Pharmaceuticals最新文献

{"title":"Oligodendroglioma of the Hippocampus: A Case Report and Systematic Review on Therapeutic Approaches of Oligodendroglioma After WHO 2021 Classification.","authors":"Panagiotis Skouras, Georgios Giakoumettis, Charalampos Argyros, George Vavoulis, Emmanouil K Verigos, Dimitrios Giakoumettis","doi":"10.3390/ph18030349","DOIUrl":"10.3390/ph18030349","url":null,"abstract":"<p><p><b>Background:</b> Oligodendrogliomas are a molecularly distinct subtype of glioma according to the WHO 2021 tumor classification, defined as isocitrate dehydrogenase (IDH) mutations and 1p/19q co-deletion. This updated classification has changed the approach to glioma management by emphasizing the critical role of molecular diagnostics. This study explores current therapeutic strategies for adult oligodendrogliomas and contextualizes findings with a patient with a Grade 3 oligodendroglioma of the hippocampus. <b>Methods:</b> A systematic review was conducted, synthesizing evidence from 36 studies published between 2021 and 2024. The review focuses on surgical resection, PCV chemotherapy (procarbazine, lomustine, vincristine), and radiotherapy, with progression-free survival (PFS) and overall survival (OS) as primary outcomes. Moreover, a 45-year-old woman diagnosed with an IDH-mutant, 1p/19q-co-deleted Grade 3 oligodendroglioma is presented to illustrate clinical management. <b>Results:</b> The review highlights the significance of molecular profiling in personalizing treatment strategies. The findings highlight that maximal safe surgical resection combined with PCV chemotherapy and radiotherapy optimizes PFS and OS. However, our case underwent chemotherapy and radiotherapy after a multidisciplinary consultation, demonstrating favorable initial outcomes. These findings reaffirm the importance of integrating molecular insight into clinical decision-making. <b>Conclusions:</b> Advancements in molecular diagnostics have profoundly enhanced the personalization of therapy for oligodendrogliomas, yielding improved survival outcomes. Optimal management should entail a multidisciplinary approach incorporating surgery, chemotherapy, and radiotherapy, guided by molecular features. This study reinforces the necessity of molecular-driven strategies to improve survival and quality of care for patients with oligodendroglioma.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11944404/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721203","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":"Electrochemical Analysis and Inhibition Assay of Immune-Modulating Enzyme, Indoleamine 2,3-Dioxygenase.","authors":"Yasuhiro Mie, Chitose Mikami, Yoshiaki Yasutake, Yuki Shigemura, Taku Yamashita, Hirofumi Tsujino","doi":"10.3390/ph18030352","DOIUrl":"10.3390/ph18030352","url":null,"abstract":"<p><p><b>Background:</b> An accurate and rapid analysis of human indoleamine 2,3-dioxygenase (hIDO) is crucial for the development of anticancer pharmaceuticals because of the role of hIDO in promoting tumoral immune escape. However, the conventional assay of hIDO is limited by interference from reductants, which are used to reduce the heme iron to begin the hIDO catalytic reaction. <b>Methods:</b> A direct electrochemical method was applied to drive the hIDO reaction. <b>Results:</b> The nanostructured gold electrode enabled the electrochemical reduction of the heme iron of hIDO1. In the presence of substrates (tryptophan and oxygen), a bioelectrocatalytic current was observed, confirming an electrochemically driven hIDO reaction. A well-known inhibitor of hIDO, epacadostat, hindered this catalytic signal according to its concentration, demonstrating the rapid evaluation of its inhibition activity for the hIDO reaction. Through an in silico study using the proposed electrochemical assay system, we discovered a strong inhibitor candidate with a half-maximal inhibitory concentration of 10 nM. <b>Conclusions:</b> An accurate and rapid assay system in drug discovery for hIDO and kynureine pathway-targeted immunotherapy has been developed.