Journal of Experimental Pharmacology最新文献

{"title":"<i>Syzygium aromaticum</i> Attenuates Cerebellar Oxidative Stress: An Integrated in silico, in vitro, and in vivo Evaluation of Multi-Target Antioxidant Mechanisms.","authors":"Ekom Monday Etukudo, Ibe Michael Usman, Augustine Oviosun, Vivian Onyinye Ojiakor, Wusa Makena, Elna Owembabazi, Patrick Maduabuchi Aja, Emeka Anyanwu","doi":"10.2147/JEP.S630837","DOIUrl":"10.2147/JEP.S630837","url":null,"abstract":"<p><strong>Introduction: </strong>The central role of oxidative stress in neuronal injury and the progression of neurological disorders underscores the need to identify multi-target agents capable of restoring redox homeostasis. This study evaluated the antioxidant and pharmacological potential of <i>Syzygium aromaticum</i> ethyl acetate fraction (SEAF) using integrated phytochemical, computational, and experimental approaches.</p><p><strong>Methods: </strong>GC-MS was used to characterize the phytochemical composition of the ethyl acetate fraction of <i>Syzygium aromaticum</i> (SEAF). Thirteen phytometabolites with relative peak areas ≥1.0% were selected for ADME-Tox profiling and molecular docking against monoamine oxidase B (MAO-B) and 5-lipoxygenase (5-LOX). In vitro antioxidant assays, acute oral toxicity testing, and in vivo evaluation of cerebellar oxidative stress biomarkers were subsequently performed.</p><p><strong>Results: </strong>GC-MS identified eugenyl acetate (43.08%), eugenol (18.86%), and β-caryophyllene (1.64%) as the predominant metabolites. The prioritized phytometabolites exhibited favorable predicted ADME-Tox profiles and notable binding energies for MAO-B (up to -8.4 kcal/mol) and 5-LOX (up to -6.8 kcal/mol), involving key interactions with HIS367 and HIS372 in MAO-B and GLN363, TYR435, and CYS172 in 5-LOX, comparable to the standard ligands. Although ascorbic acid exhibited greater radical-scavenging and ferric-reducing potencies than SEAF in the DPPH and FRAP assays, respectively, SEAF showed higher total antioxidant activity than ascorbic acid. In vivo, SEAF administration was relatively safe up to 2000 mg/kg and significantly increased cerebellar superoxide dismutase and catalase activities while reducing malondialdehyde levels in HgCl₂-treated mice, with effects comparable to vitamin E. SEAF preserved cerebellar cortex histoarchitecture and Nissl substance in Purkinje cells against mercuric chloride-evoked oxidative damage.</p><p><strong>Conclusion: </strong><i>Syzygium aromaticum</i> exhibited potent antioxidant effects through combined radical scavenging, enzymatic enhancement, modulation of oxidative stress-related targets, and preservation of cerebellar histoarchitecture, supporting its potential as a candidate for further preclinical development.</p>","PeriodicalId":15846,"journal":{"name":"Journal of Experimental Pharmacology","volume":"18 ","pages":"630837"},"PeriodicalIF":0.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13546071/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148897455","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":"Multi-Target Anti-Steatotic Effects of Andrographolide in MAFLD: Insights from Network Pharmacology and in vitro Study.","authors":"Hiba Adnan Aziz Abu Omaima, Abbas Hasan Burhan, Wiqar Adnan Azeez Aboomaima, Ali Mahmoudi","doi":"10.2147/JEP.S625161","DOIUrl":"10.2147/JEP.S625161","url":null,"abstract":"<p><strong>Background: </strong>Metabolic Associated Fatty Liver Disease (MAFLD) is a prevalent metabolic disorder with no effective approved pharmacotherapy. Andrographolide, a bioactive diterpenoid from <i>Andrographis paniculata</i>, has anti-inflammatory and antioxidant properties, but its mechanisms in MAFLD remain unclear.</p><p><strong>Methods: </strong>An integrated computational and experimental approach was applied. Network pharmacology was used to identify shared targets between andrographolide and MAFLD using public drug-target and disease databases. Protein-protein interaction analysis, pathway enrichment, and molecular docking with hub proteins were then performed. For experimental validation, hepatic steatosis was induced in HUH7 cells with oleic acid (1 mM, 24 h) and treated with andrographolide (14 µM). Lipid accumulation was measured by Oil Red O staining, and hub gene expression was analyzed by qRT-PCR.