DARU Journal of Pharmaceutical Sciences最新文献

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Chitosan-carboxymethyl tara gum polyelectrolyte complex matrix tablets for sustained gastrointestinal drug dissolution using paracetamol as a model drug. 壳聚糖-羧甲基塔拉胶多电解质复合基质片用于胃肠药物持续溶出,以扑热息痛为模型药物。
IF 2.8 4区 医学
DARU Journal of Pharmaceutical Sciences Pub Date : 2026-06-29 DOI: 10.1007/s40199-026-00620-2
Md Sahil Shanawaz Alam, Tapan Kumar Giri, Kaushik Mukherjee
{"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}
引用次数: 0
Bridging solubility, stability, and translation: advances in carbon nanotube-based drug delivery systems. 桥接溶解度、稳定性和转译:基于碳纳米管的药物传递系统的进展。
IF 2.8 4区 医学
DARU Journal of Pharmaceutical Sciences Pub Date : 2026-06-29 DOI: 10.1007/s40199-026-00623-z
Priyanka R, Jeevan Gowda, Deepika A M, Mallamma T, Prasiddi Naik, Prakash Goudanavar
{"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}
引用次数: 0
Aprepitant's neuroprotective effects on methylphenidate-induced biochemical/mitochondrial dysfunction, neuroinflammation, and mood-related behavior alterations. 阿瑞吡坦对哌甲酯诱导的生化/线粒体功能障碍、神经炎症和情绪相关行为改变的神经保护作用
IF 2.8 4区 医学
DARU Journal of Pharmaceutical Sciences Pub Date : 2026-06-24 DOI: 10.1007/s40199-026-00610-4
Ladan Akbarpournikghalb, Parisa Pourdehghan Shahrestani, Mahnaz Gomi, A Wallace Hayes, Mahdieh Gholami, Majid Motaghinejad
{"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 (H<sub>2</sub>O<sub>2</sub>), 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}
引用次数: 0
Cephaeline promotes ferroptosis in breast cancer via p53/SLC7A11/GPX4 axis. 头孢林通过p53/SLC7A11/GPX4轴促进乳腺癌铁下垂。
IF 2.8 4区 医学
DARU Journal of Pharmaceutical Sciences Pub Date : 2026-06-19 DOI: 10.1007/s40199-026-00619-9
Xiaohong Li, Jinghan Yu, Beibei Lin, Yudiao Gong
{"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}
引用次数: 0
Bio-guided identification of novel antiparasitic natural products from Gardenia imperialis K. Schum (Rubiaceae). 栀子抗寄生虫新产物的生物导向鉴定。
IF 2.8 4区 医学
DARU Journal of Pharmaceutical Sciences Pub Date : 2026-06-19 DOI: 10.1007/s40199-026-00618-w
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
{"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-CC<sub>50</sub> >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}
引用次数: 0
A cost-efficient internal standard approach for busulfan quantification: MS-based investigation of adduct formation in therapeutic drug monitoring. 一种具有成本效益的内标方法用于磺胺定量:治疗药物监测中加合物形成的质谱研究。
IF 2.8 4区 医学
DARU Journal of Pharmaceutical Sciences Pub Date : 2026-06-15 DOI: 10.1007/s40199-026-00615-z
Erfan Jahan Mehmani, Niloofar Rastegarpanah, Issa Zarei, Massoud Amanlou
{"title":"A cost-efficient internal standard approach for busulfan quantification: MS-based investigation of adduct formation in therapeutic drug monitoring.","authors":"Erfan Jahan Mehmani, Niloofar Rastegarpanah, Issa Zarei, Massoud Amanlou","doi":"10.1007/s40199-026-00615-z","DOIUrl":"10.1007/s40199-026-00615-z","url":null,"abstract":"<p><strong>Background: </strong>Busulfan plays a central role in conditioning regimens for hematopoietic stem cell transplantation (HSCT). However, its narrow therapeutic index and substantial interpatient pharmacokinetic variability necessitate precise therapeutic drug monitoring (TDM). Because busulfan is highly lipophilic, many LC-MS/MS assays rely on costly stable-isotope-labeled internal standards (e.g., busulfan-d8), which limits their routine application in resource-constrained settings.</p><p><strong>Methods: </strong>This study aimed to synthesize cost-effective structural analogs of busulfan and evaluate their chromatographic behavior and cation-adduct formation as potential alternative internal standards. Four dimethanesulfonate analogs were synthesized from symmetrical n-diols (n = 3-6) under alkaline conditions (47-55% yields). The synthesized analogs were evaluated as candidate internal standards by investigating their cation-adduct formation behavior using liquid chromatography-electrospray ionization-quadrupole time-of-flight high-resolution mass spectrometry (LC-ESI-qTOF-HRMS).