首页 > 最新文献

Steroids最新文献

英文 中文
Antifungal ergostane-type steroids from endophytic fungus Xylaria sp. VDL4 内生真菌Xylaria sp. VDL4抗真菌麦角酮型类固醇。
IF 2.3 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-01-01 Epub Date: 2025-11-22 DOI: 10.1016/j.steroids.2025.109722
Jiao Yao , Lin-Hong Lu , Sheng-Yun Wei , Ting Wu , Wei Yang , Wei-Hua Wang , Fa-Zhong Yang , Yun-Xian Li , Ping Zhao , Guo-Lei Zhu
Three ergostane-type steroids, including one rare C-29 methylated xylarstane A (1) and one C22,23-epoxied xylarstane B (2), along with one reported compound 3, were isolated from the endophytic fungus Xylaria sp. VDL4 harbored within the medicinal plant Vaccinium dunalianum. The structures of novel compounds were elucidated through comprehensive spectroscopic analysis, DP4+-validated theoretical 13C nuclear magnetic resonance (NMR) calculations, and electronic circular dichroism (ECD) calculations. The antifungal activities of the isolates against four phytopathogens were assessed in vitro. Compounds 1 and 3 exerted significant inhibition against Alternaria solani and Botrytis cinerea respectively, both with minimal inhibitory concentration (MIC) of 12.5 μg/mL, comparing with the positive control (Carbendazim and Thiabendazole, MICs = 12.5–25.0 μg/mL).
从药用植物dunalianum中的内生真菌Xylaria sp. VDL4中分离到3个麦角甾类化合物,包括1个罕见的C-29甲基化木larstane A(1)和1个C22,23-环氧化木larstane B(2),以及1个已报道的化合物3。通过综合光谱分析、DP4+验证的理论13C核磁共振(NMR)计算和电子圆二色性(ECD)计算,对新化合物的结构进行了阐明。体外鉴定了分离物对4种植物病原菌的抑菌活性。与阳性对照(多菌灵和噻苯达唑,MIC = 12.5 ~ 25.0 μg/mL)相比,化合物1和3对番茄赤霉和灰霉菌分别具有显著的抑制作用,最小抑制浓度(MIC)均为12.5 μg/mL。
{"title":"Antifungal ergostane-type steroids from endophytic fungus Xylaria sp. VDL4","authors":"Jiao Yao ,&nbsp;Lin-Hong Lu ,&nbsp;Sheng-Yun Wei ,&nbsp;Ting Wu ,&nbsp;Wei Yang ,&nbsp;Wei-Hua Wang ,&nbsp;Fa-Zhong Yang ,&nbsp;Yun-Xian Li ,&nbsp;Ping Zhao ,&nbsp;Guo-Lei Zhu","doi":"10.1016/j.steroids.2025.109722","DOIUrl":"10.1016/j.steroids.2025.109722","url":null,"abstract":"<div><div>Three ergostane-type steroids, including one rare C-29 methylated xylarstane A (<strong>1</strong>) and one C22,23-epoxied xylarstane B (<strong>2</strong>), along with one reported compound <strong>3</strong>, were isolated from the endophytic fungus <em>Xylaria</em> sp. VDL4 harbored within the medicinal plant <em>Vaccinium dunalianum</em>. The structures of novel compounds were elucidated through comprehensive spectroscopic analysis, DP4<sup>+</sup>-validated theoretical <sup>13</sup>C nuclear magnetic resonance (NMR) calculations, and electronic circular dichroism (ECD) calculations. The antifungal activities of the isolates against four phytopathogens were assessed <em>in vitro.</em> Compounds <strong>1</strong> and <strong>3</strong> exerted significant inhibition against <em>Alternaria solani</em> and <em>Botrytis cinerea</em> respectively, both with minimal inhibitory concentration (MIC) of 12.5 μg/mL, comparing with the positive control (Carbendazim and Thiabendazole, MICs = 12.5–25.0 μg/mL).</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"225 ","pages":"Article 109722"},"PeriodicalIF":2.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145597679","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}
引用次数: 0
Cortisol-to-cortisone and testosterone-to-androstenedione concentration ratios in nails: Their determination methods based on LC/MS/MS and differences from the serum concentration ratios in the literature 指甲中皮质醇与可的松、睾酮与雄烯二酮的浓度比:基于LC/MS/MS的测定方法及与文献中血清浓度比的差异
IF 2.3 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-01-01 Epub Date: 2025-11-02 DOI: 10.1016/j.steroids.2025.109707
Himena Ishikawa, Sakurako Tanaka, Kenjiro Shibata, Tatsuya Higashi
A fingernail clipping is expected to be a specimen suited for the detection of the medium-to-long term abnormal production of steroids. There are reports demonstrating that the concentration ratios of cortisol (F) to cortisone (E) and testosterone (T) to androstenedione (AD) in nails are significantly different from those in serum. However, the concentration ratios in the nails were determined with a small number of samples in some instances and differed from study to study, in addition to which, their gender differences remain poorly understood. Determining the differences in the concentration ratios between the nails and serum with a sufficient number of samples by gender and discussing a factor causing these differences will help for an accurate interpretation of the results in the nail-based steroid tests. In this study, we first developed and validated liquid chromatography/electrospray ionization-tandem mass spectrometry methods for determining the F/E and T/AD ratios in thumbnail clippings, then demonstrated that the F/E (in both sexes) and T/AD (in male) ratios in the nails were significantly lower than those in the serum reported in the literature. We found that steroids which are present at the higher concentrations in the nail than expected from their serum concentrations, such as E and AD, are bound to albumin at a high rate in the serum. As the affinities of corticoids and androgens to albumin are low (Ka, 103–104 M−1), we concluded that the albumin-bound fractions can be the sources of the nail-incorporated steroids as well as the free fractions.
