Pharmaceuticals最新文献

{"title":"Chemical Analysis of Plasma-Activated Culture Media by Ion Chromatography.","authors":"Marcello Locatelli, Miryam Perrucci, Marwa Balaha, Tirtha-Raj Acharya, Nagendra-Kumar Kaushik, Eun-Ha Choi, Monica Rapino, Vittoria Perrotti","doi":"10.3390/ph18020199","DOIUrl":"10.3390/ph18020199","url":null,"abstract":"<p><p><b>Background</b>: Currently, the procedures and methods applied in biological and medical fields for the determination of reactive oxygen and nitrogen species (RONS), primarily rely on spectrophotometric techniques, which involve the use of colorimetric reagents. While these methods are widely accepted, they exhibit significant limitations from an analytical standpoint, particularly due to potential inaccuracies, artifacts, and pronounced susceptibility to matrix effects. The purpose of this Technical Note is to demonstrate the application of ion chromatography-a robust and well-established analytical technique-for the quantification of RONS produced in cell culture media through the exposure to cold atmospheric plasma (CAP), an innovative therapeutic approach for cancer treatment, known as CAP indirect treatment. In addition, the present protocol proposes to apply the pharmacokinetics principles to the RONS generated in plasma-treated liquids (PTLs) following CAP exposure. <b>Methods</b>: The strategy involves elucidating the kinetic profiles of certain characteristic species by evaluating their half-life in the specific media used for cell cultures and investigating their \"pharmacokinetic\" (PK) profile. In this approach the drug dose is represented by the plasma power and the infusion time corresponds to the exposure time of the culture medium to CAP. Volume-dependent results were shown, focusing on nitrites and nitrates activities, justifying cellular inhibition. <b>Results</b>: This methodology enables the correlation of the PTL biological effects on different cell lines with the PK profiles (dose/time) obtained via ion chromatography. <b>Conclusions</b>: In conclusion, being a simple and green method, it could be used as an alternative to toxic reactions and analytical techniques with higher detection limits, while achieving good resolution.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 2","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11858801/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143503514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Comparative Effect of 12-Week Dietary Intervention of Policosanol (Raydel^®) and Red Yeast Rice (RYR, Kobayashi) in Managing Dyslipidemia and Organ Damage in Hyperlipidemic Zebrafish.","authors":"Kyung-Hyun Cho, Ashutosh Bahuguna, Ji-Eun Kim, Sang Hyuk Lee, Yunki Lee, Cheolmin Jeon","doi":"10.3390/ph18020200","DOIUrl":"10.3390/ph18020200","url":null,"abstract":"<p><strong>Background: </strong>A comparative 12-week dietary intervention of red yeast rice (RYR, <i>Beni-koji</i>, Kobayashi, Japan) and Cuban policosanol (PCO, Raydel^®, Thornleigh, Australia) was assessed for dyslipidemia, antioxidant status, and vital organ functionality in hyperlipidemic zebrafish.</p><p><strong>Methods: </strong>Hyperlipidemic zebrafish were supplemented with a high-cholesterol diet (HC, final 4%, <i>w</i>/<i>w</i>) infused with either a powdered RYR tablet (final 1.0%, <i>w</i>/<i>w</i>), a PCO tablet (final 1.0%, <i>w</i>/<i>w</i>), or a combination of 0.5% (<i>w</i>/<i>w</i>) each of RYR and PCO powder for 12 weeks. Subsequently, blood and organs were collected and processed for biochemical and histological examination.</p><p><strong>Results: </strong>RYR and PCO consumption showed a substantial effect against HC-induced hyperlipidemia by reducing the total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C). Exclusively, PCO supplementation revealed a significant elevation in the HC-diminished high-density lipoprotein cholesterol (HDL-C). In addition, PCO supplementation showed a significant elevation in plasma ferric ion-reducing ability (FRA) and sulfhydryl content, as well as alleviating the blood glucose level of hyperlipidemic zebrafish. The most noteworthy impact, with a significant two-fold (<i>p</i> < 0.001) augmentation of HC-diminished plasma paraoxonase (PON) activity, was observed in response to PCO. In contrast, the RYR supplementation failed to establish curative effects against HC-disturbed plasma antioxidant variables and blood glucose levels. The histological outcome revealed a severe toxicological impact of the RYR on the liver, reflected by fatty liver changes and three-fold heightened IL-6 production compared to HC control. Contrastingly, PCO exhibited significant hepatoprotection and effectively neutralized the hepatic toxicity triggered by HC and RYR. Also, RYR showed kidney atrophy, intense ROS generation, apoptosis, and senescence. Conversely, the PCO supplementation protected the kidney from HC- and RYR-induced toxicity. Likewise, PCO supplementation notably alleviated histological alterations and oxidative stress in the brain, ovary, and testis of hyperlipidemic zebrafish.