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

Liposomal topical drug administration surpasses alternative methods in glaucoma therapeutics: a novel paradigm for enhanced treatment. 在青光眼治疗中，脂质体局部给药超越了其他方法：一种新型的强化治疗范例。

IF 2.8 4区医学

Journal of Pharmacy and Pharmacology Pub Date : 2024-11-23 DOI: 10.1093/jpp/rgae129

Nor Asyikin Nordin, Muhammad Zulfiqah Sadikan, Lidawani Lambuk, Sabarisah Hashim, Syahira Airuddin, Nur-Azida Mohd Nasir, Rohimah Mohamud, Jamal Ibrahim, Ramlah Kadir

{"title":"Liposomal topical drug administration surpasses alternative methods in glaucoma therapeutics: a novel paradigm for enhanced treatment.","authors":"Nor Asyikin Nordin, Muhammad Zulfiqah Sadikan, Lidawani Lambuk, Sabarisah Hashim, Syahira Airuddin, Nur-Azida Mohd Nasir, Rohimah Mohamud, Jamal Ibrahim, Ramlah Kadir","doi":"10.1093/jpp/rgae129","DOIUrl":"https://doi.org/10.1093/jpp/rgae129","url":null,"abstract":"Objectives: Glaucoma is a leading cause of permanent blindness. Despite therapeutic advancements, glaucoma management remains challenging due to limitations of conventional drug delivery, primarily topical eye drops, resulting in suboptimal outcomes and a global surge in cases. To address these issues, liposomal drug delivery has emerged as a promising approach.Key findings: This review explores the potential of liposomal-based medications, with a particular focus on topical administration as a superior alternative to enhance therapeutic efficacy and improve patient compliance compared to existing treatments. This writing delves into the therapeutic prospects of liposomal formulations across different administration routes, as evidenced by ongoing clinical trials. Additionally, critical aspects of liposomal production and market strategies are discussed herein.Summary: By overcoming ocular barriers and optimizing drug delivery, liposomal topical administration holds the key to significantly improving glaucoma treatment outcomes.","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695624","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

Inhaled exogenous thymosin beta 4 suppresses bleomycin-induced pulmonary fibrosis in mice via TGF-β1 signalling pathway. 吸入外源性胸腺肽β4通过TGF-β1信号通路抑制博莱霉素诱导的小鼠肺纤维化

IF 2.8 4区医学

Journal of Pharmacy and Pharmacology Pub Date : 2024-11-23 DOI: 10.1093/jpp/rgae143

Rui Yu, Shimeng Li, Li Chen, Enbo Hu, Dan Chai, Zhichao Liu, Qianyi Zhang, Yunyun Mao, Yanfang Zhai, Kai Li, Yanhong Liu, Xiaohe Li, Honggang Zhou, Cheng Yang, Junjie Xu

{"title":"Inhaled exogenous thymosin beta 4 suppresses bleomycin-induced pulmonary fibrosis in mice via TGF-β1 signalling pathway.","authors":"Rui Yu, Shimeng Li, Li Chen, Enbo Hu, Dan Chai, Zhichao Liu, Qianyi Zhang, Yunyun Mao, Yanfang Zhai, Kai Li, Yanhong Liu, Xiaohe Li, Honggang Zhou, Cheng Yang, Junjie Xu","doi":"10.1093/jpp/rgae143","DOIUrl":"https://doi.org/10.1093/jpp/rgae143","url":null,"abstract":"Objectives: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and fibrotic interstitial lung disease. The two drugs indicated for IPF have limited efficacy and there is an urgent need to develop new drugs. Thymosin β4 (Tβ4) is a natural endogenous repair factor whose antifibrotic effects have been reported. This study aimed to evaluate the effect of exogenous recombinant human thymosin beta 4 (rhTβ4) on pulmonary fibrosis.Methods: Pulmonary fibrosis was induced in mice with bleomycin, and rhTβ4 was administrated by nebulization following three strategies: early dosing, mid-term dosing, and late dosing. The rhTβ4 efficacy was assessed by hydroxyproline, lung function, and lung histopathology. In vitro, the effects of rhTβ4 on fibroblast and lung epithelial cell phenotypes, as well as the TGF-β1 pathway, were evaluated.Key findings: Aerosol administration of rhTβ4 could alleviate bleomycin-induced pulmonary fibrosis in mice at different stages of fibrosis. Studies conducted in vitro suggested that rhTβ4 could suppress lung fibroblasts from proliferating, migrating, and activation via regulating the TGF-β1 signalling pathway. In vitro, rhTβ4 also inhibited the epithelial-mesenchymal transition-like process of pulmonary epithelial cells.Conclusions: This study suggests that nebulized rhTβ4 is a potential treatment for IPF.","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695621","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

