IF 2.3 4区医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Steroids

Pub Date : 2026-01-09 DOI: 10.1016/j.steroids.2026.109746

Lourin Nasr Aziz, Mohamed Omar Mahmoud, Ibrahim Taha Ibrahim

Background

Dexamethasone-induced hyperlipidemia is a well-documented metabolic complication associated with prolonged glucocorticoid therapy. The present study aims to investigate the potential protective effects of the selected natural antioxidants luteolin and oleuropein against dexamethasone-induced hyperlipidemia.

Methodology

The study was conducted on five groups of female Wistar rats, including a normal control group, a dexamethasone-induced hyperlipidemia group, and three treatment groups. The treatment groups consisted of dexamethasone-administered rats receiving luteolin or oleuropein (100 mg/kg BW) individually or in combination (luteolin + oleuropein) for a duration of one month.

Results

Dexamethasone induced hyperlipidemia, hepatic injury, and oxidative stress, as evidenced by increased levels of aspartate aminotransferase (AST; +154%), alanine aminotransferase (ALT; +121%), total cholesterol (TC; +75%), triglycerides (+132%), and malondialdehyde (+85%), while reducing catalase and glutathione by approximately 50.5% and 62%, respectively, compared with the control group. Treatment with either luteolin or oleuropein individually mitigated these changes (AST: −47.0% and − 46.4%; ALT: −37.2% and − 36.4%; TC: −34.8% and − 33.1%; triglycerides: −41.7% and − 40.5%; malondialdehyde: −28.4% and − 26.0%; catalase: +79.2% and + 74.8%; and glutathione: +104.8% and + 102.3%, respectively). Combined treatment provided the greatest protection, and histological examination revealed partial restoration of normal hepatic architecture.

Conclusion

The study suggests that luteolin and oleuropein help counteract dexamethasone-induced hyperlipidemia. Their administration reduced oxidative stress and liver enzyme levels (AST, ALT, and ALP) and improved lipid profiles, indicating their potential as therapeutic agents against glucocorticoid-related metabolic disturbances. The enhanced effectiveness observed in the combined treatment groups likely reflects synergistic activity between these compounds.

地塞米松诱导的高脂血症是一种有充分证据的代谢并发症，与长期糖皮质激素治疗有关。本研究旨在探讨天然抗氧化剂木犀草素和橄榄菊素对地塞米松诱导的高脂血症的潜在保护作用。方法采用5组雌性Wistar大鼠，包括正常对照组、地塞米松诱导高脂血症组和3个治疗组。给药组由地塞米松给药大鼠单独或联合（木犀草素+橄榄苦苷）给予木犀草素或橄榄苦苷（100 mg/kg BW），疗程1个月。结果地塞米松诱导高脂血症、肝损伤和氧化应激，表现为天冬氨酸转氨酶（AST; +154%）、丙氨酸转氨酶（ALT; +121%）、总胆固醇（TC; +75%）、甘油三酯（+132%）和丙二醛（+85%）水平升高，而过氧化氢酶和谷胱甘肽水平分别较对照组降低约50.5%和谷胱甘肽水平62%。木犀草素或橄榄苦苷单独治疗可减轻这些变化（AST: - 47.0%和- 46.4%;ALT: - 37.2%和- 36.4%;TC: - 34.8%和- 33.1%；甘油三酯：- 41.7%和- 40.5%；丙二醛：- 28.4%和- 26.0%；过氧化氢酶：+79.2%和+ 74.8%；谷胱甘肽：分别+104.8%和+ 102.3%）。综合治疗提供了最大的保护，组织学检查显示肝脏结构部分恢复正常。结论木犀草素和橄榄苦苷有助于对抗地塞米松诱导的高脂血症。它们的使用降低了氧化应激和肝酶水平（AST、ALT和ALP），改善了脂质谱，表明它们有潜力作为治疗糖皮质激素相关代谢紊乱的药物。在联合治疗组中观察到的增强效果可能反映了这些化合物之间的协同作用。

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引用次数: 0

Identification of multiple cardiotonic steroids in faecal material of untreated humans and rat strains. 未经处理的人和大鼠菌株粪便中多种强心类固醇的鉴定。

