Journal of Experimental Pharmacology最新文献

{"title":"Intraperitoneal Administration of Cardiolipin Enhances Mitochondrial Respiration in Skeletal Muscle of Male Mice.","authors":"Amanda Laplante, Andreas Bergdahl","doi":"10.2147/JEP.S598396","DOIUrl":"https://doi.org/10.2147/JEP.S598396","url":null,"abstract":"<p><strong>Purpose: </strong>Cardiolipin is a phospholipid located in the inner mitochondrial membrane and is released following myocardial ischemia-reperfusion injury. While cardiolipin has documented effects in several tissues, its impact on skeletal muscle function and mitochondrial respiration remains unclear. The purpose of this study was to investigate the effects of exogenously elevated cardiolipin on aerobic capacity and mitochondrial respiratory function in skeletal muscle using a mouse model.</p><p><strong>Methods: </strong>Male C57BL/6 mice were randomized into an experimental group (n = 11) receiving cardiolipin injections and a control group (n = 12) receiving a placebo solution. Mice were injected twice weekly for 6 weeks with 0.1 mL of cardiolipin (0.5 mg/mL) or placebo. Voluntary running distance was monitored throughout the intervention. Aerobic capacity was assessed at baseline, week 3, and week 6 by measuring time to exhaustion during treadmill running at a constant speed of 16 m min^-1. Following the intervention, mice were euthanized, the vastus lateralis muscle was excised, and mitochondrial respiratory capacity was evaluated using high-resolution respirometry. Mitochondrial density was assessed by immunoblotting.</p><p><strong>Results: </strong>Mice receiving cardiolipin exhibited increased skeletal muscle oxygen consumption compared with controls. No differences in mitochondrial density were observed between groups, suggesting that the enhanced oxygen consumption was not associated with increased mitochondrial content but may instead reflect alterations in mitochondrial respiratory efficiency.</p><p><strong>Conclusion: </strong>Exogenously elevated cardiolipin is associated with enhanced skeletal muscle mitochondrial respiratory function without altering mitochondrial density, which may indicate improved mitochondrial efficiency. These findings provide novel insight into the potential role of cardiolipin in skeletal muscle energy metabolism and aerobic performance. Future studies should explore the combined effects of cardiolipin administration and exercise training on skeletal muscle respiratory capacity and further investigate the underlying mechanisms.</p>","PeriodicalId":15846,"journal":{"name":"Journal of Experimental Pharmacology","volume":"18 ","pages":"598396"},"PeriodicalIF":0.0,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13110803/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147773350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances on Ethnobotanical, Phytochemical, and Preclinical Studies of <i>Strobilanthes crispus</i> and <i>Strobilanthes cusia</i> (Acanthaceae) for Drug Development Purpose: A Narrative Review.","authors":"Rani Rubiyanti, Yasmiwar Susilawati, Siti Mariam Binti Abdul Wahab, Jutti Levita","doi":"10.2147/JEP.S590628","DOIUrl":"10.2147/JEP.S590628","url":null,"abstract":"<p><p>Plants of the genus <i>Strobilanthes</i> are one of the most widespread vegetation in Southeast Asia. More than 100 metabolites, including alkaloids, fatty acids and derivatives, flavonoids and flavonoid glycosides, phenolic acids, sterols, and terpenoids, have been identified from these plants. The scope of this review, which covers ethnobotanical, phytochemical, and preclinical aspects of <i>Strobilanthes crispus</i> and <i>Strobilanthes cusia</i> (Acanthaceae), is limited to articles published between 2015 and 2025. It confirms that these plants are still being investigated globally, with the most reported in numerous in vitro and in vivo studies on the leaves. Considering the noteworthy findings of the in vitro and in vivo studies, which mainly point to <i>S. crispus</i>, this plant may be established as a plant-based antimicrobial, anti-inflammatory, anticancer, or hypoglycemic agent, which may be attributed to its indolo-quinazoline alkaloid and flavonoids. Despite promising pharmacological evidence, there are limited human studies during the selected publication period. However, several articles have described ethnopharmacological surveys of medicinal plants in China, Malaysia, and Thailand, which documented the folkloric use of these two plants. It should be taken to notice that the lack of human studies requires further clinical trials to validate pharmacological activity, efficacy, and safety, and confirm its potential as a therapeutic agent.