</p><p><strong>Results: </strong>Each analog formed distinct cation adducts (H<sup>+</sup>, Li<sup>+</sup>, Na<sup>+</sup>, K<sup>+</sup>, and NH4<sup>+</sup>), with sodium adducts demonstrating the greatest stability in mixed-ion environments. Among the synthesized compounds, 1,6-hexanediol dimethanesulfonate (compound 4) exhibited the most favorable chromatographic retention and adduct stability, supporting its suitability as a structural internal-standard candidate.</p><p><strong>Conclusion: </strong>These findings provide mechanistic and analytical evidence to support the selection of a cost-efficient internal standard for busulfan quantification. However, full bioanalytical validation in biological matrices will be required before routine clinical implementation.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":"34 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13269584/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148249586","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}
引用次数: 0
Plant-derived exosome-like nanovesicles as programmable bio-organic excipients: a next-generation platform for precision and immuno-silent drug delivery. 植物来源的外泌体样纳米囊泡作为可编程的生物有机赋形剂:精确和免疫沉默药物递送的下一代平台。
IF 2.8 4区 医学
DARU Journal of Pharmaceutical Sciences Pub Date : 2026-06-13 DOI: 10.1007/s40199-026-00617-x
Chetana Krushna Belkare, Omkar Vishnu Daware
{"title":"Plant-derived exosome-like nanovesicles as programmable bio-organic excipients: a next-generation platform for precision and immuno-silent drug delivery.","authors":"Chetana Krushna Belkare, Omkar Vishnu Daware","doi":"10.1007/s40199-026-00617-x","DOIUrl":"10.1007/s40199-026-00617-x","url":null,"abstract":"<p><strong>Purpose: </strong>There is increasing demand for advanced drug delivery systems that improve therapeutic efficacy while minimizing toxicity. Conventional pharmaceutical excipients, though historically considered inert, often exhibit limitations such as immunogenicity, toxicity, poor intracellular delivery, and inadequate functionality for biologics and nucleic acid-based therapies. Recently, plant-derived exosome-like nanovesicles (PDENs) have emerged as promising bio-organic nanomaterials with favourable biocompatibility and delivery potential. This article critically reviews PDENs as programmable bio-organic excipients.</p><p><strong>Methods: </strong>A structured literature review was conducted using PubMed, Scopus, Web of Science, and Google Scholar for studies published from 2010 to 2026. Reports covering isolation, physicochemical properties, engineering strategies, formulation approaches, biological functions, translational challenges, and regulatory aspects of PDENs were analyzed.</p><p><strong>Results: </strong>PDENs exhibit favorable properties including nanoscale size, lipid bilayer structure, intrinsic biological activity, low immunogenicity in preclinical studies, and favorablebiocompatibility. They demonstrate efficient drug loading, improved formulation stability, enhanced cellular uptake, and the ability to traverse biological barriers. Their performance can be further optimized through surface engineering, hybrid systems, and stimuli-responsive delivery strategies. In addition, PDENs may act as co-therapeutic agents due to their antioxidant, anti-inflammatory, and immunomodulatory effects. However, challenges remain in batch consistency, scalable manufacturing, stability, classification, and quality control.</p><p><strong>Conclusion: </strong>PDENs represent an evolution from conventional excipients to programmable bio-organic systems integrating drug delivery, targeting, and therapeutic functions. They hold strong promise for precision medicine and nanotherapeutics, but clinical translation requires advances in scalable production, Quality by Design implementation, safety evaluation, and regulatory harmonization.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":"34 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13264654/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148249591","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}
引用次数: 0
The paradoxical protective effect of malnutrition in acetaminophen-induced liver injury. 对乙酰氨基酚引起的肝损伤中营养不良的矛盾保护作用。
IF 2.8 4区 医学