</p><p><strong>Results: </strong>In silico analysis identified 253 shared targets, with TNF, IL6, AKT1, TP53, IL1B, JUN, VEGFA, STAT3, CASP3, and EGFR as major hubs. Enrichment analysis highlighted lipid metabolism, and inflammation signaling pathways. Molecular docking showed strong binding to AKT1 (-7.7 kcal/mol), EGFR (-7.5 kcal/mol), and STAT3 (-7.2 kcal/mol). In vitro, andrographolide reduced oleic acid-induced lipid accumulation by 38% (p = 0.0032). qRT-PCR revealed significant downregulation of AKT1 (73.5%, p = 0.0159), EGFR (72.0%, p = 0.0137), and STAT3 (53.6%, p = 0.0220) mRNA expression in andrographolide-treated steatotic hepatocytes. These transcript-level changes are correlative observations and do not confirm direct inhibition of AKT1, EGFR, or STAT3 protein activity, which requires phosphorylation-specific validation. The mRNA findings suggest a potential association between andrographolide treatment and modulation of these signaling pathways at the transcriptional level.</p><p><strong>Conclusion: </strong>Andrographolide alleviates hepatic steatosis and is associated with transcriptional modulation of AKT1, EGFR, and STAT3 mRNA. However, protein-level validation is absent, and these findings should be considered hypothesis-generating rather than mechanistic proof of target inhibition. The results support further investigation of andrographolide as a potential multi-target therapeutic candidate for MAFLD.</p>","PeriodicalId":15846,"journal":{"name":"Journal of Experimental Pharmacology","volume":"18 ","pages":"625161"},"PeriodicalIF":0.0,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13505541/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148818572","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":"Beyond Antioxidant Activity: Redox-Inflammatory Network Modulation as a Framework for the Multi-Organ Pharmacology of <i>Moringa oleifera</i>.","authors":"Marie Louise Sezerano, Emery Niyonkuru","doi":"10.2147/JEP.S626205","DOIUrl":"https://doi.org/10.2147/JEP.S626205","url":null,"abstract":"<p><p><i>Moringa oleifera</i> (<i>M. oleifera</i>) is a multipurpose medicinal plant with over 160 catalogued bioactive compounds and reported activity across metabolic, inflammatory, infectious, and neoplastic diseases, yet its pharmacology has remained mechanistically fragmented, limiting translational interpretation. In this narrative review, we synthesize evidence from in silico analyses, cellular systems, animal models, and human studies to evaluate whether structurally diverse phytochemicals-including glucosinolates, isothiocyanates, flavonoids, and phenolic acids-converge on interconnected redox and inflammatory regulatory networks centered on NF-κB and Nrf2/Keap1 signaling, offering a plausible systems-level explanation for their coordinated effects on immune function, oxidative stress, and metabolic homeostasis. Preclinical evidence for this convergence is extensive and consistent, with documented effects on inflammatory signaling, oxidative stress regulation, and cell fate determination relevant to hepatoprotection, cardiometabolic regulation, neuroprotection, and tumor biology. Clinical evidence, by contrast, is considerably more limited: available trials report modest and inconsistent benefits for glycemic control, cardiovascular parameters, and immune-related outcomes, constrained by heterogeneous phytochemical composition, minimal pharmacokinetic characterization, and variable extraction and formulation methods. Safety data indicate general tolerability at commonly used doses, though reproductive effects and herb-drug interactions remain incompletely defined. Collectively, current evidence positions <i>M. oleifera</i> as a mechanistically plausible, multi-target modulator of redox and inflammatory networks rather than a validated therapeutic agent; realizing its clinical potential will require standardized preparations, rigorous pharmacokinetic profiling, biomarker-anchored trial design, and evaluation in well-powered controlled trials.