Steroids最新文献

{"title":"Kobochromone A, a polyphenol in Carex kobomugi, suppresses androgen signaling induced by 11-oxygenated androgens and enhances the efficacy of AKT inhibitors in triple-negative breast cancer cells","authors":"Masatoshi Tanio ,&nbsp;Yuri Miyamoto ,&nbsp;Tomofumi Saka ,&nbsp;Yudai Kudo ,&nbsp;Riri Hayashi ,&nbsp;Shinya Kawano ,&nbsp;Yuta Yoshino ,&nbsp;Naohito Abe ,&nbsp;Eiji Yamaguchi ,&nbsp;Yuki Arai ,&nbsp;Hirohito Kashiwagi ,&nbsp;Masayoshi Oyama ,&nbsp;Akichika Itoh ,&nbsp;Akira Ikari ,&nbsp;Satoshi Endo","doi":"10.1016/j.steroids.2025.109692","DOIUrl":"10.1016/j.steroids.2025.109692","url":null,"abstract":"<div><div>Breast cancer is the most common cancer in women, with triple-negative breast cancer (TNBC) accounting for approximately 20% of cases. TNBC lacks estrogen receptors (ER), progesterone receptors (PR), and epidermal growth factor receptor 2 (HER2) expression, which makes targeted therapies ineffective. The luminal androgen receptor (LAR) subtype of TNBC expresses androgen receptor (AR), highlighting the need for treatment strategies that target androgen signaling. Recently, the role of 11-oxygenated androgens, in addition to conventional androgens such as testosterone and dihydrotestosterone, in androgen-related diseases in women has gained increased attention.</div><div>In this study, we investigated the involvement of 11-oxygenated androgens in LAR TNBC and explored the anti-androgenic effects of Kobochromone A (KC-A), a natural compound derived from <em>Carex kobomugi</em>. KC-A inhibits the androgen-synthesizing enzyme dehydrogenase/reductase short-chain dehydrogenase/reductase family member 11 (DHRS11) and suppresses AR expression. Using the AR-positive TNBC cell line MDA-MB-453, we demonstrated that 11-oxygenated androgens activate androgen signaling and promote cell proliferation. KC-A significantly inhibited androgen signaling by reducing nuclear AR localization and decreasing transmembrane protease, serine 2, and c-Myc expression. Furthermore, KC-A synergistically enhanced antiproliferative effects of the AKT inhibitor capivasertib (Cap), promoted apoptosis, and further suppressed AR expression. The primary therapeutic mechanisms of KC-A were identified as its dual actions: inhibition of DHRS11 and suppression of AR expression. These findings suggest that KC-A, either alone or in combination with AKT inhibitors, may offer a promising therapeutic strategy for LAR TNBC by targeting androgen signaling. Further studies are needed to confirm the efficacy and safety of KC-A in clinical applications.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"223 ","pages":"Article 109692"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145182200","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":"Mineralocorticoid receptor antagonism of vamorolone: Evidence from LIONHEART and VISION-DMD clinical trials","authors":"Ana de Vera ,&nbsp;Paula R Clemens ,&nbsp;Utkarsh J Dang ,&nbsp;Catherine Dutreix ,&nbsp;Ekaterina Gresko ,&nbsp;Michela Guglieri ,&nbsp;Laura Hagerty ,&nbsp;Shabir Hasham ,&nbsp;Jesse Damsker ,&nbsp;Yetrib Hathout ,&nbsp;Aki Linden ,&nbsp;Anders Berglund ,&nbsp;Rebecca Tobin ,&nbsp;Karim Wahbi ,&nbsp;Eric P Hoffman","doi":"10.1016/j.steroids.2025.109689","DOIUrl":"10.1016/j.steroids.2025.109689","url":null,"abstract":"<div><div>The effect of vamorolone, the first dissociative corticosteroid for Duchenne muscular dystrophy (DMD), at the mineralocorticoid receptor (MR) was investigated in the Phase 1 mechanistic LIONHEART study and using serum samples from boys with DMD in the pivotal VISION-DMD trial. In LIONHEART, 30 healthy adult males were randomized 1:1:1 to vamorolone 20 mg/kg, eplerenone 200 mg, or no treatment arms. A fludrocortisone challenge was administered between –9<!--> <!--> h and 24 h after treatment. The LIONHEART primary outcome was urinary Na⁺/K⁺ ratio; additional outcomes were pharmacokinetics, urine Na⁺ and K⁺ concentrations, and safety. In VISION-DMD, boys with DMD aged 4–7 years were treated with vamorolone 2 or 6 mg/kg/d for 48 weeks or with prednisone 0.75 mg/kg/d or placebo for 24 weeks followed by vamorolone 2 or 6 <!--> <!-->mg/kg/d for 20 weeks following a 4-week washout. Serum sample analysis from VISION-DMD used the SomaScan® 7 K assay. In LIONHEART, vamorolone reversed the decrease in urinary Na⁺/K⁺ ratio induced by fludrocortisone, confirming vamorolone MR antagonism. The maximum MRA effect of vamorolone was observed at 4–6<!--> <!--> h post dose and was detectable until approximately 10<!--> <!--> h post dose. Vamorolone reversed fludrocortisone induced Na⁺ retention with no evidence of decreased potassium excretion. Vamorolone 20 mg/kg was well tolerated, and results were consistent with known PK parameters. The VISION-DMD results showed vamorolone-specific increases in renin serum levels, as well as klotho, and calcium carrier proteins fetuin A and B, consistent with an MR antagonist effect. The available data confirm the MR antagonistic effect of vamorolone in humans. LIONHEART: NCT06649409; VISION-DMD: NCT03439670.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"223 ","pages":"Article 109689"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145076153","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":"2025-10-01","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}