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11944389/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143720359","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":"Computationally Guided Design, Synthesis, and Evaluation of Novel Non-Hydroxamic Histone Deacetylase Inhibitors, Based on <i>N</i>-Trifluoroacetamide as a Zinc-Binding Group, Against Breast Cancer.","authors":"Gerardo Morales-Herrejón, Juan Benjamín García-Vázquez, Cynthia Fernández-Pomares, Norbert Bakalara, José Correa-Basurto, Humberto L Mendoza-Figueroa","doi":"10.3390/ph18030351","DOIUrl":"10.3390/ph18030351","url":null,"abstract":"<p><p><b>Background</b>: Histone deacetylases (HDACs) are enzymes that deacetylate histone proteins, impacting the transcriptional repression and activation of cancer-associated genes such as P53 and Ras. The overexpression of HDACs in breast cancer (BC) underscores their significance as therapeutic targets for modulating gene expression through epigenetic regulation. <b>Methods</b>: In this study, a novel series of SAHA (suberoylanilide hydroxamic acid) analogs were designed using an in silico ligand-based strategy. These analogs were then synthesized and evaluated for their HDAC-inhibitory capacity as well as their antiproliferative capacity on breast cancer cells. These compounds retained an aliphatic LINKER, mimicking the natural substrate acetyl-lysine, while differing from the hydroxamic fragment present in SAHA. <b>Results</b>: The synthesized compounds exhibited HDAC inhibitory activity, suggesting potential for binding to these pharmacological targets. Compounds <b>5b</b>, <b>6a</b>, and <b>6b</b> were identified as promising candidates in the evaluation on breast cancer cell lines MCF-7 and MDA-MB-231 at 72 h. Specifically, compound <b>6b</b>, which contains an <i>N</i>-trifluoroacetyl group as a zinc-binding group (ZBG), demonstrated an IC₅₀ of 76.7 µM in the MDA-MB-231 cell line and 45.7 µM in the MCF-7 cell line. In the non-tumorigenic cell line, the compound exhibited an IC₅₀ of 154.6 µM. Conversely, SAHA exhibited an almost negligible safety margin with regard to its cytotoxic activity when compared to breast cancer cells and healthy cells (MCF-10A). This observation underscores the elevated toxicity exhibited by hydroxamic acid-derived molecules. <b>Conclusions</b>: The bioisosteric modification of ZBG by <i>N</i>-trifluoroacetyl in <b>6a</b> and <b>6b</b> demonstrated favorable cytotoxic activity, exhibiting a higher safety margin. This study underscores the challenge of identifying novel ZBGs to replace hydroxamic acid in the development of HDAC inhibitors, with the objective of enhancing their physicochemical and toxicological profile for utilization in BC treatment.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11944851/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721138","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 Efficacy of Fluvoxamine in Anxiety Disorders and Obsessive-Compulsive Disorder: An Overview of Systematic Reviews and Meta-Analyses.","authors":"Michel Haddad, Luiz Henrique Junqueira Dieckmann, Thiago Wendt Viola, Melissa Ribeiro de Araújo, Naielly Rodrigues da Silva, Jair de Jesus Mari","doi":"10.3390/ph18030353","DOIUrl":"10.3390/ph18030353","url":null,"abstract":"<p><p><b>Objective</b>: This systematic review aims to evaluate the efficacy of fluvoxamine in the treatment of anxiety disorders and obsessive-compulsive disorder (OCD) by synthesizing evidence from systematic reviews and meta-analyses. <b>Methods</b>: We conducted a literature search in PubMed and the Cochrane Central Register of Controlled Trials, focusing on fluvoxamine's efficacy in generalized anxiety disorder (GAD), social anxiety disorder (SAD), panic disorder (PD), and OCD. We included systematic reviews and meta-analyses of randomized controlled trials (RCTs) comparing fluvoxamine to a placebo or other drugs. The quality of evidence from the included reviews was assessed using A Measurement Tool to Assess Systematic Reviews-version 2 (AMSTAR-2). <b>Results</b>: The study included fourteen systematic reviews (five for OCD, three for SAD, and six for PD), covering thirty-seven RCTs (sixteen for OCD, six for SAD, and fifteen for PD), with a total of 3621 patients (1745 with OCD, 1034 with SAD, and 842 with PD). A high-quality systematic review demonstrated that fluvoxamine is superior to a placebo in improving symptoms and the response rates for OCD. Three meta-analyses comparing fluvoxamine to clomipramine in OCD found no significant differences in efficacy regarding symptom improvement. Two additional systematic reviews, both rated as high quality, confirmed the superiority of fluvoxamine in reducing symptom severity and improving the response rates in patients with SAD compared to a placebo. However, the findings for PD were inconsistent. A meta-analysis, also rated as high quality, found that while fluvoxamine showed better response rates than a placebo, the difference was not statistically significant. <b>Conclusions</b>: Overall, the efficacy of fluvoxamine in the treatment of OCD and SAD was demonstrated. While some reviews highlighted its potential in alleviating GAD, its impact on panic-specific outcomes remained inconsistent.