Silencing c-myc gene by siRNA delivered by cationic niosomes in MCF-7 cells. 在 MCF-7 细胞中用阳离子纳米囊递送 siRNA 沉默 c-myc 基因。

IF 2.8 4区医学

Journal of Pharmacy and Pharmacology Pub Date : 2024-11-22 DOI: 10.1093/jpp/rgae146

Shatha N Abdeljaber, Alaa A Aljabali, Bahaa Altrad, Mohammad A Obeid

{"title":"Silencing c-myc gene by siRNA delivered by cationic niosomes in MCF-7 cells.","authors":"Shatha N Abdeljaber, Alaa A Aljabali, Bahaa Altrad, Mohammad A Obeid","doi":"10.1093/jpp/rgae146","DOIUrl":"https://doi.org/10.1093/jpp/rgae146","url":null,"abstract":"Objectives: Gene therapy has a strong potential to treat different cancer types cancers with high therapeutic outcomes. c-myc is believed to be responsible for more than 15% of all gene regulation and functions as a transcription factor for proteins essential for cell proliferation. This study aimed to develop niosome nanocarriers to knockdown c-myc expression using anti-c-myc short-interfering RNA (siRNA) in MCF-7 cells. Altering the activity of the c-myc proto-oncogene has been identified as an important element in minimizing cancer cell growth because anti-c-myc siRNA degrades c-myc mRNA.Methods: Noisomes were prepared from Tween 85, cholesterol, and didodecyldimethylammonium bromide at 50:40:10 and 40:40:20 molar ratios. Anti-c-myc siRNA was loaded in the prepared niosomes and then applied on MCF-7 cells.Key findings: Niosomes had a total positive charge formed electrostatic interactions with siRNA. Niosomes were spherical with a size range of 70-100 nm. The prepared niosomes were nontoxic to MCF-7 cells, with IC50 values of >250 µg/ml for both formulations. After encapsulation of anti-c-myc siRNA, nioplexes reduced c-myc mRNA expression by more than 50% compared with the untreated cells. Empty niosomes did not affect c-myc mRNA expression levels, indicating that the effect was due to siRNA rather than the particles themselves.Conclusions: This study provides evidence that niosomes can function as suitable carriers for siRNA delivery to knockdown the c-myc oncogene in MCF-7 cells, thus reducing cancer cell growth.","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142687173","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 : 2024-11-20 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":"https://doi.org/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":""},"PeriodicalIF":2.8,"publicationDate":"2024-11-20","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

Protein phosphatase 2A inhibitors: a possible pharmacotherapy for benzodiazepine dependence. 蛋白磷酸酶 2A 抑制剂：治疗苯并二氮杂卓依赖症的一种可能药物疗法。

IF 2.8 4区医学

Journal of Pharmacy and Pharmacology Pub Date : 2024-11-15 DOI: 10.1093/jpp/rgae136

Chisa Kobayashi, Nobue Kitanaka, Masanori Nakai, F Scott Hall, Kazuo Tomita, Kento Igarashi, Tomoaki Sato, George R Uhl, Junichi Kitanaka