指甲修剪有望成为一个标本适合检测中长期异常生产的类固醇。有报道表明,指甲中皮质醇(F)与可的松(E)和睾酮(T)与雄烯二酮(AD)的浓度比与血清中有显著差异。然而,在某些情况下,指甲中的浓度比是用少量样本确定的,并且在研究中有所不同,除此之外,它们的性别差异仍然知之甚少。在有足够数量的样本的情况下,按性别确定指甲和血清之间的浓度比率差异,并讨论造成这些差异的因素,将有助于准确解释基于指甲的类固醇测试结果。在这项研究中,我们首先建立并验证了液相色谱/电喷雾电离-串联质谱法测定指甲剪报中的F/E和T/AD比值,然后证明指甲中的F/E(两性)和T/AD(男性)比值明显低于文献报道的血清。我们发现,在指甲中存在的类固醇浓度高于其血清浓度,如E和AD,在血清中以高速率与白蛋白结合。由于皮质激素和雄激素对白蛋白的亲和力较低(Ka, 103-104 M−1),我们得出结论,白蛋白结合部分可能是指甲结合类固醇和游离部分的来源。
{"title":"Cortisol-to-cortisone and testosterone-to-androstenedione concentration ratios in nails: Their determination methods based on LC/MS/MS and differences from the serum concentration ratios in the literature","authors":"Himena Ishikawa,&nbsp;Sakurako Tanaka,&nbsp;Kenjiro Shibata,&nbsp;Tatsuya Higashi","doi":"10.1016/j.steroids.2025.109707","DOIUrl":"10.1016/j.steroids.2025.109707","url":null,"abstract":"<div><div>A fingernail clipping is expected to be a specimen suited for the detection of the medium-to-long term abnormal production of steroids. There are reports demonstrating that the concentration ratios of cortisol (F) to cortisone (E) and testosterone (T) to androstenedione (AD) in nails are significantly different from those in serum. However, the concentration ratios in the nails were determined with a small number of samples in some instances and differed from study to study, in addition to which, their gender differences remain poorly understood. Determining the differences in the concentration ratios between the nails and serum with a sufficient number of samples by gender and discussing a factor causing these differences will help for an accurate interpretation of the results in the nail-based steroid tests. In this study, we first developed and validated liquid chromatography/electrospray ionization-tandem mass spectrometry methods for determining the F/E and T/AD ratios in thumbnail clippings, then demonstrated that the F/E (in both sexes) and T/AD (in male) ratios in the nails were significantly lower than those in the serum reported in the literature. We found that steroids which are present at the higher concentrations in the nail than expected from their serum concentrations, such as E and AD, are bound to albumin at a high rate in the serum. As the affinities of corticoids and androgens to albumin are low (<em>Ka</em>, 10<sup>3</sup>–10<sup>4</sup> M<sup>−1</sup>), we concluded that the albumin-bound fractions can be the sources of the nail-incorporated steroids as well as the free fractions.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"225 ","pages":"Article 109707"},"PeriodicalIF":2.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145442332","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}
引用次数: 0
Dehydroepiandrosterone impact on smooth muscle contractile activity by a nongenomic action 脱氢表雄酮通过非基因组作用影响平滑肌收缩活动
IF 2.3 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-01-01 Epub Date: 2025-11-14 DOI: 10.1016/j.steroids.2025.109717
Mercedes Perusquía
Dehydroepiandrosterone (DHEA) is the most abundant steroid hormone in primates; however, its levels decline with age in both men and women. Numerous studies have documented diverse biological activities of DHEA. This article reviews the current understanding of how DHEA regulates the contractile function of vascular and nonvascular smooth muscle (SM), specifically examining its relaxant properties mediated through nongenomic mechanisms. It summarizes both older and recent findings on DHEA and its role in regulating SM contractile activity. Moreover, it also discusses the potential mechanisms underlying its relaxation effects, including the structural–functional differences in the DHEA molecule and its ability to induce relaxation in various types of SM. Overall, DHEA introduces a novel aspect to the regulation of functional processes involved in SM contractile activity.
脱氢表雄酮(DHEA)是灵长类动物体内含量最多的类固醇激素;然而,在男性和女性中,它的水平都会随着年龄的增长而下降。大量研究证明了脱氢表雄酮的多种生物活性。本文综述了目前对DHEA如何调节血管和非血管平滑肌(SM)收缩功能的理解,特别是通过非基因组机制研究其松弛特性。它总结了DHEA的旧的和最近的发现和它在调节SM收缩活动中的作用。此外,它还讨论了其松弛作用的潜在机制,包括DHEA分子的结构-功能差异及其在不同类型SM中诱导松弛的能力。总的来说,脱氢表雄酮引入了一个新的方面,涉及SM收缩活动的功能过程的调节。
{"title":"Dehydroepiandrosterone impact on smooth muscle contractile activity by a nongenomic action","authors":"Mercedes Perusquía","doi":"10.1016/j.steroids.2025.109717","DOIUrl":"10.1016/j.steroids.2025.109717","url":null,"abstract":"<div><div>Dehydroepiandrosterone (DHEA) is the most abundant steroid hormone in primates; however, its levels decline with age in both men and women. Numerous studies have documented diverse biological activities of DHEA. This article reviews the current understanding of how DHEA regulates the contractile function of vascular and nonvascular smooth muscle (SM), specifically examining its relaxant properties mediated through nongenomic mechanisms. It summarizes both older and recent findings on DHEA and its role in regulating SM contractile activity. Moreover, it also discusses the potential mechanisms underlying its relaxation effects, including the structural–functional differences in the DHEA molecule and its ability to induce relaxation in various types of SM. Overall, DHEA introduces a novel aspect to the regulation of functional processes involved in SM contractile activity.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"225 ","pages":"Article 109717"},"PeriodicalIF":2.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145518585","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}
引用次数: 0
Semi-synthetic sapogenin derivatives inhibit inflammation-induced tumorigenic signaling alterations in prostate carcinogenesis 半合成皂苷元衍生物抑制前列腺癌发生中炎症诱导的致瘤信号改变。
