Journal of Pharmacy and Pharmacology最新文献_第5页

Exploring the potential of vaginal drug delivery: innovations, efficacy, and therapeutic prospects. 探索阴道给药的潜力：创新、疗效和治疗前景。

IF 3.2 4区医学

Journal of Pharmacy and Pharmacology Pub Date : 2025-09-04 DOI: 10.1093/jpp/rgaf045

Eva Sanchez Armengol, Florina Veider, Gioconda Millotti, Gergely Kali, Andreas Bernkop-Schnürch, Flavia Laffleur

{"title":"Exploring the potential of vaginal drug delivery: innovations, efficacy, and therapeutic prospects.","authors":"Eva Sanchez Armengol, Florina Veider, Gioconda Millotti, Gergely Kali, Andreas Bernkop-Schnürch, Flavia Laffleur","doi":"10.1093/jpp/rgaf045","DOIUrl":"10.1093/jpp/rgaf045","url":null,"abstract":"Vaginal drug delivery has gained significant interest due to its numerous advantages, such as good blood flow, bypassing the first-pass effect, low systemic side effects, and potential for sustained release of pharmaceuticals. Initially targeting contraception and local effects from antibacterial, antifungal, and antiviral agents, recent advancements have broadened its scope. Notably, microbicide formulations showed promise against sexually transmitted diseases, offering superior protection and effective hormone therapies due to the vagina's large surface area and high permeability. The main agents used in vaginal delivery include contraceptives, prostaglandins, steroids, and antimicrobial substances, administered through tablets, suppositories, ointments, gels, creams, and vaginal rings. However, challenges such as slow dissolution and short residence time necessitate novel delivery systems. Mucoadhesive polymers are particularly valuable for enhancing drug absorption and extending treatment options. Comparative studies indicate that vaginal absorption of drugs like human growth hormone and insulin surpasses other parenteral routes. The development of standardized in vitro and in vivo testing methods remains crucial due to the diverse drug systems. While vaginal drug delivery offers benefits, such as high vascularization, low enzymatic activity, and increased bioavailability, it also faces drawbacks, including limited drug compatibility, sensitivity to vaginal pH, patient compliance issues, and potential local irritation. This review aims to elucidate the pathway, propose standardized methods for specific therapeutic areas, and highlight novel formulations like hydrogels and lipid nanoparticles for treating various diseases.","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"1149-1165"},"PeriodicalIF":3.2,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144497394","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

YLKTT, a potent biopeptide that ameliorates oxygen-glucose deprivation-induced neuronal cell ferroptosis by ACSL4/GPX4 and SLC7A11/GPX4 axis. YLKTT是一种有效的生物肽，通过ACSL4/GPX4和SLC7A11/GPX4轴改善氧-葡萄糖剥夺诱导的神经元细胞铁凋亡。

IF 3.2 4区医学

Journal of Pharmacy and Pharmacology Pub Date : 2025-09-04 DOI: 10.1093/jpp/rgaf037

Yujie Wu, Yansu Ji, Xin Jin, Guangjing Xu, Xiaoyu Wang, Saisai Song, Rui Li, Yuhan Wang, Rui Liu, Zheng Li