</p>","PeriodicalId":15846,"journal":{"name":"Journal of Experimental Pharmacology","volume":"18 ","pages":"590628"},"PeriodicalIF":0.0,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13091594/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147722955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mangiferin Mitigates Ketamine-Induced Dopaminergic and Glial Dysregulation and Modulates Nrf2 Expression in a Rat Schizophrenia-Like Model.","authors":"Victoria Onyemachi Chukwu, Godson Emeka Anyanwu, Nto Johnson Nto, Augustine Uche Agu, Amechi U Katchy, Vivian Onyinye Ojiakor, Chinyere Nkemjika Anyanwu","doi":"10.2147/JEP.S589790","DOIUrl":"https://doi.org/10.2147/JEP.S589790","url":null,"abstract":"<p><strong>Introduction: </strong>Schizophrenia involves dopaminergic dysregulation, oxidative stress, and glial activation within motor-cognitive circuits. Mangiferin, a polyphenolic C-glucoside from <i>Mangifera indica</i>, exerts antioxidant and anti-inflammatory effects partly via modulation of nuclear factor erythroid 2-related factor 2 (Nrf2) signaling. This study evaluated whether mangiferin attenuates ketamine-induced behavioral and neurobiological alterations along the basal ganglia-substantia nigra-cerebellar axis in rats.</p><p><strong>Methods: </strong>Male Wistar rats were assigned to seven groups (n = 6) and received vehicle, ketamine (50 mg/kg/day, i.p. 7 days), mangiferin (25-75 mg/kg, p.o. 14 days), ketamine plus mangiferin (25, 50, 75 mg/kg), or ketamine plus risperidone (2 mg/kg, p.o). Y-maze and open-field tests were conducted at baseline, after ketamine, and after treatment. Striatum, substantia nigra, and cerebellum were analyzed for dopamine (HPLC), oxidative stress markers, inflammatory mediators, and immunohistochemistry for GFAP and Nrf2.</p><p><strong>Results: </strong>Ketamine produced behavioral alterations characterized by reduced exploratory activity, hyperlocomotion, and anxiety-like behavior, alongside elevated dopamine, reduced antioxidant enzyme activities, increased lipid peroxidation and pro-inflammatory mediators, enhanced GFAP immunoreactivity, and decreased Nrf2 immunoreactivity. Mangiferin, particularly at 50-75 mg/kg, increased Y-maze arm entries toward control values (indicating improved locomotor activity), restored antioxidant defenses, reduced oxidative and inflammatory indices toward control levels, reduced astrocytosis, and increased Nrf2 immunoreactivity. Risperidone improved behavior and neuroinflammatory indices but showed less consistent normalization of redox markers and Nrf2 compared with high-dose mangiferin.</p><p><strong>Discussion: </strong>These findings indicate that mangiferin attenuates ketamine-induced behavioral, oxidative, inflammatory, and glial alterations in motor-cognitive circuits and are consistent with modulation of redox-glial interactions, including Nrf2-associated antioxidant signaling. Collectively, the results support further evaluation of mangiferin and related Nrf2-modulating natural products as adjunctive strategies targeting redox-glial dysfunction in schizophrenia.