DARU Journal of Pharmaceutical Sciences最新文献

{"title":"Poly (lactic-co-glycolic acid) nanoplatforms for triple-negative breast cancer: current progress, advances, and future outlook.","authors":"Aakash Sharma, Ashwini Kumar Mishra, Pooja Mathur, Rahul Pratap Singh, Laxmi Rani","doi":"10.1007/s40199-026-00613-1","DOIUrl":"10.1007/s40199-026-00613-1","url":null,"abstract":"<p><p>Triple-negative breast cancer (TNBC) is a highly aggressive subtype with the poorest prognosis and the highest recurrence rates. PLGA nanoplatforms show great potential as delivery systems for treating aggressive TNBC. A wide variety of nanoplatforms have been developed and evaluated for potential use in TNBC imaging and treatment. Poly (lactic-co-glycolic acid) (PLGA) is a biodegradable and biocompatible polymer used in the design of various types of nanoplatforms. PLGA is FDA approved and enables the encapsulation of multiple anticancer agents for targeted, sustained release. By incorporating various functional elements into PLGA or PLGA nanoplatforms, enhanced tumour targeting and diagnostic capabilities can be achieved. The interior space or surface of PLGA can be used to adsorb hydrophobic or hydrophilic drug molecules. This review examines recent developments in the design of PLGA nanoformulations that mimic biological barriers to enhance the therapeutic effectiveness of anticancer drugs against TNBC. Structural engineering significantly affects drug delivery capabilities. The current review provides insights into the pathophysiological pathways of TNBC, encompassing the pharmacokinetic challenges of current treatment strategies. The primary focus of this review is to collate and discuss novel PLGA based drug delivery strategies, the biocompatibility of PLGA, the significance of combination therapies, clinical relevance, and FDA approval. We also present the mechanisms underlying multidrug resistance and systemic toxicity, and discuss how smart responsive systems can be used to overcome these barriers. In addition, we emphasize the challenges posed by regulatory guidelines for TNBC and PLGA, as well as scale-up and reproducibility issues. The PLGA based drug delivery approaches are also reviewed in the context of recent preclinical and clinical studies. Future research and development in this domain may focus on critical aspects such as AI guided design and multifunctional systems, integration with precision medicine and personalized therapy, and combination with immunotherapy to enhance the efficacy and safety of PLGA based delivery systems.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":"34 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13356155/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148419548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circadian-guided asthma therapy: compressed-coated chronotherapeutic tablets for precision early-morning drug delivery.","authors":"Kumari Sindhu, Parveen Kumar, Amit Kumar, Devanand Jha, Ajay Pratap Singh Chauhan","doi":"10.1007/s40199-026-00626-w","DOIUrl":"10.1007/s40199-026-00626-w","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Early-morning worsening of asthma, most often observed between 03:00 and 06:00 am, arises from circadian regulation of airway smooth muscle tone, enhanced nocturnal release of inflammatory mediators, and the physiological nadir of endogenous cortisol levels. During this vulnerable interval, patients experience marked airway narrowing; however, conventional oral and inhaled therapies frequently fail to maintain adequate drug concentrations, highlighting the need for delivery systems capable of chronologically programmed pulsatile release.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;This review aims to critically evaluate recent advances in compressed-coated chronotherapeutic tablets (CCCTs) for early-morning asthma, with emphasis on polymer selection, hydration swelling-rupture mechanisms, and material characteristics governing lag-time precision, and to explore the interplay between circadian pathophysiology and pharmacokinetic-pharmacodynamic alignment in optimizing pulsatile oral drug delivery.