{"title":"YLKTT, a potent biopeptide that ameliorates oxygen-glucose deprivation-induced neuronal cell ferroptosis by ACSL4/GPX4 and SLC7A11/GPX4 axis.","authors":"Yujie Wu, Yansu Ji, Xin Jin, Guangjing Xu, Xiaoyu Wang, Saisai Song, Rui Li, Yuhan Wang, Rui Liu, Zheng Li","doi":"10.1093/jpp/rgaf037","DOIUrl":"10.1093/jpp/rgaf037","url":null,"abstract":"Objectives: Shuxuetong injection (SXT) treats cerebral ischemic injury by inhibiting apoptosis. However, the specific active ingredient responsible for this effect and its mechanism of action remain unclear.Methods: In previous research, we identified the small peptide YLKTT in SXT, which has shown protective effects on astrocytes subjected to oxygen-glucose deprivation/reoxygenation (OGD/R). In this study, we utilized transcriptomics technology to predict the specific target genes and pathways of YLKTT in the context of stroke treatment. We further validated these predictions through RT-PCR, lipid peroxidation assays, Western blotting, and other related methods.Key findings: The transcriptomics results indicated that YLKTT could further alleviate ischemia-reperfusion injury by inhibiting ferroptosis, with the specific pathway likely involving the regulation of glutathione peroxidase 4 (GPX4) by ACSL4 and SLC7A11. Experimental results demonstrated that YLKTT interfered with the SLC7A11/GPX4 and ACSL4/GPX4 pathways, thereby enhancing antioxidant capacity, inhibiting the accumulation of lipid peroxidation, and ultimately reversing OGD-induced ferroptosis. Additionally, erastin significantly reduced SLC7A11 mRNA and protein levels and decreased GPX4 levels, while YLKTT was able to reverse these changes.Conclusions: YLKTT can exert anti-ferroptosis effects through the ACSL4/GPX4 and SLC7A11/GPX4 pathways, thereby improving the treatment of cerebral ischemic injury.","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"1244-1254"},"PeriodicalIF":3.2,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560458","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

Anticancer potential of PEDF peptides. PEDF肽的抗癌潜力。

IF 3.2 4区医学

Journal of Pharmacy and Pharmacology Pub Date : 2025-09-04 DOI: 10.1093/jpp/rgaf043

Enas Bani-Ahmad, Joshua Dass, Crispin R Dass

{"title":"Anticancer potential of PEDF peptides.","authors":"Enas Bani-Ahmad, Joshua Dass, Crispin R Dass","doi":"10.1093/jpp/rgaf043","DOIUrl":"10.1093/jpp/rgaf043","url":null,"abstract":"Objectives: Pigment epithelium-derived factor (PEDF) has demonstrated a wide range of activities, the most notable of which is its role in cancer.Methods: Articles were sourced from Scopus with the following keywords-PEDF, peptide(s), cancer, tumour, and tumour. There was no limit set on date of publication, and the language of publication was set to English.Key findings: Researchers have found two functional epitopes in the PEDF sequence: a 34-mer peptide that mainly inhibits angiogenesis and a 44-mer peptide that mainly promotes differentiation and neurotrophic functions in certain cell lines. Furthermore, studies have demonstrated that shorter peptides in the 34-mer significantly contribute to its angiogenic activity. PEDF peptide functions as an anticancer agent through various mechanisms. The most salient feature is the blockade of angiogenesis by reducing VEGF levels. Angiogenesis is critical in tumour expansion, and it is known as the process whereby new blood vessels are formed from capillaries.Conclusions: Researchers have studied several PEDF peptides in various types of cancer, including ovarian, breast, lung, osteosarcoma, and myeloma. This underscores the potential significance of the various PEDF peptides, given their known ability to influence angiogenesis and other biological processes.","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"1166-1174"},"PeriodicalIF":3.2,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144285040","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

Curcuma longa L. extract and residue prevent Alzheimer's disease in mice by regulating microglia and TLR4/NF-κB signaling pathway. 姜黄提取物和残渣通过调节小胶质细胞和TLR4/NF-κB信号通路预防小鼠阿尔茨海默病。

IF 3.2 4区医学

Journal of Pharmacy and Pharmacology Pub Date : 2025-09-04 DOI: 10.1093/jpp/rgaf034

Zhihui Xu, Jianlin Li, Xiaotong Liu, Liaoyuan Liu, Weixiong Lin, Dongmei Sun, Yu Zeng

