首页 > 最新文献

Steroids最新文献

英文 中文
Dehydroepiandrosterone sulphate (DHEAS) supplementation impacts adrenal cortex morphophysiology of aged female gerbils 补充脱氢表雄酮硫酸盐(DHEAS)对老年雌性沙鼠肾上腺皮质形态生理的影响
IF 2.1 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-04-23 DOI: 10.1016/j.steroids.2025.109618
Carolina Marques Bedolo , Isabella Carolina Cozim , Vitor Grigio , Gabriel Ribeiro Bernussi , Stella Bicalho Silva , Luiz Henrique Alves Guerra , Silvana Gisele Pegorin Campos , Patricia Simone Leite Vilamaior , Ellen Cristina Rivas Leonel , Sebastião Roberto Taboga
During the process of aging, it is common for women to take dehydroepiandrosterone sulphate (DHEAS) supplements to prevent adrenopause. However, the potential effects of this supplementation on the adrenal cortex have not yet been fully elucidated. Therefore, the present study aimed to analyze the effects of DHEAS supplementation on the adrenal cortex of female Mongolian gerbils during the aging process. The experiment was conducted by dividing the aged female gerbils (18 months of age) into two groups (n = 5). The control group received no treatment, while the experimental group received 60 mg/kg of DHEAS for 5 weeks. The adrenal glands of both groups were then subjected to morphological, hormonal and immunohistochemistry analyses. The results showed that DHEAS supplementation led to a significant increase in the accumulation of lipofuscin granules in the adrenal cells. Furthermore, decreases in ERα and ERβ and the enzymes CYP17 and 17βHSD, and an increase in the 5α-reductase enzyme in the adrenal cortex were also observed. The results suggest that DHEAS supplementation has a negative feedback effect on the adrenal cortex, affecting its morphophysiology and, consequently, the gland’s functionality. In addition, DHEAS supplementation does not reverse all aspects of the effects of aging on adrenal gland homeostasis.
在衰老过程中,女性通常服用硫酸脱氢表雄酮(DHEAS)补充剂来预防肾上腺素暂停。然而,这种补充剂对肾上腺皮质的潜在影响尚未完全阐明。因此,本研究旨在分析在衰老过程中补充DHEAS对雌性蒙古沙鼠肾上腺皮质的影响。实验将成年雌性沙鼠(18月龄)分为两组(n = 5),对照组不给药,实验组给药60 mg/kg DHEAS,持续5周。然后对两组肾上腺进行形态学、激素和免疫组织化学分析。结果表明,补充DHEAS可显著增加肾上腺细胞中脂褐素颗粒的积累。肾上腺皮质ERα、ERβ和CYP17、17βHSD均降低,5α-还原酶升高。结果表明,补充DHEAS对肾上腺皮质具有负反馈作用,影响其形态生理,从而影响腺体的功能。此外,补充DHEAS并不能逆转衰老对肾上腺稳态的所有影响。
{"title":"Dehydroepiandrosterone sulphate (DHEAS) supplementation impacts adrenal cortex morphophysiology of aged female gerbils","authors":"Carolina Marques Bedolo ,&nbsp;Isabella Carolina Cozim ,&nbsp;Vitor Grigio ,&nbsp;Gabriel Ribeiro Bernussi ,&nbsp;Stella Bicalho Silva ,&nbsp;Luiz Henrique Alves Guerra ,&nbsp;Silvana Gisele Pegorin Campos ,&nbsp;Patricia Simone Leite Vilamaior ,&nbsp;Ellen Cristina Rivas Leonel ,&nbsp;Sebastião Roberto Taboga","doi":"10.1016/j.steroids.2025.109618","DOIUrl":"10.1016/j.steroids.2025.109618","url":null,"abstract":"<div><div>During the process of aging, it is common for women to take dehydroepiandrosterone sulphate (DHEAS) supplements to prevent adrenopause. However, the potential effects of this supplementation on the adrenal cortex have not yet been fully elucidated. Therefore, the present study aimed to analyze the effects of DHEAS supplementation on the adrenal cortex of female Mongolian gerbils during the aging process. The experiment was conducted by dividing the aged female gerbils (18 months of age) into two groups (n = 5). The control group received no treatment, while the experimental group received 60 mg/kg of DHEAS for 5 weeks. The adrenal glands of both groups were then subjected to morphological, hormonal and immunohistochemistry analyses. The results showed that DHEAS supplementation led to a significant increase in the accumulation of lipofuscin granules in the adrenal cells. Furthermore, decreases in ERα and ERβ and the enzymes CYP17 and 17βHSD, and an increase in the 5α-reductase enzyme in the adrenal cortex were also observed. The results suggest that DHEAS supplementation has a negative feedback effect on the adrenal cortex, affecting its morphophysiology and, consequently, the gland’s functionality. In addition, DHEAS supplementation does not reverse all aspects of the effects of aging on adrenal gland homeostasis.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"218 ","pages":"Article 109618"},"PeriodicalIF":2.1,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143867803","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
Mendelian randomization studies of testosterone exposure: A systematic review 睾酮暴露的孟德尔随机化研究:系统回顾
IF 2.1 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-04-14 DOI: 10.1016/j.steroids.2025.109615
Annika Magdalena Rhomberg-Kauert , Morten Tulstrup , Christoffer Badsted , Henrik Horwitz , Ida M. Heerfordt

