Steroids最新文献

{"title":"Design and discovery of novel heteroaryl substituted pregnenolone derivatives as potent anti-neuroinflammatory agents targeting LPS-stimulated BV-2 microglial cells","authors":"Siqi Xu ,&nbsp;Ling Fang ,&nbsp;Jianfeng Cai ,&nbsp;Shuopo Fang ,&nbsp;Huide Zhu ,&nbsp;Fei Lin ,&nbsp;Xiaorui Cai","doi":"10.1016/j.steroids.2025.109588","DOIUrl":"10.1016/j.steroids.2025.109588","url":null,"abstract":"<div><div>A new family of steroidal compounds based on a heteroaryl-4,5-dihydropyrazole thiazolinone core structure was designed and synthesized through structural modifications. The anti-neuroinflammatory activity of these compounds was evaluated in lipopolysaccharide (LPS)-stimulated murine microglial BV-2 cells <em>in vitro</em>. Among the synthesized compounds, <strong>10b</strong> and <strong>10d</strong> effectively inhibited nitric oxide (NO) production, with compound <strong>10b</strong> emerging as the most potent anti-neuroinflammatory agent (IC₅₀ = 2.05 μM). Compound <strong>10b</strong> demonstrated significantly greater inhibitory effects than progesterone (<strong>prog</strong>) (IC₅₀ = 3.23 μM) and reduced NO production in a concentration-dependent manner. Furthermore, compound <strong>10b</strong> attenuated the release of pro-inflammatory mediators, including tumour necrosis factor (TNF)-α, interleukin-1β (IL-1β), interleukin-6 (IL-6), and prostaglandin E2 (PGE2). It also inhibited the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Mechanistic studies revealed that compound <strong>10b</strong> significantly suppressed the transcriptional activity of nuclear factor kappa B (NF-κB) in activated microglial cells and prevented NF-κB p65 activation and IκBα degradation. These effects were likely mediated by the inhibition of c-Jun <em>N</em>-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) signaling pathways. Additionally, molecular docking studies suggested that the anti-neuroinflammatory effects of compound <strong>10b</strong> may result from its hydrophobic and hydrophilic interactions with iNOS and COX-2, supporting its proposed mechanism of action. In summary, these findings suggest that compound <strong>10b</strong> exerts anti-neuroinflammatory effects in LPS-stimulated BV-2 microglial cells by modulating key inflammatory pathways, including NF-κB and MAPK signaling.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"216 ","pages":"Article 109588"},"PeriodicalIF":2.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143534689","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":"Steroids from the mushroom Ganoderma shandongense and their AChE inhibitory activities","authors":"Yaqin Huo ,&nbsp;Shiyuan Ma ,&nbsp;Xihan He ,&nbsp;Yuxi Wang ,&nbsp;Haisheng Yuan","doi":"10.1016/j.steroids.2025.109574","DOIUrl":"10.1016/j.steroids.2025.109574","url":null,"abstract":"<div><div>Investigation of the solid culture of <em>Ganoderma shandongense</em> led to the isolation of 15 compounds, including one new steroid (compound <strong>1</strong>) and fourteen known ones (compounds <strong>2</strong>–<strong>15</strong>). Their structures were determined via extensive the nuclear magnetic resonance (NMR) spectroscopic analyses and quantum chemical calculations. Compounds <strong>3</strong>, <strong>9</strong>, and <strong>14</strong> exhibited inhibitory activities against acetylcholinesterase (AChE), with half maximal inhibitory concentration (IC₅₀) values of 29.4, 29.4 and 33.2 µM, respectively. Furthermore, molecular docking studies were undertaken to elucidate the interaction mechanisms between the compounds and the amino acid residues of AChE.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"216 ","pages":"Article 109574"},"PeriodicalIF":2.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143504290","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":"Analysis of genes implicated in non-obstructive azoospermia","authors":"Junwei Wang ,&nbsp;Shuhui Wang ,&nbsp;Meng Wang ,&nbsp;Jinfei Yang","doi":"10.1016/j.steroids.2025.109583","DOIUrl":"10.1016/j.steroids.2025.109583","url":null,"abstract":"<div><div>Non-obstructive azoospermia (NOA) is the most common cause of male infertility, accounting for approximately 60 % of azoospermia cases. In recent years, gene mutations have emerged as the primary factor under investigation for the etiology of NOA. Therefore, finding the cause and pathogenesis of NOA at the genetic level has become one of the current research hotspots. Genetic analysis of NOA patients revealed that gene mutations primarily concentrate in protein-coding regions and non-coding RNAs, predominantly occurring in cases of non-obstructive azoospermia. Hence, understanding the relationship between these gene mutations and NOA can not only provide new ideas for treatment, but also provide a theoretical basis for revealing the pathogenesis of NOA. This article comprehensively reviews recent advancements in identifying genes that are intricately associated with azoospermia. These results will provide meaningful guidance for the future development of NOA-targeted therapeutic drugs.