{"title":"Curcuma longa L. extract and residue prevent Alzheimer's disease in mice by regulating microglia and TLR4/NF-κB signaling pathway.","authors":"Zhihui Xu, Jianlin Li, Xiaotong Liu, Liaoyuan Liu, Weixiong Lin, Dongmei Sun, Yu Zeng","doi":"10.1093/jpp/rgaf034","DOIUrl":"10.1093/jpp/rgaf034","url":null,"abstract":"Background: Curcuma longa L. (CL) is renowned for its various health benefits and has shown potential in alleviating Alzheimer's disease (AD). The post-aqueous extraction residues (CLR) may retain valuable nutritional components. The research aimed to explore their chemical composition and neuroprotective mechanism against Aβ1-42-induced AD mice.Methods: We employed UPLC-Q-Exactive/MS to characterize the chemical constituents of CL and CLR. An HPLC method was developed to quantify three predominant curcuminoids. To investigate their neuroprotective effects against Aβ1-42-induced AD mice, we assessed cognitive function using the Morris water maze and evaluated neuronal damage through histopathological examination. Molecular mechanisms were explored using immunofluorescence, ELISA, and qRT-PCR assays.Results: The study unveiled 47 and 36 compounds in CL and CLR, respectively, and eight significant differential components. HPLC analysis revealed that CLR contained substantial curcuminoids. In Aβ1-42-induced AD mice, CL and CLR improved spatial learning and memory ability, ameliorated pathological alterations in the hippocampal region, and regulated overactivated microglia. Moreover, CL and CLR inhibited the TLR4/NF-κB inﬂammatory pathway.Conclusion: CL and CLR exhibit the anti-AD effect by regulating microglia and suppressing the TLR4/NF-κB signaling pathway, which provides a scientific basis for future nutraceutical and pharmaceutical development.","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"1192-1202"},"PeriodicalIF":3.2,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144159757","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

Investigating the neuroprotective role of Synta-66 in type-2 diabetes mellitus-induced dementia in rats. Synta-66在2型糖尿病痴呆大鼠中的神经保护作用。

IF 3.2 4区医学

Journal of Pharmacy and Pharmacology Pub Date : 2025-09-04 DOI: 10.1093/jpp/rgaf036

Ashi Mannan, Maneesh Mohan, Shareen Singh, Sonia Dhiman, Thakur Gurjeet Singh

{"title":"Investigating the neuroprotective role of Synta-66 in type-2 diabetes mellitus-induced dementia in rats.","authors":"Ashi Mannan, Maneesh Mohan, Shareen Singh, Sonia Dhiman, Thakur Gurjeet Singh","doi":"10.1093/jpp/rgaf036","DOIUrl":"10.1093/jpp/rgaf036","url":null,"abstract":"Objectives: This study explores the potential inhibitory effects of Synta-66 at doses of 1 and 5 mg/kg, with a particular emphasis on the role of ORAI-I in amyloidogenesis, a common mechanism that underlies type-2 diabetes mellitus (T2DM) and Alzheimer's disease (AD).Methods: Induction of T2DM-induced AD by the high-fat diet (HFD)-Streptozotocin (STZ)-Aβ25-35 model. Assessment of behavioral parameters like polydipsia, polyphagia, Morris water maze, and passive avoidance test; biochemical estimation of glucose, insulin, oxidative stress (superoxide dismutase (SOD), glutathione (GSH), catalase (Cat), and thiobarbituric acid reactive substances (TBARS)), neuroinflammation (interleukin-1 beta (IL-1β), interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-α), and nuclear factor-kappa B (NF-κβ)), Aβ level, through ELISA technique, and calcium levels via atomic absorption spectrometer.Key findings: Synta-66 (5 and 10 mg/kg) results in a reduction in food and water intake, as well as a reduction in memory impairment in the Morris water maze and passive avoidance test. Furthermore, it normalizes glucose, insulin, and antioxidant elements (SOD, GSH, and Cat) level, while decreasing TBARS levels. In addition, ELISA data demonstrated a reduction in neuroinflammation (downregulation of IL-1β, IL-6, TNF-α, and NF-κβ), Aβ accumulation, and calcium levels by Synta-66 (5 and 10 mg/kg).Conclusion: Consequently, ORAI can play a crucial role in the mediation of amyloidogenesis induced by T2DM, thereby establishing a connection between T2DM and AD. Therefore, Synta-66 has the potential to treat and prevent the progression of T2DM to AD.","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"1222-1243"},"PeriodicalIF":3.2,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144275190","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