Background

Testosterone impacts reproductive health, cardiovascular function, and metabolism. Considering the use of testosterone therapy and anabolic steroid misuse, understanding its health effects is important. While randomized clinical trials provide short-term insights, and observational studies struggle with confounding factors, Mendelian randomization offers an alternative by using genetic variations to explore causal relationships.

Method

A systematic search was performed using MEDLINE to identify studies published from inception to October 2024. We included studies that conducted a Mendelian randomization analysis to evaluate associations between testosterone exposure and any health outcomes in males.

Results

Twenty-nine Mendelian randomization studies were included, examining a broad spectrum of health outcomes linked to testosterone exposure. Cardiovascular and metabolic health, alongside prostate cancer risk, were the most frequently studied areas. Most studies indicated that higher testosterone levels were associated with adverse cardiovascular outcomes, such as increased risks of thromboembolism, ischemic heart disease, and heart failure. Elevated levels of genetically predicted free testosterone consistently showed a correlation with increased prostate cancer risk. The relationship between testosterone and type 2 diabetes remained inconclusive. Neuropsychiatric and musculoskeletal outcomes received less attention, while dermatological, infectious, and respiratory health were minimally explored.

Conclusion

This review provides information about the causal relationships between testosterone exposure and health outcomes, contributing to the ongoing discourse on testosterone-related health risks and benefits. The included studies exhibit great heterogeneity.
睾酮影响生殖健康、心血管功能和新陈代谢。考虑到使用睾酮治疗和合成代谢类固醇滥用,了解其对健康的影响是重要的。虽然随机临床试验提供了短期的见解,观察性研究与混杂因素作斗争,但孟德尔随机化通过使用遗传变异来探索因果关系提供了另一种选择。方法采用MEDLINE系统检索自成立至2024年10月发表的研究。我们纳入了进行孟德尔随机分析的研究,以评估男性睾酮暴露与任何健康结果之间的关系。结果纳入了29项孟德尔随机化研究,研究了与睾酮暴露有关的广泛的健康结果。心血管和代谢健康以及前列腺癌风险是最常被研究的领域。大多数研究表明,较高的睾酮水平与不良心血管结果相关,如血栓栓塞、缺血性心脏病和心力衰竭的风险增加。基因预测的游离睾酮水平升高始终显示出与前列腺癌风险增加相关。睾酮和2型糖尿病之间的关系尚无定论。神经精神病学和肌肉骨骼的结果得到的关注较少,而皮肤病学、传染病和呼吸系统健康的研究则很少。结论:本综述提供了睾酮暴露与健康结果之间因果关系的信息,有助于对睾酮相关健康风险和益处的持续讨论。纳入的研究显示出很大的异质性。
{"title":"Mendelian randomization studies of testosterone exposure: A systematic review","authors":"Annika Magdalena Rhomberg-Kauert ,&nbsp;Morten Tulstrup ,&nbsp;Christoffer Badsted ,&nbsp;Henrik Horwitz ,&nbsp;Ida M. Heerfordt","doi":"10.1016/j.steroids.2025.109615","DOIUrl":"10.1016/j.steroids.2025.109615","url":null,"abstract":"<div><h3>Background</h3><div>Testosterone impacts reproductive health, cardiovascular function, and metabolism. Considering the use of testosterone therapy and anabolic steroid misuse, understanding its health effects is important. While randomized clinical trials provide short-term insights, and observational studies struggle with confounding factors, Mendelian randomization offers an alternative by using genetic variations to explore causal relationships.</div></div><div><h3>Method</h3><div>A systematic search was performed using MEDLINE to identify studies published from inception to October 2024. We included studies that conducted a Mendelian randomization analysis to evaluate associations between testosterone exposure and any health outcomes in males.</div></div><div><h3>Results</h3><div>Twenty-nine Mendelian randomization studies were included, examining a broad spectrum of health outcomes linked to testosterone exposure. Cardiovascular and metabolic health, alongside prostate cancer risk, were the most frequently studied areas. Most studies indicated that higher testosterone levels were associated with adverse cardiovascular outcomes, such as increased risks of thromboembolism, ischemic heart disease, and heart failure. Elevated levels of genetically predicted free testosterone consistently showed a correlation with increased prostate cancer risk. The relationship between testosterone and type 2 diabetes remained inconclusive. Neuropsychiatric and musculoskeletal outcomes received less attention, while dermatological, infectious, and respiratory health were minimally explored.