</p>","PeriodicalId":15846,"journal":{"name":"Journal of Experimental Pharmacology","volume":"18 ","pages":"589790"},"PeriodicalIF":0.0,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13069952/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147673873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Livogrit Ameliorates Thioacetamide-Induced Liver Fibrosis and Dyslipidemia in Rat Model by Regulating Oxidative Stress and Hepatic Collagen Levels, in a Non-Mutagenic Manner.","authors":"Acharya Balkrishna, Sunil Shukla, Sandeep Sinha, Himanshu Jangid, Savita Lochab, Anurag Varshney","doi":"10.2147/JEP.S548399","DOIUrl":"https://doi.org/10.2147/JEP.S548399","url":null,"abstract":"<p><strong>Background: </strong>Liver fibrosis represents a serious health challenge and is the outcome of chronic liver diseases like cirrhosis and hepatitis. This study was designed to evaluate the anti-fibrotic and anti-dyslipidemic effects of Livogrit (a tri-herbal formulation) on Thioacetamide (TAA)-induced rat model of fibrosis; and its mutagenic potential in Ames test.</p><p><strong>Methods: </strong>The study employed TAA-induced Sprague-Dawley rat to evaluate Livogrit's anti-fibrotic potentials, as well as associated dyslipidemia. Quantification of phytometabolites present in Livogrit was conducted using UHPLC-DAD analysis. The pharmacological effects of Livogrit were assessed by measuring hepatic enzyme markers AST, ALT, and ALP; serum lipid profile markers TG, TC, HDL, and LDL; anti-oxidative enzymes SOD and catalase. In addition, histopathological changes in hepatic tissue were assessed. Changes in body weight, relative liver weight, hydroxyproline, and collagen levels were also evaluated. Silymarin served as the experimental reference standard. Finally, Livogrit was also tested for its mutagenic potential through Ames assay.</p><p><strong>Results: </strong>UHPLC-DAD analysis of Livogrit revealed presence of several bioactive metabolites. Livogrit effectively attenuated TAA-induced hepatotoxicity and fibrosis. Treatment with Livogrit reduced elevated ALT, AST, ALP, TG, TC, LDL, nitrite, hydroxyproline, and collagen levels while improving HDL, SOD, and catalase levels. Livogrit also regulated LDL/HDL and TC/HDL ratios. Livogrit treatment normalized the detrimental effects of TAA on the liver histo-architecture, in terms of inflammatory and fibrotic changes. Ames test also confirmed that Livogrit was non-mutagenic at highest tested concentration, with or without metabolic (S9) activation.</p><p><strong>Conclusion: </strong>Livogrit demonstrated preclinical potential for the effective management of hepatic fibrosis and dyslipidemia, in a non-mutagenic manner. This study paves a way for detailed non-clinical safety experiments and clinical investigations of Livogrit in patients with hepatic fibrosis under controlled conditions.</p>","PeriodicalId":15846,"journal":{"name":"Journal of Experimental Pharmacology","volume":"18 ","pages":"548399"},"PeriodicalIF":0.0,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13005633/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147499227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Carica Papaya</i> Linn. Leaf Extracts Induced the Proliferation of Mice's Peritoneal Macrophages and Bone Marrow Cells, Along with Cytokine Modulation in Cell Culture.","authors":"Wendwaoga Arsène Nikiema, Guillaume Sylvestre Sanou, André Zoulyél Da, Harouna Sore, Boris Honoré Amadou Ouedraogo, Kongnimissom Apoline Sondo, Rawéléguinbasba Armel Flavien Kabore, Rasmané Semdé, Moussa Ouedraogo","doi":"10.2147/JEP.S562891","DOIUrl":"https://doi.org/10.2147/JEP.S562891","url":null,"abstract":"<p><strong>Purpose: </strong><i>Carica papaya</i> is used alone or with other herbs in traditional medicine to treat infectious diseases; nonetheless, comprehensive scientific validation of this claim is limited. We conducted this preliminary study to explore its immunomodulatory potential through cytokine modulation.</p><p><strong>Methods: </strong>An aqueous ethanolic crude extract of plant leaves was evaluated for phytochemical groups, total flavonoid, and phenolic content using aluminum chloride and Folin-Ciocalteu's methods. The crude extract and its derived fractions were compared with thin-layer chromatography, and antioxidant properties were assessed using the 2,2'-diphenyl-1-picrylhydrazyl radical scavenging assay and the Ferric Ion Reducing Antioxidant Power assay. Additionally, the effects of the extracts on cell proliferation, cytokine, and nitric oxide release by mouse peritoneal macrophages and bone marrow multipotent cells in culture were evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, the Enzyme-Linked Immunosorbent Assay (ELISA), and the Griess reagent. The cells were collected from Swiss strain mice (12 mice).