IF 2.3 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-01-01 Epub Date: 2025-11-23 DOI: 10.1016/j.steroids.2025.109723
Bilge Debelec-Butuner , Mert Burak Ozturk , Ozgur Tag , Ismail Hakki Akgun , Erdal Bedir
Prostatic inflammation plays a pivotal role in prostate cancer development and progression via altering key cellular mechanisms, including proliferation, metastasis, and angiogenesis. Therefore, the use of anti-inflammatory drugs could provide a valid contribution to PCa prevention and treatment. In our research, we explored semi-synthetic derivatives of cycloastragenol (CA) and astragenol (AG) to assess their potential to inhibit inflammation-mediated tumorigenic signaling.
Building on our previous findings, which demonstrated their inhibitory activity on NFκB, we discovered that these molecules also suppress inflammation-induced cell proliferation and migration through distinct mechanisms. They effectively alleviated inflammation by reducing levels of ROS, NO, and VEGF expression. Furthermore, these molecules partially restored the expression of AR and the tumor suppressor NKX3.1, both of which are critical in prostate tumorigenesis within an inflammatory microenvironment. They also reversed inflammation-induced activation of Akt and β-catenin signaling, suggesting their potential to inhibit inflammation-related prostate tumorigenesis. Our study further demonstrated that these molecules exhibited dose-dependent effects on inducing cell cycle arrest and apoptosis, as evidenced by increased p21 and decreased BCL-2 protein levels, leading to activated cell death and suppressed cellular migration.
In conclusion, these semi-synthetic sapogenol derivatives demonstrate significant potential as anti-inflammatory and anticancer agents, offering a promising approach for targeting prostatic inflammation and inflammation-driven prostate carcinogenesis.
前列腺炎症通过改变关键的细胞机制,包括增殖、转移和血管生成,在前列腺癌的发生和发展中起着关键作用。因此,使用抗炎药物可以为PCa的预防和治疗提供有效的贡献。在我们的研究中,我们探索了环黄芪醇(CA)和黄芪醇(AG)的半合成衍生物,以评估它们抑制炎症介导的致瘤信号传导的潜力。在我们之前的研究结果的基础上,我们发现这些分子对NFκB具有抑制活性,我们发现这些分子也通过不同的机制抑制炎症诱导的细胞增殖和迁移。它们通过提高ROS、NO和VEGF的表达水平有效地减轻炎症。此外,这些分子部分恢复了AR和肿瘤抑制因子NKX3.1的表达,这两者在炎症微环境下的前列腺肿瘤发生中都是至关重要的。它们还逆转了炎症诱导的Akt和β-catenin信号的激活,表明它们有抑制炎症相关前列腺肿瘤发生的潜力。我们的研究进一步证明,这些分子在诱导细胞周期阻滞和凋亡方面表现出剂量依赖性,p21升高,BCL-2蛋白水平降低,导致细胞活化死亡,抑制细胞迁移。总之,这些半合成皂苷醇衍生物显示出作为抗炎和抗癌药物的巨大潜力,为针对前列腺炎症和炎症驱动的前列腺癌提供了一种有希望的方法。
{"title":"Semi-synthetic sapogenin derivatives inhibit inflammation-induced tumorigenic signaling alterations in prostate carcinogenesis","authors":"Bilge Debelec-Butuner ,&nbsp;Mert Burak Ozturk ,&nbsp;Ozgur Tag ,&nbsp;Ismail Hakki Akgun ,&nbsp;Erdal Bedir","doi":"10.1016/j.steroids.2025.109723","DOIUrl":"10.1016/j.steroids.2025.109723","url":null,"abstract":"<div><div>Prostatic inflammation plays a pivotal role in prostate cancer development and progression via altering key cellular mechanisms, including proliferation, metastasis, and angiogenesis. Therefore, the use of anti-inflammatory drugs could provide a valid contribution to PCa prevention and treatment. In our research, we explored semi-synthetic derivatives of cycloastragenol (<strong>CA</strong>) and astragenol (<strong>AG</strong>) to assess their potential to inhibit inflammation-mediated tumorigenic signaling.</div><div>Building on our previous findings, which demonstrated their inhibitory activity on NFκB, we discovered that these molecules also suppress inflammation-induced cell proliferation and migration through distinct mechanisms. They effectively alleviated inflammation by reducing levels of ROS, NO, and VEGF expression. Furthermore, these molecules partially restored the expression of AR and the tumor suppressor NKX3.1, both of which are critical in prostate tumorigenesis within an inflammatory microenvironment. They also reversed inflammation-induced activation of Akt and β-catenin signaling, suggesting their potential to inhibit inflammation-related prostate tumorigenesis. Our study further demonstrated that these molecules exhibited dose-dependent effects on inducing cell cycle arrest and apoptosis, as evidenced by increased p21 and decreased BCL-2 protein levels, leading to activated cell death and suppressed cellular migration.</div><div>In conclusion, these semi-synthetic sapogenol derivatives demonstrate significant potential as anti-inflammatory and anticancer agents, offering a promising approach for targeting prostatic inflammation and inflammation-driven prostate carcinogenesis.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"225 ","pages":"Article 109723"},"PeriodicalIF":2.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145605725","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}
引用次数: 0
Exposure-response of serum biomarkers to vamorolone, a dissociative corticosteroidal anti-inflammatory drug, in 4- to <7-year children 4- 7岁以下儿童血清生物标志物对游离性皮质甾体抗炎药——氨莫洛酮的暴露反应
IF 2.3 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-01-01 Epub Date: 2025-11-19 DOI: 10.1016/j.steroids.2025.109721
Swati Mummidivarpu , Utkarsh J. Dang , Michael Ziemba , Yetrib Hathout , Paula R. Clemens , Jesse Damsker , Laura Hagerty , William J. Jusko , Edward C. Smith , Jean K. Mah , Michela Guglieri , Yoram Nevo , Nancy Kuntz , Craig M. McDonald , Monique M. Ryan , Diana Castro , Richard S. Finkel , Laurie S. Conklin , John M. McCall , Kanneboyina Nagaraju , Eric P. Hoffman