</p>","PeriodicalId":15846,"journal":{"name":"Journal of Experimental Pharmacology","volume":"18 ","pages":"626205"},"PeriodicalIF":0.0,"publicationDate":"2026-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13488686/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148793899","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":"Lipid Metabolism Modulation by a Flavonoid-Standardized <i>Citrus Bergamia</i> Extract in an Asian Population: Findings From a Double-Blind, Placebo-Controlled Clinical Trial.","authors":"Xiaoyan Yu, Fabio Amone, Vincenzo Zaccaria, Alessandro Di Minno, Maria Daglia, Violetta Insolia, Vincenzo Nobile","doi":"10.2147/JEP.S614937","DOIUrl":"10.2147/JEP.S614937","url":null,"abstract":"<p><p>Genetic factors, dietary habits, and lifestyle may influence individual responses to supplementation, including the bergamot flavanones naringin and naringenin, which are implicated in lipid modulation. The aim of this double-blind, placebo-controlled clinical trial (RCT) is to assess the effects of the supplementation for four months of a standardised bergamot extract at the dosage of 375 mg/day, providing 150 mg/day of flavonoids, on lipid parameters of 108 East Asian adults with LDL-Cholesterol (LDL-C) 100-159 mg/day, since to date, the RCTs have been conducted on Caucasian subjects only. After 4 months, total Cholesterol and LDL-C decreased (-7.3% and -7.0%) with no clinically relevant safety changes regarding hepatic/renal biochemistry, weight, and blood pressure.</p>","PeriodicalId":15846,"journal":{"name":"Journal of Experimental Pharmacology","volume":"18 ","pages":"614937"},"PeriodicalIF":0.0,"publicationDate":"2026-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13464414/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148720894","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":"Simvastatin Mitigates Kidney Injury via Inhibition of the TNF-α/α-SMA Signaling Pathway in a Subtotal Nephrectomy Model.","authors":"Putu Nita Cahyawati, Erly Sintya, Anak Agung Sri Agung Aryastuti, Asri Lestarini, Pande Ayu Naya Kasih Permatananda","doi":"10.2147/JEP.S612787","DOIUrl":"10.2147/JEP.S612787","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to investigate the preventive effect of simvastatin on the subtotal nephrectomy model by analysing key mediators of inflammation and fibrosis.</p><p><strong>Methods: </strong>A total of 30 male Swiss mice were used in this study. The animals were divided into five groups (six/group): the sham group (Sham), the nephrectomy group (Neph), and three simvastatin groups (Simv) with a stepwise dose of simvastatin (5, 10, or 20 mg/kgBW). Kidney function was assessed by measuring serum creatinine, blood urea nitrogen (BUN), and proteinuria. Interstitial fibrosis was evaluated by Sirius red staining, α-SMA expression was evaluated by immunohistochemistry, and TNF-α expression was evaluated by real-time PCR.</p><p><strong>Results: </strong>Subtotal nephrectomy significantly impaired renal function, increased interstitial fibrosis, and upregulated TNF-α and α-SMA expression. Simvastatin treatment dose-dependently reduced serum creatinine and proteinuria, although the reduction in BUN was not significantly different from the Neph group. Simvastatin also significantly attenuated interstitial fibrosis (8.62±2.43 in Simv5 group, 4.15±1.67 in Simv10, and 2.62±0.63 in Simv20 groups), decreased the expression of TNF-α (0.42±0.27 in Simv5, 0.39±0.18 in Simv10, and 0.23±0.21 in Simv20) and α-SMA (3.85±0.97 in Simv5, 2.74±0.61 in Simv10, and 1.59±0.45 in Simv20 groups) in dose-dependent manner, compared with the Neph group (all p < 0.05). Path analysis demonstrated that TNF-α indirectly contributed to renal fibrosis by promoting α-SMA expression, whereas α-SMA had a significant direct effect on interstitial fibrosis (p=0.038).</p><p><strong>Conclusion: </strong>This study found that the renoprotective effect of simvastatin in a subtotal nephrectomy model may be mediated by inhibition of the TNF-α/α-SMA signalling pathway, with α-SMA acting as a key mediator linking inflammation to renal fibrosis.</p>","PeriodicalId":15846,"journal":{"name":"Journal of Experimental Pharmacology","volume":"18 ","pages":"612787"},"PeriodicalIF":0.0,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13453420/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148701438","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":"Toxicological Evaluation of the Liver and Kidneys of Rats Exposed to <i>Myrothamnus Flabellifolius</i> Crude Aqueous Extract.","authors":"Trust Nyirenda, Elliot Nyagumbo, Samson Chengetanai, Fabian Maunganidze, Ashwell Rungano Ndhlala, Jacob Mufunda, Michael Bhebhe","doi":"10.2147/JEP.S608152","DOIUrl":"10.2147/JEP.S608152","url":null,"abstract":"<p><strong>Background: </strong><i>Myrothamnus flabellifolius</i> (<i>M. flabellifolius</i>) herb is widely used across Southern Africa, often with poorly defined or unrestricted dosing and limited safety considerations across its diverse ethnomedicinal applications.