Steroids最新文献

{"title":"Target-specific high-throughput screening of anti-inflammatory phytosteroids for autoimmune diseases: A molecular docking-dynamics simulation approach","authors":"Alaka Sahoo ,&nbsp;Sudhir Kumar Paidesetty ,&nbsp;Maitreyee Panda","doi":"10.1016/j.steroids.2025.109601","DOIUrl":"10.1016/j.steroids.2025.109601","url":null,"abstract":"<div><div>Without proper pathophysiology and recommended therapy, synthetic steroids are widely used as a first-line option for the management of autoimmune diseases. However, their prolonged use often leads to severe side effects such as osteoporosis, hypertension, cardiovascular, gastrointestinal complications, etc. To search for potential and safer therapeutic options, the present study aims to explore the potency and drug-ability profiles of anti-inflammatory phytosteroids (PSs). In a target-specific approach, we have selected three key molecular targets: glucocorticoid receptor/GR (PDB ID: 4P6W), cyclooxygenase-2/COX2 (PDB ID: 5F1A), and inducible nitric oxide synthase/iNOS (PDB ID: 4NOS) for a docking study of 167) selected PSs. The drug-chemistry profiles (physicochemical, toxicity, pharmacokinetic, drug-ability, etc.) of PSs were also assessed using various bioinformatics and chemoinformatics tools. The above assessment suggested that withaminilide B (PS46) is a lead candidate with higher drug-ability properties. Further, the drug stability and kinetic behaviour of the lead with the GR target ‘GR-withaminilide B’ in comparison with the control drug, ‘GR-triamcinolone acetonide’ docking complex, were studied through molecular dynamics (MD) simulation at 200 nanosecond with free energy calculation (MM/PBSA). Overall findings suggested that PSs exhibit distinct drug-ability profiles based on their functional attachments with a steroidal core moiety, where withaminilide B is a lead PSs among all to be used as alternative/ complementary candidates expected with limited adverse effects. Further experimentation is essential before mainstream application, but the study provided a platform to select drug-able candidates with a higher chance of experimental success and accelerate the drug discovery process within limited resources.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"217 ","pages":"Article 109601"},"PeriodicalIF":2.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143693394","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":"BSS-4, a diosgenin analogue, reduces carrageenan-induced paw inflammation in rat","authors":"Marisol Casimiro-Rosas ,&nbsp;Irving Parra ,&nbsp;Jesús Sandoval-Ramírez ,&nbsp;María A. Fernández Herrera ,&nbsp;Yousef Tizabi ,&nbsp;Isabel Martínez-García ,&nbsp;Liliana Mendieta","doi":"10.1016/j.steroids.2025.109602","DOIUrl":"10.1016/j.steroids.2025.109602","url":null,"abstract":"<div><div>Inflammation is an adaptive response that ensures the survival of the organism in the face of injuries or trauma primarily via the immune system. However, overactivation of this process can be detrimental to the point of fatality. To overcome this overactivation, immunosuppressant agents such as steroids and non-steroidal anti-inflammatory drugs (NSAIDs) are used. Given the limitations of these drugs, including their side effects, an urgent need for development of potent and safer anti-inflammatory drugs is evident. Diosgenin, a steroidal saponin (a glycoside found in plants) and its analog, BSS-4 are gaining ground in this respect. Our objective in this study was to determine the effectiveness of BSS-4 in an established model of inflammation and provide clues on its mechanism of action. Carrageenan (Carr)-induced paw edema was used to evaluate the effectiveness of two doses of BSS-4 (0.5 and 1 mg/kg administered intraperitoneally) in adult male Wistar rats. Plantar edema was induced by subcutaneous injection of 50 µL of carrageenan (1 %) into the plantar aponeurosis of the right paw. Inflammatory cytokine markers, tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β) were quantified in this paw region using immunohistochemical assays. BSS-4 at 0.5 mg/kg dose, significantly reduced the paw edema up to three hours after administration. Concomitantly, TNF-α and IL-1β immunostaining were significantly reduced. BSS-4 also preserved the tissue architecture as assessed by hematoxylin and eosin (H&amp;E) staining. These results indicate that BSS-4 can impart potent anti-inflammatory effects as well as reductions in TNF-α and IL-1β in an inflammatory rat model.