</p><p><strong>Results: </strong><i>Carica papaya</i> leaf crude extract contained alkaloids, tannins, flavonoids, anthraquinones, and terpenoids. The crude extract's total phenolic and flavonoid contents were 14.07±5.76 gallic acid equivalents and 22.58±3.05 quercetin equivalents per gram of extract. The crude extract showed more potent antioxidant activity. Crude extract and fractions stimulated the proliferation of peritoneal macrophages at 1-10μg/mL and bone marrow multipotent cells at 0.01-0.3μg/mL in a concentration-dependent manner. Interleukin-6 and tumor necrosis factor-α production were significantly increased, while interleukin-1β production was inhibited in treated peritoneal macrophages. Treated bone marrow cells increased granulocyte-macrophage colony-stimulating factor, stem cell factor, and thrombopoietin secretion and decreased interleukin-3 production. Nitric oxide production was 10-20 times higher in bone marrow compared to peritoneal macrophage cells.</p><p><strong>Conclusion: </strong><i>Carica papaya</i> leaf crude extract and fractions exhibit immunomodulatory effects by promoting cytokine release and peritoneal macrophage and bone marrow cell proliferation, explaining the use of <i>C. papaya</i> in infectious diseases in traditional medicine. Further exploration is needed for applications in immune-related diseases.</p>","PeriodicalId":15846,"journal":{"name":"Journal of Experimental Pharmacology","volume":"18 ","pages":"562891"},"PeriodicalIF":0.0,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12931400/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147306768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytotoxicity and Coagulation Effects of Methanolic Extracts of <i>Punica granatum, Quercus infectoria, and Achillea millefolium</i>: an in vitro Study.","authors":"Neda Mohamadi, Aida Najafi, Fatemeh Ganjeizadeh Rohani, Amir Asadi, Simin Sharifi","doi":"10.2147/JEP.S580084","DOIUrl":"https://doi.org/10.2147/JEP.S580084","url":null,"abstract":"<p><strong>Objective: </strong>Considering the historical use of three plant species <i>Punica granatum, Quercus infectoria</i>, and <i>Achillea millefolium</i> in traditional medicine for hemostatic purposes, along with the variation observed in some experimental research, the aim of this study was to comparatively evaluate the effect of methanol extracts derived from these three medicinal plants on blood clotting time in vitro.</p><p><strong>Methods: </strong>Methanolic (70%) extracts of <i>P. granatum</i> flower, <i>Q. infectoria</i> galls and <i>A. millefolium</i> aerial parts were prepared by maceration method. The total tannin and phenolic content were determined using a colorimetric method. The cytotoxic activity of extracts on NIH/3T3 cell lines was evaluated by the colorimetric MTT assay. Non-toxic concentrations were tested in vitro on blood coagulation profiles including prothrombin time (PT) and activated partial thromboplastin time (aPTT) of healthy human volunteers.</p><p><strong>Results: </strong><i>Q. infectoria</i> had the highest phenolic content at 287.18 mg gal/g, followed by <i>P. granatum</i> and <i>A. millefolium. P. granatum</i> exhibited the highest tannin content (119.21 mg catechin/g DW), followed by <i>Q. infectoria</i> (109.30 mg catechin/g DW) and <i>A. millefolium</i> (54.35mg catechin/g DW). The highest total flavonoid content was found in <i>P. granatum, A. millefolium</i>, and <i>Q. infectoria</i> with 98, 85.5, 5.22 mg Rutin/g DW, respectively. Non-toxic concentrations were selected to perform coagulation experiments. Based on the plant-derived coagulation assays, pomegranate extract notably reduced the PT to 11.57 ± 0.37 s compared with the control value of 14.47 ± 0.41 s. Conversely, gall oak extract markedly increased the coagulation time to 17.07 ± 1.07 s. Similarly, pomegranate significantly decreased aPTT to 33.83 ± 0.79 s relative to the control (36.30 ± 2.04 s), whereas gall oak considerably prolonged it to 50.00 ± 2.04 s.