</div></div><div><h3>Conclusion</h3><div>This review provides information about the causal relationships between testosterone exposure and health outcomes, contributing to the ongoing discourse on testosterone-related health risks and benefits. The included studies exhibit great heterogeneity.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"218 ","pages":"Article 109615"},"PeriodicalIF":2.1,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143834813","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
Synthesis, NMR and X-ray characterization of dibenzoannulated dimeric steroid spiroketals. Evaluation of cytotoxicity and anti-inflammatory activity 二苯并环二聚体甾体螺旋酮的合成、核磁共振和x射线表征。细胞毒性和抗炎活性的评价
IF 2.1 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-04-13 DOI: 10.1016/j.steroids.2025.109614
Rsuini U. Gutiérrez-Aguilar , Juan A. Antolín-González , Nimsi Campos-Xolalpa , Salud Perez-Gutierrez , Marcos Flores-Álamo , Josué Vazquez-Chavez , Martín A. Iglesias-Arteaga
Two dibenzoannulated dimeric steroid spiroketals were obtained from cholesterol and 1,4-phenylenedimethanol. The key step in synthetic protocol is a Pd-catalyzed double spiroketalization in an adduct obtained from the double Sonogashira coupling of the 5α and 5β diastereomers of 4,5-secocholestan-5-ol. A detailed NMR characterization supported by Single Crystal X-ray Diffraction studies corroborated the obtained structures. While no cytotoxic effect was observed, the obtained compounds produced a significant reduction in the production of nitric oxide in macrophages stimulated with Lipopolysaccharide (LPS), indicating a potential anti-inflammatory activity.
我们从胆固醇和 1,4-亚苯基二甲醇中获得了两种二苯并annulated 二聚甾类螺酮。合成方案的关键步骤是在 4,5-secocholestan-5-醇的 5α 和 5β 非对映异构体双 Sonogashira 偶联得到的加合物中进行钯催化双螺酮化。详细的核磁共振表征和单晶 X 射线衍射研究证实了所获得的结构。虽然没有观察到细胞毒性作用,但获得的化合物能显著减少巨噬细胞在脂多糖(LPS)刺激下产生的一氧化氮,这表明它们具有潜在的抗炎活性。
{"title":"Synthesis, NMR and X-ray characterization of dibenzoannulated dimeric steroid spiroketals. Evaluation of cytotoxicity and anti-inflammatory activity","authors":"Rsuini U. Gutiérrez-Aguilar ,&nbsp;Juan A. Antolín-González ,&nbsp;Nimsi Campos-Xolalpa ,&nbsp;Salud Perez-Gutierrez ,&nbsp;Marcos Flores-Álamo ,&nbsp;Josué Vazquez-Chavez ,&nbsp;Martín A. Iglesias-Arteaga","doi":"10.1016/j.steroids.2025.109614","DOIUrl":"10.1016/j.steroids.2025.109614","url":null,"abstract":"<div><div>Two dibenzoannulated dimeric steroid spiroketals were obtained from cholesterol and 1,4-phenylenedimethanol. The key step in synthetic protocol is a Pd-catalyzed double spiroketalization in an adduct obtained from the double Sonogashira coupling of the 5α and 5β diastereomers of 4,5-secocholestan-5-ol. A detailed NMR characterization supported by Single Crystal X-ray Diffraction studies corroborated the obtained structures. While no cytotoxic effect was observed, the obtained compounds produced a significant reduction in the production of nitric oxide in macrophages stimulated with Lipopolysaccharide (LPS), indicating a potential anti-inflammatory activity.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"218 ","pages":"Article 109614"},"PeriodicalIF":2.1,"publicationDate":"2025-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143867804","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
Evaluation of the diagnostic value of G protein-coupled estrogen receptor (GPER) in COVID-19 cases at Tokat Province 托卡特省G蛋白偶联雌激素受体(GPER)对COVID-19病例诊断价值的评价
IF 2.1 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-04-11 DOI: 10.1016/j.steroids.2025.109605
Figen Guzelgul , Ergul Belge Kurutas

