IF 2.3 4区医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Steroids

Pub Date : 2026-02-01 DOI: 10.1016/j.steroids.2026.109750

Muhammad Hammad Mustafa, Fayyaz-Ur Rehman, Muhammad Ali, Mohsin Javed, Nazir Ahmad, Tayyaba Shafique, Ammar Zidan, Ali Bahadur, Shahid Iqbal, Sajid Mahmood, Abd-ElAziem Farouk, Ibrahim Jafri

引用次数: 0

Steroidal alkaloids: Exploring new therapeutic frontiers in cardiovascular diseases. 甾体生物碱：探索心血管疾病的新治疗前沿。

IF 2.3 4区医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Steroids

Pub Date : 2026-01-29 DOI: 10.1016/j.steroids.2026.109758

Madhura Bapat, Kalyani Barve

Cardiovascular diseases (CVDs) still remain one of the leading causes of mortality worldwide, requiring novel therapeutic approaches. Steroidal alkaloids, a unique class of naturally bioactive compounds, have showcased promising pharmacological qualities in cardiovascular health. This review article explores the structural classification, pharmacokinetics, and pharmacodynamics properties of such alkaloids, emphasizing their potential therapeutic effects in CVDs. Key cardiovascular activities of these alkaloids include antihypertensive, vasodilatory, antiarrhythmic, and lipid-lowering effects, primarily mediated through receptor interactions, ion channel modulation, and enzyme inhibition. Clinical and preclinical research studies provide preliminary proof of efficacy, though significant research gaps still remain, including very clinical trials and incomplete mechanistic understanding. Furthermore, safety concerns regarding dose-response relationships, toxicity, and drug interactions must be addressed before clinical translation. Novel trends such as, targeted delivery systems, synthetic derivatives and multi-targeted approaches throw light upon the future potential of alkaloids in cardiovascular therapy. This review establishes the need for well-designed clinical trials and structure-activity relationship (SAR) studies to optimize these molecules for cardiovascular drug development. Further research studies integrating omics technologies and exploring the role of steroidal alkaloids in rare cardiovascular disorders could increase their therapeutic applicability.

心血管疾病（cvd）仍然是世界范围内死亡的主要原因之一，需要新的治疗方法。甾体生物碱是一类独特的天然生物活性化合物，在心血管健康方面具有良好的药理作用。本文综述了这类生物碱的结构分类、药代动力学和药效学特性，强调了它们在心血管疾病中的潜在治疗作用。这些生物碱的主要心血管活性包括抗高血压、血管舒张、抗心律失常和降脂作用，主要通过受体相互作用、离子通道调节和酶抑制介导。临床和临床前研究提供了有效性的初步证据，尽管仍然存在重大的研究空白，包括非常临床的试验和不完整的机制理解。此外，在临床转化之前，必须解决有关剂量-反应关系、毒性和药物相互作用的安全问题。新的趋势，如靶向给药系统、合成衍生物和多靶向方法，揭示了生物碱在心血管治疗中的未来潜力。这篇综述建立了精心设计的临床试验和构效关系（SAR）研究的必要性，以优化这些分子用于心血管药物的开发。结合组学技术，进一步研究甾体生物碱在罕见心血管疾病中的作用，可以提高其治疗的适用性。

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引用次数: 0

LCA and 3-oxo-LCA mitigate dietary oxysterols-induced loss of barrier function in intestinal epithelial cells. LCA和3-氧-LCA可减轻膳食氧化甾醇诱导的肠上皮细胞屏障功能丧失。

IF 2.3 4区医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Steroids

Pub Date : 2026-01-28 DOI: 10.1016/j.steroids.2026.109749

Gayatri Reghu, Ashna Fathima, Narendran Swaminathan, Rajeev Sakhuja, Trinath Jamma

Loss of intestinal barrier integrity is a hallmark of many intestinal inflammations and associated diseases, including inflammatory bowel disease (IBD) and colorectal cancer (CRC). One of the primary factors contributing to intestinal epithelial barrier damage is a diet high in cholesterol. The non-enzymatically oxidized forms of dietary cholesterol, collectively known as oxysterols, have recently gained attention as mediators of various inflammatory conditions. In addition, oxysterols have been found to cause intestinal barrier damage via the loss of tight junction protein expression and promote inflammation. Secondary bile acids of host-gut microbial origin, and several other gut-microbiota-derived metabolites, are known to modulate intestinal inflammation. Here, we have studied the roles of two secondary bile acids in restoring barrier integrity and reducing the extent of dietary oxysterol-induced damage in intestinal epithelial cells. We found that oxysterols exert their damaging effects by inducing matrix metalloproteinases (MMP-2 and MMP-9) and activating NF-κB, which is coupled with the production of pro-inflammatory cytokines and chemokines (CCL2, CCL5, & IL-8). Additionally, we also show that the secondary bile acids lithocholic acid (LCA) and dehydrolithocholic acid (3-oxo-LCA) counteract dietary oxysterol-induced loss of barrier function (TEER & FITC-dextran flux). Overall, these findings provide supportive evidence for the potential role for secondary bile acids in maintaining barrier integrity and modulating inflammation in intestinal epithelial cells exposed to dietary oxysterols in vitro.