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"217 ","pages":"Article 109602"},"PeriodicalIF":2.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143693390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stress responses in blood donors: Oral fluid hormone dynamics and implications for donor support","authors":"Agata Alterio ,&nbsp;Matteo Feltracco ,&nbsp;Giovanna Mazzi ,&nbsp;Beatrice Rosso ,&nbsp;llaria Prosdocimi ,&nbsp;Andrea Gambaro","doi":"10.1016/j.steroids.2025.109604","DOIUrl":"10.1016/j.steroids.2025.109604","url":null,"abstract":"<div><div>Glucocorticoids (cortisol and cortisone) hormones are potential biomarkers for monitoring physiological stress in humans. These hormones are released into the bloodstream but are also detectable in other biological matrixes such as oral fluid. Oral fluid hormone levels reflect those found in the blood, but oral fluid sampling is quicker and non-invasive, making it a viable alternative matrix for studying stress markers. This study investigates the stress response of blood donors at three different donation moments by analyzing cortisol and cortisone levels in oral fluid samples. To simultaneously detect these analytes, we developed and validated a new highly sensitive method using high-performance liquid chromatography coupled to a triple quadrupole mass spectrometer (HPLC-MS/MS). Glucocorticoid hormones were found in all samples with cortisone exhibiting higher concentrations than cortisol. Statistical results revealed a weakly negative trend over time for both analytes levels, indicating that the most crucial donation moment is upon donors’ arrival. A notable distinction was found in the evolution of the glucocorticoid hormones in different locations, suggesting that different environmental factors influence stress level more than the act of donation itself.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"217 ","pages":"Article 109604"},"PeriodicalIF":2.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143734753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microbial steroid biotransformation: Regio- and stereo selective 17β-reduction by Priestia aryabhattai","authors":"Yogeswari Sudhakar ,&nbsp;Reddy Krishna Manasa ,&nbsp;Dhanapal Priyadarshini ,&nbsp;Sagar Chandrakant Dalsaniya ,&nbsp;Gurrala Sheelu ,&nbsp;Thenkrishnan Kumaraguru","doi":"10.1016/j.steroids.2025.109600","DOIUrl":"10.1016/j.steroids.2025.109600","url":null,"abstract":"<div><div>The conversion of 17-oxosteroids to 17β-hydroxysteroids stands as a pivotal process in the synthesis of numerous steroidal drugs and intermediates. This study explored the potential of the strain <em>Priestia aryabhattai</em> (IICT-BC-1279) to catalyze the reduction of the C-17 carbonyl group in androst-4-ene-3,17-dione (AD), resulting in the exclusive production of testosterone (TS) through its 17β-hydroxysteroid dehydrogenase (17β-HSD) activity. Optimal conditions for this reduction were achieved at pH 7.0 and 25 °C, with supplementation of AD as an inducer (0.01 g/L), 1 % Tween 80 (w/v) and ethanol as co-solvent. Under these optimized parameters, 0.5 g/L AD was efficiently converted to TS as a sole product, achieving a yield of &gt; 95 % and diastereomeric excess (<em>d.e</em>) of &gt; 99 % within 48 h. The absence of by-products in this microbial 17β-reduction process simplifies product purification, highlighting the strain’s potential as a valuable biocatalyst for this essential transformation. Additionally, the conversion of androsta-1,4-diene-3,17-dione (ADD) to (+)-Boldenone (BD) was studied to explore substrate scope.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"217 ","pages":"Article 109600"},"PeriodicalIF":2.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143683854","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":"Unleashing the pharmacological potential of taste receptors in reproductive processes beyond their gustatory role","authors":"Nourhan Magdy ,&nbsp;Noha F. Abdelkader ,&nbsp;Hala F. Zaki ,&nbsp;Ahmed S. Kamel","doi":"10.1016/j.steroids.2025.109603","DOIUrl":"10.1016/j.steroids.2025.109603","url":null,"abstract":"<div><div>Traditionally, taste receptors (TRs) have been understood to reside within the taste buds on the tongue, serving as initiators for different taste perceptions. However, recent research has expanded our understanding, revealing that TRs are found throughout the body and perform a wide range of functions beyond taste perception as non-tasting functions. These receptors, along with their genetic variations, have