Objective

Factors affecting the clinical course of COVID-19, an infectious respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in humans, are still poorly understood. G protein-coupled estrogen receptor (GPER) is a protein encoded by the GPER gene in humans. GPER is activated by binding to estradiol, a female sex hormone, leading to mediation of estradiol’s rapid cellular effects. In this study, which was conducted for the first time, we aimed to investigate GPER levels and their diagnostic value in COVID-19 patients.

Methods

A total of 71 individuals [Female/Male (n = 36/35) range of ages 32 ∼ 62] were enrolled in this study and categorized into three groups: the patient group consisted of individuals diagnosed with COVID-19 and receiving supportive treatment in the intensive care unit (ICU), the mild group consisted of COVID-19 patients who received outpatient treatment, and the control group. Enzyme-linked immunosorbent assay (ELISA) was used to measure serum GPER levels.

Results

The general sex distribution of the patients was analyzed, revealing that 35(49.3 %) were male and 36(50.7 %) were female. GPER levels were significantly increased in severe COVID-19 females compared to control and mild course groups (p < 0.05). A GPER cut-off value of 2.95 ng/mL showed diagnostic accuracy in severe COVID-19 cases.

Conclusion

This study, conducted for the first time, demonstrates that GPER levels are significantly associated with COVID-19 severity in female patients, suggesting that GPER may serve as a diagnostic marker for the progression of COVID-19.
目的影响 COVID-19 (一种由严重急性呼吸系统综合征冠状病毒 2(SARS-CoV-2)引起的人类呼吸道传染病)临床病程的因素仍然鲜为人知。G 蛋白偶联雌激素受体(GPER)是一种由人类 GPER 基因编码的蛋白质。GPER 与雌性激素雌二醇结合后被激活,从而介导雌二醇对细胞的快速作用。本研究首次对 COVID-19 患者的 GPER 水平及其诊断价值进行了研究。方法:本研究共纳入 71 名患者[女性/男性(n = 36/35),年龄在 32 ∼ 62 岁之间],并将其分为三组:患者组包括确诊为 COVID-19 并在重症监护室(ICU)接受支持性治疗的患者;轻度组包括接受门诊治疗的 COVID-19 患者;对照组。结果分析了患者的性别分布,结果显示男性 35 人(49.3%),女性 36 人(50.7%)。与对照组和轻度病程组相比,重度 COVID-19 女性患者的 GPER 水平明显升高(p < 0.05)。该研究首次表明,女性患者的GPER水平与COVID-19的严重程度明显相关,这表明GPER可作为COVID-19病情发展的诊断标志物。
{"title":"Evaluation of the diagnostic value of G protein-coupled estrogen receptor (GPER) in COVID-19 cases at Tokat Province","authors":"Figen Guzelgul ,&nbsp;Ergul Belge Kurutas","doi":"10.1016/j.steroids.2025.109605","DOIUrl":"10.1016/j.steroids.2025.109605","url":null,"abstract":"<div><h3>Objective</h3><div>Factors affecting the clinical course of COVID-19, an infectious respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in humans, are still poorly understood. G protein-coupled estrogen receptor (GPER) is a protein encoded by the GPER gene in humans. GPER is activated by binding to estradiol, a female sex hormone, leading to mediation of estradiol’s rapid cellular effects. In this study, which was conducted for the first time, we aimed to investigate GPER levels and their diagnostic value in COVID-19 patients.</div></div><div><h3>Methods</h3><div>A total of 71 individuals [Female/Male (n = 36/35) range of ages 32 ∼ 62] were enrolled in this study and categorized into three groups: the patient group consisted of individuals diagnosed with COVID-19 and receiving supportive treatment in the intensive care unit (ICU), the mild group consisted of COVID-19 patients who received outpatient treatment, and the control group. Enzyme-linked immunosorbent assay (ELISA) was used to measure serum GPER levels.</div></div><div><h3>Results</h3><div>The general sex distribution of the patients was analyzed, revealing that 35(49.3 %) were male and 36(50.7 %) were female. GPER levels were significantly increased in severe COVID-19 females compared to control and mild course groups (p &lt; 0.05). A GPER cut-off value of 2.95 ng/mL showed diagnostic accuracy in severe COVID-19 cases.</div></div><div><h3>Conclusion</h3><div>This study, conducted for the first time, demonstrates that GPER levels are significantly associated with COVID-19 severity in female patients, suggesting that GPER may serve as a diagnostic marker for the progression of COVID-19.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"218 ","pages":"Article 109605"},"PeriodicalIF":2.1,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143823520","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