</p><p><strong>Objective: </strong>This study investigated the effects of <i>M. flabellifolius</i> crude aqueous extract on rat liver and kidneys.</p><p><strong>Methods: </strong><i>M. flabellifolius</i> crude aqueous extract was screened for its bioactive components. Safety was assessed using single and 28-day repeated oral dose toxicity studies. In the former, male and female Sprague-Dawley rats (n = 12 per group; 6 per sex) received <i>M. flabellifolius</i> stem and leaf crude aqueous extract at doses of 0, 500, 1000, 2000, 5000 and 10000 mg/kg and were observed for 14 days for clinical signs, body weight changes, and mortality. Based on the absence of clinical signs and lethality, the same dose range was applied in the 28-day repeated oral dose toxicity study in which female rats (n = 6 per group) received treatment. At the end of the study, blood samples were collected for biochemical analysis, while liver and kidney samples were harvested for relative organ weight and histopathological examination.</p><p><strong>Results: </strong>Phytochemical screening confirmed the presence of tannins, flavonoids, coumarins and terpenoids in the extract. Treatment in both single and 28-day repeated oral dose toxicity studies showed no clinical signs or mortality; body/relative organ weights changes were non-significant (<i>p</i> > 0.05). The oral no-observed-adverse-effect level (NOAEL) was 10000 mg/kg in both sexes. Biochemical indices showed non-significant changes (<i>p</i> > 0.05), whereas liver and kidney histoarchitecture remained unremarkable.</p><p><strong>Conclusion: </strong><i>M. flabellifolius</i> crude aqueous extracts exhibited a wide safety margin with no detectable hepatorenal toxicity. Its confirmed bioactive phytochemicals valorizes ethnomedicinal use.</p>","PeriodicalId":15846,"journal":{"name":"Journal of Experimental Pharmacology","volume":"18 ","pages":"608152"},"PeriodicalIF":0.0,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13381113/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148604003","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":"Exploratory Review on Male Fertility Potential of Acetyl-Eugenol: Mechanistic Insights, Experimental Evidence, and Therapeutic Prospects.","authors":"Ismahil Adekunle Adeniyi, Umar Uthman Shehu, Emmanuel Orire Ikuomola, Ekementeabasi Aniebo Umoh, Ibe Michael Usman, Daniel Udofia Owu, Joshua Ojodale Aruwa","doi":"10.2147/JEP.S614711","DOIUrl":"10.2147/JEP.S614711","url":null,"abstract":"<p><p>Male infertility contributes to nearly half of all infertility cases worldwide and is closely linked to oxidative stress, inflammation, endocrine imbalance, and environmental toxicant exposure, all of which impair spermatogenesis and sperm function. Interest in naturally derived bioactive compounds has increased due to their potential multitarget therapeutic effects and relatively favorable safety profiles. Acetyl-eugenol, a structural derivative of eugenol found in Syzygium aromaticum and other aromatic plants, has demonstrated antioxidant, anti-inflammatory, and cytoprotective activities in experimental studies. This review critically evaluates the potential role of acetyl-eugenol in male reproductive health, focusing on its pharmacological properties and proposed mechanisms of action. Available preclinical evidence suggests that acetyl-eugenol may reduce oxidative stress by scavenging reactive oxygen species, enhancing endogenous antioxidant defenses, and modulating inflammatory pathways such as NF-κB signaling. It may also contribute to the preservation of testicular structure and function, including protection of Sertoli and Leydig cells. However, current evidence remains limited and is derived predominantly from in vitro and animal studies, with very limited direct evidence in humans. Many proposed reproductive benefits are inferred from studies involving eugenol or related compounds rather than acetyl-eugenol specifically. In addition, conflicting findings regarding dose-dependent toxicity, insufficient pharmacokinetic data, and the absence of standardized clinical studies limit definitive conclusions regarding efficacy and safety. Overall, acetyl-eugenol represents a promising candidate for mitigating oxidative stress-associated male reproductive dysfunction, but its therapeutic potential remains preliminary. Further well-designed experimental and clinical studies are necessary to clarify its mechanisms, safety profile, and translational relevance in male infertility management.