</p><p><strong>Conclusion: </strong>Methanolic extracts of <i>P. granatum</i> show promise as procoagulants, while <i>Q. infectoria</i> acts as an anticoagulant, and <i>A. millefolium</i> remains neutral in this context.</p>","PeriodicalId":15846,"journal":{"name":"Journal of Experimental Pharmacology","volume":"18 ","pages":"580084"},"PeriodicalIF":0.0,"publicationDate":"2026-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12927844/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147284107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Empagliflozin Improves Learning and Memory Deficits in Streptozotocin-Induced Hyperglycemic Male Wistar Rats.","authors":"Israa H Isawi, Nour A Al-Sawalha, Fatema Mahmoud, Islam Al-Khawaldeh, Karem H Alzoubi","doi":"10.2147/JEP.S561692","DOIUrl":"https://doi.org/10.2147/JEP.S561692","url":null,"abstract":"<p><strong>Background: </strong>Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a relatively new class of antidiabetic agents that lower blood glucose independently of insulin by inhibiting renal SGLT2 in the proximal tubule, thereby increasing urinary glucose and sodium excretion. Empagliflozin (Empa), an FDA-approved SGLT2 inhibitor, exhibits antioxidant, anti-inflammatory, and additional metabolic effects beyond glycemic control. Given the high expression of SGLT2 in the central nervous system and the established link between cognitive impairment, chronic hyperglycemia, oxidative stress, and inflammation, this study investigated Empa's neuroprotective potential on learning and memory deficits in streptozotocin-induced hyperglycemic male Wistar rats.</p><p><strong>Methods: </strong>Hyperglycemia was induced using streptozotocin (40 mg/kg/IP), followed by Empa treatment (10 mg/kg/day/PO). Cognitive performance was evaluated using the radial arm water maze, assessing learning and both short-term and long-term memory. Concurrently, hippocampal oxidative stress markers and key molecular mediators, including brain-derived neurotrophic factor (BDNF) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), were measured to elucidate possible underlying neuroprotective mechanisms.</p><p><strong>Results: </strong>Hyperglycemic rats exhibited significant impairments in learning, short-term memory, and long-term memory compared to normoglycemic controls. Empa treatment significantly improved short-term memory, restoring performance to near-control levels. However, its impact on long-term memory was minimal. Unexpectedly, Empa induced only modest, non-statistically significant changes in hippocampal oxidative stress markers and BDNF and NF-κB levels.</p><p><strong>Conclusion: </strong>The findings underscore the complexity of oxidative stress and inflammatory pathways involved in hyperglycemia-associated cognitive impairment. The beneficial effects of Empa on short-term memory may involve alternative mechanisms unrelated to oxidative stress modulation. Further studies involving extended durations, higher dosages, or larger sample sizes are warranted to better elucidate the neuroprotective mechanisms of Empa.</p>","PeriodicalId":15846,"journal":{"name":"Journal of Experimental Pharmacology","volume":"18 ","pages":"561692"},"PeriodicalIF":0.0,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12912132/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146219875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative Computational and Transcriptional Analysis of NF-κB and HIF-1α Modulation Following Doxorubicin Treatment in Triple-Negative Breast Cancer Cells.","authors":"Nurul Utami, Arif Setiawansyah, Muhammad Hasan Bashari, Hermin Aminah Usman, Raden Yohana Azhar, Astrid Feinisa Khairani","doi":"10.2147/JEP.S576572","DOIUrl":"https://doi.org/10.2147/JEP.S576572","url":null,"abstract":"<p><strong>Purpose: </strong>Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype with limited targeted treatment options. Doxorubicin remains a cornerstone of TNBC treatment; however, its molecular effects beyond canonical cytotoxic mechanisms are not fully characterized. This study aimed to explore NF-κB- and HIF-1α-related transcriptional responses associated with doxorubicin treatment in TNBC cells using an integrative computational and experimental approach, in line with global cancer research priorities supporting Sustainable Development Goal (SDG) 3: Good Health and Well-Being.