From root to Recovery: The role of herbs in polycystic ovary syndrome management 从根源到恢复:草药在多囊卵巢综合征治疗中的作用
IF 2.1 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-04-08 DOI: 10.1016/j.steroids.2025.109606
Noor-Ul-Ain Zafar , Rahmatullah Qureshi , Ayesha Siddiqa , Syed Azaz Mustafa Naqvi , Fareeha Waheed , Zia-ur-Rehman Mashwani , Amir Ali , Kayley Aileen Hernández Ramírez , Gabriela Medina-Pérez , Armando Pelaez-Acero , Ajaz Ahmad
Polycystic ovarian syndrome (PCOS) is a prevalent complicated endocrine condition affecting women, caused by both hereditary and environmental factors. It often emerges during the reproductive years (15–35 years) and now affects 1 out of 10 women worldwide. PCOS is distinguished by high androgen levels, particularly testosterone, as well as the appearance of many ovarian cysts (more than 10), which result in anovulation, infertility, and irregular menstrual periods. Furthermore, PCOS is associated with a variety of endocrine and metabolic abnormalities, including obesity, hirsutism, acne, diabetes, insulin resistance, and poor glucose tolerance. PCOS treatment includes allopathic, Ayurvedic, and natural therapies, as well as lifestyle changes. In comparison to allopathic treatments, herbal medicines are recognized for their cost-effectiveness, efficacy, and favourable role in PCOS management/treatment. This literature review briefly examines PCOS diagnosis, symptoms, hormonal imbalance, causes, related risk factors, and management, with a particular emphasis on the role of herbal remedies in PCOS treatment. This review highlights several medicinal plants with potential therapeutic benefits for various health conditions. These herbs have demonstrated efficacy in managing ailments such as hypothyroidism, hyperplasia, obesity, diabetes, menorrhagia, sleep disturbances, cardiovascular disorders, hyperlipidemia, hirsutism, infertility, and irregular menstrual cycles. The information was sourced from PubMed and multiple review articles. Various herbs, whether used individually, in combination, or as extracts, may help reduce risk factors associated with polycystic ovary syndrome (PCOS).
多囊卵巢综合征(PCOS)是一种常见的影响女性的复杂内分泌疾病,由遗传和环境因素共同引起。它通常出现在生育年龄(15-35岁),现在全世界每10名妇女中就有1名受到影响。多囊卵巢综合征的特点是雄激素水平高,尤其是睾丸激素水平高,同时出现许多卵巢囊肿(超过10个),导致无排卵、不孕和月经不规律。此外,多囊卵巢综合征与多种内分泌和代谢异常有关,包括肥胖、多毛症、痤疮、糖尿病、胰岛素抵抗和葡萄糖耐受性差。多囊卵巢综合征的治疗包括对抗疗法、阿育吠陀疗法和自然疗法,以及生活方式的改变。与对抗疗法相比,草药因其成本效益、疗效和在多囊卵巢综合征管理/治疗中的有利作用而得到认可。本文献综述简要探讨多囊卵巢综合征的诊断、症状、激素失衡、病因、相关危险因素和管理,特别强调草药在多囊卵巢综合征治疗中的作用。本文综述了几种对各种健康状况具有潜在治疗效益的药用植物。这些草药已被证明对治疗甲状腺功能减退、增生、肥胖、糖尿病、月经过多、睡眠障碍、心血管疾病、高脂血症、多毛症、不孕症和月经周期不规律等疾病有疗效。这些信息来自PubMed和多篇评论文章。各种草药,无论是单独使用,组合使用,还是作为提取物,都可以帮助减少与多囊卵巢综合征(PCOS)相关的风险因素。
{"title":"From root to Recovery: The role of herbs in polycystic ovary syndrome management","authors":"Noor-Ul-Ain Zafar ,&nbsp;Rahmatullah Qureshi ,&nbsp;Ayesha Siddiqa ,&nbsp;Syed Azaz Mustafa Naqvi ,&nbsp;Fareeha Waheed ,&nbsp;Zia-ur-Rehman Mashwani ,&nbsp;Amir Ali ,&nbsp;Kayley Aileen Hernández Ramírez ,&nbsp;Gabriela Medina-Pérez ,&nbsp;Armando Pelaez-Acero ,&nbsp;Ajaz Ahmad","doi":"10.1016/j.steroids.2025.109606","DOIUrl":"10.1016/j.steroids.2025.109606","url":null,"abstract":"<div><div>Polycystic ovarian syndrome (PCOS) is a prevalent complicated endocrine condition affecting women, caused by both hereditary and environmental factors. It often emerges during the reproductive years (15–35 years) and now affects 1 out of 10 women worldwide. PCOS