</p>","PeriodicalId":15846,"journal":{"name":"Journal of Experimental Pharmacology","volume":"18 ","pages":"614711"},"PeriodicalIF":0.0,"publicationDate":"2026-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13283397/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148301885","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":"High-Concentration Cyanidin-3-O-Glucoside Attenuates Palmitic Acid-Induced Oxidative Stress via ROS Suppression in Pancreatic β-Cells.","authors":"Sasirin Chitwattananont, Sutthipong Sawasvirojwong, Chatchai Muanprasat","doi":"10.2147/JEP.S562755","DOIUrl":"10.2147/JEP.S562755","url":null,"abstract":"<p><strong>Background: </strong>Type 2 diabetes mellitus (T2DM) is characterized by progressive β-cell dysfunction driven in part by palmitic acid (PA)-induced lipotoxicity. Cyanidin-3-O-glucoside (C3G) possesses antioxidant properties, but its temporal and mechanistic effects at higher concentrations remain poorly defined.</p><p><strong>Objective: </strong>This study aimed to investigate the continuous effects of high‑concentration of C3G on PA‑induced β‑cell apoptosis, with emphasis on time‑dependent efficacy and underlying antioxidant mechanisms.</p><p><strong>Methods: </strong>MIN6 cells were treated with PA (500 µM) in the presence or absence of C3G (500 µM). Cell viability was assessed by MTT assay, apoptosis by flow cytometry and cell death assay, oxidative stress by DCFDA and DPPH assays, and ER-stress related C/EBP homologous protein (CHOP) and apoptotic cleaved caspase-3 expression by Western blot analysis.</p><p><strong>Results: </strong>PA (500 µM) significantly reduced MIN6 cell viability, whereas continuous exposure to C3G (500 µM) restored viability, corresponding to a 40.9% increase (p < 0.001) compared with PA treatment alone. Flow cytometry showed that PA reduced live cells from 78.6% to 41.0% and increased early and late apoptotic populations to 27.7% and 28.2%, respectively, whereas C3G co-treatment reduced apoptosis to 17.7%. Consistently, cell death assays confirmed that C3G lowered apoptotic cells from 30.7% to 5.0% (p < 0.001 vs PA-treated groups) and restored viability to 93.1%, comparable to vehicle controls. Reactive oxygen species (ROS) assays, including DCFDA and DPPH, further demonstrated that C3G reduced PA‑induced ROS by 26.5% (p < 0.01 vs PA alone), consistent with free radical‑scavenging activity. Western blot analyses revealed that PA markedly upregulated CHOP and cleaved caspase‑3, which was suppressed by co‑treatment with C3G, confirming the attenuation by C3G of ER stress‑mediated apoptotic signaling. These findings imply that C3G rapidly counteracts oxidative stress-induced apoptosis.</p><p><strong>Conclusion: </strong>High-concentration C3G mitigates PA-induced oxidative stress and ER stress-associated apoptosis in β-cells, supporting its potential as a therapeutic agent for T2DM.</p>","PeriodicalId":15846,"journal":{"name":"Journal of Experimental Pharmacology","volume":"18 ","pages":"562755"},"PeriodicalIF":0.0,"publicationDate":"2026-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13217715/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148138484","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":"Hesperidin Mitigates Bisphenol-A Induced Oxidative Stress, Endocrine Disruption and Testicular Damage in Adult Male Wistar Rats.","authors":"Augustine Oviosun, Ezinne Chidinma Oviosun, Ibe Micheal Usman, Chinyere Nkemjika Anyanwu, Vivian Onyinye Ojiakor, Emmanuel Anayochukwu Esom, Emeka Godson Anyanwu","doi":"10.2147/JEP.S595476","DOIUrl":"10.2147/JEP.S595476","url":null,"abstract":"<p><strong>Introduction: </strong>Bisphenol A (BPA), a well-known endocrine disruptor, is newly emerging as causing male infertility by endocrine disturbances, induction of oxidative stress and testicular toxicity. This study investigates the protective role of hesperidin against BPA-induced testicular toxicity in male Wistar rats.