Journal of Pharmacy and Pharmacology最新文献

{"title":"c-MET tyrosine kinase inhibitors reverse multidrug resistance in breast cancer cells by targeting ABCG2 transporter.","authors":"Somayeh Nazari, Fatemeh Mosaffa, Alireza Poustforoosh, Luciano Saso, Omidreza Firuzi, Fatemeh Moosavi","doi":"10.1093/jpp/rgaf008","DOIUrl":"https://doi.org/10.1093/jpp/rgaf008","url":null,"abstract":"<p><strong>Background: </strong>Overcoming multidrug resistance (MDR), which is often caused by the overexpression of ATP binding cassette (ABC) transporters in cancer cells remains a major challenge for cancer treatment. Receptor tyrosine kinase inhibitors have demonstrated potential in reversing MDR. This study aimed to investigate the effects of c-MET RTKIs on the reversal of MDR induced by ABCG2 in breast cancer cells.</p><p><strong>Methods: </strong>MTT assay was employed to assess antiproliferative activity of c-MET inhibitors, including cabozantinib, crizotinib, and PHA665752. The accumulation of the fluorescent probe mitoxantrone was evaluated by flow cytometry. The drug-drug interaction in combination treatments was analyzed using CalcuSyn software.</p><p><strong>Results: </strong>The combination of cabozantinib, crizotinib, and PHA665752 with mitoxantrone resulted in synergistic effects in MDR cells. This was demonstrated by the mean CI values of 0.32 ± 0.07, 0.53 ± 0.05, and 0.59 ± 0.03, respectively. In the same cells, c-MET inhibitors enhanced the accumulation of mitoxantrone, with accumulation ratios ranging from 1.6 to 3.8, while no change was found in parental MCF-7 cells. Computational analysis revealed that the drug-binding region of ABCG2 transporters could be a viable target for these compounds.</p><p><strong>Conclusion: </strong>c-MET inhibitors hold potential as effective agents for reversing MDR in ABCG2-medicated drug-resistant cancer cells.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143575572","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}

{"title":"Mechanism of Guishao Yigong decoction in treating colorectal cancer based on network pharmacology and experimental validation.","authors":"Yuwen Fan, Quyi Wang, Yun Zhang, Yu Wang, Wenwen Li, Shu Jiang, Ji-Nao Duan","doi":"10.1093/jpp/rgae045","DOIUrl":"10.1093/jpp/rgae045","url":null,"abstract":"<p><strong>Objectives: </strong>To explore the effective components of Guishao Yigong decoction (GYD) in the treatment of colorectal cancer and reveal its potential mechanism of action.</p><p><strong>Methods: </strong>Through network pharmacology, the main target and signaling pathway of GYD therapy for colorectal cancer (CRC) were found. Subsequently, the effect of GYD was verified by in vitro cell viability measurements, colony formation, and scratch healing tests. The effects of GYD on metabolic pathways in vivo were found through plasma metabolomics. Finally, flow cytometry and qPCR experiments were used to verify the cycle-blocking effect of GYD on CRC cells.</p><p><strong>Key findings: </strong>Based on the network pharmacological analysis and molecular docking technology, it was found that GYD could restrain the growth of CRC cells by affecting lipid metabolic pathways and mitogen-activated protein kinase (MAPK) signaling pathways. A series of cell experiments showed that GYD could inhibit the proliferation, migration and clonogenic ability of CRC cells. Furthermore, the plasma metabolomics results showed that GYD could affect the production of unsaturated fatty acids in mice. Flow cytometry and qPCR experiments further proved that GYD blocked the CRC cells in the G1 phase and modulated the expression of cell cycle-related targets, such as AKT, TP53, CDKN1A, and CDK2.</p><p><strong>Conclusions: </strong>All the results indicated that GYD could regulate the related metabolism of unsaturated fatty acids. Thus, the cell cycle was blocked and the expressions of the key proteins such as AKT and TP53 were regulated, which achieved the purpose of intervention in colorectal cancer.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"430-445"},"PeriodicalIF":2.8,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142348962","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}

