Steroids最新文献

{"title":"Vitamin D potentiation of metformin hepatoprotective activities: Concurrent targeting of carbohydrate enzymatic pathways and PCSK9/AGEs-regulated oxidative stress mechanisms in type 2 diabetic male Wistar rats","authors":"Halimat Amin Abdulrahim ,&nbsp;Adeyemi Fatai Odetayo ,&nbsp;Muhammad Bashir Amosa ,&nbsp;John Oluwapelumi Olumoye ,&nbsp;Wasiu Abiodun Hassan ,&nbsp;Ivan Ayomide Ebadan ,&nbsp;Kehinde Yusuf Yusuf ,&nbsp;Gloria Toluwase Abodunrin ,&nbsp;Samuel Oluwaseyi Adefolarin ,&nbsp;Ayodeji Johnson Ajibare ,&nbsp;Temilade Olatunji ,&nbsp;Tahir Abdussalam ,&nbsp;Kazeem Bidemi Okesina ,&nbsp;Luqman Aribidesi Olayaki","doi":"10.1016/j.steroids.2025.109685","DOIUrl":"10.1016/j.steroids.2025.109685","url":null,"abstract":"<div><h3>Background</h3><div>Emerging evidence indicates that metformin-based combination therapy may offer better glycemic control and improved tolerability compared to diabetes monotherapy. Building on this, vitamin D was considered a potential adjunct to metformin for managing type 2 diabetes. Although vitamin D is primarily recognized for its role in calcium regulation, it also appears to influence glucose metabolism and other non-skeletal functions. Therefore, this study was designed to evaluate the hepatoprotective effects of vitamin D and metformin in diabetic rats.</div></div><div><h3>Methodology</h3><div>Thirty (30) male Wistar rats were randomized into five treatment groups as follows: control, diabetes (DM) untreated, DM treated with vitamin D (25 µg/kg), DM treated with metformin (180 mg/kg), and DM treated with both vitamin D (25 µg/kg) and metformin (180 mg/kg). All treatments were via the oral route and lasted for 28 days.</div></div><div><h3>Results</h3><div>Vitamin D and/or metformin improved glucose and lipid imbalances caused by diabetes. These benefits were linked to enhanced activity of key liver enzymes involved in glucose metabolism, including hexokinase, phosphofructokinase, pyruvate kinase, glucose-6-phosphate dehydrogenase, G-6-phosphatase, and lactate dehydrogenase. Additionally, treatment with vitamin D and/or metformin counteracted diabetes-induced increases in pro-oxidant levels, restored both enzymatic and non-enzymatic antioxidant defenses, and reduced inflammation. This oxido-inflammatory response appeared to be connected to oxidative signaling mediated by proprotein convertase subtilisin/kexin type 9 (PCSK9), highlighting a potential mechanism underlying the protective effects of these therapies.</div></div><div><h3>Conclusion</h3><div>Vitamin D enhanced the antidiabetic effects of metformin by further improving the activity of carbohydrate-metabolizing enzymes and modulating PCSK9-mediated oxidative signaling. This suggests that vitamin D can boost metformin’s efficacy in regulating glucose-lipid metabolism and reducing oxidative stress in diabetes.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"223 ","pages":"Article 109685"},"PeriodicalIF":2.3,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145024148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction notice to \"Design, synthesis and biological evaluation of betulinic acid derivatives as potential inhibitors of 3CL-protease of SARS-CoV-2\" [STE 202 (2024) 109351].","authors":"Yaowen Liu, Tianqing Nie, Jinjun Hou, Huali Long, Zijia Zhang, Min Lei, Yechun Xu, Wanying Wu","doi":"10.1016/j.steroids.2025.109652","DOIUrl":"10.1016/j.steroids.2025.109652","url":null,"abstract":"","PeriodicalId":21997,"journal":{"name":"Steroids","volume":" ","pages":"109652"},"PeriodicalIF":2.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144660227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to \"Advances in the understanding of androgen receptor structure and function and in the development of next-generation AR-targeted therapeutics\". [Steroids 210 (2024) 109486].","authors":"Wendy Effah, Marjana Khalil, Dong-Jin Hwang, Duane D Miller, Ramesh Narayanan","doi":"10.1016/j.steroids.2025.109661","DOIUrl":"10.1016/j.steroids.2025.109661","url":null,"abstract":"","PeriodicalId":21997,"journal":{"name":"Steroids","volume":" ","pages":"109661"},"PeriodicalIF":2.