Tingting He, Siwen Hui, Wenzhang Dai, Xiaorong Hou, Jing Zhao, Jia Zhao, Jincai Wen, Wen Kan, Xiaohe Xiao, Xiaoyan Zhan, Zhaofang Bai","doi":"10.1093/jpp/rgad103","DOIUrl":"10.1093/jpp/rgad103","url":null,"abstract":"<p><strong>Objectives: </strong>Breast cancer is a common malignancy in women. More than 90% of breast cancer deaths are caused by metastasis. Epimedii Folium (EF) is a commonly used herb with anti-tumor benefits, but its underlying mechanisms and active components for breast cancer prevention are little understood. This study assessed the therapeutic role of Icariside I (ICS I) in Epimedium flavonoids (EF) on lung metastasis of breast cancer, including the underlying mechanism.</p><p><strong>Methods: </strong>Western blot, RT-qPCR, wound healing assay, colony formation assay, and flow cytometry were used to investigate the inhibition of breast cancer cells growth and migration by EF and ICS I through disrupting the IL-6/STAT3 pathway. Combined with 4T1 breast cancer model in mice, Western blot, RT-qPCR, Hematoxylin and Eosin staining, immunohistochemistry were used to evaluate the therapeutic role of ICS I in proliferation, apoptosis, invasion, and metastasis of breast cancer.</p><p><strong>Key findings: </strong>EF can inhibit STAT3 phosphorylation and reduce the colony formation and migration of breast cancer cells. Detecting the active ingredients in EF, we found ICS I can reduce the activation of STAT3 in 4T1 breast cancer cells, impair colony formation and migration. Moreover, ICS I induced cells G1 phase arrest and modulated Cyclin D1, CDK4, bcl-2, and bax to inhibit proliferation and survival of breast cancer cells. Similarly, the in vivo studies demonstrated that ICS I significantly suppressed tumor development and lung metastasis in the 4T1 mouse model. Tumor cells in vehicle group were arranged in a spoke-like pattern with obvious heterogeneity, and multinucleated tumor giant cells were seen. But, the tumor cells in the ICS I group were disorganized and necrotic lysis was seen in some areas. In ICS I-treated group, tumors' STAT3 phosphorylation level, IL-6, Cyclin D1, CDK4, bcl-2, and vimentin expression were downregulated, bax and cleaved caspase 3 expression were upregulated. In the lung tissue, we could find less metastasis of breast cancer cells and less lung injury in the ICS I group. Besides, the expression of metastasis-related genes MMP9 and vimentin was decreased in the lung tissue of ICS I group.</p><p><strong>Conclusions: </strong>These findings suggest that ICS I can inhibit breast cancer proliferation, apoptosis, invasion and metastasis probably via targeting IL-6/STAT3 pathway. Therefore, ICS I has the potential to become an innovative therapeutic candidate to breast cancer prevention and treatment.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136397918","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}
Objectives Oxytropis DC is a perennial plant of Fabaceae family, which is widely distributed in the northern temperate zone. It is known as “locoweed” because of its toxic component swainsonine. However, it is widely used in Tibetan medicine and Mongolian medicine, mainly for the treatment of heat-clearing and detoxifying, pain-relieving, anti-inflammatory, hemostasis, and other diseases. To provide a basis for the further development and utilization of Oxytropis DC, the pieces of literature about the application, phytochemistry, pharmacological action, and toxicity of Oxytropis DC were reviewed and analyzed. Key findings A total of 373 chemical constituents were found from Oxytropis DC, including flavonoids, alkaloids, steroids, terpenoids, and others. Pharmacological actions mainly include antitumor, antioxidation, anti-inflammatory, analgesic, antibacterial, antifibrosis, and other pharmacological actions, among them, the antitumor effect is particularly prominent. Summary At present, studies on its pharmacological effects are mainly concentrated on the extracts, some flavonoids, and alkaloids. In the follow-up studies, research on the pharmacological activities of the other chemical constituents in Oxytropis should be strengthened. It has the potential to pave the way for research and development of novel Oxytropis medicines.
目标 Oxytropis DC 是豆科多年生植物,广泛分布于北温带。因其有毒成分獐牙菜碱而被称为 "獐牙菜"。但在藏医和蒙医中应用广泛,主要用于治疗清热解毒、止痛、消炎、止血等疾病。为进一步开发利用牛膝,对有关牛膝的应用、植物化学、药理作用、毒性等方面的文献进行了综述和分析。主要研究结果 从牛至中发现了 373 种化学成分,包括黄酮类、生物碱类、甾体类、萜类等。药理作用主要包括抗肿瘤、抗氧化、抗炎、镇痛、抗菌、抗纤维化等药理作用,其中抗肿瘤作用尤为突出。小结 目前,对其药理作用的研究主要集中在提取物、部分黄酮类化合物和生物碱等方面。在后续研究中,应加强对牛膝中其他化学成分药理活性的研究。这有可能为研究和开发新型牛膝药物铺平道路。
{"title":"The genus Oxytropis DC: application, phytochemistry, pharmacology, and toxicity","authors":"Bingkang Wang, Zhenhua Tian, Shiyue Lang, Qinghe Kong, Xue Liu, Yueru Chen, Min Hua, Qian Zhou, Xiaofei Yu, Hao Feng, Fulin Wang, Honglei Zhou","doi":"10.1093/jpp/rgae048","DOIUrl":"https://doi.org/10.1093/jpp/rgae048","url":null,"abstract":"Objectives Oxytropis DC is a perennial plant of Fabaceae family, which is widely distributed in the northern temperate zone. It is known as “locoweed” because of its toxic component swainsonine. However, it is widely used in Tibetan medicine and Mongolian medicine, mainly for the treatment of heat-clearing and detoxifying, pain-relieving, anti-inflammatory, hemostasis, and other diseases. To provide a basis for the further development and utilization of Oxytropis DC, the pieces of literature about the application, phytochemistry, pharmacological action, and toxicity of Oxytropis DC were reviewed and analyzed. Key findings A total of 373 chemical constituents were found from Oxytropis DC, including flavonoids, alkaloids, steroids, terpenoids, and others. Pharmacological actions mainly include antitumor, antioxidation, anti-inflammatory, analgesic, antibacterial, antifibrosis, and other pharmacological actions, among them, the antitumor effect is particularly prominent. Summary At present, studies on its pharmacological effects are mainly concentrated on the extracts, some flavonoids, and alkaloids. In the follow-up studies, research on the pharmacological activities of the other chemical constituents in Oxytropis should be strengthened. It has the potential to pave the way for research and development of novel Oxytropis medicines.","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140830742","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}