Thymol suppressed tumor growth in vitro and in vivo through inducing calcium overload in colorectal cancer. 百里香酚通过诱导结直肠癌钙超载抑制肿瘤生长。

IF 3.2 4区医学

Journal of Pharmacy and Pharmacology Pub Date : 2025-09-04 DOI: 10.1093/jpp/rgaf040

Hao Lin, Zongjun Chen, Weizhong Yang, Xianwei Wang

{"title":"Thymol suppressed tumor growth in vitro and in vivo through inducing calcium overload in colorectal cancer.","authors":"Hao Lin, Zongjun Chen, Weizhong Yang, Xianwei Wang","doi":"10.1093/jpp/rgaf040","DOIUrl":"10.1093/jpp/rgaf040","url":null,"abstract":"Background: Thymol, a bioactive phenolic compound, has proven to possess multiple anti-cancer activities, yet the function and underlying mechanism in colorectal cancer (CRC) remain unclear.Objectives: To shed light on the possible therapeutic effects of thymol in CRC based on calcium homeostasis regulation, and seek to explore the molecular pathways of calcium overload in the thymol-induced anti-CRC activity.Methods: The effects of thymol on cell proliferation, viability, apoptosis, anti-inflammatory effects, and calcium overload phenotype were investigated in HCT116 and CT26 cells. In addition, the in vivo therapeutic efficacies of thymol on CT26 xenograft tumor were also researched. Furthermore, molecular mechanisms of thymol-induced calcium overload were detected by Western blot, RT-qPCR, and immunofluorescence assays.Results: We demonstrated that thymol significantly inhibited the proliferation, viability, and induced apoptosis of HCT116 and CT26 cells. And, thymol suppressed the secretion of inflammatory factors. Furthermore, thymol promoted cell damage mediated by increased mitochondrial membrane potential in both two cells. In addition, thymol triggered the energy metabolism inhibition induced by calcium overload in HCT116 and CT26 cells. Besides, in vivo experiments based on CT26 xenograft tumor model also validated the positive anti-CRC activities.Conclusions: Thymol inhibits CRC partially through inducing calcium overload, which provides an innovative solution for developing anti-CRC drugs.","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"1264-1276"},"PeriodicalIF":3.2,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248469","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

Dendrobium officinale Kimura et Migo: traditional uses, agricultural technology, processing, chemical composition, pharmacological mechanisms, toxicology, and applications. 木村石斛：传统用途、农业技术、加工、化学成分、药理机制、毒理学及应用。

IF 3.2 4区医学

Journal of Pharmacy and Pharmacology Pub Date : 2025-08-29 DOI: 10.1093/jpp/rgaf074

Xiaolian Liu, Jijiao Wu, Bolin Zhao, Lin Wen, Chuipeng Liang, Zihao Sun, Jia Luo, Xiaofang Li

{"title":"Dendrobium officinale Kimura et Migo: traditional uses, agricultural technology, processing, chemical composition, pharmacological mechanisms, toxicology, and applications.","authors":"Xiaolian Liu, Jijiao Wu, Bolin Zhao, Lin Wen, Chuipeng Liang, Zihao Sun, Jia Luo, Xiaofang Li","doi":"10.1093/jpp/rgaf074","DOIUrl":"https://doi.org/10.1093/jpp/rgaf074","url":null,"abstract":"Objectives: Dendrobium officinale has been used as a medicinal and edible plant for more than 2000 years. It was often used by the ancients to nourish the body, brew baijiu and brew tea. The review's objective was to examine the traditional uses, agricultural technology, processing, chemical composition, pharmacological mechanisms (in vitro/vivo), toxicology, and applications of D. officinale conducted over the past 10 years.Methods: Using online databases including Web of Science, PubMed, Google Scholar, and CNKI, the following search phrases were used to look for the data: D. officinale, D. officinale Kimura et Migo, pharmacology, and toxicology. All studies on the genus from 2014 to 2025 were included in this review.Key findings: Numerous reports indicate that the biological activity of D. officinale are diverse and include hepatoprotective properties, immunomodulatory effects, antioxidant properties, therapy of metabolic syndrome, anticancer properties, and improvement of gastrointestinal function. D. officinale is considered to have minimal toxicity, and is currently predominantly marketed as a dietary supplement.Conclusions: D. officinale has the potential to be developed and utilized in the fields of medicine, health care, and regimen. It is recommended that clinical studies on D. officinale be expanded to ascertain its safety and efficacy for human use.","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144958313","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