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144718661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to \"Sonogashira coupling-based synthesis and in vitro cytotoxic evaluation of C-2 alkynyl derivatives of withaferin A\" [Steroids 212 (2024) 109526].","authors":"Shabir Ahmad Mir, Sameera Firdous, Mir Shahid Maqbool, Gulzar Hussain, Mohammad Yaqoob Bhat, Fayaz A Malik, Syed Khalid Yousuf","doi":"10.1016/j.steroids.2025.109660","DOIUrl":"10.1016/j.steroids.2025.109660","url":null,"abstract":"","PeriodicalId":21997,"journal":{"name":"Steroids","volume":" ","pages":"109660"},"PeriodicalIF":2.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144699561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Are dexamethasone implants a safe and effective breakthrough in uveitis treatment? A systematic review and meta-analysis","authors":"Kai-Yang Chen ,&nbsp;Hoi-Chun Chan ,&nbsp;Chi-Ming Chan","doi":"10.1016/j.steroids.2025.109675","DOIUrl":"10.1016/j.steroids.2025.109675","url":null,"abstract":"<div><h3>Background</h3><div>Uveitis encompasses inflammatory conditions affecting the iris, ciliary body, and choroid. Its management relied on corticosteroids, immunosuppressive agents, and, more recently, biologic therapies. The development of sustained-release intravitreal corticosteroid delivery systems, like dexamethasone intravitreal implants, has revolutionized the treatment of posterior uveitis.</div></div><div><h3>Objectives</h3><div>To critically appraise the evidence of the safety and efficacy of dexamethasone implants in managing Uveitis.</div></div><div><h3>Methods</h3><div>A systematic review of the safety and efficacy of dexamethasone implants in managing Uveitis was conducted. A comprehensive and systematic electronic database search was conducted in Scopus, PubMed, Cochrane Library, ScienceDirect, Google Scholar, and Wiley Online Library for studies published from their inception to the present date. Modified PICOS criteria were used to screen and select the eligible studies from the potential articles retrieved from the database search. Studies were considered if they included patients with uveitis. A comprehensive risk of bias assessment was conducted using the Newcastle Ottawa Scale (NOS) for cohort studies, the Risk of Bias in Non-Randomized Studies (ROBINS-I) tool for non-randomized trials, the risk of bias visualization tool (ROB 2.0) tool for RCTs, and the National Institutes of Health (NIH) quality assessment tool for Interventional case-series. Data were then procedurally extracted and analyzed.</div></div><div><h3>Results</h3><div>The study selection process identified 29 studies, including 1,086 eyes. Dexamethasone implant significantly reduced central retinal/macular thickness at all time points: 150.4 μm at 1 month (p &lt; 0.001), 200.8 μm at 3 months (p &lt; 0.001), and 225.5 μm at 6–24 months (p &lt; 0.001). Inflammation control was achieved in 80.8 % of cases (p &lt; 0.001). Visual acuity improvements were modest at 6 months (p = 0.078) but significant long-term (p &lt; 0.001). However, the dexamethasone implant resulted in cataract formation (p = 0.010), with a recurrence rate of 0.501 (p = 0.968).</div></div><div><h3>Conclusion</h3><div>Dexamethasone implants offer clinically significant benefits, resulting in substantial reductions in central retinal thickness, improvements in visual acuity, and effective control of inflammation in patients with uveitis.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"223 ","pages":"Article 109675"},"PeriodicalIF":2.3,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144883756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Salivary 1,25(OH)2D3 & cortisol as biomarkers of anxiety, depression, and periodontitis: a comparative cross-sectional study","authors":"Sara Rafique ,&nbsp;Sadaf Ahmed ,&nbsp;Shamoon Noushad","doi":"10.1016/j.steroids.2025.109674","DOIUrl":"10.1016/j.steroids.2025.109674","url":null,"abstract":"<div><h3>Purpose</h3><div>This study examines the correlation between salivary levels of 1,25(OH)₂D₃ (calcitriol) and cortisol in healthy individuals and patients with anxiety and depression, both with and without periodontitis. The innovative evaluation of salivary 1,25(OH)₂D₃, which is impervious to seasonal fluctuations, could facilitate the early identification and prevention of psychiatric and oral conditions by utilizing salivary biomarkers derived from the oral environment.