Steroids最新文献

{"title":"Beta-Ecdysone protects osteocytes from excess glucocorticoids via Akt1-mediated regulation of Connexin43","authors":"Anna Xie ,&nbsp;Libo Wang ,&nbsp;Yu Zhang,&nbsp;Sunzhengyuan Zhang,&nbsp;Jinlong Cao,&nbsp;Chenglong Wang,&nbsp;Hongjin Wu,&nbsp;Weiwei Dai","doi":"10.1016/j.steroids.2025.109693","DOIUrl":"10.1016/j.steroids.2025.109693","url":null,"abstract":"<div><div>Glucocorticoid-induced osteoporosis (GIOP) is a leading cause of secondary osteoporosis (OP). β-Ecdysone (βEcd), a naturally occurring estrogen analog, was evaluated for its ability to mitigate the effects of glucocorticoids (GCs) on osteocytes, the crucial cells in bone remodeling. In GIOP mouse model induced by dexamethasone (Dex), micro-CT, biomechanical testing, silver nitrate staining, and hematoxylin-eosin (HE) staining were employed, demonstrating that βEcd effectively attenuated Dex-induced decreases in bone mass and strength, and alleviated Dex induced reduction in osteocyte dendrite and viability. Network pharmacology analysis predicted that the therapeutic efficacy of βEcd against GIOP is mediated through the crucial targets such as protein kinase B (Akt1), with significant enrichment in pathways including apoptosis and phosphoinositide 3-kinase (PI3K)-Akt signaling. In vitro, the osteocyte-like MLO-Y4 cells were treated with 10 μM Dex for 48 h in the presence or absence of βEcd or the PI3K inhibitor LY294002 (LY). Crystal violet staining and connexin43 (CX43) immunofluorescence (IF) staining were employed, and western blot was used to assess the levels of Akt1, phospho (p)-Akt, CX43, p-CX43, and apoptosis-related factors. Hoechst staining and annexin V/PI apoptosis assays were also used to evaluate apoptosis. The results demonstrated that βEcd counteracted Dex-induced apoptosis by modulating Akt1 and CX43 expression in MLO-Y4 cells, while inhibition of Akt activity reversed these effects, suggesting that βEcd targets the Akt1 gene. The findings indicate that βEcd protects osteocytes from GC-induced apoptosis through Akt-mediated regulation of CX43, highlighting its potential as a therapeutic approach for the prevention and treatment of GIOP.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"224 ","pages":"Article 109693"},"PeriodicalIF":2.3,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145239818","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":2.3,"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":"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":"2025-09-25","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":"Steroidal scaffold dichotomy: pathogenic role of 7-ketocholesterol versus protective FXR-antagonistic actions of guggulsterone in metabolic regulation","authors":"Sarvesh Sabarathinam ,&nbsp;Nila Ganamurali","doi":"10.1016/j.steroids.2025.109691","DOIUrl":"10.1016/j.steroids.2025.109691","url":null,"abstract":"<div><div>Obesity-associated Dyslipidemia and inflammation are aggravated by the accumulation of toxic oxysterols, particularly 7-ketocholesterol (7-KC), which amplifies oxidative stress and metabolic dysfunction. The steroidal scaffold is a central determinant of whether such molecules exert protective or pathogenic effects. This review highlights the dichotomy between 7-KC, a cytotoxic oxysterol, and Guggulsterone, a Phytosteroids with therapeutic potential. Guggulsterone retains the tetracyclic steroid backbone, enabling it to mimic endogenous sterols while functioning as a farnesoid X receptor (FXR) antagonist. By relieving FXR-mediated suppression of CYP7A1, Guggulsterone enhances bile acid synthesis, promotes cholesterol clearance, and improves lipid profiles. Additionally, its structural features confer anti-inflammatory activity via NF-κB inhibition, contrasting with the pro-oxidant nature of 7-KC. The concept of steroid scaffold mimicry underscores the potential of Phytosteroids as blueprints for drug design, offering a path toward innovative therapies for obesity-linked metabolic disorders.