is distinguished by high androgen levels, particularly testosterone, as well as the appearance of many ovarian cysts (more than 10), which result in anovulation, infertility, and irregular menstrual periods. Furthermore, PCOS is associated with a variety of endocrine and metabolic abnormalities, including obesity, hirsutism, acne, diabetes, insulin resistance, and poor glucose tolerance. PCOS treatment includes allopathic, Ayurvedic, and natural therapies, as well as lifestyle changes. In comparison to allopathic treatments, herbal medicines are recognized for their cost-effectiveness, efficacy, and favourable role in PCOS management/treatment. This literature review briefly examines PCOS diagnosis, symptoms, hormonal imbalance, causes, related risk factors, and management, with a particular emphasis on the role of herbal remedies in PCOS treatment. This review highlights several medicinal plants with potential therapeutic benefits for various health conditions. These herbs have demonstrated efficacy in managing ailments such as hypothyroidism, hyperplasia, obesity, diabetes, menorrhagia, sleep disturbances, cardiovascular disorders, hyperlipidemia, hirsutism, infertility, and irregular menstrual cycles. The information was sourced from PubMed and multiple review articles. Various herbs, whether used individually, in combination, or as extracts, may help reduce risk factors associated with polycystic ovary syndrome (PCOS).</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"218 ","pages":"Article 109606"},"PeriodicalIF":2.1,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143816324","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
Genetic insights into vitamin D deficiency: a case-control study of GC and CYP24A1 gene polymorphism 维生素D缺乏症的遗传学见解:GC和CYP24A1基因多态性的病例对照研究。
IF 2.1 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-04-06 DOI: 10.1016/j.steroids.2025.109607
Usama , Aslam Khan , Muhammad Kashif Raza , Khurram Abbas , Lamjed Mansour , Aktar Ali , Muhammad Imran
Despite the sunny climate, vitamin D deficiency is highly prevalent in several parts of the world. Several risk factors are associated with VD deficiency, including single nucleotide polymorphism and post-translational modifications in its transport protein, known as vitamin D binding protein (DBP) or GC and CYP24A1, a protein associated with its degradation. Our study explores the impact of rs4588 and rs7041 in the GC gene, along with CYP24A1 rs4809960 and rs2585428, on serum vitamin D and the risk of vitamin D insufficiency. This study enrolled 114 healthy controls and 239 vitamin D-deficient subjects. SNPs were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The G/T genotype of D432E and the A/A genotype of T436K in the GC gene were observed to be risk factors for vitamin D deficiency. Overall, a significant (P < 0.05) association was observed between the D432E and T436K polymorphism and vitamin D deficiency. Polymorphic genotypes of CYP24A1 rs4809960 and rs2585428 polymorphisms were significantly associated with a higher risk of Vitamin D deficiency. D432E and T436K polymorphisms were associated with decreased vitamin D and increased PTH levels in vitamin D-deficient individuals. Similarly, both CYP24A1 polymorphisms were significantly associated with a higher risk of vitamin D deficiency. Also, a negative association was observed between sufficient serum levels of 25-hydroxyvitamin D and PTH levels.
尽管气候晴朗,但维生素D缺乏症在世界上一些地区非常普遍。几种危险因素与VD缺乏有关,包括其转运蛋白的单核苷酸多态性和翻译后修饰,称为维生素D结合蛋白(DBP)或GC和CYP24A1,一种与其降解相关的蛋白质。我们的研究探讨了GC基因rs4588和rs7041以及CYP24A1 rs4809960和rs2585428对血清维生素D和维生素D不足风险的影响。这项研究招募了114名健康对照者和239名维生素d缺乏者。采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)测定snp。GC基因中D432E的G/T基因型和T436K的A/A基因型是维生素D缺乏的危险因素。总体而言,P