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;An extensive and systematic literature search was conducted across PubMed, Scopus, Web of Science, and Google Scholar, covering publications from January 2000 to November 2025, using terms including chronotherapy, pulsatile drug delivery, compressed-coated tablets, press-coated tablets, lag-time systems, circadian asthma, and oral chronotherapeutic formulations. Preclinical, clinical, formulation, mechanistic, and translational reports published in English were critically analysed to synthesise advances in formulation design, material engineering, biopharmaceutical performance, and clinical relevance of CCCTs for early-morning asthma.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Compressed-coated chronotherapeutic tablets (CCCTs) offer a robust oral pulsatile platform that can be designed to provide a defined lag phase followed by rapid drug release after bedtime administration, with lag-time precision governed predominantly by polymer hydration, swelling, and rupture behaviour. Appropriately timed drug exposure aligned with circadian pathophysiology was found to enhance bronchodilation and anti-inflammatory efficacy while minimizing unnecessary nocturnal exposure. Preclinical findings and emerging clinical evidence supporting circadian-aligned delivery are summarized, together with key translational considerations including biorelevant dissolution testing, in vitro-in vivo correlation, scale-up challenges, and regulatory expectations for pulsatile oral systems.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;By integrating chronobiology with formulation engineering and quality-by-design principles, CCCTs represent a rational and adaptable strategy for synchronizing oral asthma therapy with endogenous biological rhythms. This review positions CCCT-based chronotherapy as a promising approach to improve early-morning symptom control and underlines the critical challenges that must be addressed to enable successful clinical trans","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":"34 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13355969/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148419506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deep fused explainable neural architecture for the automatic recognition of therapeutic medicinal plants.","authors":"Pooja Govindaraj, N Sasikaladevi","doi":"10.1007/s40199-026-00624-y","DOIUrl":"10.1007/s40199-026-00624-y","url":null,"abstract":"<p><strong>Background: </strong>Medicinal plants have been utilized for centuries for their beneficial properties and significant impact on traditional medical systems worldwide. Indian medicinal plants and their therapeutic properties have recently gained increased attention from the global healthcare community. Accurate identification and classification of medicinal plants ensure proper therapeutic applications. However, botanists manually identify these plants, which is subjective, labor-intensive, and time-consuming.</p><p><strong>Objective: </strong>The main objective of this study is to develop an accurate and automated classification of these medicinal plants for diverse applications such as conservation initiatives, quality assurance, and the formulation of novel herbal treatments.</p><p><strong>Methods: </strong>A Deep Fused Explainable Neural Architecture termed MedPlantNet is proposed for robust recognition of medicinal plant leaves. The deep discriminative features are extracted from the medicinal plant images using a fine-tuned Deep Convolutional Neural Network (DCNN). A customized Support Vector Machine is developed to efficiently classify these extracted deep features. To enhance model interpretability, a meta-visualization framework incorporating Grad-CAM and Occlusion Sensitivity visualization is implemented to identify the regions of the image that contribute to the classification decisions. We utilized the Mendeley benchmark Medicinal plant leaf database with 30 classes to train and evaluate the model.</p><p><strong>Results: </strong>To assess the effectiveness of the proposed model, accuracy, specificity, sensitivity, and AUC are calculated. The proposed system outperforms existing state-of-the-art (SOTA) algorithms for medicinal plant classification, achieving an optimal maximum validation accuracy of 99.87% and AUC of 1. To further validate the generalizability external validation was performed on Bangladeshi medicinal plant dataset and MedLeaves dataset where the proposed model MedPlantNet attained 99.27% and 99.80% validation accuracy respectively.