</div></div><div><h3>Methods</h3><div>This comparative cross-sectional study involved 152 participants from the Department of Periodontology at Jinnah Medical and Dental College, Karachi, Pakistan. Anxiety and depression were evaluated with the Aga Khan University Anxiety and Depression Scale, while periodontitis was assessed via clinical attachment loss and probing pocket depth. Salivary 1,25(OH)₂D₃ and cortisol levels were quantified with an Enzyme-Linked-Immunosorbent-Assay (ELISA). The statistical evaluation encompassed one-way ANOVA, Kruskal-Wallis tests, post hoc comparisons, and correlation and regression analyses.</div></div><div><h3>Results</h3><div>The mean 1,25(OH)₂D₃ levels were significantly lower in patients with anxiety and depression (AD) and those with both anxiety, depression, and periodontitis (ADP) (130.78 ± 8.52 pmol/L and 33.44 ± 26.17 pmol/L) compared to healthy controls (HC) (220.92 ± 11.63 pmol/L, <em>p</em> &lt; 0.05), demonstrating a strong negative correlation (AD: <em>r</em> = −0.936, <em>p</em> &lt; 0.05, ADP: <em>r</em> = −0.932, <em>p</em> &lt; 0.05). Conversely, cortisol levels were significantly higher in case groups (AD: 6.41 ± 0.54 nmol/L, ADP: 7.8 ± 1.09 nmol/L) than in healthy controls (4.22 ± 0.61 nmol/L, <em>p</em> &lt; 0.05), showing a strong positive correlation (AD: <em>r</em> = 0.922, <em>p</em> &lt; 0.05, ADP: r = 0.496, p &lt; 0.002). Regression analysis identified cortisol and 1,25(OH)₂D₃ as significant predictors of anxiety, depression, and periodontitis (<em>p</em> &lt; 0.05).</div></div><div><h3>Conclusion</h3><div>Salivary 1,25(OH)₂D₃ and cortisol serve as potential non-invasive markers for the early detection of anxiety, depression, and periodontitis.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"222 ","pages":"Article 109674"},"PeriodicalIF":2.3,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144859620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biotransformation of 22-hydroxy-23,24-bisnorchol-4-ene-3-one by Gibberella fujikuroi CICC 40272-A to discover novel C22 steroid derivatives","authors":"Ran He ,&nbsp;Wan Cui ,&nbsp;Ming Song ,&nbsp;Yongbo Song ,&nbsp;Xueqi Guo ,&nbsp;Xiaofei Liu ,&nbsp;Ying Cui ,&nbsp;Xinyu Zheng ,&nbsp;Xinyue Wang ,&nbsp;Yingchen Zhou ,&nbsp;Jiayi Han ,&nbsp;Guogang Zhang ,&nbsp;Fuju Wang ,&nbsp;Weizhuo Xu","doi":"10.1016/j.steroids.2025.109673","DOIUrl":"10.1016/j.steroids.2025.109673","url":null,"abstract":"<div><div>The microbial transformation of steroids offers a sustainable and selective approach to synthesize pharmacologically valuable derivatives. This study investigated the biotransformation of 22-hydroxy-23,24-bisnorchol-4-ene-3-one (4-HBC) by <em>Gibberella fujikuroi</em> CICC 40272-A to produce novel C22 steroid derivatives. Among seven screened fungal strains, <em>G. fujikuroi</em> exhibited superior regio- and stereo-selective hydroxylation activity. High performance liquid chromatography (HPLC) and thin layer chromatography (TLC) analyses revealed the formation of a major metabolite, identified as 7β,11α-dihydroxy-23,24-bisnorchol-4-ene-3-one (7β,11α-diOH-HBC) via NMR and MS, confirming the introduction of two hydroxyl groups at positions 7β and 11α. Optimization of fermentation conditions through single-factor and orthogonal experiments demonstrated that a medium containing 50 g/L galactose, 10 g/L NaNO₃, and pH 5.5, combined with 3 % inoculum, 1 g/L 4-HBC, and 96 h transformation time, achieved a maximum transformation rate of 65.88 %. Methanol (2 % v/v) was identified as the optimal cosolvent, enhancing substrate solubility while minimizing cytotoxicity. The study highlights <em>G. fujikuroi</em> CICC 40272-A as an effective biocatalyst for stereoselective steroid hydroxylation, providing an efficient and eco-friendly strategy to produce 7β,11α-diOH-HBC. These findings advance the application of microbial systems in pharmaceutical synthesis, emphasizing their potential to replace energy-intensive chemical processes in steroid derivative production.