IF 2.3 4区医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Steroids

Pub Date : 2026-01-07 DOI: 10.1016/j.steroids.2026.109747

Zelie F Masso, Hannah Bint Ebrahim Mullah, Anza Thiba, Sarhana Dinat, Ekene E Nweke Supervisor, Gavin R Norton, Angela J Woodiwiss, A Duncan Cromarty, Geoffrey P Candy

Endogenous cardiotonic steroid (CTS) concentrations are raised in cardiovascular diseases. CTSs undergo gastro-hepatobiliary recirculation, with the gut being an important route of elimination, yet the presence of CTSs in faecal material is seldom reported. This study investigated methods to extract and identify the presence of CTSs in faecal material of rats and humans without prior treatment.

Methods: Freeze-dried faecal material from different untreated rat strains was extracted using various solvents, with separation and identification of CTSs using HPLC/MS. Preliminary results were obtained from human faecal material.

Results: Multiple CTSs were identified in faecal material, with marinobufagenin (MBG) predominant. Telocinobufagin was only detected in certain rat strains, whereas the extraction methods used did not recover ouabain. MBG and digoxin were elevated in Dahl salt sensitive rats fed supplementary salt. Bufalin was present in most spontaneously hypertensive rats (SHRs) but was not detectable in Wistar Kyoto rats (WKY). Conversely, digitoxin was detected in most WKYs but only few SHRs. Levels of digitoxin and bufalin remained relatively constant over 24 days in untreated rats. Solvent selection was critical in determining the CTSs extracted from human faecal material.

Conclusions: Multiple CTSs were detected in faecal material of untreated rats and humans Steroids varied between rat strains and aligned with phenotype. Extraction requires further solvent optimisation and the use of tandem MS/MS is essential to reliably detect the profile of CTSs present. Analysis of CTSs present in readily available faecal material will enable studies to determine relationships between CTSs, the microbiome and disease progression.

内源性强心剂类固醇（CTS）浓度在心血管疾病中升高。CTSs经过胃-肝胆再循环，肠道是重要的清除途径，但粪便中存在CTSs的报道很少。本研究探讨了在未经处理的情况下，从大鼠和人的粪便中提取和鉴定CTSs的方法。方法：采用不同溶剂提取不同处理大鼠菌株的冻干粪便，采用高效液相色谱/质谱法分离鉴定CTSs。初步结果是从人类粪便材料中获得的。结果：在粪便中发现多种CTSs，以marinobufagenin （MBG）为主。仅在某些大鼠菌株中检测到远端肌球蛋白，而所采用的提取方法无法回收瓦巴因。补充盐对达尔盐敏感大鼠MBG和地高辛升高。在大多数自发性高血压大鼠（SHRs）中存在蟾毒灵，但在Wistar Kyoto大鼠（WKY）中未检测到蟾毒灵。相反，在大多数WKYs中检测到洋地黄素，而在少数SHRs中检测到洋地黄素。在未经治疗的大鼠中，地黄霉素和蟾毒灵的水平在24 天内保持相对恒定。溶剂选择是确定从人类粪便中提取的CTSs的关键。结论：在未经治疗的大鼠和人的粪便中检测到多种CTSs，类固醇在大鼠品系之间存在差异，并与表型一致。萃取需要进一步的溶剂优化，串联质谱/质谱的使用对于可靠地检测cts的存在是必不可少的。对粪便中存在的CTSs进行分析将使研究能够确定CTSs、微生物组和疾病进展之间的关系。

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引用次数: 0

l-arginine mitigates endocrine and spermatogenesis disruptions in cisplatin-exposed male Wistar rats by modulating iNOS/NO/NF-kB and Nrf2/HO-1 signaling l-精氨酸通过调节iNOS/NO/NF-kB和Nrf2/HO-1信号通路，减轻顺铂暴露雄性Wistar大鼠的内分泌和精子发生中断。

IF 2.3 4区医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Steroids

Pub Date : 2025-12-18 DOI: 10.1016/j.steroids.2025.109738

O.O. Obembe , G.A. Oyeniyi , P.J. Ashonibare , T.M. Akhigbe , E.A. Ashamu , R.E. Akhigbe