</p><p><strong>Conclusion: </strong>MedPlantNet provides an automatic framework for medicinal plant identification based on deep feature extraction, classification and explainable visualization techniques. The results obtained indicate its potential utility in supporting biodiversity conservation, quality assurance and herbal medicine research.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":"34 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13356203/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148419593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic targeting of COX-2 in head and neck cancer: Mechanistic and clinical perspectives.","authors":"Reena Gupta, Bilal Khaleel Midhin, Sabir Ali Siddiqui, Mohammad Abohassan, Pareshkumar N Patel, Gunjan Singh, Vimal Arora, Priya Priyadarshini Nayak, Muhammad Shahid Iqbal, Zainb A Taleb","doi":"10.1007/s40199-026-00612-2","DOIUrl":"10.1007/s40199-026-00612-2","url":null,"abstract":"<p><p>Cyclooxygenase-2 (COX-2) is a key player in inflammation; it is often over-activated in HNSCC, which consequently increases the levels of prostaglandin E2 (PGE2) (an inflammatory mediator) leading to tumor proliferation, angiogenesis, epithelial-mesenchymal transition (EMT), immune evasion, metastasis, and therapy resistance. In this review, we describe the available molecular regulation and biological function of COX-2 in HNSCC with respect to its interactions with various signaling mediators (EGFR, NF-κB, PI3K/Akt, etc.) involved in chronic inflammation. We also summarize preclinical and clinical studies examining selective COX-2 inhibitors, combinations of COX-2 inhibitors with anti-EGFR agents/chemoradiation, and potential approaches for immune modulation/ferroptosis sensitization. Although high levels of COX-2 expression have been associated with a poor prognosis and unfavorable clinicopathological characteristics; the current evidence base cannot agree on this due to the data being very heterogeneous and based largely on small or early phase studies. Pathway redundancy, biomarker differences, and potential for cardiovascular toxicity are challenges for the clinical application of targeted therapy against COX-2. In this review, we review COX-2 as a leading therapeutic target for HNSCC with an emphasis on the transition from molecular pathology to clinical application. We prioritize the discussion on (i) established clinical evidence and prognostic value, (ii) robust preclinical data supporting therapeutic combinations, and (iii) emerging strategies such as ferroptosis-sensitization and immune-modulatory approaches.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":"34 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13315433/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148344035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Wistar rat model experiments for increasing intraocular pressure: a systematic review.","authors":"Anush Nayak, Deveswaran R, Swati Sinha, Avinash Prabhu","doi":"10.1007/s40199-026-00622-0","DOIUrl":"10.1007/s40199-026-00622-0","url":null,"abstract":"<p><strong>Background: </strong>Glaucoma is a leading cause of irreversible vision loss, with elevated intraocular pressure (IOP) being the primary modifiable risk factor. Experimental models that reliably induce ocular hypertension (OHT) are essential for understanding disease mechanisms and evaluating therapeutic interventions. Wistar rats are widely used due to their ocular anatomy and suitability for repeated IOP measurements.</p><p><strong>Methods: </strong>This systematic review was conducted in accordance with PRISMA guidelines and included studies published from 2000 onwards. Multiple databases were searched to identify experimental studies inducing OHT in Wistar rats. Data on model type, peak IOP, duration of elevation, and measurement techniques were extracted. Methodological quality was assessed using the SYRCLE risk of bias tool.</p><p><strong>Results: </strong>A total of 27 studies were included. Considerable heterogeneity was observed in the onset, magnitude, and duration of IOP elevation across models. Corticosteroid models showed gradual IOP increase, typically peaking around 3-4 weeks. Intracameral injection models induced rapid IOP spikes, whereas microsphere-based approaches demonstrated more sustained elevation. Episcleral vein ligation and cauterization models resulted in immediate and prolonged IOP elevation, while laser photocoagulation produced moderate to high increases with sustained effects. The circumlimbal suture model exhibited a biphasic response, with an initial spike followed by prolonged elevation. Variability in IOP measurements was influenced by differences in tonometry and experimental protocols.