DARU Journal of Pharmaceutical Sciences Pub Date : 2026-06-12 DOI: 10.1007/s40199-026-00611-3
Vinitha D'Souza, Varsha Augustin, Madhura R J, Murali Badanthadka
{"title":"The paradoxical protective effect of malnutrition in acetaminophen-induced liver injury.","authors":"Vinitha D'Souza, Varsha Augustin, Madhura R J, Murali Badanthadka","doi":"10.1007/s40199-026-00611-3","DOIUrl":"10.1007/s40199-026-00611-3","url":null,"abstract":"<p><strong>Background: </strong>Malnutrition is believed to aggravate drug-induced liver injury (DILI). However, the relationship between protein malnutrition (PMN) and acetaminophen (APAP)-induced liver injury (AILI) remains unclear, particularly in low and middle income countries (LMIC) where PMN is common.</p><p><strong>Objective: </strong>This study aimed to investigate the role of PMN on AILI in female BALB/c mice.</p><p><strong>Methodology: </strong>PMN was induced in 15 week old female BALB/c mice by feeding a low protein diet (LPD, 10% protein) after weaning, while control mice received a normal diet (ND, 18% protein). Initially, APAP-induced lethality was assessed at different doses. Subsequently, mice were challenged with a single oral dose of APAP (300 mg/kg) to evaluate liver injury markers, oxidative stress, inflammatory cytokines, CYP2E1 expression and activity, histopathology, PCNA expression, and pharmacokinetic (PK) parameters.</p><p><strong>Results: </strong>At a single oral dose of 500 mg/kg, APAP-induced lethality was high in the LPD group (3/4). Reducing the dose to 400 mg/kg abolished lethality in the LPD group (0/6) but not in the ND group (4/6). At 300 mg/kg, lethality was absent in both groups. Liver injury assessed by ALT, AST, and ALP levels was greater in the ND group than in the LPD group. Higher oxidative stress and cytokine levels (TNF-α and IL-6), increased PCNA expression, and pronounced histological alterations were observed in ND mice. PK analysis showed greater C<sub>max</sub>, T<sub>max</sub>, and AUC<sub>0-4</sub> values in the LPD group, indicating altered APAP metabolism. In addition, ND mice exhibited greater CYP enzyme expression and activity, suggesting enhanced APAP bioactivation and increased susceptibility to liver injury.</p><p><strong>Conclusion: </strong>Our findings highlight the paradoxical vulnerability of the ND group to AILI and death. Therefore, PMN could be the reason for fewer APAP overdose-related deaths in developing countries. Further, unravelling the precise molecular mechanisms induced by nutritional changes is critical for understanding the paradoxical decline in liver injury associated with PMN.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":"34 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13263372/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148223782","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}
引用次数: 0
The effects of resveratrol on glycemic indices and lipid profile in patients with type 2 diabetes: an umbrella review and meta-analysis. 白藜芦醇对2型糖尿病患者血糖指数和血脂的影响:综述和荟萃分析
IF 2.8 4区 医学
DARU Journal of Pharmaceutical Sciences Pub Date : 2026-06-10 DOI: 10.1007/s40199-026-00609-x
Faezeh Ghalichi, Roghayeh Molani-Gol, Faezeh Tejareh, Laleh Payahoo
{"title":"The effects of resveratrol on glycemic indices and lipid profile in patients with type 2 diabetes: an umbrella review and meta-analysis.","authors":"Faezeh Ghalichi, Roghayeh Molani-Gol, Faezeh Tejareh, Laleh Payahoo","doi":"10.1007/s40199-026-00609-x","DOIUrl":"10.1007/s40199-026-00609-x","url":null,"abstract":"<p><strong>Background: </strong>Growing evidence supports the therapeutic role of nutraceuticals as complementary and alternative therapies in patients with type 2 diabetes mellitus (T2DM). Resveratrol, a natural polyphenol compound has been shown to modulate metabolically disturbances include insulin resistance and lipid profile disturbances.</p><p><strong>Objectives: </strong>This umbrella review and meta-analysis study conducted to assess the effect of resveratrol on glycemic indices and lipid profile in T2DM.