</p><p><strong>Conclusions: </strong>This comparative study establishes PCO's therapeutic effect against the challenges posed by HC, while RYR emerged with serious toxicological concerns towards the liver, kidney, and other organs of hyperlipidemic zebrafish.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 2","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11859080/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143502904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In Silico Approach for Antibacterial Discovery: PTML Modeling of Virtual Multi-Strain Inhibitors Against <i>Staphylococcus aureus</i>.","authors":"Valeria V Kleandrova, M Natália D S Cordeiro, Alejandro Speck-Planche","doi":"10.3390/ph18020196","DOIUrl":"10.3390/ph18020196","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Infectious diseases caused by <i>Staphylococcus aureus</i> (<i>S. aureus</i>) have become alarming health issues worldwide due to the ever-increasing emergence of multidrug resistance. In silico approaches can accelerate the identification and/or design of versatile antibacterial chemicals with the ability to target multiple <i>S. aureus</i> strains with varying degrees of drug resistance. Here, we develop a perturbation theory machine learning model based on a multilayer perceptron neural network (PTML-MLP) for the prediction and design of versatile virtual inhibitors against <i>S. aureus</i> strains. <b>Methods</b>: To develop the PTML-MLP model, chemical and biological data associated with antibacterial activity against <i>S. aureus</i> strains were retrieved from the ChEMBL database. We applied the Box-Jenkins approach to convert the topological indices into multi-label graph-theoretical indices; the latter were used as inputs for the creation of the PTML-MLP model. <b>Results</b>: The PTML-MLP model exhibited accuracy higher than 80% in both training and test sets. The physicochemical and structural interpretation of the PTML-MLP model was performed through the fragment-based topological design (FBTD) approach. Such interpretations permitted the analysis of different molecular fragments with favorable contributions to the multi-strain antibacterial activity and the design of four new drug-like molecules using different fragments as building blocks. The designed molecules were predicted/confirmed by our PTML model as multi-strain inhibitors of diverse <i>S. aureus</i> strains, thus representing promising chemotypes to be considered for future synthesis and biological testing of versatile anti-<i>S. aureus</i> agents. <b>Conclusions</b>: This work envisages promising applications of PTML modeling for early antibacterial drug discovery and related antimicrobial research areas.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 2","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11858522/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143503535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Perspectives on Berberine and the Regulation of Gut Microbiota: As an Anti-Inflammatory Agent.","authors":"Quintero Vargas Jael Teresa de Jesús, Juan-Carlos Gálvez-Ruíz, Adriana Alejandra Márquez Ibarra, Mario-Alberto Leyva-Peralta","doi":"10.3390/ph18020193","DOIUrl":"10.3390/ph18020193","url":null,"abstract":"<p><p>Berberine is a promising agent for modulating the intestinal microbiota, playing a crucial role in human health homeostasis. This natural compound promotes the growth of beneficial bacteria such as <i>Bacteroides</i>, <i>Bifidobacterium</i>, and <i>Lactobacillus</i> while reducing harmful bacteria such as <i>Escherichia coli</i>. Clinical and preclinical studies demonstrate that Berberine helps regulate T2D and metabolic disorders, improves blood glucose levels during T2D, and reduces lipid profile and chronic inflammation, especially when combined with probiotics. Berberine represents a promising adjuvant therapy for inflammatory diseases, particularly intestinal disorders, due to its multifaceted actions of inhibiting proinflammatory cytokines and pathways during IBS, IBD, and UC and its modulation of gut microbiota and/or enhancement of the integrity of the intestinal epithelial barrier. This review establishes the basis for future treatment protocols with berberine and fully elucidates its mechanisms.