{"title":"Protein phosphatase 2A inhibitors: a possible pharmacotherapy for benzodiazepine dependence.","authors":"Chisa Kobayashi, Nobue Kitanaka, Masanori Nakai, F Scott Hall, Kazuo Tomita, Kento Igarashi, Tomoaki Sato, George R Uhl, Junichi Kitanaka","doi":"10.1093/jpp/rgae136","DOIUrl":"https://doi.org/10.1093/jpp/rgae136","url":null,"abstract":"Objectives: Benzodiazepines (BZDs) activate the γ-aminobutyric acid (GABA) subtype A (GABAA) receptors, and thus are widely used medicines for the treatment of anxiety and insomnia. For chronic use, tolerance to BZDs is a major problem. Patients with chronic insomnia that develop tolerance to BZDs lose therapeutic effects but also potentially suffer from BZD dependence resulting in BZD withdrawal. The development of such treatments is important for the appropriate use of BZDs.Methods: Research articles regarding investigation of BZD dependence were searched on PubMed, Embase, and Scopus databases using keywords \"benzodiazepine\", \"dependence\", \"treatment\".Key findings: When BZDs are taken chronically, continuous GABAA binding results in up-regulation of α-amino-3-hydroxy-5-methyl-4-lisoxazolepropionic acid (AMPA) glutamate receptor function and release of brain-derived neurotrophic factor (BDNF). Released BDNF binds to its specific receptor tropomyosin-related kinase receptor B (TrkB). Enhanced BDNF-TrkB signaling activates protein phosphatase 2A (PP2A). Activated PP2A dephosphorylates GABAA receptors, resulting in the downregulation of the GABAA receptor function. Reduced GABAA receptor function augments long-term potentiation (LTP), AMPA-mediated glutamatergic neuroplasticity, by reducing LTP inhibition by GABAA receptor function. Augmented LTP enhances extreme anxiety, which leads to BZD dependence.Conclusion: Therefore, iInhibiting dephosphorylation of the GABAA receptor by PP2A, PP2A inhibitors could reduce LTP and anxiety, restoring BZD effectiveness and resulting in possible therapeutic effects for BZD dependence.","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639290","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 : 2024-11-14 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":"https://doi.org/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":""},"PeriodicalIF":2.8,"publicationDate":"2024-11-14","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 regulatory effects of mitragynine on P-glycoprotein transporter. 麻黄碱对 P-糖蛋白转运体的调节作用

IF 2.8 4区医学

Journal of Pharmacy and Pharmacology Pub Date : 2024-11-14 DOI: 10.1093/jpp/rgae131

Muhammad Asyraf Abduraman, Azimah Amanah, Shahrul Bariyah Sahul Hamid, Mohammad Farris Iman Leong Abdullah, Shaida Fariza Sulaiman, Mei Lan Tan

{"title":"The regulatory effects of mitragynine on P-glycoprotein transporter.","authors":"Muhammad Asyraf Abduraman, Azimah Amanah, Shahrul Bariyah Sahul Hamid, Mohammad Farris Iman Leong Abdullah, Shaida Fariza Sulaiman, Mei Lan Tan","doi":"10.1093/jpp/rgae131","DOIUrl":"https://doi.org/10.1093/jpp/rgae131","url":null,"abstract":"Objectives: Kratom preparation containing Mitragyna speciosa Korth plant is frequently used as a recreational drug. Mitragynine, a major alkaloid isolated from M. speciosa, is often detected concurrently with other drugs during forensic analysis, indicating a safety concern. P-glycoprotein (P-gp) is a multidrug transporter. Modulation of P-gp transport activity by drugs or herbal compounds in the brain may lead to drug-herb interactions, resulting in neurotoxicity. We aim to determine the effects of mitragynine on the P-gp regulation and possible neurotoxicity.Methods: The effects of mitragynine on the P-gp regulation were investigated in human brain capillary endothelial cells (hCMEC/D3) using molecular docking and dynamic simulation and an optimized bidirectional transport assay, respectively. Repeated-dose treatment and neurotoxicity assessment were carried out using a blood-brain barrier model and polimerase chain reaction (PCR) array.Key findings: Mitragynine inhibits the P-gp transport activity via binding onto the nucleotide-binding domain site and forms a stable interaction with the P-gp protein complex. Nontoxic concentrations of mitragynine (<4 μM) and substrate drugs (0.001 μM) in the cells significantly enhanced endothelial cell permeability and elicited signs of neurotoxicity in PC-12 cells.Conclusions: Mitragynine is likely a P-gp inhibitor, hence concurrent administration of kratom products with P-gp substrates may lead to clinically significant interactions and neurotoxicity.","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142622680","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