Background

Even though cisplatin is highly effective in cancer treatment, its toxicity to non-target organs, such as the testes, remains a concern. Studies have shown that cisplatin induces testicular toxicity by activating an oxido-inflammatory response. Conversely, arginine exerts antioxidant and anti-inflammatory properties. Aim: Hence, the current study assessed the impact of arginine on cisplatin-induced testicular toxicity. In addition, the involvements of iNOS/NO/NF-kB and Nrf2/HO-1 signaling, which are key pathways in cisplatin toxicity, were probed. Materials and methods: Twenty-four male Wistar rats were acclimatized for two weeks and then randomized into 4 equal groups; control, arginine-treated, cisplatin-treated, and cisplatin + arginine-treated. Results: Arginine significantly attenuated cisplatin-induced reductions in sperm concentration, motility, and viability and increased the percentage of abnormal sperm morphology. More so, arginine markedly suppressed cisplatin-induced reductions in daily and total spermatid production, and circulating levels of GnRH, FSH, LH, and testosterone. Additionally, arginine improved cisplatin-induced distortion in testicular histology. These findings were associated with arginine-driven mitigation of cisplatin-induced rise in MDA, TNF-α, IL-6, IL-1β, iNOS, and NF-kB and cisplatin-induced decline in GSH, TAC, IL-10, NO, and Nrf2 levels and GR, SOD, catalase, and HO-1 activities. Conclusion: Summing up, arginine mitigated cisplatin-induced testicular endocrine and spermatogenesis disruption via the modulation of iNOS/NO/NF-kB and Nrf2/HO-1 signaling.

背景：尽管顺铂非常有效，但其对非靶器官的毒性，如睾丸毒性，仍然值得关注。研究表明，顺铂通过激活氧化炎症反应诱导睾丸毒性。相反，精氨酸具有抗氧化和抗炎特性。目的：因此，本研究评估精氨酸对顺铂致睾丸毒性的影响。此外，我们还探讨了顺铂毒性的关键通路iNOS/NO/NF-kB和Nrf2/HO-1信号通路的参与情况。材料与方法：将24只雄性Wistar大鼠驯化2周后随机分为4组；对照，精氨酸治疗，顺铂治疗，顺铂 + 精氨酸治疗。结果：精氨酸显著减轻顺铂引起的精子浓度、活力和活力降低，并增加异常精子形态的百分比。更重要的是，精氨酸显著抑制顺铂诱导的每日和总精子生成的减少，以及GnRH、FSH、LH和睾酮的循环水平。此外，精氨酸改善了顺铂引起的睾丸组织学扭曲。这些发现与精氨酸驱动的顺铂诱导的MDA、TNF-α、IL-6、IL-1β、iNOS和NF-kB升高的缓解以及顺铂诱导的GSH、TAC、IL-10、NO和Nrf2水平以及GR、SOD、过氧化氢酶和HO-1活性的下降有关。结论：综上所述，精氨酸通过调节iNOS/NO/NF-kB和Nrf2/HO-1信号通路减轻顺铂诱导的睾丸内分泌和精子发生的破坏。

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引用次数: 0

Novel heterosteroids induce anabolic effects in human skeletal muscle cells: An integrated analysis of anabolic and catabolic signaling pathways 新型异体类固醇诱导人类骨骼肌细胞的合成代谢作用：合成代谢和分解代谢信号通路的综合分析。

IF 2.3 4区医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Steroids

Pub Date : 2025-12-13 DOI: 10.1016/j.steroids.2025.109737

Linda Fabiola Pérez-Pérez , Gabriel Guerrero-Luna , Adrián Mendoza-Montalvo , Nadia Olazo-Márquez , Miguel López-Bartolo , Pedro Pablo González-Pérez , Jorge R. Juárez , Sylvain Bernès , Maura Cárdenas-García , María Guadalupe Hernández-Linares

The aim of this study was to investigate the anabolic potential of novel heterosteroids in human skeletal muscle cells. A library of new heterosteroids was synthesized by selectively modifying the A and B rings of steroidal sapogenins (diosgenin, sarsasapogenin, and hecogenin), with six library members (S1, D3, D5, D7, D8 and D13) subsequently tested in vitro. Compound selection was based on computational modeling intracellular signaling pathways regulating muscle hypertrophy and atrophy, coupled with pharmacological potential evaluation using cheminformatics tools.