肠道屏障完整性的丧失是许多肠道炎症和相关疾病的标志，包括炎症性肠病（IBD）和结直肠癌（CRC）。导致肠上皮屏障受损的主要因素之一是高胆固醇饮食。膳食胆固醇的非酶氧化形式，统称为氧化甾醇，最近作为各种炎症条件的介质引起了人们的关注。此外，已发现氧化甾醇通过失去紧密连接蛋白的表达而引起肠道屏障损伤并促进炎症。宿主肠道微生物来源的次生胆汁酸，以及其他几种肠道微生物来源的代谢物，已知可调节肠道炎症。在这里，我们研究了两种次级胆汁酸在恢复肠屏障完整性和减少膳食氧化甾醇诱导的肠上皮细胞损伤程度中的作用。我们发现，氧甾醇通过诱导基质金属蛋白酶（MMP-2和MMP-9）和激活NF-κB来发挥其破坏作用，这与促炎细胞因子和趋化因子（CCL2、CCL5和IL-8）的产生相结合。此外，我们还表明，二级胆汁酸石胆酸（LCA）和脱氢石胆酸（3-氧基-LCA）可以抵消膳食中氧化甾醇引起的屏障功能丧失（TEER和fitc -葡聚糖通量）。总的来说，这些发现为二级胆汁酸在体外暴露于膳食甾醇的肠上皮细胞中维持屏障完整性和调节炎症的潜在作用提供了支持性证据。

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引用次数: 0

N-acetyl-cysteine alleviates nandrolone decanoate-induced hippocampal cell apoptosis in rats via reversing protein expressions of S1P1, Akt and FOXO3a signaling pathway n -乙酰半胱氨酸通过逆转S1P1、Akt和FOXO3a信号通路蛋白表达，减轻癸酸诺龙诱导的大鼠海马细胞凋亡

IF 2.3 4区医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Steroids

Pub Date : 2026-01-28 DOI: 10.1016/j.steroids.2026.109759

Alireza Shirpoor , Zahra Zarrini , Roya Naderi

Illicit use of nandrolone can result in apoptosis in the hippocampus tissue but the underlying mechanism is unknown. The present study evaluated the role of S1P1/Akt/FOXO3a pathway in hippocampus cell apoptosis following exposure to nandrolone decanoate either alone or in combination with N-acetyl-cysteine. Twenty-four male Wistar rats were randomly divided into three groups (n = 8): control, nandrolone (10 mg/kg; intramuscularly; three times per week), and nandrolone + N-acetyl-cysteine (150 mg/kg; intraperitoneally). After six weeks of treatment, the number of apoptotic cells was significantly increased in the nandrolone treated group compared with the control group. Compared to control group, nandrolone group showed significant upregulation of NOX2, iNOS, 8-OHdG, P-FOXO3a/FOXO3a and lactate dehydrogenase (LDH) protein expression in rat hippocampus cells. Conversely, the protein expressions of P-Akt/Akt and S1P1 were significantly downregulated in hippocampus tissue of rats treated with nandrolone compared with control rats. Co-administration of N-acetyl-cysteine with nandrolone significantly reduced the apoptotic index and reversed the expressions of S1P1, P-Akt/Akt and P-FOXO3a/FOXO3a in the hippocampus neurons compared with the nandrolone group. These findings suggest that S1P1/Akt/FOXO3a signaling pathway may at least in part play an important role in the progression of apoptosis induced by nandrolone exposure, providing new insights into the pathogenesis and potential treatment of nandrolone-induced hippocampal damage.

非法使用诺龙可导致海马组织细胞凋亡，但其潜在机制尚不清楚。本研究评估了S1P1/Akt/FOXO3a通路在单独或联合n -乙酰半胱氨酸暴露后海马细胞凋亡中的作用。24只雄性Wistar大鼠随机分为3组（n = 8）：对照组、诺龙（10 mg/kg，肌肉注射，每周3次）和诺龙+ n -乙酰半胱氨酸（150 mg/kg，腹腔注射）。治疗6周后，与对照组相比，诺龙治疗组的凋亡细胞数量明显增加。与对照组相比，诺龙组大鼠海马细胞中NOX2、iNOS、8-OHdG、P-FOXO3a/FOXO3a及乳酸脱氢酶（LDH）蛋白表达显著上调。相反，与对照大鼠相比，诺龙处理大鼠海马组织中P-Akt/Akt和S1P1蛋白表达明显下调。与诺龙组相比，n -乙酰半胱氨酸与诺龙共给药可显著降低海马细胞凋亡指数，逆转海马神经元中S1P1、P-Akt/Akt和P-FOXO3a/FOXO3a的表达。这些研究结果表明，S1P1/Akt/FOXO3a信号通路可能在诺龙暴露诱导的海马细胞凋亡进程中至少部分发挥重要作用，为诺龙诱导的海马损伤的发病机制和潜在治疗提供了新的见解。