{"title":"Ginsenoside Rb1 ameliorates hippocampal neuroinflammation in rats after intracerebral hemorrhage by inactivating the TLR4/NF-kB pathway.","authors":"Xi Liu, Yuying Wang, Ling Han, Xing Li, Yan Zhong, Jilin Zhou, Xiyun Fei, Min Peng, Jixin Duan, Zhijun Zhong","doi":"10.1093/jpp/rgae145","DOIUrl":"10.1093/jpp/rgae145","url":null,"abstract":"<p><strong>Purpose: </strong>This work elucidated the therapeutic effect and mechanism of ginsenoside Rb1 on intracerebral hemorrhage (ICH).</p><p><strong>Methods: </strong>ICH rat models were treated by ginsenoside Rb1. Modified neurological deficit score, and Y-maze and Morris water-maze tests were performed on rats. Hippocampal neuronal damage was observed by Nissl staining. Rat primary astrocytes were exposed to ginsenoside Rb1, Hemin, and lipopolysaccharide (LPS). TNF-α, IL-1β, and IL-6 levels were assessed via enzyme-linked immunosorbent assay. TLR4/NF-kB pathway activity was appraised by Western blot. Immunofluorescence staining was for hippocampal glial fibrillary acidic protein (GFAP) expression and P65 protein location in hippocampus and astrocytes.</p><p><strong>Results: </strong>In rats after ICH, ginsenoside Rb1 ameliorated neurological impairment and hippocampal neuronal damage; improved learning and memory ability; reduced brain water content; decreasedhippocampal TNF-α, IL-1β, and IL-6; inactivated TLR4/NF-kB pathway; and declined hippocampal GFAP expression. In rat primary astrocytes exposed to Hemin, ginsenoside Rb1 declined TNF-α, IL-1β, and IL-6; inactivated TLR4/NF-kB pathway; and hindered P65 protein entry into nucleus. However, these functions of ginsenoside Rb1 on the Hemin-induced astrocytes were abolished by LPS.</p><p><strong>Conclusion: </strong>Ginsenoside Rb1 has promising future for clinical ICH treatment, which exerts therapeutic effect on ICH by ameliorating hippocampal neuroinflammation via inactivating the TLR4/NF-kB pathway.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"386-395"},"PeriodicalIF":2.8,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142729722","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}

{"title":"Impact of nanostructured formulations for schistosomiasis treatment: a systematic review of in vivo preclinical evidence.","authors":"Laís de Castro Carvalho Silva, Luís Felipe Cunha Dos Reis, Luiz Cosme Cotta Malaquias, Flávia Chiva Carvalho, Rômulo Dias Novaes, Marcos José Marques","doi":"10.1093/jpp/rgae155","DOIUrl":"10.1093/jpp/rgae155","url":null,"abstract":"<p><strong>Background: </strong>Schistosomiasis is a neglected tropical disease caused by Schistosoma sp., and praziquantel (PZQ) is the first-line treatment. However, traditional PZQ formulations have low solubility and fast metabolism, limiting its effectiveness. Thus, nanoparticles have been proposed to improve the bioavailability and efficacy of poorly soluble antischistosomal drugs.</p><p><strong>Aims: </strong>This systematic review used in vivo preclinical studies to map the available evidence and compare the efficacy of free PZQ and PZQ-based nanostructured formulations (N-PZQ) for schistosomiasis treatment.</p><p><strong>Methods: </strong>PubMed, Embase, Scopus, and Web of Science were searched, and 1186 experimental studies published between 1974 and 2024 were screened. Parasitological, histopathological, pharmacokinetic, and toxicological outcomes were evaluated.</p><p><strong>Results: </strong>Twelve relevant studies were identified exploring N-PZQ formulations based on liposomes, nanoliposomes, and nanocrystals. N-PZQ demonstrated better therapeutic efficacy than free PZQ, reducing parasite load, modifying oogram profiles, and down-regulating liver granuloma development (number and size). N-PZQ also exhibited improved pharmacokinetic profile, with enhanced bioavailability and longer half-life, as well as reduced toxicity (cytotoxicity, genotoxicity, and hepatotoxicity) compared to free PZQ.</p><p><strong>Conclusion: </strong>PZQ-based nanostructured formulations represent a promising strategy to enhance schistosomiasis treatment by improving chemotherapy efficacy, optimizing antiparasitic responses, pharmacokinetics, and reducing drug toxicity.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"341-351"},"PeriodicalIF":2.8,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007252","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}