Objectives

Corticosteroid agonists of the glucocorticoid receptor are a mainstay of therapeutics for pro-inflammatory conditions. Vamorolone is a novel partial agonist that is differentiated from the other members of the corticosteroid class by non-metabolism by 11β-hydroxysteroid dehydrogenases, antagonism of the mineralocorticoid receptor, and differential co-factor binding. Our objective was to define the pharmacodynamic response of serum proteins to vamorolone.

Methods

Clinical trial participants with Duchenne muscular dystrophy (4 to <7 yr; n = 39; mean [SD] age = 5.3 [1.0]) enrolled in a multiple ascending dose study of vamorolone were studied (24-fold dose range). Dose-response and exposure–response of 1,305 serum proteins were defined by intra-subject longitudinal changes (baseline vs. Day 14).

Results

Dose-response analysis identified 159 of 1,305 serum proteins as dose-responsive to vamorolone (12 % of proteins tested; 20 % increased, 80 % decreased). Two inflammatory networks showed drug-responsive suppression. One centered on extracellular serine proteases and lymphotoxins (PI3, KLK7, KLK8, KLK11, lymphotoxins A, B) converging on NFκB. The second centered on cytokines (CCL22/MDC, CCL21, CCL14, CXCL12) and IL23 signaling. In the IL23 network, acutely responsive anti-inflammatory proteins included increases of an inhibitor of IL17 signaling (IL17RC) and decreases of IL23 (IL12B:IL23A). A protein associated with resistance to environmental microbes, PTP1C, showed strong induction and is a novel candidate for aspects of corticosteroid efficacy. Two networks of cell-associated proteins were identified as drug responsive that may represent muscle tissue response (efficacy): connective tissue remodeling upstream of Notch signaling, and plasma membrane proteins impinging on AKT1 signaling.

Conclusion

The serum proteome pharmacodynamics of the response to vamorolone was defined.
目的:糖皮质激素受体的皮质类固醇激动剂是治疗促炎条件的主要药物。Vamorolone是一种新型的部分激动剂,与其他皮质类固醇类药物不同,它不被11β-羟基类固醇脱氢酶代谢,对矿物皮质激素受体具有拮抗作用,并与差异辅因子结合。我们的目的是确定血清蛋白对氨摩洛酮的药效学反应。结果:剂量反应分析发现1305种血清蛋白中有159种对氨莫洛酮有剂量反应(12% %检测蛋白,20% %升高,80% %降低)。两个炎症网络显示药物反应性抑制。一个集中在细胞外丝氨酸蛋白酶和淋巴毒素(PI3, KLK7, KLK8, KLK11,淋巴毒素A, B)上,它们聚集在NFκB上。第二个集中于细胞因子(CCL22/MDC, CCL21, CCL14, CXCL12)和il - 23信号。在il - 23网络中,急性反应性抗炎蛋白包括il - 17信号抑制剂(IL17RC)的增加和il - 23 (IL12B:IL23A)的减少。一种与环境微生物耐药性相关的蛋白PTP1C显示出很强的诱导作用,是皮质类固醇疗效方面的新候选蛋白。两个细胞相关蛋白网络被确定为药物反应,可能代表肌肉组织反应(功效):Notch信号上游的结缔组织重塑和影响AKT1信号的质膜蛋白。结论:确定了对氨莫洛酮反应的血清蛋白质组药效学。
{"title":"Exposure-response of serum biomarkers to vamorolone, a dissociative corticosteroidal anti-inflammatory drug, in 4- to <7-year children","authors":"Swati Mummidivarpu ,&nbsp;Utkarsh J. Dang ,&nbsp;Michael Ziemba ,&nbsp;Yetrib Hathout ,&nbsp;Paula R. Clemens ,&nbsp;Jesse Damsker ,&nbsp;Laura Hagerty ,&nbsp;William J. Jusko ,&nbsp;Edward C. Smith ,&nbsp;Jean K. Mah ,&nbsp;Michela Guglieri ,&nbsp;Yoram Nevo ,&nbsp;Nancy Kuntz ,&nbsp;Craig M. McDonald ,&nbsp;Monique M. Ryan ,&nbsp;Diana Castro ,&nbsp;Richard S. Finkel ,&nbsp;Laurie S. Conklin ,&nbsp;John M. McCall ,&nbsp;Kanneboyina Nagaraju ,&nbsp;Eric P. Hoffman","doi":"10.1016/j.steroids.2025.109721","DOIUrl":"10.1016/j.steroids.2025.109721","url":null,"abstract":"<div><h3>Objectives</h3><div>Corticosteroid agonists of the glucocorticoid receptor are a mainstay of therapeutics for pro-inflammatory conditions. Vamorolone is a novel partial agonist that is differentiated from the other members of the corticosteroid class by non-metabolism by 11β-hydroxysteroid dehydrogenases, antagonism of the mineralocorticoid receptor, and differential co-factor binding. Our objective was to define the pharmacodynamic response of serum proteins to vamorolone.</div></div><div><h3>Methods</h3><div>Clinical trial participants with Duchenne muscular dystrophy (4 to &lt;7 yr; n = 39; mean [SD] age = 5.3 [1.0]) enrolled in a multiple ascending dose study of vamorolone were studied (24-fold dose range). Dose-response and exposure–response of 1,305 serum proteins were defined by intra-subject longitudinal changes (baseline vs. Day 14).</div></div><div><h3>Results</h3><div>Dose-response analysis identified 159 of 1,305 serum proteins as dose-responsive to vamorolone (12 % of proteins tested; 20 % increased, 80 % decreased). Two inflammatory networks showed drug-responsive suppression. One centered on extracellular serine proteases and lymphotoxins (PI3, KLK7, KLK8, KLK11, lymphotoxins A, B) converging on NFκB. The second centered on cytokines (CCL22/MDC, CCL21, CCL14, CXCL12) and IL23 signaling. In the IL23 network, acutely responsive anti-inflammatory proteins included increases of an inhibitor of IL17 signaling (IL17RC) and decreases of IL23 (IL12B:IL23A). A protein associated with resistance to environmental microbes, PTP1C, showed strong induction and is a novel candidate for aspects of corticosteroid efficacy. Two networks of cell-associated proteins were identified as drug responsive that may represent muscle tissue response (efficacy): connective tissue remodeling upstream of Notch signaling, and plasma membrane proteins impinging on AKT1 signaling.</div></div><div><h3>Conclusion</h3><div>The serum proteome pharmacodynamics of the response to vamorolone was defined.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"225 ","pages":"Article 109721"},"PeriodicalIF":2.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145565177","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}
引用次数: 0
Discovery of dihydrobetulinic acid as a potent small molecule CD73 inhibitor 二氢白桦酸作为一种有效的CD73小分子抑制剂的发现。
IF 2.3 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-01-01 Epub Date: 2025-11-19 DOI: 10.1016/j.steroids.2025.109719
Hongling Wang , Yanming Zhang , Chunyang Lou , Xuliang Chang , Hang Yang , Daozuan Zhang , Haijun Ma , Zhenyuan Miao
Betulinic acid (BA) is a pentacyclic triterpene compound with various biological activities. Herein, we designed and synthesized a series of dihydrobetulinic acid (DHBA) and its derivatives for the discovery of potent ecto-5′-nucleotidase (CD73) inhibitors. Biological evaluation of DHBA and its derivatives led to the disclosure of three active compounds DHBA, ZM792 and ZM905. Further investigation of antitumor immunity revealed that DHBA could effectively restore the function of CD4+ T cells. These results provide novel insights for future endeavors in developing novel agents derived from natural product targeting CD73 enzyme.
白桦酸(BA)是一种具有多种生物活性的五环三萜化合物。在此,我们设计并合成了一系列二氢白桦酸(DHBA)及其衍生物,以发现有效的外5'-核苷酸酶(CD73)抑制剂。通过对DHBA及其衍生物的生物学评价,发现了三种活性化合物DHBA、ZM792和ZM905。进一步的抗肿瘤免疫研究发现,DHBA能有效恢复CD4+ T细胞的功能。这些结果为未来开发靶向CD73酶的天然产物衍生的新型药物提供了新的见解。
{"title":"Discovery of dihydrobetulinic acid as a potent small molecule CD73 inhibitor","authors":"Hongling Wang ,&nbsp;Yanming Zhang ,&nbsp;Chunyang Lou ,&nbsp;Xuliang Chang ,&nbsp;Hang Yang ,&nbsp;Daozuan Zhang ,&nbsp;Haijun Ma ,&nbsp;Zhenyuan Miao","doi":"10.1016/j.steroids.2025.109719","DOIUrl":"10.1016/j.steroids.2025.109719","url":null,"abstract":"<div><div>Betulinic acid (BA) is a pentacyclic triterpene compound with various biological activities. Herein, we designed and synthesized a series of dihydrobetulinic acid (DHBA) and its derivatives for the discovery of potent ecto-5′-nucleotidase (CD73) inhibitors. Biological evaluation of DHBA and its derivatives led to the disclosure of three active compounds DHBA, <strong>ZM792</strong> and <strong>ZM905</strong>. Further investigation of antitumor immunity revealed that DHBA could effectively restore the function of CD4<sup>+</sup> T cells. These results provide novel insights for future endeavors in developing novel agents derived from natural product targeting CD73 enzyme.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"225 ","pages":"Article 109719"},"PeriodicalIF":2.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145565144","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}
引用次数: 0
Protective effect of vitamin D on high-fat-diet-induced metabolic dysfunction-associated steatotic liver disease in mice 维生素D对小鼠高脂肪饮食诱导的代谢功能障碍相关脂肪变性肝病的保护作用
IF 2.3 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-01-01 Epub Date: 2025-11-17 DOI: 10.1016/j.steroids.2025.109718
Amal A. Mohamed , Wael Hafez , Said El-Feky , Mona G. Khalil , Amina S. Soliman , Karima Nasraldin , Ingy M. Ibrahim , Hanan A. Hegazy , Weam Shaheen , Abbas M. Abbas , Hager Shaheen , Marian FL. Abdelmalak , Hany N. Azzam , Omnia Ezzat , Noheir Ashraf Ibrahem Fathy Hassan , Omer Al Dulaimi , Naglaa K. Madkour