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"222 ","pages":"Article 109673"},"PeriodicalIF":2.3,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144812334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective effects of coenzyme Q10 against trihexyphenidyl-induced testicular oxidative damage: modulation of antioxidant enzymes, inflammatory markers, hormonal and steroidogenic pathways in rats","authors":"Lateef Olabisi Okeleji ,&nbsp;Moses Agbomhere Hamed ,&nbsp;Ayoola Isaac Jegede ,&nbsp;Mega Obukohwo Oyovwi ,&nbsp;Ayodeji Folorunsho Ajayi","doi":"10.1016/j.steroids.2025.109664","DOIUrl":"10.1016/j.steroids.2025.109664","url":null,"abstract":"<div><h3>Background</h3><div>Trihexyphenidyl is clinically effective for Parkinson’s disease and antipsychotic-induced extrapyramidal symptoms. However, its abuse potential and adverse effects on male reproductive health are significant concerns. Coenzyme Q10 (CoQ10), a potent antioxidant, is known to protect reproductive tissues from injury. This study investigated the protective effects of CoQ10 against trihexyphenidyl-induced testicular damage in male Wistar rats.</div></div><div><h3>Methods</h3><div>Twenty male Wistar rats (160–180 g) were randomly allocated into four groups (n = 5/group): control (Tween 80), trihexyphenidyl (1.5 mg/kg), CoQ10 (10 mg/kg), and trihexyphenidyl + CoQ10. Treatments were administered orally for 60 days. Testicular tissue biomarkers and serum hormone levels were analyzed.</div></div><div><h3>Results</h3><div>Trihexyphenidyl treatment significantly reduced relative paired epididymal and testicular weights, along with serum levels of Follicle Stimulating Hormone (FSH), Luteinizing Hormone, and Testosterone. It also decreased the activity of steroidogenic enzymes (3β-HSD, 17β-HSD) and antioxidant enzymes (SOD, GPx, Catalase) compared to controls. Conversely, trihexyphenidyl increased markers of oxidative stress (MDA, 8-OHdG), inflammation (TNF-α, MPO, IL-1β), apoptosis (caspase-3), and altered lactate/pyruvate levels, accompanied by significant histopathological damage. Co-administration of CoQ10 with trihexyphenidyl significantly attenuated these detrimental effects, restoring biochemical parameters and improving testicular architecture.</div></div><div><h3>Conclusion</h3><div>Coenzyme Q10 effectively protects against trihexyphenidyl-induced testicular toxicity by mitigating oxidative stress, inflammation, and apoptosis, while preserving steroidogenic enzyme activity and hormonal balance. These findings highlight CoQ10’s potential as a therapeutic agent to counteract the reproductive side effects of trihexyphenidyl.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"222 ","pages":"Article 109664"},"PeriodicalIF":2.3,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144749404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endocannabinoid and steroid hormone levels during and after pregnancy in fingernail samples from mothers and their infants","authors":"Clarissa Daniela Voegel ,&nbsp;Matilde Murari ,&nbsp;Pearl La Marca-Ghaemmaghami ,&nbsp;Thomas Kraemer ,&nbsp;Tina Maria Binz ,&nbsp;Tanja Restin","doi":"10.1016/j.steroids.2025.109663","DOIUrl":"10.1016/j.steroids.2025.109663","url":null,"abstract":"<div><div>Stress exposure and protective biological factors such as steroid hormones and endocannabinoids (eCBs) play a crucial role in pregnancy and birth outcomes. The keratinized nail matrix is a convenient medium for long-term hormone monitoring. However, data on changes in steroid hormone and eCB concentrations in human fingernails during pregnancy and the postpartum period remain limited. The aim of this longitudinal pilot study is to explore such changes in the fingernails of pregnant women and their infants. The study also seeks to identify optimal sampling time points for future research and to explore the feasibility of fingernail analysis as a non-invasive sampling method in perinatal stress research. A pilot study was conducted