{"title":"Genetic insights into vitamin D deficiency: a case-control study of GC and CYP24A1 gene polymorphism","authors":"Usama ,&nbsp;Aslam Khan ,&nbsp;Muhammad Kashif Raza ,&nbsp;Khurram Abbas ,&nbsp;Lamjed Mansour ,&nbsp;Aktar Ali ,&nbsp;Muhammad Imran","doi":"10.1016/j.steroids.2025.109607","DOIUrl":"10.1016/j.steroids.2025.109607","url":null,"abstract":"<div><div>Despite the sunny climate, vitamin D deficiency is highly prevalent in several parts of the world. Several risk factors are associated with VD deficiency, including single nucleotide polymorphism and post-translational modifications in its transport protein, known as vitamin D binding protein (DBP) or GC and CYP24A1, a protein associated with its degradation. Our study explores the impact of rs4588 and rs7041 in the GC gene, along with CYP24A1 rs4809960 and rs2585428, on serum vitamin D and the risk of vitamin D insufficiency. This study enrolled 114 healthy controls and 239 vitamin D-deficient subjects. SNPs were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The G/T genotype of D432E and the A/A genotype of T436K in the GC gene were observed to be risk factors for vitamin D deficiency. Overall, a significant (P &lt; 0.05) association was observed between the D432E and T436K polymorphism and vitamin D deficiency. Polymorphic genotypes of CYP24A1 rs4809960 and rs2585428 polymorphisms were significantly associated with a higher risk of Vitamin D deficiency. D432E and T436K polymorphisms were associated with decreased vitamin D and increased PTH levels in vitamin D-deficient individuals. Similarly, both CYP24A1 polymorphisms were significantly associated with a higher risk of vitamin D deficiency. Also, a negative association was observed between sufficient serum levels of 25-hydroxyvitamin D and PTH levels.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"218 ","pages":"Article 109607"},"PeriodicalIF":2.1,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143812327","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
Stress responses in blood donors: Oral fluid hormone dynamics and implications for donor support 献血者的应激反应:口服液激素动力学和对献血者支持的影响
IF 2.1 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-03-28 DOI: 10.1016/j.steroids.2025.109604
Agata Alterio , Matteo Feltracco , Giovanna Mazzi , Beatrice Rosso , llaria Prosdocimi , Andrea Gambaro
Glucocorticoids (cortisol and cortisone) hormones are potential biomarkers for monitoring physiological stress in humans. These hormones are released into the bloodstream but are also detectable in other biological matrixes such as oral fluid. Oral fluid hormone levels reflect those found in the blood, but oral fluid sampling is quicker and non-invasive, making it a viable alternative matrix for studying stress markers. This study investigates the stress response of blood donors at three different donation moments by analyzing cortisol and cortisone levels in oral fluid samples. To simultaneously detect these analytes, we developed and validated a new highly sensitive method using high-performance liquid chromatography coupled to a triple quadrupole mass spectrometer (HPLC-MS/MS). Glucocorticoid hormones were found in all samples with cortisone exhibiting higher concentrations than cortisol. Statistical results revealed a weakly negative trend over time for both analytes levels, indicating that the most crucial donation moment is upon donors’ arrival. A notable distinction was found in the evolution of the glucocorticoid hormones in different locations, suggesting that different environmental factors influence stress level more than the act of donation itself.
糖皮质激素(皮质醇和可的松)是监测人体生理压力的潜在生物标志物。这些激素会释放到血液中,但也能在口腔液等其他生物基质中检测到。口腔液中的激素水平反映了血液中的激素水平,但口腔液采样更快、无创伤,因此是研究压力标记物的一种可行的替代基质。本研究通过分析口腔液样本中的皮质醇和可的松水平,研究献血者在三个不同献血时刻的压力反应。为了同时检测这些分析物,我们开发并验证了一种新的高灵敏度方法,该方法采用高效液相色谱-三重四极杆质谱联用仪(HPLC-MS/MS)。在所有样本中都发现了糖皮质激素,其中可的松的浓度高于皮质醇。统计结果显示,这两种分析物的水平随时间呈微弱的负趋势,表明最关键的捐献时刻是在捐献者到达时。糖皮质激素在不同地点的变化有明显差异,这表明不同环境因素对压力水平的影响大于捐赠行为本身。