Background

Genetics, inflammation, and nutrition contribute to the pathogenesis of metabolic dysfunction–associated steatotic liver disease (MASLD).

Aim

This preclinical study evaluated the protective effect of vitamin D supplementation against high-fat-diet–induced MASLD in a mouse model and compared physiological, inflammatory, and molecular responses across high-fat and low-fat dietary regimens, with and without vitamin D co-administration.

Methods

Forty-five healthy male albino Swiss mice (aged 6 weeks; 30 ± 10 g) were randomly assigned to five groups (n = 9 each): control (standard diet), HFD (high-fat diet), HFD + vitamin D, LFD (low-fat diet), and LFD + vitamin D. Vitamin D (20 000 IU/kg/week) was administered via drinking water for 12 weeks. Body weight, visceral adiposity, and liver indices were recorded, while serum biochemical markers, inflammatory cytokines, and expression of Toll-like receptor 7 (TLR7) and microRNA-155 (miR-155) were analyzed at endpoint.

Results

HFD-fed mice exhibited marked increases in ALT (51.44 ± 9.68 U/L), AST (56.67 ± 13.29 U/L), ALP (135.01 ± 16.19 U/L), AFP (28.56 ± 5.31 ng/mL), CRP (20.87 ± 5.56 mg/L), total cholesterol (225.00 ± 27.16 mg/dL), LDL (137.56 ± 28.66 mg/dL), and triglycerides (210.56 ± 28.71 mg/dL), accompanied by reduced HDL (30.24 ± 9.86 mg/dL) compared with controls. Pro-inflammatory cytokines TNF-α (28.33 ± 2.96 pg/mL), IL-6 (121.78 ± 8.98 pg/mL), and the expression of TLR7 (2.92 ± 0.83) and miR-155 (2.75 ± 0.77) were significantly elevated relative to normal-fed mice (miR-155: 0.84 ± 0.26). Vitamin D supplementation significantly ameliorated these metabolic and inflammatory disturbances.