The anabolic activity of these compounds was evaluated in the ATCC PCS-950–010 HSkM cell line, which represents normal human skeletal muscle cells. Among the compounds tested, D5 and D7 increased protein synthesis by approximately 22 % and 14 %, respectively. Compound D8 exhibited the most pronounced effect, increasing cell proliferation by approximately 50 %. Molecular docking and microarray analyses confirmed that D8 stimulates anabolism through AKT, ERK and MAPK activation, revealing the complex interplay between MAPK, PI3K and GPCR signaling pathways in the regulation of muscle cell proliferation. These findings suggest that compounds D8, D5, and D7 warrant further investigation in the context of muscle anabolism as potential therapeutic agents for targeting muscle atrophy.

本研究的目的是研究新型异体类固醇在人类骨骼肌细胞中的合成代谢潜力。通过选择性修饰甾体皂苷元（薯蓣皂苷元、菝葜皂苷元和异构体皂苷元）的A环和B环，合成了一个新的异源甾体文库，并对文库中的6个成员（S1、D3、D5、D7、D8和D13）进行了体外检测。化合物的选择基于调节肌肉肥大和萎缩的细胞内信号通路的计算建模，结合化学信息学工具的药理潜力评估。这些化合物的合成代谢活性在ATCC PCS-950-010 HSkM细胞系（代表正常的人类骨骼肌细胞）中进行了评估。在测试的化合物中，D5和D7分别增加了大约22 %和14 %的蛋白质合成。化合物D8表现出最显著的效果，增加细胞增殖约50% %。分子对接和芯片分析证实D8通过激活AKT、ERK和MAPK刺激合成代谢，揭示了MAPK、PI3K和GPCR信号通路在调节肌肉细胞增殖中的复杂相互作用。这些发现表明，在肌肉合成代谢的背景下，化合物D8、D5和D7作为针对肌肉萎缩的潜在治疗剂值得进一步研究。

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引用次数: 0

The effects of tamoxifen and its metabolites on circulating estrogen metabolites among pre- and postmenopausal women 他莫昔芬及其代谢物对绝经前和绝经后妇女循环雌激素代谢物的影响。

IF 2.3 4区医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Steroids

Pub Date : 2025-12-10 DOI: 10.1016/j.steroids.2025.109736

Rajrupa Ghosh , Ruth M. Pfeiffer , Cody Ramin , Xia Xu , Paul C. Turner , Xin He , Rebecca Troisi , Shaoqi Fan , Gretchen L. Gierach , Cher M. Dallal

Purpose

Circulating estrogen metabolites of the 2-, 4- or 16-hydroxyestrone (OH) pathways may be differentially associated with breast cancer risk due to varying estrogenic and genotoxic activity. However, little is known about the influence of tamoxifen, an effective endocrine therapy, or its metabolites on estrogen metabolism.

Methods

Among women referred to tamoxifen therapy, 15 circulating estrogens and estrogen metabolites (EMs) were measured at baseline (pre-tamoxifen) and 12 months post-tamoxifen initiation using liquid chromatography-tandem mass spectrometry. Changes in EMs were assessed among women postmenopausal at baseline (n = 23) using paired t-tests. Using linear regression, cross-sectional associations between circulating tamoxifen, its three metabolites, and EMs were assessed 12-months post-tamoxifen among pre- (n = 33) and postmenopausal women (n = 27; includes four women who transitioned to postmenopausal during follow-up).

Results

Twelve months post-tamoxifen initiation, mean total EM concentrations decreased by 13.8% among postmenopausal women, primarily driven by decreases in 2-OH (15.3%) and 16-OH (17.2%) metabolites (p < 0.05). Among women premenopausal at 12-month follow-up, circulating tamoxifen was positively associated with estrone (β = 1.24), estradiol (β =1.39), 2-OH metabolites (2-OHE1: β = 0.72, 2-ME1: β = 1.15), and all 16-OH metabolites (p < 0.05). The tamoxifen metabolite, endoxifen, was positively associated with estrone (β = 10.1) and estradiol (β = 12.4), and select 2-OH and 16-OH metabolites (p < 0.05). Positive associations were also observed between 4-hydroxy-tamoxifen and estrone, 2-OHE1, 2-ME1, 4-ME1, and E3 (p<0.05). Among postmenopausal women, only N-desmethyltamoxifen was significantly associated with 3ME1 (β = 0.18, p = 0.02).