</p><p><strong>Methodology: </strong>The rats were divided into six groups (n=7): control (normal saline); BPA-only (50 mg/kg); hesperidin-only at 50 mg/kg and 100 mg/kg; and two pre-treated groups receiving hesperidin (50 and 100 mg/kg) followed by BPA (50 mg/kg). All treatments were administered orally for 8 weeks. Post-treatment analyses included testicular weight, volume, and diameter measurements; serum testosterone, FSH, and LH levels; oxidative stress markers (MDA, SOD, CAT, GPx, and GSH); and histological and morphometric evaluation of the testis.</p><p><strong>Result and discussion: </strong>BPA exposure significantly reduced testicular dimensions, decreased serum testosterone, FSH, and LH. Histopathological examination revealed degeneration of seminiferous tubules, germ-cell depletion, reduced counts of spermatogonia, spermatocytes, spermatids, Sertoli and Leydig cells. BPA significantly induced oxidative stress, evidenced by increased MDA and decreased SOD, CAT, GPx, and GSH. Hesperidin significantly mitigated these effects by restoring testicular morphology, hormonal profiles, enhancing oxidative stress markers, improving histology and cell populations.</p><p><strong>Conclusion: </strong>Hesperidin demonstrates protective properties against BPA-induced testicular and endocrine toxicity in rats, likely as a result of its antioxidant properties.</p>","PeriodicalId":15846,"journal":{"name":"Journal of Experimental Pharmacology","volume":"18 ","pages":"595476"},"PeriodicalIF":0.0,"publicationDate":"2026-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13207936/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148042642","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":"Sub-Acute Toxicity Evaluation and Antiurolithiatic Activity of <i>Tribulus terrestris</i> Ethanol Extract in Rats.","authors":"Ahmed Al-Mohamadi, Imadeldin M Taj Eldin, Doa'a Ibrahim, Ameen M Alwossabi","doi":"10.2147/JEP.S609388","DOIUrl":"10.2147/JEP.S609388","url":null,"abstract":"<p><strong>Background: </strong><i>Tribulus terrestris</i> (<i>T. terrestris</i>) is traditionally used in the management of urinary disorders; however, evidence regarding its safety upon repeated administration and its antiurolithiatic efficacy remains limited. This study aimed to evaluate both the sub-acute toxicity and antiurolithiatic potential of the ethanol extract of <i>T. terrestris</i> (EETT) in experimental rats.</p><p><strong>Methods: </strong>Sub-acute toxicity was assessed in Wistar rats (n = 30; 5 males and 5 females per group) following 28-day repeated oral administration of EETT (500 and 1000 mg/kg). Antiurolithiatic activity was evaluated in an ethylene glycol/ammonium chloride-induced nephrolithiasis model (n = 36; 6 rats per group), where EETT (150, 300, and 450 mg/kg, intraperitoneally) was administered and compared with potassium citrate. Hematological, biochemical, and histopathological parameters were analyzed.</p><p><strong>Results: </strong>EETT exhibited no mortality or treatment-related toxicity, with no significant alterations in body weight, relative organ weights, hematological indices, or serum biochemical parameters. Histological examination confirmed normal tissue architecture in treated animals. In the nephrolithiasis model, EETT significantly (<i>P</i> < 0.05) reduced elevated serum creatinine, urea, calcium, and potassium levels in a dose-dependent manner. Histopathological findings revealed decreased calcium oxalate crystal deposition and preservation of renal structure, particularly at higher doses, with effects comparable to potassium citrate.</p><p><strong>Conclusion: </strong>The findings demonstrate that EETT possesses a favorable safety profile alongside significant antiurolithiatic activity. This dual evidence supports its potential as a therapeutic candidate for nephrolithiasis and warrants further pharmacological and clinical investigation.</p>","PeriodicalId":15846,"journal":{"name":"Journal of Experimental Pharmacology","volume":"18 ","pages":"609388"},"PeriodicalIF":0.0,"publicationDate":"2026-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13182832/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147973080","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}