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"223 ","pages":"Article 109691"},"PeriodicalIF":2.3,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145157805","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":"Duration of vitamin D supplementation modulates the association between cardiovascular disease and high-sensitivity C-reactive protein across body mass index strata","authors":"Theocharis Koufakis ,&nbsp;Theofylaktos Georgiadis ,&nbsp;Areti Kourti ,&nbsp;Katerina Thisiadou ,&nbsp;Paraskevi Karalazou ,&nbsp;Alexander Kokkinos ,&nbsp;Michael Doumas ,&nbsp;Kalliopi Kotsa ,&nbsp;Kali Makedou","doi":"10.1016/j.steroids.2025.109690","DOIUrl":"10.1016/j.steroids.2025.109690","url":null,"abstract":"<div><h3>Background</h3><div>Cardiovascular disease (CVD) and higher body mass index (BMI) are linked to chronic low-grade inflammation. It is unclear whether vitamin D modifies the association between CVD and inflammatory biomarkers uniformly across BMI strata. We therefore tested whether vitamin D status and supplementation modify the CVD–biomarker association and whether any modification differs by BMI category.</div></div><div><h3>Methods</h3><div>In a cross-sectional cohort of adults free of acute infection (N = 88; 20 with normal BMI, 34 with overweight, and 34 with obesity), four inflammatory biomarkers were assessed: high-sensitivity C-reactive protein (hs-CRP), presepsin, ferritin, and β-defensin-2. Outcomes were modeled on the natural-log scale with age and sex as covariates. We tested the interaction between BMI and CVD and evaluated whether vitamin D variables [25(OH)D concentrations, supplementation status, supplementation duration, sufficiency category] modified the CVD–biomarker relationship, including prespecified three-way interactions among CVD, vitamin D, and BMI.</div></div><div><h3>Results</h3><div>No interaction between BMI and CVD was detected for any biomarker. For hs-CRP, a significant three-way interaction among CVD, vitamin D supplementation duration, and BMI was observed (p = 0.008) and was robust to sensitivity analyses [duration capped at three or six months; additional adjustment for 25(OH)D and supplementation status]. With longer supplementation, the CVD–hs-CRP difference widened in the moderate-BMI category and attenuated in the higher-BMI category. Other biomarkers showed no comparable interactions.</div></div><div><h3>Conclusion</h3><div>Vitamin D exposure—particularly supplementation duration—may modulate CVD-related inflammation in a BMI-dependent manner. Replication in larger studies is warranted.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"223 ","pages":"Article 109690"},"PeriodicalIF":2.3,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145150876","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":"Design, synthesis and characterization of novel cholesterol derivatives: Anti-cancer activity, ADMET profiling and DFT insights","authors":"Anmol Verma ,&nbsp;Poonam Rawat ,&nbsp;Sanyukta Shukla ,&nbsp;Ranvijay Pratap Singh ,&nbsp;Pratishtha Gupta ,&nbsp;Shama Parveen ,&nbsp;Monisha Banerjee ,&nbsp;Arun Sethi ,&nbsp;Saurabh Kumar Singh","doi":"10.1016/j.steroids.2025.109687","DOIUrl":"10.1016/j.steroids.2025.109687","url":null,"abstract":"<div><div>In the present work, Steglich esterification and Mizoroki-Heck reaction have been carried out for the synthesis of novel cholesterol derivatives. The synthesized derivatives <strong>2, 3, 4, 5</strong> and <strong>6</strong> were purified through column chromatography and characterized by ¹H, ¹³C NMR, FT-IR spectroscopy, and mass spectrometry. The geometries of all the compounds were optimized in the ground state by the density function theory at the B3LYP/6-31G(d,p) level. The <em>in vitro</em> evaluation of compounds <strong>2 (IC₅₀ 17), 3 (IC₅₀ 11), 4 (IC₅₀ 14)</strong> and <strong>6 (IC₅₀ 20)</strong> for their anti-cancer activity against SiHa cells demonstrated an increased apoptotic activity in comparison to the parent compound <strong>1 (IC₅₀ 24)</strong> i.e. cholesterol. The Molecular docking studies were carried out against two proteins bearing the protein data bank (PDB) ID 2B9D and 1R9W to investigate the inhibitory action of the derivatives. The result of molecular docking showed appreciable interactions of <strong>2, 3, 4, 5</strong> and <strong>6</strong> with the selected proteins as compared to <strong>1</strong>. The <em>in vitro</em> and molecular docking studies show that the synthesized molecules can prove to be better anti-cancer agents on other cancer cells also. The computational analysis data and the experimental data were in conformation with each other. ADMET analysis was carried out using the admetSAR database and Swiss ADME.