been linked to various human health conditions. They are activated by an array of substances, including hormones, nutrients, and toxins, indicating their involvement in numerous biological processes. Specifically, in males, TRs are notably present in the testes and epididymis, where they contribute to the hormonal production, spermatogenesis, and sperm maturation. In females, these receptors are found in the ovaries, uterus, and myometrium, playing crucial roles in ovulation, menstrual cycle regulation, and embryo implantation. There are a lot of missed areas regarding TRs research that imposes to fulfill the gaps in the current understanding of their role in reproduction. This review aims to provide a comprehensive overview of the emerging roles of extraoral TRs in reproductive health, highlighting their physiological and pathophysiological significance in various reproductive processes. As well, grabbing the attention towards the release of new pharmacological interventions to manage conception and contraception in male and female was considered.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"217 ","pages":"Article 109603"},"PeriodicalIF":2.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143724183","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":"Isoxazolyl steroid blocks the Shh signaling pathway and the expression of MMP-2 and MMP-9 in cervical carcinoma cell lines","authors":"Olga Timoshenko ,&nbsp;Elena Kugaevskaya ,&nbsp;Tatiana Gureeva ,&nbsp;Galina Morozevich ,&nbsp;Alexey Lupatov ,&nbsp;Arif Mekhtiev ,&nbsp;Anton Rudovich ,&nbsp;Vladimir Zhabinskii ,&nbsp;Vladimir Khripach ,&nbsp;Andrey Lisitsa","doi":"10.1016/j.steroids.2025.109599","DOIUrl":"10.1016/j.steroids.2025.109599","url":null,"abstract":"<div><div>Cervical cancer is the fourth leading cause of cancer death among women worldwide. Matrix metalloproteinases MMP-2 and MMP-9 play a leading role in the processes of invasion and metastasis in cervical cancer. Research on the development of MMP inhibitors not yielded the expected results due to their serious side effects. Study of signaling pathways involved in regulation of MMPs expression is of great importance for search of new classes of therapeutic drugs. Aberrant activation of the Sonic Hedgehog (Shh) signaling pathway is associated with increased MMPs in many types of human cancer. This study investigated the inhibitory action of 17β-((3-butylisoxazol-5-yl)methyl)-androst-5-en-3β-ol on the Shh signaling pathway key genes (Ptch, Smo, Gli) expression and MMP-2, MMP-9 genes expression in human cervical carcinoma cell lines (SiHa and CaSki) and keratinocytes (HaCaT). Cyclopamine was used for comparative analysis. Gene expression analysis was performed using real-time PCR; the effects on survival and cell cycle were studied using the MTT test and flow cytometry method. 17β-((3-butylisoxazol-5-yl)methyl)-androst-5-en-3β-ol had higher cytotoxicity and more effectively blocked the Shh signaling pathway genes and MMP-2 and MMP-9 genes compared to cyclopamine in all cell lines. The results obtained demonstrate potential of 17β-((3-butylisoxazol-5-yl)methyl)-androst-5-en-3β-ol as the anticancer drug that simultaneously block the Shh signaling pathway and MMP expression. We are confident that the search for substances capable of simultaneously affecting several key components involved in tumor progression is of great importance for the creation of next-generation therapeutic agents.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"217 ","pages":"Article 109599"},"PeriodicalIF":2.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143658723","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":"Evaluation of the short-term stability of 6α-chloro-testosterone, 6β-bromo-androstenedione and 6-oxo-androstenedione in dimethylsulfoxide and methanol using liquid and gas chromatography − mass spectrometry","authors":"Dayamin Martínez_Brito ,&nbsp;Patrizia Leogrande ,&nbsp;Xavier de la Torre ,&nbsp;Francesco Botrè","doi":"10.1016/j.steroids.2025.109597","DOIUrl":"10.1016/j.steroids.2025.109597","url":null,"abstract":"<div><div>This work studied the short-term stability of 6α-chloro-testosterone (6-CT), 6β-bromo-androstenedione (6-BrAED) and 6-oxo-androstenedione (6-oxo-AED) in methanol (MeOH) and dimethylsulfoxide (DMSO) solutions by gas and liquid chromatography coupled to mass spectrometry.