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引用次数: 0

Donepezil enhances the testicular protective effect of metformin in diabetic rats by modulating steroidogenic signaling and Bax/Bcl-2/Caspase-3 pathway 多奈哌齐通过调节类固醇信号通路和Bax/Bcl-2/Caspase-3通路增强二甲双胍对糖尿病大鼠睾丸的保护作用

IF 2.3 4区医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Steroids

Pub Date : 2026-01-27 DOI: 10.1016/j.steroids.2026.109748

Roland Eghoghosoa Akhigbe , Joseph Chimezie , Ajibola Ayomide Odeyemi , Stella Olamide Oyesode , Favour Adesogan , Abimbola Ayoola Oladipo , Precious Jesutofunmi Ashonibare , Tunmise Maryanne Akhigbe , Ebenezer Adeola Ashamu , Michael A. Olamoyegun

Background

Type 2 diabetes mellitus (T2DM) induces testicular damage through xanthine oxidase (XO)/uric acid (UA)/caspase-3-driven oxidative stress and apoptosis. Although metformin is effective in managing diabetes, combined therapy is more effective. Though donepezil protects against neuronal and retinal damage in diabetic rats, its role in diabetes-induced testicular damage is yet to be reported.

Aim

This study investigated the protective effects of combined metformin and donepezil treatment on testicular dysfunction in a high-fat diet/streptozotocin-induced T2DM rat model. Also, the involvement of XO/UA and Bax/Bcl-2/caspase signaling was examined.

Methods

Forty-eight 8-week-old male Wistar rats were randomly assigned into six equal groups: control, diabetes (DM), DM+metformin, donepezil, DM+donepezil, and DM+metformin+donepezil groups.

Results

T2DM caused testicular inflammation and oxidative stress, evidenced by elevated pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), activation of NF-κB signaling, increased oxidative markers (MDA), and reduced antioxidant enzymes. T2DM also led to testicular apoptosis (increased Bax and caspase-3 and reduced Bcl-2). More so, T2DM repressed serum testosterone, FSH, and LH, and caused morphological disorganization of the testes, including germ cell loss and Leydig cell degeneration. Treatment with metformin and donepezil, singly or in combination, significantly mitigated these adverse effects, with the combined therapy demonstrating superior efficacy. The intervention suppressed XO/uric acid signaling, oxidative stress, and inflammatory responses via downregulation of NF-κB and apoptotic cascades. These results imply that donepezil and metformin work in concert to provide a potentially effective treatment strategy for reducing testicular damage caused by diabetes through modulation of oxidative, inflammatory, and apoptotic pathways, ultimately restoring testicular structure and function.

背景2型糖尿病（T2DM）通过黄嘌呤氧化酶(XO)/尿酸(UA)/caspase-3驱动的氧化应激和凋亡诱导睾丸损伤。虽然二甲双胍在控制糖尿病方面是有效的，但联合治疗更有效。虽然多奈哌齐对糖尿病大鼠的神经元和视网膜损伤有保护作用，但其在糖尿病引起的睾丸损伤中的作用尚未报道。目的探讨二甲双胍联合多奈哌齐对高脂饮食/链脲佐菌素诱导的T2DM大鼠睾丸功能障碍的保护作用。此外，我们还研究了XO/UA和Bax/Bcl-2/caspase信号的参与。方法48只8周龄雄性Wistar大鼠随机分为对照组、糖尿病（DM）组、DM+二甲双胍组、多奈哌齐组、DM+多奈哌齐组和DM+二甲双胍+多奈哌齐组。结果st2dm引起睾丸炎症和氧化应激，表现为促炎因子（IL-1β、IL-6、TNF-α）升高，NF-κB信号激活，氧化标志物（MDA）升高，抗氧化酶降低。T2DM还导致睾丸细胞凋亡（Bax和caspase-3升高，Bcl-2降低）。更重要的是，T2DM抑制血清睾酮、FSH和LH，并引起睾丸形态紊乱，包括生殖细胞丢失和间质细胞变性。二甲双胍和多奈哌齐单独或联合治疗可显著减轻这些不良反应，联合治疗显示出优越的疗效。干预通过下调NF-κB和凋亡级联抑制XO/尿酸信号、氧化应激和炎症反应。这些结果表明，多奈哌齐和二甲双胍协同作用，通过调节氧化、炎症和凋亡途径，为减少糖尿病引起的睾丸损伤提供了一种潜在的有效治疗策略，最终恢复睾丸结构和功能。

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引用次数: 0

The protective effects of luteolin and oleuropein against dexamethasone-induced hyperlipidemia 木犀草素和橄榄苦苷对地塞米松诱导的高脂血症的保护作用

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 , 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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