Conclusion

Tamoxifen and its metabolites were associated with changes in circulating EMs. Further research is needed to understand tamoxifen-induced EM changes in breast cancer prevention and management.

目的：循环雌激素代谢产物的2-，4-或16-羟孕酮（OH）途径可能与乳腺癌的风险不同，由于不同的雌激素和基因毒性活性。然而，作为一种有效的内分泌治疗药物，它莫西芬及其代谢物对雌激素代谢的影响知之甚少。方法：在接受他莫昔芬治疗的女性中，采用液相色谱-串联质谱法测定了15种循环雌激素和雌激素代谢物（EMs）在基线（他莫昔芬治疗前）和他莫昔芬治疗后12 个月的水平。使用配对t检验评估绝经后妇女基线时EMs的变化（n = 23）。使用线性回归，评估了他莫昔芬循环及其三种代谢物和EMs在服用他莫昔芬12个月后在绝经前（n = 33）和绝经后妇女（n = 27；包括4名在随访期间过渡到绝经后的妇女）中的横断面关联。结果：在服用他莫昔芬12个月后，绝经后妇女的平均总EM浓度下降了13.8%，主要是由于2-OH（15.3% %）和16-OH（17.2% %）代谢物的减少（p ）。结论：他莫昔芬及其代谢物与循环EM的变化有关。需要进一步的研究来了解他莫昔芬诱导的乳腺癌预防和管理中的EM变化。

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引用次数: 0

Endoplasmic reticulum stress and steroidogenic dysfunction in Leydig cells: Molecular mechanisms of UPR-mediated testosterone regulation 间质细胞内质网应激和类固醇生成功能障碍：uprr介导的睾酮调节的分子机制。

IF 2.3 4区医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Steroids

Pub Date : 2025-12-08 DOI: 10.1016/j.steroids.2025.109735

Luc J. Martin

This review aims to synthesize current evidence on how endoplasmic reticulum (ER) stress affects steroidogenic function in Leydig cells. It explores the mechanisms by which ER stress activates the unfolded protein response (UPR) and autophagy pathways, ultimately influencing testosterone production and cellular homeostasis. The central research question addresses how ER stress–induced signaling modulates the transcriptional regulation of key steroidogenic enzymes and contributes to age-related declines in androgen synthesis. A comprehensive literature review was conducted using recent findings from molecular, cellular, and animal studies focusing on ER stress signaling in Leydig cells. Studies examining the roles of UPR branches (PERK, IRE1, and ATF6), autophagy pathways, and pharmacological or natural compounds modulating ER stress were analyzed to identify the regulatory mechanisms being involved and potential therapeutic implications. Evidence indicates that unresolved ER stress impairs testosterone biosynthesis by suppressing the expression of genes related to steroidogenesis. Specifically, activations of XBP1, ATF4 and ATF6, as well as their nuclear translocations, may lead to the transcriptional repression of these genes. Conversely, pharmacological ER stress inhibitors and natural antioxidants may restore these protein levels, enhance testosterone production, and improve Leydig cell function. A thorough understanding of the UPR and autophagy in Leydig cells is critical for addressing male reproductive health. ER stress is established as a key factor in the pathophysiology of impaired steroidogenesis. Therefore, targeting these stress response pathways presents a promising strategy for developing novel therapeutic interventions for testosterone deficiency and associated reproductive disorders.

本文综述了内质网应激对间质细胞类固醇生成功能的影响。它探讨了内质网应激激活未折叠蛋白反应（UPR）和自噬途径的机制，最终影响睾酮的产生和细胞稳态。研究的核心问题是内质网应激诱导的信号传导如何调节关键类固醇生成酶的转录调节，并导致与年龄相关的雄激素合成下降。我们利用分子、细胞和动物研究的最新发现对间质细胞内质网应激信号进行了全面的文献综述。研究分析了UPR分支（PERK， IRE1和ATF6），自噬途径以及调节内质网应激的药理学或天然化合物的作用，以确定所涉及的调节机制和潜在的治疗意义。有证据表明，未解决的内质网应激通过抑制激素生成相关基因的表达而损害睾酮的生物合成。具体来说，XBP1、ATF4和ATF6的激活及其核易位可能导致这些基因的转录抑制。相反，内质网应激抑制药物和天然抗氧化剂可以恢复这些蛋白质水平，增加睾酮的产生，改善间质细胞的功能。全面了解普遍定期循环和间质细胞的自噬对解决男性生殖健康问题至关重要。内质网应激已被确定为类固醇生成受损病理生理的关键因素。因此，针对这些应激反应途径提出了一个有希望的策略，为开发新的治疗干预睾丸激素缺乏和相关生殖障碍。