{"title":"Copaiba essential oil carried in a self-nanoemulsifying drug delivery system improves adjuvant-induced arthritis in rats.","authors":"Ana Paula Ames-Sibin, Any Carolina Chagas-Almeida, Ana Beatriz P Souza, Ana Paula M Andrade, Juliana C Castro, Sabrina B S Ferreira, Francielli Maria S Silva-Comar, Roberto K N Cuman, Marcos L Bruschi, Maria Raquel M Natali, Anacharis B Sá-Nakaninhi, Lívia Bracht, Adelar Bracht, Jurandir F Comar","doi":"10.1093/jpp/rgae154","DOIUrl":"10.1093/jpp/rgae154","url":null,"abstract":"<p><strong>Objectives: </strong>Copaiba essential oil (CEO) is obtained through the distillation of copaiba balsam and has been used in the traditional medicine to treat inflammatory conditions. However, the highly lipophilic nature of CEO restricts its pharmaceutical use. This study evaluated the effect of CEO, carried in a self-nanoemulsifying drug delivery system (SNEDDS), on articular and systemic inflammation and liver changes in Holtzman rats with Freund's adjuvant-induced arthritis.</p><p><strong>Methods: </strong>Healthy and arthritic rats received orally for 18 days the non-formulated CEO and the one carried in a self-nanoemulsifying drug delivery system (FSNEDDS), both at doses of 50 and 100 mg/kg. The oral bioavailability of FSNEDDS was determined in healthy rats by quantifying the levels of β-caryophyllene in the plasma.</p><p><strong>Key findings: </strong>FSNEDDS exhibited more than three times greater oral bioavailability compared to non-formulated CEO. This phenomenon allowed FSNEDDS (100 mg/kg) to effectively reduce adjuvant-induced articular and systemic inflammation and oxidative stress in arthritic rats at a dose four times lower than copaiba balsam and β-caryophyllene. Furthermore, FSNEDDS did not alter the serum markers of liver damage, hepatic morphometry, and liver gluconeogenesis in healthy rats.</p><p><strong>Conclusion: </strong>FSNEDDS was effective against arthritis in rats, and unlike copaiba balsam, it does not exhibit hepatotoxicity, suggesting it could serve as a phytotherapeutic alternative in the treatment of rheumatoid arthritis.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"371-385"},"PeriodicalIF":2.8,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066391","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}