with five mothers and four corresponding infants. Nail samples were collected repeatedly at several time points during pregnancy and postpartum, while the newborns’ first six nail clippings were analyzed. Using liquid chromatography-tandem mass spectrometry (LC-MS/MS), five steroid hormones (cortisone, cortisol, androstenedione, testosterone, progesterone) and four eCBs (2-arachidonylglycerol, (2-AG), anandamide (AEA), oleoylethanolamide (OEA), palmitoylethanolamide (PEA)) were quantified. Progesterone levels in maternal nail samples increased during pregnancy, peaking around the time of delivery, while cortisol and cortisone levels started to increase in the third trimester. In contrast, eCB concentrations were lower in the third trimester compared to the second. These findings encourage further research on the use of nail samples as a promising tool for the retrospective assessment of hormonal changes and stress markers during pregnancy and the postpartum period.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"222 ","pages":"Article 109663"},"PeriodicalIF":2.3,"publicationDate":"2025-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144745117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Withaferin-A kills neuronal cells: An off-putting facet of Withania somnifera as a neuroprotectant","authors":"Nawab John Dar ,&nbsp;Bisma Gull ,&nbsp;Abid Hamid ,&nbsp;Zabeer Ahmed ,&nbsp;Muzamil Ahmad","doi":"10.1016/j.steroids.2025.109662","DOIUrl":"10.1016/j.steroids.2025.109662","url":null,"abstract":"<div><div><em>Withania somnifera</em>, commonly known as Ashwagandha, is widely utilized for treating neurological disorders in both traditional and modern medicine. While its neuroprotective effects are linked to several bioactive compounds, the individual safety profiles and potential cytotoxic effects of these compounds remain poorly understood. Previous studies from our research group have identified Withanone and Withanolide-A as neuroprotective agents. This study specifically evaluated the neurotoxic potential of Withaferin-A (WFA), a key steroidal lactone found in <em>Withania somnifera</em>, on differentiated SH-SY5Y cells. For six days, the SH-SY5Y cells were differentiated using 10 µM retinoic acid (RA). The neuronal phenotype was confirmed through morphological changes and increased expression of NeuN. Cytotoxicity assays demonstrated that WFA induces potent, dose-dependent cytotoxicity, resulting in approximately 50 %, 80 %, and 90 % cell death at concentrations of 0.6 µM, 1.2 µM, and 2.4 µM, respectively (<em>p &lt; 0.001</em>). Treatment with WFA at 1.2 µM significantly increased both intracellular and mitochondrial reactive oxygen species (ROS), as shown by fluorescence imaging (<em>p &lt; 0.001</em>). The loss of mitochondrial membrane potential was confirmed by JC-1 staining, indicating mitochondrial dysfunction. Western blot analysis indicated a dose-dependent increase in pro-apoptotic proteins Bax and Bid (<em>p &lt; 0.05</em> at 1.2 µM), an elevated Bax/Bcl-2 ratio (<em>p &lt; 0.001</em> at 1.2 µM), and enhanced activation of caspase-3, caspase-9, and cleavage of PARP-1 (<em>p &lt; 0.001</em> at 1.2 µM), indicating activation of the intrinsic apoptotic pathway. Molecular docking analysis revealed a strong binding affinity between WFA and PARP-1 (−8.2 kcal/mol), involving key residues Gly863, Ser904, and Tyr907, thereby supporting its role in PARP-1-mediated apoptosis. The computational findings were consistent with experimental observations of increased PARP-1 cleavage. This study concludes that WFA induces ROS-mediated mitochondrial dysfunction and caspase-dependent apoptosis in neuron-like cells. Consequently, future research should focus on critically assessing the safety and mechanistic effects of individual bioactive constituents of <em>Withania somnifera</em>, despite the well-established therapeutic potential of the plant.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"222 ","pages":"Article 109662"},"PeriodicalIF":2.1,"publicationDate":"2025-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144691608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}