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 2","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11858814/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143503566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New UB006 Derivatives With Higher Solubility and Cytotoxic Activity in Ovarian Cancer Cells.","authors":"Marc Reina, Xavier Ariza, Dolors Serra, Jordi Garcia, Laura Herrero","doi":"10.3390/ph18020194","DOIUrl":"10.3390/ph18020194","url":null,"abstract":"<p><strong>Background/objectives: </strong>The compound (±)-<b>UB006</b> ((4SR,5SR)-4-(hydroxymethyl)-3-methylene-5-octyldihydrofuran-2(3H)-one) is a promising anti-cancer molecule. The enantiomer (-)-<b>UB006</b> displays a potent cytotoxic effect in several tumor cell lines, particularly the ovarian cancer OVCAR-3 cell line, with a 40-fold increase in potency compared with the fatty acid synthase (FAS) inhibitor C75. Furthermore, in vivo, (-)-<b>UB006</b> reduced the tumor burden in neuroblastoma xenografts. This effect was attributed to FAS inhibition and upregulation of apoptotic markers. However, CoA adducts of UB006 presented low solubility.</p><p><strong>Methods: </strong>We synthesized several (±)-<b>UB006</b> derivatives by elongating the carbon chain of the primary alcohol and/or by adding hydroxyl groups with the aim of finding more potent and soluble anti-cancer compounds.</p><p><strong>Results: </strong>Our results showed a decrease in cytotoxicity when the carbon chain was elongated by more than two carbons. However, ethyl or propyl polyhydroxylated four-branched compounds showed an increased or maintained potency and solubility. The most promising compound was (±)-<b>UB035</b> (IC50: 2.1 ± 0.2 µM), with a 2.5-fold increase in cytotoxicity in the OVCAR-3 cell line and a >4-fold increase in solubility (>2 mM) compared with (±)-<b>UB006</b>.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 2","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11859419/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143503564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunomodulatory Effects of <i>Atractylodes lancea</i> in Healthy Volunteers with Dosage Prediction for Cholangiocarcinoma Therapy: A Modelling Approach.","authors":"Teerachat Saeheng, Juntra Karbwang, Kesara Na-Bangchang","doi":"10.3390/ph18020198","DOIUrl":"10.3390/ph18020198","url":null,"abstract":"<p><p><b>Background and Aims</b>: According to a recent study on the immunomodulatory activity of <i>Atractylodes lancea</i> (Thunb.) DC. (AL) in healthy Thai subjects, AL significantly inhibited the production of key pro-inflammatory cytokines while stimulating the production of immune cells. However, no maximum tolerated dose (MTD) and phase 2A dosage regimens were reported. The study aimed to evaluate the immunomodulatory effects of <i>Atractylodes lancea</i> (Thunb.) DC. (AL) in healthy subjects, and to recommend optimal dose regimens for intrahepatic cholangiocarcinoma (iCCA) based on toxicity criteria. <b>Methods</b>: A physiologically based pharmacokinetic (PBPK) model, combined with the toxicological approach and the immunomodulatory effect, was used for dose-finding. The safety and efficacy of each AL regimen were evaluated based on the previous study. At least a once-daily dose of 1000 mg AL significantly suppressed the production of all pro-inflammatory cytokines while significantly increasing the number of peripheral immune cells. <b>Results</b>: The developed PBPK model predicted the clinically observed data well. No significant differences in SII index values were found, but a difference in the lymphocyte-monocyte ratio was found on day 4. The dosage regimen for phase 2A is a once-daily dose of 1500 or 2000 mg. Preliminary results in phase 2A revealed that a once-daily dose of 2000 mg had a significantly higher median overall survival, progression-free survival, disease control rate, and inhibition of increased tumor size without toxicities compared with control. <b>Conclusions</b>: A PBPK model, in conjunction with a toxicological approach, could assist in finding the potential dosage regimens for a clinical study, including herbal medicine.