Potential of syringol and guaiacol in mitigating hyperglycemia associated dicarbonyl stress in rats subjected to high-fat high-fructose diet. 丁香酚和愈创木酚在大鼠高脂肪高果糖饮食中减轻高血糖相关的二羰基应激的潜力。

IF 3.2 4区医学

Journal of Pharmacy and Pharmacology Pub Date : 2025-08-25 DOI: 10.1093/jpp/rgaf071

Iqra Yousaf, Sairah Hafeez Kamran, Afshan Naseem, Hafsa Afzal, Rida Naz, Adnan Amin, Iram Gull

{"title":"Potential of syringol and guaiacol in mitigating hyperglycemia associated dicarbonyl stress in rats subjected to high-fat high-fructose diet.","authors":"Iqra Yousaf, Sairah Hafeez Kamran, Afshan Naseem, Hafsa Afzal, Rida Naz, Adnan Amin, Iram Gull","doi":"10.1093/jpp/rgaf071","DOIUrl":"https://doi.org/10.1093/jpp/rgaf071","url":null,"abstract":"Objective: The current study assessed the pharmacological potential of syringol and guaiacol, both separately and in combination, in hyperglycemia linked to dicarbonyl stress (DS).Methods: The control group (n = 5) received a standard diet with Tween 20 and disease group received high-fat high-fructose diet. The remaining four groups received metformin, syringol (100 μg/kg), guaiacol (100 μg/kg), or a combination of both (50 + 50 μg/kg) starting on the 29th day and lasting 30 days. After study completion, glucose intolerance, oxidative stress markers, glycated products, liver, renal, lipid markers along with liver and pancreatic histology were assessed. NF-κB, TNF-α, IL-6, IL-1β, and nuclear factor erythroid 2-related factor 2 (Nrf2) expression levels were estimated using reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR).Key findings: Combination therapy markedly decreased weight (31.30%), fasting blood glucose (74.92%), glucose intolerance (65.42%), and improved biochemical markers of lipid, hepatic, and renal function. The combination therapy significantly reduced (P < .05) malondialdehyde, nitric oxide, expression of NF-κB, TNF-α, IL-6, and IL-1β while increasing superoxide dismutase, catalase and reduced glutathione levels. Combination therapy significantly (P < .05) reduced HbA1c levels and increased Glo1, Glo2, and Nrf-2 levels. Histopathological variations showed reduced cellular damage in the treatment groups.Conclusion: Combination of syringol and guaiacol exhibits significant pharmacological efficacy for managing DS associated with hyperglycemia.","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144958439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exploring the effects of a multicomponent phytoceutical health product in a Drosophila melanogaster ageing and repetitive concussion model. 探索一种多成分植物药保健品在果蝇衰老和重复性脑震荡模型中的作用。

IF 3.2 4区医学

Journal of Pharmacy and Pharmacology Pub Date : 2025-08-25 DOI: 10.1093/jpp/rgaf062

Norah Alanazi, Audrey Fraysse, Elisabeth A English, Sophia Quigley, Juri A Felix, Melanie-Jayne R Howes, Dan Glassbrook, Karen Hind, Paul Chazot