{"title":"Tilianin obtained from Agastache mexicana inhibits monoamine oxidase and modifies depressive behavior in rats.","authors":"Edgar Rodríguez-Wilson, Samuel Estrada-Soto, Moisés Rubio-Osornio, Luis Tristán-López, Gabriel Navarrete-Vázquez, Abraham Gutiérrez-Hernández, Sergio Montes","doi":"10.1093/jpp/rgae117","DOIUrl":"10.1093/jpp/rgae117","url":null,"abstract":"<p><strong>Background: </strong>Agastache mexicana is used in traditional medicine to treat anxiety, insomnia, pain, among others. In a previous study, the methanolic extract exerted anxiolytic and sedative effects, as observed behaviorally, associated with one of its major components, tilianin.</p><p><strong>Objective: </strong>To assess the effect produced by the extracts and tilianin obtained from Agastache mexicana on depressive-induced behavior model and on the activity of monoamine oxidases (MAOs).</p><p><strong>Methods: </strong>The depression experimental model consisted of the forced swimming test in rats. MAOs activity was evaluated in cortex and hippocampus from the tilianin and Agastache extracts treated rats using specific inhibitors for each isoform. The quantification of monoamines was carried out using an High Performance Liquid Chromatography method.</p><p><strong>Results: </strong>An increase in the swimming time was observed in rodents treated with doses of 16 (226.6 ± 5.5 seconds) and 50 mg/kg (237.8 ± 5.7 seconds) of tilianin, methanolic (260.4 ± 3 seconds), and hydroalcoholic extracts (249.6 ± 2.6 seconds) at 100 mg/kg. MAOs activity was significantly decreased in brain tissue from animals treated with 16 and 50 mg/kg of tilianin, methanolic, and hydroalcoholic extracts at 100 mg/kg.</p><p><strong>Conclusions: </strong>The tilianin effect on monoamine oxidases inhibition is confirmed, suggesting its potential use in the treatment of certain neurological disorders.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"396-403"},"PeriodicalIF":2.8,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142391389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stachys byzantina K. Koch (Lamiaceae) as a potential ingredient for delaying skin ageing and treating hyperpigmentation disorders in pharmaceutical products.","authors":"Victor Campana Leite, José Alisson da Silva Lima, Jéssica Pereira Silva, Pedro Henrique Santos de Freitas, Luciana Poty Manso Dos Santos, Ana Paula Guarnieri, Maria Clara Machado Resende Guedes, Gilson Costa Macedo, Natália Prado da Silva, Guilherme Diniz Tavares, Elita Scio, Mara Rubia Costa Couri, Jair Adriano Kopke de Aguiar, Nícolas de Castro Campos Pinto","doi":"10.1093/jpp/rgae138","DOIUrl":"10.1093/jpp/rgae138","url":null,"abstract":"<p><strong>Objectives: </strong>This study aimed to investigate whether the plant species Stachys byzantina produces bioactives with the potential to delay the skin ageing process and treat hyperpigmentation conditions.</p><p><strong>Methods: </strong>The antioxidant action was assessed by 2,2-diphenyl-1-picrylhydrazylradical scavenging, Griess reaction, oxygen radical absorption capacity, and β-carotene bleaching assays. Inhibitory activities for tyrosinase, hyaluronidase, and elastase enzymes were tested. The antiglycation activity, the sun protection factor (SPF), and the toxicity to skin cells by MTT (3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide) assay were also evaluated.</p><p><strong>Key findings: </strong>The ethanolic extract of S. byzantina aerial parts and all fractions obtained by solvent partition inhibited the tyrosinase enzyme at different levels. The dichloromethane fraction (DF) demonstrated the highest inhibition (IC50 = 63.5 ± 10.9 µg/ml). DF also inhibited the hyaluronidase enzyme with IC50 = 369 ± 11.64 μg/ml and elastase by 40% at 500 μg/ml. This fraction showed prominent antioxidant and antiglycation activities, high SPF, and no cytotoxicity at concentrations lower than 50 μg/ml. The phenolic and flavonoid contents were 116.30 ± 6.7 (mgTAE/g) and 66.38 ± 13.5 (mgQE/g), respectively. Chlorogenic acid (23.54 ± 2.46 mg/g) and verbascoside (203.97 ± 19.8 mg/g) were identified and quantified.</p><p><strong>Conclusions: </strong>Stachys byzantina is a potential source of cosmetic and therapeutic ingredients to reduce hyperpigmentation and the impacts caused by free radicals, advanced glycation end products, and sun radiation in skin ageing.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"446-458"},"PeriodicalIF":2.8,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502629","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}

{"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":"10.1093/jpp/rgae136","url":null,"abstract":"<p><strong>Objectives: </strong>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.</p><p><strong>Methods: </strong>Research articles regarding investigation of BZD dependence were searched on PubMed, Embase, and Scopus databases using keywords \"benzodiazepine\", \"dependence\", \"treatment\".</p><p><strong>Key findings: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"335-340"},"PeriodicalIF":2.8,"publicationDate":"2025-03-04","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}