Development of a pharmacokinetic/pharmacodynamic evaluation model for osteomyelitis and usefulness of tedizolid as an alternative to vancomycin against MRSA osteomyelitis. 开发骨髓炎药代动力学/药效学评估模型，以及泰迪唑胺作为万古霉素替代品对 MRSA 骨髓炎的作用。

IF 2.8 4区医学

Journal of Pharmacy and Pharmacology Pub Date : 2024-11-06 DOI: 10.1093/jpp/rgae124

Xiaoxi Liu, Yuki Enoki, Kazuaki Taguchi, Kazuaki Matsumoto

{"title":"Development of a pharmacokinetic/pharmacodynamic evaluation model for osteomyelitis and usefulness of tedizolid as an alternative to vancomycin against MRSA osteomyelitis.","authors":"Xiaoxi Liu, Yuki Enoki, Kazuaki Taguchi, Kazuaki Matsumoto","doi":"10.1093/jpp/rgae124","DOIUrl":"https://doi.org/10.1093/jpp/rgae124","url":null,"abstract":"Objectives: This study aimed to develop a suitable osteomyelitis model for pharmacokinetic/pharmacodynamic (PK/PD) evaluation and to investigate the target PK/PD values of vancomycin and tedizolid against methicillin-resistant Staphylococcus aureus (MRSA) osteomyelitis.Methods: An osteomyelitis model was established by implanting an MRSA-exposed sterilized suture in the tibia of normal mice and mice with cyclophosphamide-induced neutropenia. The suitability of the osteomyelitis mouse model for PK/PD evaluation was assessed using vancomycin as an indicator. The target PK/PD values for tedizolid were determined using this model.Key findings: In neutropenic mice, to achieve a static effect and 1 log10 kill against MRSA, the ratios of the area under the free drug concentration-time curve for 24 h to the minimum inhibitory concentration (fAUC24/MIC) of vancomycin were 91.29 and 430.03, respectively, confirming the validity of the osteomyelitis model for PK/PD evaluation. In immunocompetent mice, the target fAUC24/MIC values of tedizolid for achieving a static effect and 1 log10 kill against MRSA were 2.40 and 49.20, respectively. Additionally, only a 0.28 log10 kill was achieved in neutropenic mice with 20 times the human equivalent dose of tedizolid.Conclusions: In patients with restored immunity, tedizolid can potentially be used as an alternative to intravenous vancomycin therapy.","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590863","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

Shikonin mitigates cyclophosphamide-induced cardiotoxicity in mice: the role of sirtuin-1, NLRP3 inflammasome, autophagy, and apoptosis. 志贺宁减轻环磷酰胺诱导的小鼠心脏毒性：sirtuin-1、NLRP3炎性体、自噬和细胞凋亡的作用

IF 2.8 4区医学

Journal of Pharmacy and Pharmacology Pub Date : 2024-11-04 DOI: 10.1093/jpp/rgae119

Fatemah A Alherz, Asmaa Saleh, Mona Y Alsheikh, Hany M Borg, Ahmed M Kabel, Maaly A Abd Elmaaboud