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"216 ","pages":"Article 109583"},"PeriodicalIF":2.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143519861","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":"Unraveling binding interactions between methasterone and bovine serum albumin (BSA): A spectroscopic and computational study","authors":"Sahar Khurshid ,&nbsp;Saima Rasheed ,&nbsp;Sven Falke ,&nbsp;Malik Shoaib Ahmad","doi":"10.1016/j.steroids.2025.109573","DOIUrl":"10.1016/j.steroids.2025.109573","url":null,"abstract":"<div><div>In this study, binding interactions between methasterone and bovine serum albumin (BSA) were analyzed using spectroscopic techniques and molecular docking. UV absorption spectroscopy showed the formation of a ground-state complex between methasterone and bovine serum albumin (BSA). Thermodynamic parameters from fluorometric analysis indicated that the hydrogen bonding and van der Waal forces were the main interacting forces between the complex and the reaction was found to be spontaneous. Molecular docking further validated it. Nano differential scanning fluorimetry showed the protein was found to be more thermally stable in the presence of methasterone. Circular dichroism spectroscopy revealed slight reduction in the helicity after binding with methasterone suggesting conformational changes to promote binding. As no prior information exists on the binding interactions between methasterone and BSA, this study provides insights into methasterone-BSA interactions, which can serve as a foundation for future investigations into its pharmacological properties.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"215 ","pages":"Article 109573"},"PeriodicalIF":2.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143473027","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":"Effect of betulinic acid on MepA efflux pump inhibition in Staphylococcus aureus: Antibacterial and molecular study","authors":"Camila Aparecida Pereira da Silva ,&nbsp;Nara juliana Santos Araújo ,&nbsp;Cícera Datiane Morais Oliveira-Tintino ,&nbsp;José Maria Barbosa Filho ,&nbsp;Gabriel Gonçalves Alencar ,&nbsp;José Bezerra de Araújo-Neto ,&nbsp;Josefa Sayonara dos Santos ,&nbsp;Juliete Bezerra Soares ,&nbsp;Carolina Bandeira Domiciano ,&nbsp;Davi Antas e Silva ,&nbsp;Henrique Douglas Melo Coutinho ,&nbsp;Jacqueline Cosmo Andrade-Pinheiro","doi":"10.1016/j.steroids.2025.109572","DOIUrl":"10.1016/j.steroids.2025.109572","url":null,"abstract":"<div><div>Infections caused by pathogenic bacteria have been responsible for a significant number of deaths in recent decades. Invasive infections caused by <em>Staphylococcus aureus</em> are highly prevalent and have high morbidity and mortality rates. Faced with the increase in multidrug-resistant bacteria, a promising strategy is the development of adjuvant molecules that enhance the effects of antibiotics, such as efflux pump inhibitors. Betulinic acid (BA) is a pentacyclic triterpene of the lupane type, found in various plant species, which has shown various pharmacological activities, including antibacterial potential. This study investigated the inhibitory action of BA on the MepA efflux pump in strains of <em>Staphylococcus aureus</em> K2068, as well as carrying out fluorescence and membrane permeability tests. The minimum inhibitory concentrations (MIC) were determined using the broth microdilution method. Subsequently, their effects on efflux pump-mediated antibiotic resistance were evaluated by reducing the MIC of the antibiotic and ethidium bromide (EtBr), while fluorimetry and permeability potential tests were carried out using the SYTOX Green fluorescence method. BA did not show intrinsic antibacterial activity, however it showed synergistic effects when associated with the antibiotics ciprofloxacin and ethidium bromide, inducing a reduction in MIC and indicating inhibitory effects on the MepA efflux pump. BA also induced a significant increase in fluorescence and demonstrated the ability to permeabilize the bacterial membrane. The results obtained show that BA has a high potential to act as an efflux pump inhibitor and could help in the treatment of resistant bacterial infections.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"215 ","pages":"Article 109572"},"PeriodicalIF":2.