{"title":"Exploring the effects of a multicomponent phytoceutical health product in a Drosophila melanogaster ageing and repetitive concussion model.","authors":"Norah Alanazi, Audrey Fraysse, Elisabeth A English, Sophia Quigley, Juri A Felix, Melanie-Jayne R Howes, Dan Glassbrook, Karen Hind, Paul Chazot","doi":"10.1093/jpp/rgaf062","DOIUrl":"https://doi.org/10.1093/jpp/rgaf062","url":null,"abstract":"Objectives: This study aims to investigate the long-term effects of multiple concussions on physical function and oxidative stress, as well as the potential protective effects of a novel phytoceutical product (CONKA1) on ageing and brain health of Drosophila melanogaster.Methods: Adult female D. melanogaster flies were exposed to repeated concussive events using a high-impact trauma (HIT) device. The effects of these impacts were assessed on lifespan, motor activity, and levels of reactive oxygen and nitrogen species (RONS) in both the brain and body. The flies were administered a multicomponent supplement (CONKA1), comprising Withania somnifera, Curcuma longa, Melissa officinalis, Rhodiola rosea, and Vaccinium myrtillus, and outcomes were compared to untreated controls.Key findings: CONKA1 improved the lifespan and motor activity and reduced oxidative stress in ageing flies. Repetitive concussion hits significantly increased long-term mobility deficits, shortened lifespan, and exacerbated oxidative stress in both the brain and body, above and beyond normal ageing. CONKA1 demonstrated mitigation of extra motor deficits, reduced lifespan, and exacerbated oxidative stress in both the brain and body of the flies.Conclusions: The findings validate that D. melanogaster is a suitable system to mimic the effects of repetitive concussions and evaluate the effects of novel health products.","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144958287","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

Toll-like receptor 4 activation potentiates voriconazole-induced hepatotoxicity via transcriptional repression of the farnesoid X receptor in murine hepatocytes. toll样受体4激活通过抑制小鼠肝细胞中farnesoid X受体的转录增强伏立康唑诱导的肝毒性。

IF 3.2 4区医学

Journal of Pharmacy and Pharmacology Pub Date : 2025-08-22 DOI: 10.1093/jpp/rgaf060

Xiaokang Wang, Chenyu Zhao, Yuxian Chen, Peng Qiu

{"title":"Toll-like receptor 4 activation potentiates voriconazole-induced hepatotoxicity via transcriptional repression of the farnesoid X receptor in murine hepatocytes.","authors":"Xiaokang Wang, Chenyu Zhao, Yuxian Chen, Peng Qiu","doi":"10.1093/jpp/rgaf060","DOIUrl":"https://doi.org/10.1093/jpp/rgaf060","url":null,"abstract":"Objectives: Voriconazole (VRC)-induced hepatotoxicity is an important consideration in the clinical application of voriconazole. This study explores the potential role of toll-like receptor (TLR) 4 activation on voriconazole-induced hepatotoxicity and its underlying mechanisms.Methods: A model of VRC- and lipopolysaccharide (LPS)-induced hepatotoxicity was constructed using C57BL/6 mice. Parallel experiments were carried out on wild-type mice (WT-LPS + VRC) and TLR4 knockout mice (KO-LPS + VRC) to examine the relationship between TLR4 activation and regulation of the farnesoid X receptor (FXR). Biochemical parameters and liver histopathology were observed. Quantitative real-time PCR and western blotting were used to assess gene and protein expression levels.Key findings: Administering voriconazole twice within a 24-h period induces hepatotoxicity in mice under LPS-induced inflammatory conditions. VRC treatment caused darkening of the bile compared to normal mice. Conversely, KO-LPS + VRC mice maintained normal hepatocyte morphology and displayed light-coloured bile. The expression of p65 in the hepatocytes of KO-LPS + VRC was less than that of the WT-LPS + VRC. Additionally, the expression of nuclear FXR in the KO-LPS + VRC group was significantly higher than in the hepatocytes of WT-LPS + VRC.Conclusions: Activation of the TLR4 signalling pathway suppresses the activity of nuclear receptor FXR, impairs hepatic bile acid metabolism, impairs VRC excretion, and contributes to VRC hepatotoxicity.","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144958414","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