</p><p><strong>Conclusion: </strong>Wistar rat models of OHT exhibit diverse temporal and mechanistic profiles, with no single model fully replicating all aspects of glaucoma. This review uniquely provides a synthesis of peak IOP, time to peak, and duration of elevation across models, offering a practical framework for model selection.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":"34 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13310872/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148344107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chitosan-carboxymethyl tara gum polyelectrolyte complex matrix tablets for sustained gastrointestinal drug dissolution using paracetamol as a model drug.","authors":"Md Sahil Shanawaz Alam, Tapan Kumar Giri, Kaushik Mukherjee","doi":"10.1007/s40199-026-00620-2","DOIUrl":"10.1007/s40199-026-00620-2","url":null,"abstract":"<p><strong>Background: </strong>Natural polysaccharides are extensively used for delivery of bioactives because of its eco-friendly, biocompatible and biodegradable characteristics. However, substantial swelling and poor rheological characteristics limits its applications as drug carriers for sustained delivery.</p><p><strong>Objective: </strong>Chitosan (CTS) and carboxymethyl tara gum (CMTG) matrix tablets were unable provide sustained drug dissolution owing to substantial swelling and low viscosity of the matrix. The present research embarks on the development of CTS and CMTG polyelectrolyte complex (PEC) matrix tablets for sustained gastrointestinal drug dissolution.</p><p><strong>Methods: </strong>PECs of CTS and CMTG were prepared by one shot addition method. The formation of the PECs was optimized in terms of % yield, FTIR, turbidity analysis, zeta potential, viscosity, and swelling studies. The PEC matrix tablets were prepared by wet granulation method.</p><p><strong>Results: </strong>At a fixed concentration of CMTG, increasing CTS concentration led to the formation of non-stoichiometric PECs with reduced % yield and poor mechanical strength making it unsuitable for tableting. At a fixed concentration of CTS, progressive increase in the concentration of CMTG resulted in the formation of stoichiometric PECs which improved the % yield and viscosity, lowered swelling index and had sufficient mechanical strength to be tableted. PEC matrix tablet F7 prepared with optimized PEC 7 (ratio between CTS and CMTG 1:3) released only 40% drug after 12 h of dissolution.</p><p><strong>Conclusion: </strong>Pending validation through in vivo and stability studies, we conclude that CTS- CMTG PEC matrix tablets can be a suitable matrix material for sustained gastrointestinal drug dissolution.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":"34 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13310873/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148344070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bridging solubility, stability, and translation: advances in carbon nanotube-based drug delivery systems.","authors":"Priyanka R, Jeevan Gowda, Deepika A M, Mallamma T, Prasiddi Naik, Prakash Goudanavar","doi":"10.1007/s40199-026-00623-z","DOIUrl":"10.1007/s40199-026-00623-z","url":null,"abstract":"<p><strong>Background: </strong>Poor aqueous solubility and physicochemical instability remain major barriers in pharmaceutical development, limiting the bioavailability, therapeutic efficacy, and translational success of numerous drug candidates. Carbon nanotubes (CNTs), owing to their high surface area, tunable surface chemistry, and unique π-conjugated structure, have emerged as multifunctional nanocarriers capable of addressing these persistent formulation challenges.</p><p><strong>Methodology: </strong>This review critically analyzes recent advances (2020-2026) in CNT-based drug delivery systems with emphasis on solubility enhancement, stability modulation, surface functionalization strategies, protein corona dynamics, dual functionalization approaches, nano-encapsulation technologies, and translational barriers. Comparative evaluation of covalent and non-covalent modification techniques, co-delivery platforms, dispersion strategies, and regulatory considerations is presented to assess their impact on clinical applicability.