</p><p><strong>Methods: </strong>Network pharmacology analysis, molecular docking, and molecular dynamics simulations were employed to explore potential pathway-level associations of doxorubicin with NF-κB and HIF-1α-related signaling. In vitro validation was performed using MTT cytotoxicity assays in MDA-MB-231 cells cultured in DMEM and RPMI-1640 media. Half-maximal inhibitory concentrations (IC₅ ₀) were determined using four-parameter logistic regression. Transcriptional responses of NF-κB and HIF-1α were evaluated by RT-qPCR under normoxic conditions.</p><p><strong>Results: </strong>Computational analyses suggested potential associations between doxorubicin and components of NF-κB and HIF-1α-related signaling pathways. In vitro assays demonstrated concentration-dependent cytotoxicity, with IC₅ ₀ values of 2.34 µM (95% CI: 2.11-2.74) in DMEM and 1.07 µM (95% CI: 0.92-1.32 µM) in RPMI-1640. RT-qPCR analysis revealed downregulation of NF-κB and HIF-1α mRNA expression following doxorubicin treatment. These findings indicate transcriptional modulation associated with doxorubicin exposure, without establishing functional pathway inhibition.</p><p><strong>Conclusion: </strong>This study provides transcriptional-level evidence suggesting the involvement of NF-κB- and HIF-1α-related pathways in the cellular response of TNBC cells to doxorubicin treatment. By integrating computational predictions with early experimental validation, the findings generate biologically plausible hypotheses for further mechanistic and functional investigations, contributing to foundational cancer research efforts aligned with SDG 3 (Good Health and Well-Being).</p>","PeriodicalId":15846,"journal":{"name":"Journal of Experimental Pharmacology","volume":"18 ","pages":"576572"},"PeriodicalIF":0.0,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12912095/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146219889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Vulgarin and Epivulgarin on Ischemia-Reperfusion-Induced Pancreatic Injury in Rats: A Biochemical, Molecular, and Histopathological Evaluation.","authors":"Hassan N Althurwi, Rehab F Abdel-Rahman, Tariq M Aljarba, Hanan A Ogaly, Saleh I Alqasoumi, Ahmed I Foudah, Maged S Abdel-Kader, Gamal A Soliman","doi":"10.2147/JEP.S563840","DOIUrl":"10.2147/JEP.S563840","url":null,"abstract":"<p><strong>Introduction: </strong>Ischemia/reperfusion (I/R) injury is a critical complication associated with pancreatic surgery, and transplantation, which frequently develops into acute pancreatitis due to increased oxidative stress and inflammatory cascades.</p><p><strong>Aim: </strong>This study aimed to assess the protective effects of vulgarin (VLG) and epivulgarin (EPV) against pancreatic I/R- injury in rats.</p><p><strong>Methods: </strong>Rats were given oral dosages of 10 or 20 mg/kg of VLG or EPV for two days prior to I/R and 24 h after reperfusion. Pancreatic I/R was induced by occluding the pancreatic blood supply for 60 minutes followed by reperfusion. Key biochemical markers including serum amylase, lipase, tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), malondialdehyde (MDA), and glutathione peroxidase (GPx) were measured. Additionally, pancreatic tissue expression of high mobility group box 1 (HMGB1) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) was assessed via immunohistochemistry.