{"title":"Calothrixin B by docking JAK2 is a potential therapeutic inhibitor for pancreatic ductal adenocarcinoma.","authors":"Yang Wang, Sayed S Esa, Rongji Yu, Sherif Abdelaziz Ibrahim, Yixin Li, Zhi Sheng, Jinzheng Wu, Hao Jiang, Xiaotang Di, Doudou Wen, Sheng Liu, Shubing Zhang","doi":"10.1093/jpp/rgae149","DOIUrl":"10.1093/jpp/rgae149","url":null,"abstract":"<p><strong>Objectives: </strong>Pancreatic cancer, a highly invasive and prognostically unfavorable malignant tumor, consistently exhibits resistance to conventional chemotherapy, leading to substantial side effects and diminished patient quality of life. This highlights the critical need for the discovery of novel, effective, and safe chemotherapy drugs. This study aimed to explore bioactive compounds, particularly natural products, as an alternative for JAK2 protein inhibitor in cancer treatment.</p><p><strong>Methods: </strong>Molecular docking, molecular dynamics, and Western blot experiments were conducted to verify the binding of Calothrixin B to JAK2 and its inhibitory effect on the JAK2-STAT3 signaling axis.</p><p><strong>Key findings: </strong>Recognizing the significant impact of JAK-STAT3 signaling pathway in pancreatic cancer, we screened the Zinc database to discover potential JAK2 inhibitors, and identified the small molecule Calothrixin B as a promising drug. Molecular simulations revealed stable interactions and the formation of hydrogen bonds between Calothrixin B and specific amino acids (Asp 994, Leu 855, and Arg 980) after a 100 ns simulation. Furthermore, we show that Calothrixin B inhibited the activity of the JAK2-STAT3 signaling pathway, arrested pancreatic cancer cells in the G1 phase, induced apoptosis, and significantly inhibited cell migration. Moreover, in vivo on a subcutaneous tumor model in nude mice confirmed that Calothrixin B effectively inhibited tumor growth in nude mice. In addition, the combination of Carlothrixin B and gemcitabine had a better inhibitory effect on pancreatic cancer cells.</p><p><strong>Conclusion: </strong>These findings introduce new avenues for Calothrixin B as promising therapy for pancreatic cancer.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"404-417"},"PeriodicalIF":2.8,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143029054","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}

{"title":"Mechanistic insights of methylcinnamate in improving oxidative stress and inflammation in acetaminophen-induced hepatotoxic mice by upregulating Nrf2 pathway.","authors":"Afshan Naseem, Humaira Majeed Khan, Aisha Umar, Mohamed S Elshikh, Reem M Aljowaie, Marek Gancarz","doi":"10.1093/jpp/rgaf001","DOIUrl":"10.1093/jpp/rgaf001","url":null,"abstract":"<p><strong>Background: </strong>Methylcinnamate (MC), a safe flavoring agent naturally found in Occimum basilicum L. is reported to have an anti-inflammatory responses in various disease models. Acetaminophen (APAP) toxicity is a significant contributor to acute liver injury, which leads to oxidative stress and inflammation. The transcriptional factor nuclear factor erythroid 2-related factor 2 (Nrf2) regulated the cellular defense mechanisms aid to antioxidant response facilitation and reduction in inflammation against various disorders.</p><p><strong>Methodology: </strong>This study evaluated the protective effects of MC in APAP-induced hepatotoxicity in mice and its anti-oxidant, anti-inflammatory, and Nrf2 mechanisms were studied. In-vitro 2,2-diphenyl-1-picrylhydrazyl assay showed the antioxidant capacity of MC. Mice were pretreated with MC (25, 50, 75, and 100 mg/kg) orally for 7 days. After a fasting period of 16 h, hepatotoxicity was induced by injecting APAP 300 mg/kg intraperitoneal on day 7. Liver profile, oxidative test, and histopathological changes were studied. Gene expression of interlukin-1β (IL-1β), interlukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), cytochrome P450 2E1 (CYP2E1), Nrf2, and NAD(P)H dehydrogenase (quinone) 1 (NQO-1) were estimated by real time quantitative polymerase chain reaction (RT-qPCR). IL-1β, IL-6, and TNF-α concentrations were also analyzed by enzyme-linked immunosorbent assay (ELISA).</p><p><strong>Results: </strong>The MC treatment showed a notable reduction in alanine transaminase, aspartate aminotransferase and alkaline phosphatase activities, and total bilirubin level of serum. Moreover, MC significantly attenuated oxidative stress by rising the antioxidant enzymes catalase, glutathione, and superoxide dismutase and reducing the malondialdehyde and nitric oxide levels in the liver. Furthermore, MC successfully mitigated the levels of IL-1β, IL-6, and TNF-α, which were estimated through RT-qPCR and ELISA. The RT-qPCR revealed a CYP2E1 enzyme inhibition and significant upregulation of hepatic Nrf2 and NQO-1 levels after MC therapy. Histopathological analysis showed improvement in liver injury within the MC treatment groups.</p><p><strong>Conclusion: </strong>It was concluded from this study that pretreatment of MC had successfully protected the liver through anti-inflammatory, anti-oxidant activity upon subsequent activation of Nrf2.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"418-429"},"PeriodicalIF":2.8,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143033376","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}