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143415358","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":"Extraction of diosgenin using different techniques from fenugreek seeds- A review","authors":"Sharavan Kumar ,&nbsp;B.M. Praveen ,&nbsp;Aralihalli Sudhakara ,&nbsp;Prajwal Sherugar ,&nbsp;Yashoda Malgar Puttaiahgowda","doi":"10.1016/j.steroids.2024.109543","DOIUrl":"10.1016/j.steroids.2024.109543","url":null,"abstract":"<div><div>Diosgenin, falls under the category of steroidal saponin present in fenugreek seeds (<em>Trigonella foenum-graecum</em>) in the amount of 0.2–09%. This compound possesses certain pharmacological characteristics like anti-inflammatory, anti-cancer, anti-oxidant etc., that render it a desirable component in the medicinal and nutraceutical industries. Various methods such as, conventional solvent extraction, green extraction methods like Soxhlet extraction, microwave-assisted extraction (MAE), maceration methods, ultrasound-assisted extraction (UAE) and supercritical fluid extraction methods are employed to extract diosgenin from fenugreek seeds. Fundamentals such as solvent choice, pre-treatment techniques, and optimization parameters, affect the diosgenin extraction process. Furthermore, the quantification of diosgenin is governed by analytical methods(chromatography and spectroscopy), underscoring the significance of standardizing diosgenin levels to set the stage for upcoming pharmacological research. However there have been very negligible resources which focuses on conventional and novel techniques for extraction of diosgenin from Fenugreek seeds. This review aims to provide combined insights into the diverse methodologies employed for diosgenin extraction from fenugreek seeds and their implications in pharmaceutical research.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"214 ","pages":"Article 109543"},"PeriodicalIF":2.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142795210","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":"The effect of resistance training and nandrolone decanoate administration on cardiac tissue in mice","authors":"Yechiel Atias,&nbsp;Tavor Ben-Zeev,&nbsp;Chagai Levi,&nbsp;Lior Binman,&nbsp;Jay R. Hoffman","doi":"10.1016/j.steroids.2024.109559","DOIUrl":"10.1016/j.steroids.2024.109559","url":null,"abstract":"<div><div><strong>Purpose:</strong> This study examined the effect of resistance training (RT) by itself and in combination with supraphysiological administration of nandrolone decanoate (ND) on the inflammatory, apoptotic, and oxidative stress response in cardiac tissue. The effect of the training and androgen intervention on adiponectin expression, a potential cardio protectant was also examined. <strong>Methods:</strong> Forty male C57Bl/6J mice, 3 months of age were randomized into four groups (n = 10 per group). Two groups of animals performed a 3-day per week RT program for 7-weeks, while the other two groups remained sedentary (SED). The RT and SED animals were further randomized into an androgen group (RTA and SEDA, respectively) or a sham group (RTS and SEDS, respectively). Animals in the RTA and SEDA groups received 38-mg·kg⁻¹ injected once per week. Mice from RTS and SEDS received sham injections. <strong>Results:</strong> Main effects for group indicated that RT resulted in significant elevations in NFκβ (p &lt; 0.001), glutamine peroxidase (GPX) (p = 0.007) and adiponectin (p &lt; 0.001). Main effects for treatment indicated that ND administration resulted in greater elevations in NFκβ (p = 0.01) and TNF-α (p = 0.017). In addition, TNF-α expression was greater in RTA compared to RETS (p = 0.006) and the adiponectin response in RTA was greater (p’s &lt; 0.05) than all other groups. A significant correlation was noted between average training volume during the RT program and GPX expression (r = 0.716, p &lt; 0.001). <strong>Conclusion:</strong> Results indicate that RT and ND administration can increase markers of apoptosis and inflammation. Elevations in adiponectin expression suggest that it may act as a compensatory mechanism supporting cardiovascular health.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"214 ","pages":"Article 109559"},"PeriodicalIF":2.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915689","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 of novel α-spinasterol derivatives and their inhibitory effects on CCL17 and CCL22 chemokine expression","authors":"Hyejin Moon ,&nbsp;Hongjoon Yoon ,&nbsp;Hana Jung,&nbsp;Tae Hoon Lee,&nbsp;Hakwon Kim","doi":"10.1016/j.steroids.2024.109553","DOIUrl":"10.1016/j.steroids.2024.109553","url":null,"abstract":"<div><div>Natural α-spinasterol is well known for its various biological activities. In this study, we investigated the anti-inflammatory effects of newly synthesized α-spinasterol derivatives by tracking the expression of CCL17 and CCL22 chemokines, which serve as biomarkers for immune cell trafficking in skin inflammation. Initially, the 3-epimer of α-spinasterol, which results from inversion of stereochemistry at the C-3 position of α-spinasterol, was