</p><p><strong>Methods: </strong>The study was performed by using the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines (PRISMA) checklist. The PubMed, Web of Sciences, and Google Scholar databases were used to search the published papers up to 2025. The AMSTAR questionnaire was used for assessing the quality of eligible studies. Additionally, The Cochran Q test and I<sup>2</sup> statistics were used for examining heterogeneity.</p><p><strong>Results: </strong>Of 10 meta-analyses evaluating the resveratrol effects on glycemic indices and lipid profile showed no significant effects on fasting blood sugar, glycosylated hemoglobin A1c (HbA1c), insulin, homeostatic model assessment for insulin resistance (HOMA-IR), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), triglyceride (TG), total cholesterol (TC), despite significant heterogeneity. Nevertheless, based on SMD analyses, resveratrol supplementation showed only significant effects on LDL-C reduction. Also, significant decline in serum insulin level was observed for sample size ≥ 500 and study number ≥ 10.</p><p><strong>Conclusion: </strong>Given the high heterogeneity and limitations attributed to the study, resveratrol supplementation was not considered as a beneficial agent in declining glycemic indices and lipid profile in patients with T2DM.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":"34 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13253897/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148216786","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}
引用次数: 0
ALKBH5 promotes the progression of cisplatin-resistant oral squamous cell carcinoma by regulating FOXA1 expression via m6A RNA methylation : Funding. ALKBH5通过m6A RNA甲基化调节FOXA1表达促进顺铂耐药口腔鳞状细胞癌的进展:资助
IF 2.8 4区 医学
DARU Journal of Pharmaceutical Sciences Pub Date : 2026-06-06 DOI: 10.1007/s40199-026-00614-0
Ying Wang, Hui-Xin Yang, Yu-Jia Gu, Mei Tian, Qi-Feng Geng
{"title":"ALKBH5 promotes the progression of cisplatin-resistant oral squamous cell carcinoma by regulating FOXA1 expression via m<sup>6</sup>A RNA methylation : Funding.","authors":"Ying Wang, Hui-Xin Yang, Yu-Jia Gu, Mei Tian, Qi-Feng Geng","doi":"10.1007/s40199-026-00614-0","DOIUrl":"10.1007/s40199-026-00614-0","url":null,"abstract":"<p><strong>Background: </strong>Oral squamous cell carcinoma (OSCC) accounts for the vast majority of oral cancer cases. Accumulating evidence has implicated both AlkB homolog 5 (ALKBH5) and forkhead box protein A1 (FOXA1) in the emergence of cisplatin resistance in OSCC. This study aimed to define their functional roles and elucidate the underlying molecular mechanisms.</p><p><strong>Methods: </strong>The expression of ALKBH5, FOXA1, and YTHDF2 was assessed by qPCR and Western blot. Cisplatin-resistant cell lines (H357 CisR and SCC4 CisR) were established via stepwise dose escalation. To investigate key functional phenotypes, a series of assays were employed: CCK-8 for viability, colony formation for proliferation, and Transwell for migration and invasion. Bioinformatics (SRAMP, RM2Target) predicted m⁶A sites on FOXA1 and its binding with ALKBH5, which were validated by MeRIP-qPCR and RIP. FOXA1 mRNA stability was measured by actinomycin D assay.</p><p><strong>Results: </strong>ALKBH5 and FOXA1 were upregulated in cisplatin-resistant OSCC, with FOXA1 essential for maintaining oncogenic phenotypes. Bioinformatic and biochemical analyses confirmed FOXA1 as a direct target of ALKBH5. ALKBH5 demethylates FOXA1 mRNA, stabilizing its transcript and enhancing its expression by inhibiting YTHDF2-mediated degradation. Functionally, ALKBH5 overexpression reversed the tumor-suppressive effects of FOXA1 knockdown.</p><p><strong>Conclusion: </strong>Our study demonstrates that ALKBH5 promotes cisplatin resistance in OSCC through m<sup>6</sup>A-dependent demethylation of FOXA1 transcripts, highlighting the ALKBH5-FOXA1 axis as a promising therapeutic target for overcoming this resistance.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":"34 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13242349/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148194559","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}
引用次数: 0
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