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引用次数: 0

The impact of reproductive steroids on autosomal dominant polycystic kidney disease progression in women 生殖类固醇对女性常染色体显性多囊肾病进展的影响

IF 2.3 4区医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Steroids

Pub Date : 2025-12-05 DOI: 10.1016/j.steroids.2025.109726

Noor Saeed Hasan, Warren Thomas

Autosomal dominant polycystic kidney disease (ADPKD) is a disease characterized by the growth of fluid filled cysts in the kidney. ADPKD arises due to a heritable mutation in the polycystic kidney disease 1 gene (PKD1) and polycystic kidney disease 2 gene (PKD2) ultimately leading to kidney failure. Incidence in males and females is equivalent, but differences arise in progression. This review brings together various studies regarding the impact of cyclic hormone changes on ADPKD progression, bringing attention to gaps in knowledge that needs to be addressed. Circulating hormones play a crucial role in the pathogenesis of the disease, particularly the renin angiotensin system. The physiological actions of estrogen tend to have a protective effect on the kidney, contributing to a slowed progression in females. The hormonal changes of the menstrual cycle and at menopause result in changes in pathology via blood pressure fluctuation, promotion of renal repair and prevention of renal scarring and damage. Signaling pathways that are involved in cyst growth such as cAMP, mTOR, MAPK/ERK, and PI3K/Akt are modulated by estrogen, providing insights into potential mechanisms. Estrogen-based hormonal therapy is being investigated for its efficacy in improving renal function post menopause.

常染色体显性多囊肾病（ADPKD）是一种以肾脏中充满液体的囊肿生长为特征的疾病。ADPKD是由多囊肾病1基因（PKD1）和多囊肾病2基因（PKD2）的遗传突变引起的，最终导致肾衰竭。男性和女性的发病率是相等的，但在进展中会出现差异。这篇综述汇集了关于循环激素变化对ADPKD进展影响的各种研究，引起了人们对需要解决的知识空白的关注。循环激素在疾病的发病机制中起着至关重要的作用，特别是肾素血管紧张素系统。雌激素的生理作用往往对肾脏有保护作用，有助于减缓女性的进展。月经周期和绝经期的激素变化通过血压波动、促进肾脏修复和预防肾脏瘢痕和损伤导致病理变化。参与囊肿生长的信号通路，如cAMP、mTOR、MAPK/ERK、PI3K/Akt等，均受雌激素调控，为进一步了解其潜在机制提供了依据。以雌激素为基础的激素治疗正在研究其改善绝经后肾功能的功效。

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引用次数: 0

An unexpected oxidative E/F ring opening in the side chain of steroid sapogenins produced by silica gel supported Jones Reagent 用硅胶支撑的琼斯试剂制备甾体皂苷元侧链上出现意外的氧化E/F环开口。

IF 2.3 4区医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Steroids

Pub Date : 2025-11-27 DOI: 10.1016/j.steroids.2025.109725

Juan E. Hernández-Martínez, Karen M. Ruíz-Pérez, Jacqueline Sanchez-Flores, Martin A. Iglesias-Arteaga

In contrast with previous results in which the spiroketal side chain of steroid sapogenin has proven to be unreactive to Jones Reagent, treatment these sapogenins with silica gel-supported Jones Reagent triggered the oxidative opening of the spirostanic side chain producing moderate to good yields of sapogenoic acids that bear carbonyl functions at C-16 and C-22 and a C-26 carboxylic group. Based on these findings, a procedure that allows the synthesis of sapogenoic acids minimizing contamination by chromium salts was designed.