Conclusions

Vitamin D supplementation mitigated HFD-induced hepatic injury, dyslipidemia, and inflammatory activation by modulating the miR-155/TLR7 axis. These findings highlight vitamin D as a potential adjunctive strategy for preventing or attenuating MASLD progression under high-fat dietary conditions.
背景:遗传、炎症和营养与代谢功能障碍相关的脂肪变性肝病(MASLD)的发病机制有关。目的:本临床前研究在小鼠模型中评估了维生素D补充对高脂肪饮食诱导的MASLD的保护作用,并比较了高脂肪和低脂肪饮食方案在有和没有维生素D联合给药的情况下的生理、炎症和分子反应。方法:健康雄性瑞士白化小鼠45只(6 周,30 ± 10 g),随机分为5组(每组 = 9只):对照组(标准饮食)、HFD(高脂饮食)、HFD +维生素D、LFD(低脂饮食)和LFD +维生素D。维生素D(20000 IU/kg/周)通过饮用水给予,持续12 周。记录体重、内脏脂肪和肝脏指标,并在终点分析血清生化指标、炎症因子、toll样受体7 (TLR7)和microRNA-155 (miR-155)的表达。结果:HFD-fed老鼠表现出显著增加ALT(51.44 ±9.68 U / L)、AST(56.67 ±13.29 U / L),高山(135.01 ±16.19 U / L),法新社(28.56 ±5.31  ng / mL)、c反应蛋白(20.87 ±  5.56 mg / L),总胆固醇(225.00 ±27.16  mg / dL),低密度脂蛋白(137.56 ±28.66  mg / dL),和甘油三酯(210.56 ±28.71  mg / dL),伴随着降低高密度脂蛋白(30.24 ±9.86  mg / dL)与控制。 促炎细胞因子TNF -α(28.33±2.96  pg / mL), il - 6(121.78 ±8.98  pg / mL),和TLR7的表达式(2.92 ±0.83 )和mir - 155(2.75 ± 0.77)显著升高相对于normal-fed老鼠(mir - 155: 0.84 ±0.26 )。补充维生素D可显著改善这些代谢和炎症紊乱。结论:补充维生素D可通过调节miR-155/TLR7轴减轻hfd诱导的肝损伤、血脂异常和炎症激活。这些发现强调了维生素D作为预防或减轻高脂肪饮食条件下MASLD进展的潜在辅助策略。
{"title":"Protective effect of vitamin D on high-fat-diet-induced metabolic dysfunction-associated steatotic liver disease in mice","authors":"Amal A. Mohamed ,&nbsp;Wael Hafez ,&nbsp;Said El-Feky ,&nbsp;Mona G. Khalil ,&nbsp;Amina S. Soliman ,&nbsp;Karima Nasraldin ,&nbsp;Ingy M. Ibrahim ,&nbsp;Hanan A. Hegazy ,&nbsp;Weam Shaheen ,&nbsp;Abbas M. Abbas ,&nbsp;Hager Shaheen ,&nbsp;Marian FL. Abdelmalak ,&nbsp;Hany N. Azzam ,&nbsp;Omnia Ezzat ,&nbsp;Noheir Ashraf Ibrahem Fathy Hassan ,&nbsp;Omer Al Dulaimi ,&nbsp;Naglaa K. Madkour","doi":"10.1016/j.steroids.2025.109718","DOIUrl":"10.1016/j.steroids.2025.109718","url":null,"abstract":"<div><h3>Background</h3><div>Genetics, inflammation, and nutrition contribute to the pathogenesis of metabolic dysfunction–associated steatotic liver disease (MASLD).</div></div><div><h3>Aim</h3><div>This preclinical study evaluated the protective effect of vitamin D supplementation against high-fat-diet–induced MASLD in a mouse model and compared physiological, inflammatory, and molecular responses across high-fat and low-fat dietary regimens, with and without vitamin D co-administration.</div></div><div><h3>Methods</h3><div>Forty-five healthy male albino Swiss mice (aged 6 weeks; 30 ± 10 g) were randomly assigned to five groups (n = 9 each): control (standard diet), HFD (high-fat diet), HFD + vitamin D, LFD (low-fat diet), and LFD + vitamin D. Vitamin D (20 000 IU/kg/week) was administered via drinking water for 12 weeks. Body weight, visceral adiposity, and liver indices were recorded, while serum biochemical markers, inflammatory cytokines, and expression of Toll-like receptor 7 (TLR7) and microRNA-155 (miR-155) were analyzed at endpoint.</div></div><div><h3>Results</h3><div>HFD-fed mice exhibited marked increases in ALT (51.44 ± 9.68 U/L), AST (56.67 ± 13.29 U/L), ALP (135.01 ± 16.19 U/L), AFP (28.56 ± 5.31 ng/mL), CRP (20.87 ± 5.56 mg/L), total cholesterol (225.00 ± 27.16 mg/dL), LDL (137.56 ± 28.66 mg/dL), and triglycerides (210.56 ± 28.71 mg/dL), accompanied by reduced HDL (30.24 ± 9.86 mg/dL) compared with controls. Pro-inflammatory cytokines TNF-α (28.33 ± 2.96 pg/mL), IL-6 (121.78 ± 8.98 pg/mL), and the expression of TLR7 (2.92 ± 0.83) and miR-155 (2.75 ± 0.77) were significantly elevated relative to normal-fed mice (miR-155: 0.84 ± 0.26). Vitamin D supplementation significantly ameliorated these metabolic and inflammatory disturbances.</div></div><div><h3>Conclusions</h3><div>Vitamin D supplementation mitigated HFD-induced hepatic injury, dyslipidemia, and inflammatory activation by modulating the miR-155/TLR7 axis. These findings highlight vitamin D as a potential adjunctive strategy for preventing or attenuating MASLD progression under high-fat dietary conditions.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"225 ","pages":"Article 109718"},"PeriodicalIF":2.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145557784","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}
引用次数: 0
Nutrient manipulation regulates growth and steroidal alkaloid production in plant cultures of Solanum viarum Dunal 营养调控对龙葵生长和甾体生物碱产生的影响。
IF 2.3 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-12-01 Epub Date: 2025-10-15 DOI: 10.1016/j.steroids.2025.109700
Archana Prasad , Preeti Patel , Abhishek Niranjan , Gauri Saxena , Debasis Chakrabarty