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"223 ","pages":"Article 109687"},"PeriodicalIF":2.3,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081393","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":"2025-09-14","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":"Quercetin-cyclodextrin combination effects on cytochrome P450 genes, oxidative stress and ovarian function in PCOS rats","authors":"Fatemeh Taghipour ,&nbsp;Hadi Samadian ,&nbsp;Razieh Dalirfardouei ,&nbsp;Sara Soleimani Asl ,&nbsp;Nastaran Barati ,&nbsp;Tayebe Artimani","doi":"10.1016/j.steroids.2025.109688","DOIUrl":"10.1016/j.steroids.2025.109688","url":null,"abstract":"<div><div>This study investigates the effect of the quercetin/cyclodextrin (Que/β-CD) complex on oxidative stress, cytochrome P450 gene expression, and ovarian tissue structure in a rat polycystic ovary syndrome (PCOS) model. The Que/β-CD complexes were synthesized using the solvent evaporation method and characterized via scanning electron microscope (SEM) imaging and fourier transform infrared (FTIR) spectroscopy. Thirty female Wistar rats (6 weeks old, 160–180 g) with regular estrous cycles were randomly divided into six experimental groups: control, PCOS, PCOS treated with Que, PCOS adminstrated the β-CD, PCOS recivied metformin, and PCOS given Que/β-CD complex. Following model induction and treatments, tissue and gene expression analyses were performed. Characterization confirmed the successful synthesis of Que/β-CD complex. PCOS rats showed increased weight and higher number of atretic follicles compared to the controls (p &lt; 0.01), which were effectively decreased after Que/β-CD treatment. Additionally, PCOS rats had reduced corpora lutea and CYP19A expression levels (p &lt; 0.01), which were enhanced after Que/β-CD administration. Elevated CYP11A and CYP17A gene expression in PCOS rats markedly diminished with Que/β-CD treatment, indicating an improvement in disease symptoms. Oxidant levels, higher in PCOS rats (p &lt; 0.01), meaningfully decreased after treatment with metformin, Que, or Que/β-CD (p &lt; 0.0001, p &lt; 0.001, and p &lt; 0.001, respectively).</div><div>Overall, Que/β-CD treatment in the PCOS model resulted in to a significant decrease in body and ovary weights, number of cysts, atretic follicles, and oxidative stress markers, accompanied by a notable increase in corpora lutea, CYP19A expression, and antioxidant activity. These findings highlight Que/β-CD’s therapeutic potential in managing PCOS symptoms.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"223 ","pages":"Article 109688"},"PeriodicalIF":2.3,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058664","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":"Synthesis and preliminary biological evaluation of novel steroidal compounds as antibacterial agents","authors":"Anna Esposito ,&nbsp;Maria Stabile ,&nbsp;Antonella Migliaccio ,&nbsp;Eliana De Gregorio ,&nbsp;Stefano D’Errico ,&nbsp;Annalisa Guaragna","doi":"10.1016/j.steroids.2025.109686","DOIUrl":"10.1016/j.steroids.2025.109686","url":null,"abstract":"<div><div>Antimicrobial resistance is currently one of the most serious and alarming threats to human health; therefore, the identification of novel antimicrobial agents is a compelling need. Recently, we identified the heterocyclic steroid PYED-1 as a novel promising antibacterial and antibiofilm agent. In an effort to broaden the repertoire of active compounds and elucidate the structural features responsible for their antibacterial activity, two novel derivatives of PYED-1 have been conceived herein. The target compounds have been readily obtained in few steps and with very good yields. The antibacterial activity has been evaluated against <em>S. aureus</em> and <em>A. baumannii</em> strains, as examples of Gram-positive and -negative bacteria, by the broth microdilution method, while hemolysis assay has been used for the assessment of cytotoxicity. One of the two derivatives was able to inhibit the growth of <em>S. aureus</em> strains with lower MIC values (8 µg/mL) compared with those of PYED-1 (16 µg/mL) without showing hemolytic effect suggesting therefore a favorable safety profile. Overall, this study provides further indications on the functional groups required for the antibacterial activity of these novel steroidal derivatives.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"223 ","pages":"Article 109686"},"PeriodicalIF":2.3,"publicationDate":"2025-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145030601","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":"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}