Journal of Pharmacy and Pharmacology最新文献

{"title":"Capsaicin: pharmacological applications and prospects for drug designing.","authors":"Anshita Gupta, Renjil Joshi, Lokkanya Dewangan, Kamal Shah, Deependra Soni, Umesh K Patil, Nagendra Singh Chauhan","doi":"10.1093/jpp/rgae150","DOIUrl":"10.1093/jpp/rgae150","url":null,"abstract":"<p><strong>Objectives: </strong>A primary objective of this review is to summarize the evidence-based pharmacological applications of capsaicin, particularly its use to manage pain and treat various health conditions. A second goal of the review is to research how recent technological advances are improving the bioavailability and therapeutic index of capsaicin, as well as the development of novel capsaicin-mimetics that are able to enhance therapeutic responses in various human diseases.</p><p><strong>Methods: </strong>In the review, numerous human clinical trials and preclinical studies are examined to determine how effective, safe, and optimal dosages of capsaicin can be used in pain management and therapeutic applications. Furthermore, it discusses capsaicin's mechanisms of action, specifically its interactions with the transient receptor potential vanilloid 1 (TRPV1) channel. As a result of this review, the potential of nanotechnology systems for bypassing the limits of capsaicin's pungency is discussed. The review takes into account individual factors such as pain tolerance and skin sensitivity.</p><p><strong>Key findings: </strong>For topical applications, capsaicin is typically used in concentrations ranging from 0.025% to 0.1%, with higher concentrations being used under medical supervision for neuropathic pain. The formulation can come in the form of creams, gels, or patches, which provide sustained release over the course of time. A condition such as arthritis or neuropathy can be relieved with capsaicin as it depletes substance P from nerves. Neuropathy and osteoarthritis as well as musculoskeletal disorders have been treated successfully with this herbal medicine. A major mechanism through which capsaicin relieves pain is through activating TRPV1 channels, which induce calcium influx and neurotransmitter release. Additionally, it affects the transcription of genes related to pain modulation and inflammation, particularly when disease conditions or stress are present. There have been recent developments in technology to reduce capsaicin's pungency and improve its bioavailability, including nanotechnology.</p><p><strong>Conclusions: </strong>It is proven that capsaicin is effective in pain management as well as a variety of therapeutic conditions because of its ability to deplete substance P and desensitize nerve endings. Although capsaicin is highly pungent and associated with discomfort, advancements in delivery technologies and the development of capsaicin-mimetics promise improved therapeutic outcomes. There is a great deal of complexity in the pharmacological action of capsaicin due to its interaction with TRPV1 channels and its ability to affect gene transcription. There is a need for further research and development in order to optimize capsaicin's clinical applications and to enhance its therapeutic index in a variety of human diseases.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"459-474"},"PeriodicalIF":2.8,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807440","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":"In vitro antidiabetic activity of Treculia africana leaf extracts: identification of chlorogenic acid and α-mangostin.","authors":"Victorine Lorette Yimgang, Elisa Pangrazzi, Francine Medjiofack Djeujo, Yanick Kevin Dongmo Melogmo, Franklin Loïc Tchinda Taghu, Rufin Marie Toghueo Kouipou, Fabrice Fekam Boyom, Guglielmina Froldi","doi":"10.1093/jpp/rgaf003","DOIUrl":"10.1093/jpp/rgaf003","url":null,"abstract":"<p><strong>Objective: </strong>This research studied two extracts from Treculia africana leaves for their potential against hyperglycaemia-related disorders.</p><p><strong>Methods: </strong>The influence of the extracts on α-glucosidase activity and albumin glycation was investigated, and cell viability was estimated in HT-29 human colorectal cells. Phenolic and flavonoid contents and antiradical activity were also detected. The extracts were examined using HPLC-DAD analysis.</p><p><strong>Key findings: </strong>The methanol and dichloromethane leaf extracts showed a significant concentration-dependent inhibition of α-glucosidase activity (IC50= 3.73 and 21.28 µg/ml, respectively). Both extracts also inhibited ribose-induced glycation of bovine serum albumin from 250 µg/ml. Phytochemical analysis revealed the presence of chlorogenic acid and α-mangostin in the extracts. The extracts did not change HT-29 cell viability up to 250 µg/ml, thus showing very low cytotoxicity.</p><p><strong>Conclusions: </strong>The methanol leaf extract of T. africana inhibited α-glucosidase activity in a concentration-dependent manner, supporting the use of the leaves in traditional medicine to control hyperglycaemia. Chlorogenic acid and α-mangostin, the latter identified for the first time in this species, were found in the T. africana leaves. Further, in vivo studies and pilot clinical trials should be conducted using standardized T. africana leaf extracts to evaluate their potential effectiveness in diabetes mellitus.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"501-510"},"PeriodicalIF":2.8,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"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}