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11944676/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721174","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":"Correction: Bakr et al. Efficacy of Quercetin and Quercetin Loaded Chitosan Nanoparticles Against Cisplatin-Induced Renal and Testicular Toxicity via Attenuation of Oxidative Stress, Inflammation, and Apoptosis. <i>Pharmaceuticals</i> 2024, <i>17</i>, 1384.","authors":"Alaa F Bakr, Riham A El-Shiekh, Mohamed Y Mahmoud, Heba M A Khalil, Mohammad H Alyami, Hamad S Alyami, Omneya Galal, Dina F Mansour","doi":"10.3390/ph18030348","DOIUrl":"10.3390/ph18030348","url":null,"abstract":"<p><p><b>Error in Figure</b> [...].</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11945078/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721142","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":"Nanostructured Strategies for Melanoma Treatment-Part II: Targeted Topical Delivery of Curcumin via Poloxamer-Based Thermosensitive Hydrogels.","authors":"Valentina Paganini, Daniela Monti, Patrizia Chetoni, Susi Burgalassi, Andrea Cesari, Fabio Bellina, Silvia Tampucci","doi":"10.3390/ph18030337","DOIUrl":"10.3390/ph18030337","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Curcumin (CUR) is a natural compound with notable antitumor properties but faces limitations in topical applications due to poor aqueous solubility, instability, and insufficient skin penetration. To overcome these challenges, a nanomicellar formulation (TPGS30ELP15) was developed to enhance CUR solubility, stability, and skin penetration. This study aimed at evaluating the skin permeation and retention of CUR when delivered through nanomicelles alone or combined with a thermosensitive hydrogel for potential melanoma therapy. <b>Methods</b>: A CUR-loaded nanomicellar formulation containing CUR 5 mM was developed, characterized by particle sizes of 12-25 nm. Skin permeation studies utilized pig ear skin to assess CUR localization using both HPLC quantitative analysis and confocal microscopy. To improve patient comfort and application efficiency, the nanomicellar dispersion was incorporated into a thermosensitive hydrogel based on 16% Kolliphor^® P407 and was able to undergo a sol-gel transition at skin temperature (32-36 °C). Formulations were evaluated for physicochemical properties, stability, and CUR distribution within skin layers using in vitro permeation assays. <b>Results</b>: CUR-loaded nanomicelles demonstrated selective localization in the viable epidermis (100-150 µm depth), bypassing the stratum corneum. The addition of the thermosensitive hydrogel enhanced CUR retention and distribution, prolonging contact at the application site and providing a gradual release profile. The hydrogel's sol-gel transition properties can facilitate ease of use and patient compliance. The combined system effectively delivered CUR to the basal epidermis, a target site for melanoma treatment, achieving therapeutically relevant drug concentrations. <b>Conclusions</b>: The incorporation of CUR-loaded nanomicelles into a thermosensitive hydrogel enhanced the solubility, stability, and targeted delivery of CUR to skin layers. This dual system represents a promising strategy for improving topical drug delivery for melanoma therapy, addressing limitations associated with CUR's physicochemical properties while ensuring patient-friendly application and gradual drug release.