与之前的结果相反，类固醇皂苷元的螺旋形侧链已被证明对琼斯试剂无反应，用硅胶支撑的琼斯试剂处理这些皂苷元触发螺旋形侧链的氧化打开，产生中等到良好产量的皂苷酸，这些皂苷酸具有C-16和C-22的羰基功能和C-26的羧基。基于这些发现，设计了一种程序，允许合成皂苷酸，最大限度地减少铬盐的污染。

引用次数: 0

LC-MS/MS quantitation of the primary reduced metabolites of progesterone in serum during the third trimester of human pregnancy reveals a potential role for 20β-hydroxyprogesterone and 5β-dihydroprogesterone in functional progesterone withdrawal LC-MS/MS定量测定人类妊娠晚期血清中孕酮的主要还原代谢产物揭示了20β-羟孕酮和5β-二氢孕酮在功能性孕酮停药中的潜在作用

IF 2.3 4区医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Steroids

Pub Date : 2025-11-24 DOI: 10.1016/j.steroids.2025.109724

Edward Hinchliffe , Alexander Heazell

Progesterone (P4) is an essential steroid hormone synthesised by the placenta required for the maintenance of pregnancy. In humans, the metabolism of P4 has been implicated in functional P4 withdrawal prior to parturition. We have developed a novel liquid chromatography tandem mass spectrometry (LC-MS/MS) method for quantitation in human serum of pregnenolone, P4 and its four primary reduced metabolites; 20α-hydroxyprogesterone (20α-OHP), 20β-hydroxyprogesterone (20β-OHP), 5α-dihydroprogesterone (5α-DHP) and 5β-dihydroprogesterone (5β-DHP). Following solid phase extraction, chromatographic baseline separation of each steroid was achieved using a biphenyl stationary phase within a 10.0 min runtime, followed by MS detection on a Sciex 6500+. The LC-MS/MS method was validated in accordance with published guidelines, confirming acceptable analytical performance pertaining to linearity, imprecision, accuracy, sensitivity, matrix effects, specificity and carryover. The method was applied to a large cohort of third trimester pregnancies with verified uncomplicated neonatal outcomes. Maternal circulating concentrations of P4, 20α-OHP, 20β-OHP, and 5α-DHP positively correlated with fetal gestational age. The ratio of P4:20β-OHP declined significantly throughout the third trimester, whilst the ratio of P4:5β-DHP increased at full term from 40 weeks’ gestation. These findings may indicate a substantive role for β-reduction of P4 in the mechanics of functional P4 withdrawal, either via depletion of the overall pool of bioactive P4 or competitive binding of these metabolites to the P4 receptor in maternal and fetal tissue. Additionally, detailed characterisation of the normal maternal steroidome will facilitate the study of dysregulated placental steroidogenesis, which has been implicated in the pathogenesis of the major obstetric syndromes causing poor pregnancy outcomes.

黄体酮（P4）是由胎盘合成的维持妊娠所需的必需类固醇激素。在人类中，P4的代谢与分娩前P4的功能性戒断有关。建立了一种新的液相色谱-串联质谱（LC-MS/MS）测定人血清中孕烯醇酮、P4及其四种主要还原代谢物的方法；20α-羟孕酮（20α-OHP）、20β-羟孕酮（20β-OHP）、5α-二氢孕酮（5α-DHP）和5β-二氢孕酮（5β-DHP）。固相萃取后，使用联苯固定相在10.0 min的运行时间内实现每种类固醇的色谱基线分离，然后在Sciex 6500+上进行质谱检测。根据发布的指南对LC-MS/MS方法进行了验证，确认了与线性、不精密度、准确性、灵敏度、基质效应、特异性和结转有关的可接受的分析性能。该方法应用于一个大队列的晚期妊娠证实无并发症的新生儿结局。母体循环P4、20α-OHP、20β-OHP、5α-DHP浓度与胎龄呈正相关。P4:20β-OHP比值在妊娠晚期显著下降，而P4:5β-DHP比值从妊娠40周开始在足月升高。这些发现可能表明β-减少P4在P4功能性戒断机制中的实质性作用，可能是通过耗尽P4的整体生物活性库，也可能是通过母体和胎儿组织中这些代谢物与P4受体的竞争性结合。此外，对正常母体甾体激素的详细描述将有助于研究胎盘甾体生成失调，这与导致妊娠结局不良的主要产科综合征的发病机制有关。

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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

Steroids

Pub 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。

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