{"title":"Shikonin mitigates cyclophosphamide-induced cardiotoxicity in mice: the role of sirtuin-1, NLRP3 inflammasome, autophagy, and apoptosis.","authors":"Fatemah A Alherz, Asmaa Saleh, Mona Y Alsheikh, Hany M Borg, Ahmed M Kabel, Maaly A Abd Elmaaboud","doi":"10.1093/jpp/rgae119","DOIUrl":"10.1093/jpp/rgae119","url":null,"abstract":"Objectives: The aim of this study was to elucidate the protective potential of shikonin (SHK) on cyclophosphamide (CP)-induced cardiotoxicity in Swiss albino mice.Methods: Mice received SHK in three different doses by oral gavage daily for 14 days and CP at 100 mg/kg, intraperitoneally once on the seventh day. On the 15th day, mice were euthanized, blood collected, and hearts were removed to estimate various biochemical and histopathological parameters.Key findings: CP significantly increased serum lactate dehydrogenase, creatine kinase-MB, troponin I and NT pro-BNP, and cardiac malondialdehyde and decreased cardiac total antioxidant capacity and Nrf2, whereas increased inflammatory markers in the cardiac tissues. CP also caused hypertrophy and fibrosis in the cardiac tissues via activation of IL6/JAK2/STAT3 while depressed SIRT1 and PI3K/p-Akt pathway with consequent increased apoptosis and dysregulation of autophagy. SHK treatment reversed these changes in a dose-dependent manner and showed a significant protective effect against CP-induced cardiotoxicity via suppressing oxidative stress, inflammation, and apoptosis with modulation of autophagy via induction of SIRT1/PI3K/p-Akt signaling.Conclusions: Shikonin may be used as an adjuvant to cyclophosphamide in cancer treatment, but further research is needed to investigate its effects on cardiotoxicity in distinct animal cancer models.","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"1482-1496"},"PeriodicalIF":2.8,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142154378","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

Evaluating the protective effect of dapsone on experimental osteoarthritis models induced by MIA in male rats. 评估达索酮对 MIA 诱导的雄性大鼠实验性骨关节炎模型的保护作用。

IF 2.8 4区医学

Journal of Pharmacy and Pharmacology Pub Date : 2024-11-04 DOI: 10.1093/jpp/rgae087

Kimia Nazari, Saereh Hosseindoost, Ahmad Reza Dehpour, Yasaman Kheirandish, Hamed Shafaroodi

{"title":"Evaluating the protective effect of dapsone on experimental osteoarthritis models induced by MIA in male rats.","authors":"Kimia Nazari, Saereh Hosseindoost, Ahmad Reza Dehpour, Yasaman Kheirandish, Hamed Shafaroodi","doi":"10.1093/jpp/rgae087","DOIUrl":"10.1093/jpp/rgae087","url":null,"abstract":"Objectives: Osteoarthritis, a degenerative condition that results in significant morbidity, is typically managed with treatments aimed at symptom relief rather than addressing the underlying degeneration. Dapsone, recognized for its anti-inflammatory, antioxidant, antiexcitotoxic, and antiapoptotic properties, has demonstrated promising effects in various neurodegenerative diseases. This study explores the potential of dapsone to mitigate articular destruction, inflammation, and pain in rat models of osteoarthritis.Methods: Osteoarthritis was induced in rats by injecting MIA into the right knee joint. Dapsone was then administered intraperitoneally at 5, 10, or 20 mg/kg every 2 days for 2 weeks. Behavioural tests were done on days 0, 7, and 14. On day 14, the articular cartilage was histologically analysed using H&E staining. Serum levels of NF-kB, IL-1β, and TNF-α were evaluated by ELISA.Results: Dapsone effectively reduces pain, inflammation, and articular cartilage damage in osteoarthritis. Specifically, it improves mechanical allodynia and thermal hyperalgesia, reduces inflammatory markers (TNF-α, IL-1β, and NF-κB), and protects against cartilage destruction and chondrocyte loss, with the most significant effects at 20 mg/kg.Conclusions: Dapsone effectively prevents pain, inflammation, and cartilage damage in osteoarthritis rats, suggesting its potential as a therapeutic option for managing osteoarthritis.","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"1497-1507"},"PeriodicalIF":2.8,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141889572","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