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11945081/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721181","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":"Side Effects of Immunosuppressant Drugs After Liver Transplant.","authors":"Filippo Gabrielli, Elisa Bernasconi, Arianna Toscano, Alessandra Avossa, Alessia Cavicchioli, Pietro Andreone, Stefano Gitto","doi":"10.3390/ph18030342","DOIUrl":"10.3390/ph18030342","url":null,"abstract":"<p><p>Liver transplantation (LT) is the standard of care for both end-stage liver failure and hepatocellular carcinoma (HCC). Side effects of the main used immunosuppressive drugs have a noteworthy impact on the long-term outcome of LT recipients. Consequently, to achieve a balance between optimal immunosuppression and minimal side effects is a cornerstone of the post-LT period. Today, there are no validated markers for overimmunosuppression and underimmunosuppression, only a few drugs have therapeutic drug monitoring, and immunosuppression regimens vary from center to center and from country to country. Currently, there are many drugs with different efficacy and safety profiles. Using different agents permits a decrease in the dosage and minimizes the toxicities. A small subset of recipients achieves immunotolerance with the chance to stop immunosuppressive therapy. This article focuses on the side effects of immunosuppressive drugs, which significantly impact long-term outcomes for LT recipients. The primary aim is to highlight the balance between achieving effective immunosuppression and minimizing adverse effects, emphasizing the role of personalized therapeutic strategies. Moreover, this review evaluates the mechanisms of action and specific complications associated with immunosuppressive agents. Finally, special attention is given to strategies for reducing immunosuppressive burdens, improving patient quality of life, and identifying immunotolerant individuals.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11946649/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721179","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":"Recent Advancements in the Development of HDAC/Tubulin Dual-Targeting Inhibitors.","authors":"Christine Tran, Abdallah Hamze","doi":"10.3390/ph18030341","DOIUrl":"10.3390/ph18030341","url":null,"abstract":"<p><p>Histone deacetylases (HDACs) have become one of the main targets in cancer therapy due to their involvement in various biological processes, including gene regulation, cell proliferation, and differentiation. Microtubules, as key elements of the cell cytoskeleton, also represent important therapeutic targets in anticancer drugs research. These proteins are involved in diverse cellular functions, especially mitosis, cell signaling, and intracellular trafficking. With the emergence of multi-target therapy during the last decades, the combination of HDAC and tubulin inhibitors has been envisioned as a practical approach for optimizing the therapeutic efficacy of antitumor molecules. HDAC/tubulin dual-targeting inhibitors offer the advantages of the synergistic action of both compounds, along with a significant decrease in their respective toxicities and drug resistance. This review will detail the major recent advancements in the development of HDAC/tubulin dual inhibitors over the last decade and their impact on anticancer drugs discovery.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11945613/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143720708","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 Vitro Interactions Between Bacteriophages and Antibacterial Agents of Various Classes Against Multidrug-Resistant Metallo-β-Lactamase-Producing <i>Pseudomonas aeruginosa</i> Clinical Isolates.","authors":"Paschalis Paranos, Sophia Vourli, Spyros Pournaras, Joseph Meletiadis","doi":"10.3390/ph18030343","DOIUrl":"10.3390/ph18030343","url":null,"abstract":"<p><p><b>Background:</b> Combination therapy with antibiotics and phages has been suggested to increase the antibacterial activity of both antibiotics and phages. We tested the in vitro activity of five antibiotics belonging to different classes in combination with lytic bacteriophages against multidrug-resistant metallo-β-lactamase (MBL)-producing <i>Pseudomonas aeruginosa</i> isolates. <b>Material/Methods:</b> A total of 10 non-repetitive well-characterized MBL-producing <i>P. aeruginosa</i> isolates (5 NDM, 5 VIM) co-resistant to aminoglycosides and quinolones were used. Phage-antibiotic interactions were assessed using an ISO-20776-based broth microdilution checkerboard assay in 96-well microtitration plates. Two-fold dilutions of colistin (8-0.125 mg/L), ciprofloxacin, meropenem, aztreonam, and amikacin (256-4 mg/L) were combined with ten-fold dilutions of five different