</div><div>Solutions of 6-CT, 6-BrAED and 6-oxo-AED were prepared in MeOH and DMSO. They were stored at room temperature, +4°C and −20 °C. Measurements were made at 0, 7, 30, 60 and 90 days after solutions preparation, by liquid chromatography-tandem mass spectrometry and gas chromatography-high resolution mass spectrometry.</div><div>Although the degradation of 6-CT and 6-BrAED was extensive, the most notable result was that the higher degradation occurred in DMSO instead of MeOH. The interaction of DMSO with halogenated species and secondary hydroxyl groups favored the degradation of these compounds by forming chemically related species. No degradation of 6-oxo-AED in either MeOH or DMSO was observed.</div><div>Pronounced degradation of the 6-CT and 6-BrAED, during the derivatization reaction for the gas chromatography-mass spectrometry analysis was observed. Because of the acidic condition of the reaction and depending on the reactant, it was favored the loss of the halogen molecule or the dehydration reaction to form the unsaturated (Δ6) steroid derivative.</div><div>Our finding suggests to take duly into account the possibility of degradation processes when performing quantitative determination of 6-CT, 6-BrAED and 6-oxo-AED by chromatographic-spectrometric techniques based on the use of reference solutions stored for sufficiently long times.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"217 ","pages":"Article 109597"},"PeriodicalIF":2.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143606530","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":"New hydroxylated metabolite derived from the microbial biotransformation of 11α-acetoxyprogesterone by the endophytic fungus Phyllosticta sp. 16L1 and its cytotoxic activity","authors":"Mufeda Ahmed Hazea Gazaem ,&nbsp;Wan Nurul Nazneem Wan Othman ,&nbsp;Syed Adnan Ali Shah ,&nbsp;Mustapha Salihu ,&nbsp;Azeana Zahari ,&nbsp;Siti Hajar Sadiran ,&nbsp;Fatimah Salim","doi":"10.1016/j.steroids.2025.109584","DOIUrl":"10.1016/j.steroids.2025.109584","url":null,"abstract":"<div><div>Biotransformations catalysed by microbes are promising approach for producing a vast library of structurally diverse chemical molecules with applications in the pharmaceutical industry. The biotransformation of 11α-acetoxyprogesterone (<strong>1</strong>) by <em>Phyllosticta</em> sp. 16L1 has not been previously reported. In this study, the biotransformation of 11α-acetoxyprogesterone (<strong>1</strong>) was performed for the first time using the <em>Phyllosticta</em> sp. 16L1 strain. After an 8-day fermentation period, a new biotransformation metabolite, named as 11α-acetoxy-16α-hydroxyprogesterone (16α-hydroxy-3,20-dioxopregn-4-en-11α-yl acetate) (<strong>2</strong>) was isolated from the culture broth, along with its known isomer, 11α-acetoxy-15α-hydroxyprogesterone (<strong>3</strong>). The structure determination of the biotransformed products relied on comprehensive spectroscopic data, encompassing 1D and 2D-NMR, as well as LCMS analyses. The cytotoxic activity of the two biotransformed metabolites was assessed against selective human cancer cell lines, including hepatocellular carcinoma (HepG2), triple-negative breast cancer (MDA-MB-231), colorectal adenocarcinoma (Caco-2), and lung adenocarcinoma (A549). The results demonstrated that both metabolites <strong>2</strong> and <strong>3</strong> exhibited cytotoxic effects on the evaluated cell lines. Metabolite <strong>2</strong> showed stronger cytotoxic potential, with IC₅₀ values ranging from 6.65 to 27.75 μM, while metabolite <strong>3</strong> displayed lower potency, with IC₅₀ values between 38.20 and 162.53 μM. Notably, both metabolites exhibited minimal toxicity towards the normal liver Chang cells. Molecular docking studies were conducted to predict the binding modes and affinities of the metabolites against two targets (PDB: 5EM8 and 6V6O), both in 2D and 3D representations, with binding energies ranging from −8.5 to −7.2 kcal/mol. The results revealed that metabolites <strong>2</strong> and <strong>3</strong> interacted with key clinically significant amino acid residues, Lys745 and Met793, through conventional hydrogen bonding.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"216 ","pages":"Article 109584"},"PeriodicalIF":2.