</p><p><strong>Results: </strong>Functionalized CNTs demonstrate significantly improved aqueous dispersibility, enhanced drug-loading efficiency via π-π stacking and electrostatic interactions, and protection of labile therapeutics against enzymatic and chemical degradation. Polymer conjugation, ligand-directed targeting, and dual functionalization approaches enable controlled and stimuli-responsive release, particularly in tumour-specific microenvironments. Emerging insights into protein corona kinetics reveal their decisive role in biodistribution, immune recognition, and targeting efficiency. Recent innovations in co-delivery systems, lipid coating, and green synthesis further enhance formulation stability and bioavailability. However, challenges related to reproducible functionalization, aggregation control, scalable manufacturing, and regulatory standardisation continue to limit clinical translation.</p><p><strong>Conclusion: </strong>CNT-based drug delivery systems offer a versatile and structurally adaptable platform to bridge solubility, stability, and translational gaps in modern pharmaceutics. While substantial progress has been achieved in enhancing dispersion behaviour, drug protection, and targeting precision, successful clinical implementation will depend on predictive biocompatibility engineering, standardised characterisation protocols, and scalable safe-by-design manufacturing strategies.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":"34 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13310869/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148344098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aprepitant's neuroprotective effects on methylphenidate-induced biochemical/mitochondrial dysfunction, neuroinflammation, and mood-related behavior alterations.","authors":"Ladan Akbarpournikghalb, Parisa Pourdehghan Shahrestani, Mahnaz Gomi, A Wallace Hayes, Mahdieh Gholami, Majid Motaghinejad","doi":"10.1007/s40199-026-00610-4","DOIUrl":"10.1007/s40199-026-00610-4","url":null,"abstract":"<p><strong>Background: </strong>Chronic methylphenidate (MPH) use causes neurological and behavioral problems. Aprepitant (APR) has demonstrated neuroprotective effects.</p><p><strong>Objectives: </strong>This research investigated APR's neuroprotective effects against MPH-induced biochemical, mitochondrial, motor, and mood disturbances in rats.</p><p><strong>Method: </strong>Forty-eight male Wistar rats were divided into six groups to receive treatment for 21 days with saline, MPH, or different doses of APR combined with MPH. Behavioral tests included OFT, EPM, and FST; biochemical assessments focused on hippocampal inflammation, oxidative stress, and apoptosis pathways.</p><p><strong>Results: </strong>APR dose-dependently mitigated the MPH-induced disruptions in motor activity and mood, and increased activities of glutathione peroxidase (GPx), glutathione reductase (GR), and superoxide dismutase (SOD), along with levels of mitochondrial membrane potential (ΔΨm = MMP), reduced glutathione (GSH), total antioxidant capacity (TAC), adenosine triphosphate (ATP), and unphosphorylated Bcl-2. In MPH-treated rats, APR decreased tumor necrosis factor-α (TNF-α), interleukin-1 beta (IL-1β), oxidized glutathione (GSSG), reactive oxygen species (ROS), malondialdehyde (MDA), and hydrogen peroxide (H₂O₂), and reduced both forms of JNK, Bax, Beclin-1, and phosphorylated Bcl-2.</p><p><strong>Conclusion: </strong>APR dose-dependently alleviated MPH-induced anxiety and depression-like behaviors, restored redox and mitochondrial homeostasis, suppressed MPH-induced neuroinflammation and neuronal apoptosis, and influenced Beclin, a key regulator of autophagosome nucleation.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":"34 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13291291/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148307409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cephaeline promotes ferroptosis in breast cancer via p53/SLC7A11/GPX4 axis.","authors":"Xiaohong Li, Jinghan Yu, Beibei Lin, Yudiao Gong","doi":"10.1007/s40199-026-00619-9","DOIUrl":"10.1007/s40199-026-00619-9","url":null,"abstract":"<p><strong>Background: </strong>Cephaeline (CPL), a bioactive compound derived from the medicinal plant Ipecacuanha, has demonstrated inhibitory effects on several tumor types. Nevertheless, its role in breast cancer and the underlying molecular mechanisms remain largely unexplored.</p><p><strong>Objectives: </strong>This research aimed to investigate the anti-cancer potential of CPL in breast cancer cells.