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 2","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11860138/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143503493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Anti-Inflammatory Potential of Tricyclic Antidepressants (TCAs): A Novel Therapeutic Approach to Atherosclerosis Pathophysiology.","authors":"Majid Eslami, Marzieh Monemi, Mohammad Ali Nazari, Mohammad Hossein Azami, Parand Shariat Rad, Valentyn Oksenych, Ramtin Naderian","doi":"10.3390/ph18020197","DOIUrl":"10.3390/ph18020197","url":null,"abstract":"<p><p>Atherosclerosis, a chronic inflammatory disease, is driven by complex molecular mechanisms involving inflammatory cytokines and immune pathways. According to recent research, tricyclic antidepressants (TCAs), which are typically prescribed to treat depressive disorders, have strong anti-inflammatory effects. TCAs, including imipramine and amitriptyline, alter inflammatory signaling cascades, which include lowering the levels pro-inflammatory cytokines like TNF-α, IL-1β, and IL-6 and inhibiting NF-κB activation. By inhibiting the NLRP3 inflammasome and suppressing pathways including JAK/STAT, MAPK, and PI3K, these effects are produced, improving endothelial function and reducing oxidative stress. The intricacy of TCAs' anti-inflammatory actions has demonstrated by the existence of contradictory findings about how they alter IL-6 levels. The dependence of the heterogeneity of the reaction on the use of particular TCAs and experimental settings is shown by the fact that some studies show reduced IL-6 production, while others indicate increases or no changes. This review explores the multifaceted mechanisms through which TCAs modulate inflammatory pathways. TCAs inhibit NF-κB activation, reduce oxidative stress, and suppress the production of key inflammatory mediators, including IL-6 and TNF-α. They also regulate Toll-like receptor (TLR) signaling and NOD-, LRR-, and NLR family pyrin domain-containing protein 3 (NLRP3) inflammasome activation, reducing the release of IL-1β and IL-18, critical drivers of endothelial dysfunction and plaque instability. Given their capacity to target critical inflammatory molecules and pathways, TCAs provide great potential in the therapy of atherosclerosis, particularly for individuals with associated depression and cardiovascular risk factors. Nevertheless, further research is essential to clarify the precise molecular mechanisms, resolve inconsistencies in current findings, and establish the clinical applicability of TCAs as anti-inflammatory agents in atherosclerosis management.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 2","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11858810/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143503427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of Drug Permeation Enhancement by Using In Vitro and Ex Vivo Models.","authors":"Johan D Steyn, Anja Haasbroek-Pheiffer, Wihan Pheiffer, Morné Weyers, Suzanne E van Niekerk, Josias H Hamman, Daniélle van Staden","doi":"10.3390/ph18020195","DOIUrl":"10.3390/ph18020195","url":null,"abstract":"<p><p>Drugs administered by means of extravascular routes of drug administration must be absorbed into the systemic circulation, which involves the movement of the drug molecules across biological barriers such as epithelial cells that cover mucosal surfaces or the stratum corneum that covers the skin. Some drugs exhibit poor permeation across biological membranes or may experience excessive degradation during first-pass metabolism, which tends to limit their bioavailability. Various strategies have been used to improve drug bioavailability. Absorption enhancement strategies include the co-administration of chemical permeation enhancers, enzymes, and/or efflux transporter inhibitors, chemical changes, and specialized dosage form designs. Models with physiological relevance are needed to evaluate the efficacy of drug absorption enhancement techniques. Various in vitro cell culture models and ex vivo tissue models have been explored to evaluate and quantify the effectiveness of drug permeation enhancement strategies. This review deliberates on the use of in vitro and ex vivo models for the evaluation of drug permeation enhancement strategies for selected extravascular drug administration routes including the nasal, oromucosal, pulmonary, oral, rectal, and transdermal routes of drug administration.