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537733","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":"Theoretical study of the pyridyl-cholestane formation pathway using DFT: A stepwise mechanistic approach","authors":"Kamlesh Sharma,&nbsp;Priyanka","doi":"10.1016/j.steroids.2025.109575","DOIUrl":"10.1016/j.steroids.2025.109575","url":null,"abstract":"<div><div>The reaction mechanism of the formation of pyridyl-cholestane derivative <strong>4</strong> from a multi-component reaction involving cholestane-6-one, aromatic aldehyde, malononitrile, and ammonium acetate in presence of magnesium oxide nanoparticles (MgO NPs) as catalyst, was studied successfully by using DFT calculations. The mechanism involved condensation, cyclization, and aromatization steps which were investigated successfully theoretically. The theoretical calculations of physicochemical parameters, including Gibbs free energy, frontier molecular orbitals (FMOs), dipole moments, and hardness, of all the intermediates and transition states molecules. The study revealed the formation of key intermediates and transition states, with detailed analysis of their stability and electronic structures.</div><div>The reaction pathway begins with the formation of enamine <strong>I</strong> and α,β-unsaturated nitrile <strong>II</strong>, followed by Michael addition to produce intermediate <strong>B</strong>. The cyclization of <strong>A</strong> to intermediate <strong>B</strong>, which has the highest activation energy barrier was identified as slowest and the rate-determining step. The following steps, including cyclization (<strong>B</strong> to <strong>C</strong>) and proton transfer (<strong>C</strong> to <strong>D</strong>), exhibit progressively lower activation barriers and enhanced stability. Theoretical analysis indicates that the reaction is thermodynamically favorable, as the product is more stable than the initial reactants.</div><div>This study highlights the mechanistic insights contributing to the understanding of multi-component reactions in organic synthesis involved effectiveness of MgO NPs as a heterogeneous catalyst in enabling the efficient synthesis of pyridyl-cholestane derivative 4.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"216 ","pages":"Article 109575"},"PeriodicalIF":2.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143543248","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":"17β-estradiol delays cardiac aging through suppressing the methylation of Beclin1 in a murine model","authors":"Lili Ye ,&nbsp;Ruiyan Wang ,&nbsp;Jun Zhao ,&nbsp;Jingrong Chen ,&nbsp;Feng Wang","doi":"10.1016/j.steroids.2025.109587","DOIUrl":"10.1016/j.steroids.2025.109587","url":null,"abstract":"<div><h3>Introduction</h3><div>Cardiac endogenous senescence will gradually change and aggravate with age. Recent research showed that 17β-estradiol (17β-E2), an estrogen with numerous biological activities including the prevention of vascular senescence. However, how 17β-E2 against cardiac aging is still unknown. This work addressed the underlying mechanism with regard to Beclin1 and autophagy activity to better understand the anti-senescent effect of 17β-E2 on a well-established animal model of cardiac aging.</div></div><div><h3>Material and methods</h3><div>In this study, an aging model in female mice was established using <span>d</span>-galactose and ovariectomy. Cardiac function was evaluated by echocardiography, RNA-seq was performed to analyze the gene expression profiles of myocardial tissues from 17β-E2 treated mice. Additionally,The levels of Beclin1, LC3, <em>P</em>62, and ATG5 in myocardial tissues were assessed using qPCR and Western blotting. Methylation levels of the Beclin1 promoter region in myocardial tissues were determined by MSP and BSP.</div></div><div><h3>Results</h3><div>The findings demonstrated that cardiac aging mice treated with 17β-E2 had improved heart function. 17β-E2 restored EF(increase 1.25-fold) and FS(increase 1.2-fold) to near-normal levels. By RNA-sequencing and Gene Set Enrichment Analysis (GSEA) analysis, the autophagy signaling pathway was further enriched in the myocardial tissue of cardiac aging mice treated with 17β-E2, and we also discovered that 17β-E2 suppress the methylation of Beclin1 promoter region, which mediate the activation of autophagy signal.</div></div><div><h3>Conclusions</h3><div>Overall, our data showed that 17β-E2′s anti-senescent effect on cardiac aging mice was mediated by the crucial suppression of methylation in the Beclin1 promoter area and subsequent activation of the autophagy signal, which may present a possible therapeutic approach to prevent cardiac aging.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"216 ","pages":"Article 109587"},"PeriodicalIF":2.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143543073","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}