Solanum viarum is a valuable medicinal plant native to India and widely distributed throughout Asia. It serves as a commercially viable raw source for the steroidal drug industry, being the richest natural source of an important steroidal alkaloid- solasodine. Enhancement of solasodine content in in vitro plant cultures is always a keen interest for tissue culturists for the research and development in pharmaceutical industries. In the present study, a multiple linear regression (MLR) model was employed to investigate the synergistic effects of key nutrient components in the growth medium (Mg, Ca, Fe, N, and sucrose) for optimized growth and solasodine production in in vitro plant cultures of S. viarum. All the cultures were harvested after 35, 45, and 55 days of the culture cycle. The three models were designed to predict growth index, solasodine content, and solasodine yield in the plant cultures. The designed model was further evaluated by performing a validation experiment using ten different experimental setups, which showed a greater similarity between the predicted and experimental datasets. The results of the model-based experimental set showed that 1.4 mM Mg, 2.9 mM Ca, 1.9 µM Fe, 41.9 mM Nitrogen, and 4 % (w/v) sucrose resulted in achieving maximum solasodine yield (108.82 mg/g DW) in the plant culture of S. viarum after 54 days of harvest. The proposed MLR model offers a robust and reliable approach for predicting the optimal concentrations of micro- and macronutrients to maximize growth and solasodine accumulation in in vitro cultures of Solanum viarum. This study establishes a strategic framework that can be leveraged to enhance biomass production and secondary metabolite yield, contributing significantly to the large-scale cultivation and pharmaceutical exploitation of this valuable medicinal plant.
龙葵(Solanum viarum)是一种原产于印度的珍贵药用植物,在亚洲广泛分布。它作为一种商业上可行的甾体药物工业原料来源,是一种重要的甾体生物碱- solasodine的最丰富的天然来源。提高植物离体培养物中solasodine的含量一直是制药行业组织培养研究和开发的热点。本研究采用多元线性回归(MLR)模型,研究了生长培养基中关键营养成分(Mg、Ca、Fe、N和蔗糖)对紫葡萄(S. viarum)体外培养物生长和产茄碱的协同效应。在培养周期的35、45和55 天后收获所有的培养物。这三个模型被设计用来预测植物生长指数、茄碱含量和茄碱产量。通过使用10种不同的实验设置进行验证实验,进一步评估设计的模型,结果表明预测数据集与实验数据集之间具有更大的相似性。基于模型的实验结果表明,收获54 d后,1.4 mM Mg、2.9 mM Ca、1.9 µM Fe、41.9 mM Nitrogen和4 % (w/v)蔗糖的植株培养可获得最大的solasodine产量(108.82 Mg /g DW)。所提出的MLR模型提供了一种稳健可靠的方法来预测微量营养素和宏量营养素的最佳浓度,以最大限度地提高龙葵体外培养物的生长和茄碱积累。本研究建立了一个战略框架,可用于提高生物质产量和次生代谢物产量,为这种珍贵药用植物的大规模种植和药用开发做出重大贡献。
{"title":"Nutrient manipulation regulates growth and steroidal alkaloid production in plant cultures of Solanum viarum Dunal","authors":"Archana Prasad ,&nbsp;Preeti Patel ,&nbsp;Abhishek Niranjan ,&nbsp;Gauri Saxena ,&nbsp;Debasis Chakrabarty","doi":"10.1016/j.steroids.2025.109700","DOIUrl":"10.1016/j.steroids.2025.109700","url":null,"abstract":"<div><div><em>Solanum viarum</em> is a valuable medicinal plant native to India and widely distributed throughout Asia. It serves as a commercially viable raw source for the steroidal drug industry, being the richest natural source of an important steroidal alkaloid- solasodine. Enhancement of solasodine content in <em>in vitro</em> plant cultures is always a keen interest for tissue culturists for the research and development in pharmaceutical industries. In the present study, a multiple linear regression (MLR) model was employed to investigate the synergistic effects of key nutrient components in the growth medium (Mg, Ca, Fe, N, and sucrose) for optimized growth and solasodine production in <em>in vitro</em> plant cultures of <em>S. viarum</em>. All the cultures were harvested after 35, 45, and 55 days of the culture cycle. The three models were designed to predict growth index, solasodine content, and solasodine yield in the plant cultures. The designed model was further evaluated by performing a validation experiment using ten different experimental setups, which showed a greater similarity between the predicted and experimental datasets. The results of the model-based experimental set showed that 1.4 mM Mg, 2.9 mM Ca, 1.9 µM Fe, 41.9 mM Nitrogen, and 4 % (w/v) sucrose resulted in achieving maximum solasodine yield (108.82 mg/g DW) in the plant culture of <em>S. viarum</em> after 54 days of harvest<em>.</em> The proposed MLR model offers a robust and reliable approach for predicting the optimal concentrations of micro- and macronutrients to maximize growth and solasodine accumulation in <em>in vitro</em> cultures of <em>Solanum viarum</em>. This study establishes a strategic framework that can be leveraged to enhance biomass production and secondary metabolite yield, contributing significantly to the large-scale cultivation and pharmaceutical exploitation of this valuable medicinal plant.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"224 ","pages":"Article 109700"},"PeriodicalIF":2.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145313632","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}
引用次数: 0
Soy isoflavone Daidzein resembling the vertebrate steroid structure exhibits neuroprotection via mitochondrial biogenesis in rotenone induced Parkinson’s disease in preclinical model 类似脊椎动物类固醇结构的大豆异黄酮大豆苷元在鱼藤酮诱导的帕金森病的临床前模型中通过线粒体生物发生显示出神经保护作用。
IF 2.3 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-12-01 Epub Date: 2025-10-20 DOI: 10.1016/j.steroids.2025.109703
Vaibhavi Peshattiwar , Suraj Muke , Aakruti Kaikini , Sneha Bagle , Vikas Dighe , Sadhana Sathaye