</p><p><strong>Results: </strong>Pancreatic I/R significantly elevated serum levels of amylase (4.5-fold) and lipase (5.8-fold), oxidative stress marker; MDA (8.5-fold), as well as pro-inflammatory cytokines; TNF-α (10.4-fold) and IL-1β (5.6-fold) compared to controls (<i>p</i>≤0.01). The antioxidant GPx activity was suppressed by 84% (<i>p</i>≤0.05). Treatment with VLG and EPV dose-dependently attenuated these changes, with the highest dose of EPV reducing serum amylase by 72% and MDA by 76% compared to untreated I/R rats (<i>p</i>≤0.01). Immunohistochemical analysis revealed marked downregulation of HMGB1 and NF-κB expression in VLG and EPV-treated groups. High-dose therapies showed near normalization of numerous biochemical and molecular parameters.</p><p><strong>Conclusion: </strong>Vulgarin and epivulgarin exhibited significant protective effects against pancreatic I/R injury by reducing oxidative stress and suppressing HMGB1/NF-κB-mediated inflammatory signaling. These findings suggest the therapeutic potential of VLG and EPV in managing acute pancreatitis and related pancreatic injuries.</p>","PeriodicalId":15846,"journal":{"name":"Journal of Experimental Pharmacology","volume":"18 ","pages":"563840"},"PeriodicalIF":0.0,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13008115/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147512598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"\"Comparative Evaluation of Saussurea Lappa Root Extract Ointment and Standard Therapy on Second-Degree Burn Wound Healing in Rabbits\".","authors":"Ali A Al-Mehdar, Abdullah H Maad, Ali Salman Al-Shami, Jalal Al-Kadsi, Abdulhakim M Al-Saban, Hammood Mohammed Saad, Yaser M Al-Worafi","doi":"10.2147/JEP.S575002","DOIUrl":"10.2147/JEP.S575002","url":null,"abstract":"<p><strong>Background: </strong><i>Saussurea lappa</i> is a traditional medicinal herb valued for its anti-inflammatory, antimicrobial, and antioxidant properties. Burn wounds are highly susceptible to infection and oxidative stress, which delay healing; therefore, developing effective plant-based alternatives for burn management is of clinical importance.</p><p><strong>Objective: </strong>To investigate the phytochemical composition and healing effects of <i>Saussurea lappa</i> extract and its formulated ointment on second-degree burns in rabbit models.</p><p><strong>Methods: </strong>Roots of <i>S. lappa</i> were dried, powdered, and extracted with methanol using a Soxhlet apparatus. The extract was incorporated into ointment formulations containing 1%, 5%, and 10% concentrations. Phytochemical screening confirmed the presence of alkaloids, flavonoids, tannins, phenols, and saponins. Twenty rabbits were divided into four groups: untreated control, base ointment, standard Mebo^® ointment, and 10% <i>S. lappa</i> ointment. Second-degree burns were induced under anesthesia, and treatments were applied daily for 21 days. Wound contraction was measured using ImageJ software, and histopathological assessments were performed on days 7, 14, and 21.</p><p><strong>Results: </strong>The 10% <i>S. lappa</i> ointment demonstrated a wound closure rate of 95.1% by day 20, comparable to Mebo (96.1%) and superior to control groups. Histological analysis revealed complete re-epithelialization, dense collagen formation, and well-developed granulation tissue. The formulation remained physically stable under various storage conditions.</p><p><strong>Conclusion: </strong>The methanolic root extract of <i>Saussurea lappa</i> significantly enhanced burn wound healing in rabbits, likely due to its antioxidant, antimicrobial, and anti-inflammatory effects. The 10% <i>S. lappa</i> ointment exhibited efficacy comparable to the standard treatment, suggesting its potential as a safe, natural, and cost-effective topical therapy for burn wound management.</p>","PeriodicalId":15846,"journal":{"name":"Journal of Experimental Pharmacology","volume":"18 ","pages":"575002"},"PeriodicalIF":0.0,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13007964/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147512632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}