phages (5 × 10⁹-5 × 10⁰ PFU/mL) belonging to <i>Pakpunavirus</i>, <i>Phikzvirus, Pbunavirus</i>, and <i>Phikmvvirus</i> genus. Plates were incubated at 35 ± 2 °C for 24 h, and the minimum inhibitory concentration of antibiotics (MIC_A) and phages (MIC_P) were determined as the lowest drug and phage concentration, resulting in <10% growth based on photometric reading at 550 nm. Interactions were assessed based on the fractional inhibitory concentration index (FICi) of three independent replicates and clinical relevance based on the reversal of phenotypic resistance. The statistical significance of each drug alone and in combination with phages was assessed using GraphPad Prism 8.0. <b>Results:</b> Synergistic and additive interactions were found for 60-80% of isolates for all drugs. FICis were statistically significantly lower than 0.5 for colistin (<i>p</i> = 0.005), ciprofloxacin (<i>p</i> = 0.02), meropenem (<i>p</i> = 0.003), and amikacin (<i>p</i> = 0.002). Interactions were found at clinically achievable concentrations for colistin, meropenem, and amikacin, and a reversal of phenotypic resistance was observed for most strains (63-64%) for amikacin and meropenem. Antagonism was found for few isolates with all antibiotics tested. Phage vB_PaerM_AttikonH10 and vB_PaerP_AttikonH4 belonging to <i>Phikzvirus</i> and <i>Phikmvvirus</i> genus, respectively, showed either synergistic (FICi ≤ 0.35) or additive effects with most antibiotics tested. <b>Conclusions:</b> Synergy was observed for most drugs and phages with amikacin, showing strong synergy and reversal of phenotypic resistance against most isolates. Taking into account the wide utility of jumbo phages obtained, the findings of vB_PaerM_AttikonH10 in combination with different classes of antibiotics can enhance the activity of currently ineffective antibiotics against MBL-producing <i>P. aeruginosa</i> isolates.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11945160/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721175","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 a Standardized Botanical Mixture Comprising <i>Angelica gigas</i> Roots and <i>Pueraria lobata</i> Flowers Through the TLR2/6 Pathway in RAW 264.7 Macrophages and Cyclophosphamide-Induced Immunosuppression Mice.","authors":"Seo-Yun Jang, Hyeon-A Song, Min-Ji Park, Kyung-Sook Chung, Jong Kil Lee, Eun Yeong Jang, Eun Mi Sun, Min Cheol Pyo, Kyung-Tae Lee","doi":"10.3390/ph18030336","DOIUrl":"10.3390/ph18030336","url":null,"abstract":"<p><p><b>Background</b>: As the population ages, enhancing immune function is crucial to mitigating age-related physiological decline. Since immunostimulant drugs are known to have potential side effects, medicinal plants emerge as promising candidates offering a safer alternative. To leverage the advantages of medicinal plants with fewer side effects and develop a potent immune-enhancing agent, we investigated the efficacy of a novel immunomodulatory candidate derived from the combination of <i>Angelica gigas</i> and <i>Pueraria lobata</i> (CHL). <b>Methods</b>: In vitro, CHL was treated in RAW 264.7 macrophages at various time points, and the experiments conducted in the study were performed using ELISA, Western blot, and RT-qPCR analysis. In vivo, C57BL/6 mice were administrated CHL for 16 days (p.o.) and CTX on the three days (i.p.), and experiments were conducted with ELISA, western blot, RT-qPCR analysis, H&E staining, flow cytometry, gut microbiome, and correlation analysis. <b>Results</b>: In vitro, CHL has upregulated NO and cytokines expression, substantially enhancing the NF-κB and MAPK activation. Furthermore, CHL promoted the TAK1, TRAF6, and MyD88 via TLR2/6 signaling. In vivo, the CHL improved the reduced body weight and immune organs' indices and recovered various cytokines expression, NK cell cytotoxicity activity, and immune cell population. CHL also improved the histological structure and tight junction markers, mucin-2, and TLR2/6 in the intestines of CTX-induced mice. <b>Conclusions</b>: Overall, CHL demonstrated immunostimulatory potential by enhancing immune responses and restoring immune function, suggesting its promise as a safe and effective immune-enhancing agent.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11944983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721157","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}