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 2","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11859300/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143503518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Drug Development in Inflammatory Bowel Diseases: What Is Next?","authors":"Lorenzo Petronio, Arianna Dal Buono, Roberto Gabbiadini, Giulia Migliorisi, Giuseppe Privitera, Matteo Ferraris, Laura Loy, Cristina Bezzio, Alessandro Armuzzi","doi":"10.3390/ph18020190","DOIUrl":"10.3390/ph18020190","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Inflammatory bowel diseases (IBDs), which include Crohn's disease (CD) and ulcerative colitis (UC), are chronic conditions requiring long-term therapy to maintain remission and improve quality of life. Despite the approval of numerous drugs, IBD continues to present treatment challenges. This review aims to summarize novel therapeutic target agents in phases II and III of development, including sphingosine-1-phosphate receptor modulators (S1P), anti-interleukin-23 (IL-23), and other small molecules and monoclonal antibodies currently under investigation (e.g., anti-TL1A, obefazimod, NX-13, RIPK-inhibitors). <b>Methods</b>: A comprehensive literature search was conducted up to December 2024 to identify relevant articles published in English over the past three-five years, focusing on phase II/III studies for UC and CD. The search included databases such as PubMed, Google Scholar, and the ClinicalTrials.gov portal. <b>Results</b>: Clinical trials underline the potential of novel immunomodulators, including anti-TL1A, obefazimod, NX-13, RIPK inhibitors, and anti-IL-23p19 agents, as promising therapeutic options for IBD. Anti-IL23p19 therapies, such as risankizumab and mirikizumab, alongside guselkumab, exemplify this class's growing clinical relevance. While some are already in clinical use, others are nearing approval. <b>Conclusions</b>: Ongoing research into long-term safety and the development of personalized treatment strategies remains pivotal to enhance outcomes. Patient stratification and the strategic positioning of these therapies within the expanding treatment landscape are critical for optimizing their clinical impact.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 2","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11858795/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143503489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synergistic Interaction Between <i>Justicia spicigera</i> Extract and Analgesics on the Formalin Test in Rats.","authors":"Juan Ramón Zapata-Morales, Angel Josabad Alonso-Castro, María Leonor González-Rivera, Hugo Israel González Prado, Juan Carlos Barragán-Gálvez, Araceli Hernández-Flores, María Del Carmen Juárez-Vázquez, Fabiola Domínguez, Candy Carranza-Álvarez, Amaury de Jesús Pozos-Guillén, Juan F López-Rodríguez, Patricia Aguirre-Bañuelos, Marco Antonio Ramírez-Morales","doi":"10.3390/ph18020187","DOIUrl":"10.3390/ph18020187","url":null,"abstract":"<p><p><b>Background:</b> Combining antinociceptive drugs with different mechanisms of action can reduce the doses and the adverse effects, with a possible increase in the antinociceptive effect. This work evaluated the antinociceptive effect of the combination of an ethanol extract of <i>Justicia spicigera</i> (JSE) with naproxen (NPX) or tramadol (TML) using the formalin test in rats. <b>Methods:</b> Rats received JSE (30-200 mg/kg p.o.), NPX (50-300 mg/kg p.o.), or TML (5-50 mg/kg p.o.) 60 min before paw administration with formalin (5%). Different proportions of the combination between NPX and JSE, as well as TML and JSE, were used in the formalin test to obtain the dose-response curve of each drug and the experimental effective dose 50 (ED₅₀). The levels of IL-1β and COX2 were assessed using a Western blot analysis as a possible mechanism of action for the combination of JSE and analgesics. A pharmacokinetic study was conducted to evaluate the effect of JSE on the pharmacokinetic parameters of NPX. <b>Results:</b> The ED₅₀ values for the proportions NPX:JSE were 107.09 mg/kg (1:1), 102.44 mg/kg (3:1), and 73.82 mg/kg (1:3). The ED₅₀ values for the proportions TML:JSE were 66 mg/kg (1:1), 29.5 mg/kg (1:3), and 78 mg/kg (3:1). The combination NPX:JSE (1:3) showed the best synergistic interaction index (0.501). The pharmacokinetic study revealed that there were no significant changes in the pharmacokinetic parameters of NPX administered individually and the combination NPX:JSE. <b>Conclusions:</b> In this preclinical study, the combination NPX:JSE showed antinociceptive effects by decreasing the levels of COX2 and IL-1β without affecting NPX's pharmacokinetics.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 2","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11859130/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143503497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}