Parkinson’s disease (PD) ranks as the second most prevalent neurodegenerative disorder but is still devoid of neuroprotective treatment. Although approaches with disease modifying ability along with symptomatic relief has become an utmost necessity, the multifactorial nature of PD presents challenges for efficacy evaluation of potential test compound. This study attempts to address these issues by employing a rotenone induced PD model involving intranigral rotenone injection for evaluation of the neuroprotective efficacy of Daidzein (DZ) a soy isoflavone and a phytoestrogen. In this study, male Sprague Dawley rats after bilateral intranigral rotenone (12 μg) injection, were treated with DZ at a dose of 5, 10 and 20 mg/kg for 30 days. The neurobehavioral evaluation comprised of Rota-rod, Open field and Barnes maze test. The biochemical analysis constituting oxidative stress (Reduced glutathione, superoxide dismutase, catalase and lipid peroxidation), inflammation (TNF-α), mitochondrial alteration (complex I activity and biogenesis) was conducted on mid-brain tissue after 30 days of treatment. The Substantia nigra and striatum were subjected to immunohistochemical analysis (IHC) for TH positive neurons and Glial Fibrillary Acidic Protein. The analysis revealed significant improvement by daidzein in motor co-ordination and attenuation in cognitive deficits due to rotenone. The biochemical assessment exhibited significant decrement in oxidative stress as well as inflammation. DZ treatment also prevented complex I inhibition and promoted mitochondrial biogenesis eventually contributing to the neuroprotection apparent in IHC. Thus, the results strongly corroborate the neuroprotective potential of DZ against rotenone induced model of PD.
帕金森病(PD)是第二常见的神经退行性疾病,但仍然缺乏神经保护治疗。尽管具有疾病改变能力和症状缓解能力的方法已经成为当务之急,但帕金森病的多因素特性给潜在试验化合物的疗效评估带来了挑战。本研究试图通过鱼藤酮诱导PD模型来解决这些问题,该模型涉及鱼藤酮内注射,以评估大豆异黄酮大豆苷元(DZ)和植物雌激素的神经保护作用。雄性大鼠双侧注射鱼藤酮(12 μg)后,分别给予5、10和20 mg/kg剂量的DZ治疗30 天。神经行为评估包括旋转棒、开放场和巴恩斯迷宫测试。治疗30 d后,对中脑组织进行氧化应激(还原性谷胱甘肽、超氧化物歧化酶、过氧化氢酶和脂质过氧化)、炎症(TNF-α)、线粒体改变(复合体I活性和生物发生)的生化分析。对大鼠黑质和纹状体进行TH阳性神经元和胶质纤维酸性蛋白的免疫组化分析。分析显示,大豆苷元在运动协调和减轻鱼藤酮引起的认知缺陷方面有显著改善。生化评估显示氧化应激和炎症显著降低。DZ治疗还可以阻止复合物I的抑制,促进线粒体的生物发生,最终促进IHC中明显的神经保护。因此,结果有力地证实了DZ对鱼藤酮诱导的PD模型的神经保护作用。
{"title":"Soy isoflavone Daidzein resembling the vertebrate steroid structure exhibits neuroprotection via mitochondrial biogenesis in rotenone induced Parkinson’s disease in preclinical model","authors":"Vaibhavi Peshattiwar ,&nbsp;Suraj Muke ,&nbsp;Aakruti Kaikini ,&nbsp;Sneha Bagle ,&nbsp;Vikas Dighe ,&nbsp;Sadhana Sathaye","doi":"10.1016/j.steroids.2025.109703","DOIUrl":"10.1016/j.steroids.2025.109703","url":null,"abstract":"<div><div>Parkinson’s disease (PD) ranks as the second most prevalent neurodegenerative disorder but is still devoid of neuroprotective treatment. Although approaches with disease modifying ability along with symptomatic relief has become an utmost necessity, the multifactorial nature of PD presents challenges for efficacy evaluation of potential test compound. This study attempts to address these issues by employing a rotenone induced PD model involving intranigral rotenone injection for evaluation of the neuroprotective efficacy of Daidzein (DZ) a soy isoflavone and a phytoestrogen. In this study, male Sprague Dawley rats after bilateral intranigral rotenone (12 μg) injection, were treated with DZ at a dose of 5, 10 and 20 mg/kg for 30 days. The neurobehavioral evaluation comprised of Rota-rod, Open field and Barnes maze test. The biochemical analysis constituting oxidative stress (Reduced glutathione, superoxide dismutase, catalase and lipid peroxidation), inflammation (TNF-α), mitochondrial alteration (complex I activity and biogenesis) was conducted on mid-brain tissue after 30 days of treatment. The Substantia nigra and striatum were subjected to immunohistochemical analysis (IHC) for TH positive neurons and Glial Fibrillary Acidic Protein. The analysis revealed significant improvement by daidzein in motor co-ordination and attenuation in cognitive deficits due to rotenone. The biochemical assessment exhibited significant decrement in oxidative stress as well as inflammation. DZ treatment also prevented complex I inhibition and promoted mitochondrial biogenesis eventually contributing to the neuroprotection apparent in IHC. Thus, the results strongly corroborate the neuroprotective potential of DZ against rotenone induced model of PD.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"224 ","pages":"Article 109703"},"PeriodicalIF":2.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145337455","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}
引用次数: 0
Etienne Baulieu – In Memorial (1927–2025) 艾蒂安·鲍留——纪念(1927-2025)
IF 2.3 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-12-01 Epub Date: 2025-11-03 DOI: 10.1016/j.steroids.2025.109684
Trevor M. Penning (Editor-in-Chief STEROIDS)
{"title":"Etienne Baulieu – In Memorial (1927–2025)","authors":"Trevor M. Penning (Editor-in-Chief STEROIDS)","doi":"10.1016/j.steroids.2025.109684","DOIUrl":"10.1016/j.steroids.2025.109684","url":null,"abstract":"","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"224 ","pages":"Article 109684"},"PeriodicalIF":2.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145517276","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}
引用次数: 0
期刊
Steroids
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1