{"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":"2025-10-01","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":"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":"2025-10-01","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":"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":"2025-10-01","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":"Targeted metabolomics in PCOS mice identifies hippuric acid as a therapeutic metabolite.","authors":"Hui Lan, Bin Meng, Jianbo Li, Chenjin Duan, Shuangqing Liu, Pengxiang Qu, Hongyu Qin","doi":"10.1016/j.steroids.2025.109665","DOIUrl":"10.1016/j.steroids.2025.109665","url":null,"abstract":"<p><p>Polycystic ovary syndrome (PCOS) represents a complex endocrine disorder with profound detrimental effects on women's reproductive and metabolic health, yet the absence of specific pharmacotherapeutic interventions has resulted in a significant therapeutic gap. To elucidate the metabolic alterations in PCOS, we conducted a comprehensive targeted metabolomics analysis of plasma samples from healthy control mice and PCOS model mice, examining a panel of 197 metabolites spanning diverse metabolic classes. Our analysis revealed substantial metabolic differences between the groups, with organic acids, amino acids, and fatty acids emerging as the most abundant metabolite classes in both cohorts. Among the 197 metabolites analyzed, 86 demonstrated a Variable Importance in Projection (VIP) score > 1, with univariate analysis confirming 76 distinct metabolites showing significant alterations. Notably, the PCOS group exhibited marked increases in metabolites such as tartaric acid and docosapentaenoic acid, while hippuric acid showed the most pronounced reduction. Pathway enrichment analysis identified significant perturbations in key metabolic pathways, including amino acid metabolism, fatty acid oxidation, and the urea cycle in PCOS mice. The exogenous administration of hippuric acid led to a significant amelioration of ovarian pathology in PCOS mice, highlighting its promising therapeutic potential. These findings provide crucial insights into the altered metabolic landscape of PCOS, identifying potential biomarkers and therapeutic targets, with particular emphasis on the promising therapeutic role of hippuric acid in mitigating PCOS pathology, thereby offering a valuable avenue for further investigation and clinical translation.</p>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":" ","pages":"109665"},"PeriodicalIF":2.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144800317","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":"2025-10-01","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":"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":"Exploring the urate lowering properties of Erigeron annuus Lin. and phytosterol contributions: In vitro assays and in silico approaches","authors":"Rupali Rana ,&nbsp;Anchal Sharma ,&nbsp;Nitish Kumar ,&nbsp;Pallvi Mohanna ,&nbsp;Jyoti ,&nbsp;Aanchal Khanna ,&nbsp;Jatinder Vir Singh ,&nbsp;Preet Mohinder Singh Bedi","doi":"10.1016/j.steroids.2025.109657","DOIUrl":"10.1016/j.steroids.2025.109657","url":null,"abstract":"<div><h3>Background</h3><div>Due to the severe hypersensitivity risks associated with some xanthine oxidase (XO) inhibitors, there is a pressing need to develop novel agents with improved safety and effective ADME profiles. This study evaluates the antihyperuricemic and antioxidant potential of <em>Erigeron annuus</em> Lin. (E. annuus) using in vitro and in silico models.</div></div><div><h3>Objective</h3><div>To assess the in vitro XO inhibitory and antioxidant activities of the hydroalcoholic crude extract, fractions, and isolated compounds from the aerial parts of E. annuus Lin.</div></div><div><h3>Methods</h3><div>A hydroalcoholic extract was prepared using a Soxhlet apparatus. Column chromatography and spectroscopic techniques were employed to isolate and identify two phytosterols: RR1 (<em>β</em>-sitosterol) and RR2 (stigmasterol). A further pharmacophore-based hypothesis was developed using DE Shaw Desmond software; an in-silico profile was also evaluated using LeadIT software and Swiss ADME, respectively. XO inhibitory activity was measured using a Biotek multi-mode plate reader, and antioxidant activity was assessed via the DPPH and FRAP assay. Additionally, potent compound RR2 was also evaluated for its cytotoxicity against HepG2 cell line.</div></div><div><h3>Results</h3><div>All tested extracts and fractions inhibited XO activity, with IC₅₀ values ranging from 0.086 µg/mL to 36.71 µg/mL. Allopurinol, used as a positive control, had an IC₅₀ of 0.027 µg/mL. The hexane fraction of E. annuus exhibited the most vigorous XO inhibitory activity (IC₅₀ = 0.086 µg/mL). RR2 (stigmasterol) showed notable inhibition from this fraction with an IC₅₀ of 0.331 µg/mL. Antioxidant assays and cytoxicity study also supported the bioactivity of these fractions.</div></div><div><h3>Conclusion</h3><div>The hexane fraction of E. annuus demonstrated potent XO inhibitory activity, highlighting its potential as a source for developing herbal treatments for hyperuricemia and gout. The study validates traditional use and supports the pharmacophore hypothesis, suggesting that structural optimization of the sterol nucleus could enhance therapeutic efficacy.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"221 ","pages":"Article 109657"},"PeriodicalIF":2.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144596835","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}