synthesized using the Mitsunobu reaction. Subsequently, new compounds were synthesized by introducing azido, amino, and amide groups at the C-3 position of α-spinasterol or 3-<em>epi</em>-α-spinasterol. The anti-inflammatory activity of these compounds was evaluated by examining their inhibitory effects on the mRNA expression of CCL17 and CCL22. Among these derivatives, 3α-<strong>8</strong>, 3α-<strong>12b</strong>, and 3α-<strong>12c</strong> exhibited potential anti-inflammatory activity <em>in vitro</em>, compared to α-spinasterol. Furthermore, compound 3α-<strong>8</strong> showed even greater activity than 3α-<strong>12b</strong> and 3α-<strong>12c</strong>, underscoring its potential as a highly effective agent. These results suggest that the newly synthesized α-spinasterol derivatives hold promise as candidates for skin inflammation therapeutics.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"214 ","pages":"Article 109553"},"PeriodicalIF":2.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812970","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":"Allosteric communications between domains of nuclear receptors","authors":"Fraydoon Rastinejad","doi":"10.1016/j.steroids.2024.109551","DOIUrl":"10.1016/j.steroids.2024.109551","url":null,"abstract":"<div><div>Nuclear receptors (NRs) regulate gene expression in response to hormonal signals, influencing diverse physiological processes and diseases. Structural and dynamics investigations based on X-ray crystallography, cryo-electron microscopy (cryo-EM), hydrogen–deuterium exchange mass spectrometry, and molecular dynamics simulations, have significantly deepened our understanding of the conformational states, dynamics, and interdomain interactions of multi-domain NRs. Structural studies have examined heterodimeric complexes such as peroxisome proliferator-activated receptor gamma (PPAR-γ) with retinoid X receptor alpha (RXRα), liver X receptor beta (LXRβ) with RXRα, and retinoic acid receptor beta (RARβ) with RXRα, as well as homodimers like hepatic nuclear factor 4 alpha (HNF-4α), androgen receptor (AR), and glucocorticoid receptor (GR). These investigations highlight critical allosteric communication between ligand-binding domains (LBDs) and DNA-binding domains (DBDs), emphasizing the roles of flexible hinge regions and <em>N</em>-terminal segments in adapting to diverse DNA configurations. Both non-steroid receptor heterodimers and homodimers exhibit robust interdomain connections that mediate allosteric signaling. For instance, AR demonstrates three distinct conformational states that underscore its dynamic behavior, while GR exhibits unique ligand-dependent domain interactions shaping receptor signaling. The collective findings so far suggest a conserved mechanism of cross-domain communication across the NR family. Supported by complementary biophysical, spectroscopic, mutagenesis, and computational studies, this body of research has elucidated the nature of domain-domain interfaces and their pivotal roles in regulating the transcriptional activity of steroid and non-steroid receptors.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"214 ","pages":"Article 109551"},"PeriodicalIF":2.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142802309","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":"Improved synthesis and characterization of bile acid esters: Organogelation and supramolecular properties","authors":"Jair García-Méndez ,&nbsp;Adolfo López-Torres ,&nbsp;María A. Fernández-Herrera","doi":"10.1016/j.steroids.2025.109560","DOIUrl":"10.1016/j.steroids.2025.109560","url":null,"abstract":"<div><div>Bile acid esters and their derivatives hold significant interest due to their applications in fields such as supramolecular chemistry, biomedicine, and nanomaterials. This study revisits the synthesis and characterization of esters derived from cholic, deoxycholic, and lithocholic acids using short-chain alcohols in combination with microwave-assisted heating. The synthesized esters were analyzed for their potential as gel-forming agents, and their organogelation properties were evaluated. Microwave-assisted synthesis offers rapid and efficient esterification, leading to high yields with improved selectivity. The organogels were characterized through techniques such as differential scanning calorimetry (DSC) and scanning electron microscopy (SEM), revealing distinct structural and thermal properties. The study highlights the potential of these bile acid esters in materials science and supramolecular chemistry, contributing to the development of novel functional materials.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"214 ","pages":"Article 109560"},"PeriodicalIF":2.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142967028","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}