</p><p><strong>Methods: </strong>The IC50 of CPL was determined using the CCK-8 assay. Subsequently, the effects of CPL on cell migration and proliferation were assessed through wound healing (scratch) and colony formation assays, respectively. Additionally, MDA and GSH levels were quantified using ELISA, while ROS production was visualized via DHE staining. Intracellular iron content was measured using an iron assay kit. Furthermore, the expression levels of p53, SLC7A11, and GPX4 were evaluated using Western blot. All experiments were performed in triplicate and independently repeated at least three times, and data were analyzed using Student's t-test or one-way ANOVA, as appropriate.</p><p><strong>Results: </strong>CPL significantly inhibited the proliferation and viability of 4T1 and MDA-MB-231 breast cancer cells in a dose-dependent manner, with IC50 values of 38.89 nM and 50.29 nM, respectively, and concomitantly suppressed cell migration and colony formation at higher concentrations. It also increased intracellular MDA and ROS and downregulated GSH, SLC7A11 and GPX4, inducing ferroptosis. siRNA knockdown of p53 attenuated CPL's effects, indicating p53's key role in CPL's anti-cancer activity.</p><p><strong>Conclusions: </strong>This study provides evidence that CPL exerts anti-breast cancer effects by promoting ferroptosis through the p53/SLC7A11/GPX4 axis, highlighting its therapeutic potential as a novel agent for cancer treatment.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":"34 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13282433/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148276344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bio-guided identification of novel antiparasitic natural products from Gardenia imperialis K. Schum (Rubiaceae).","authors":"Christelle Wayoue Kom, Sylvester Osei Bobbie, Darline Dize, Cyrille Armel Njanpa Ngansop, Mariscal Brice Tchatat Tali, Lauve Rachel Tchokouaha Yamthe, Bill Baker, Fabrice Fekam Boyom","doi":"10.1007/s40199-026-00618-w","DOIUrl":"10.1007/s40199-026-00618-w","url":null,"abstract":"<p><strong>Background: </strong>Gardenia imperialis K. Schum. is a medicinal plant used in traditional medicine to treat malaria and related symptoms. This bio-guided study aimed at identifying antiparasitic compounds from G. imperialis against the causative agents of malaria (Plasmodium falciparum), visceral leishmaniasis (Leishmania donovani), and sleeping sickness (Trypanosoma brucei brucei).</p><p><strong>Methods: </strong>Crude methanolic extracts from the leaf and stem bark of G. imperialis were studied using liquid chromatography-mass spectrometry (LC-MS) and preparative medium/high-performance liquid chromatography (M/HPLC) guided by evidence of antiparasitic activity. The structures of the isolated compounds were elucidated using nuclear magnetic resonance (NMR) and MS. All the extracts, fractions, subfractions, and pure compounds were evaluated for antiparasitic activity. Cytotoxicity was tested against Vero and Raw264.7 mammalian cell lines.</p><p><strong>Results: </strong>The leaf methanolic extract (GIlMeOH) exhibited broad-spectrum antiparasitic activity (IC₅₀ < 11 µg/mL) and low cytotoxicity (median cell cytotoxicity-CC₅₀ >100 µg/mL). The dereplication of the extract and isolation yielded fractions, subfractions, and four flavonoids with improved activity (IC₅₀ values ranging from 0.67 to 23.8 µg/mL). Among the isolated flavonoids, gradenin A (3), salvigenin (4), hispidulin (1), and 5,7,3'-trihydroxy-6,4',5'-trimethoxyflavone (2) showed potent antitrypanosomal activity with IC₅₀ values of 2.8, 2.5, 16.6, and 9.7 µg/mL, respectively. The antiparasitic activities of gradenin A, salvigenin, and 5,7,3'-trihydroxy-6,4',5'-trimethoxyflavone are reported here for the first time.</p><p><strong>Conclusion: </strong>The promising antiparasitic profile of the G. imperialis leaf extract and its isolated constituents, particularly and 5,7,3'-trihydroxy-6,4',5'-trimethoxyflavone (2), gradenin A (3), and salvigenin (4), warrants further investigation into their potential as novel and selective agents against the target parasitic diseases.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":"34 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13280111/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148276351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}