{"title":"Stress responses in blood donors: Oral fluid hormone dynamics and implications for donor support","authors":"Agata Alterio ,&nbsp;Matteo Feltracco ,&nbsp;Giovanna Mazzi ,&nbsp;Beatrice Rosso ,&nbsp;llaria Prosdocimi ,&nbsp;Andrea Gambaro","doi":"10.1016/j.steroids.2025.109604","DOIUrl":"10.1016/j.steroids.2025.109604","url":null,"abstract":"<div><div>Glucocorticoids (cortisol and cortisone) hormones are potential biomarkers for monitoring physiological stress in humans. These hormones are released into the bloodstream but are also detectable in other biological matrixes such as oral fluid. Oral fluid hormone levels reflect those found in the blood, but oral fluid sampling is quicker and non-invasive, making it a viable alternative matrix for studying stress markers. This study investigates the stress response of blood donors at three different donation moments by analyzing cortisol and cortisone levels in oral fluid samples. To simultaneously detect these analytes, we developed and validated a new highly sensitive method using high-performance liquid chromatography coupled to a triple quadrupole mass spectrometer (HPLC-MS/MS). Glucocorticoid hormones were found in all samples with cortisone exhibiting higher concentrations than cortisol. Statistical results revealed a weakly negative trend over time for both analytes levels, indicating that the most crucial donation moment is upon donors’ arrival. A notable distinction was found in the evolution of the glucocorticoid hormones in different locations, suggesting that different environmental factors influence stress level more than the act of donation itself.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"217 ","pages":"Article 109604"},"PeriodicalIF":2.1,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143734753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Unleashing the pharmacological potential of taste receptors in reproductive processes beyond their gustatory role 释放味觉感受器在生殖过程中超越味觉作用的药理学潜力
IF 2.1 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-03-26 DOI: 10.1016/j.steroids.2025.109603
Nourhan Magdy , Noha F. Abdelkader , Hala F. Zaki , Ahmed S. Kamel
Traditionally, taste receptors (TRs) have been understood to reside within the taste buds on the tongue, serving as initiators for different taste perceptions. However, recent research has expanded our understanding, revealing that TRs are found throughout the body and perform a wide range of functions beyond taste perception as non-tasting functions. These receptors, along with their genetic variations, have been linked to various human health conditions. They are activated by an array of substances, including hormones, nutrients, and toxins, indicating their involvement in numerous biological processes. Specifically, in males, TRs are notably present in the testes and epididymis, where they contribute to the hormonal production, spermatogenesis, and sperm maturation. In females, these receptors are found in the ovaries, uterus, and myometrium, playing crucial roles in ovulation, menstrual cycle regulation, and embryo implantation. There are a lot of missed areas regarding TRs research that imposes to fulfill the gaps in the current understanding of their role in reproduction. This review aims to provide a comprehensive overview of the emerging roles of extraoral TRs in reproductive health, highlighting their physiological and pathophysiological significance in various reproductive processes. As well, grabbing the attention towards the release of new pharmacological interventions to manage conception and contraception in male and female was considered.
传统上,味觉感受器(TRs)被认为存在于舌头上的味蕾中,作为不同味觉感知的启动器。然而,最近的研究扩大了我们的理解,揭示了TRs在整个身体中都有发现,并且作为非味觉功能发挥着广泛的功能。这些受体及其基因变异与各种人类健康状况有关。它们被一系列物质激活,包括激素、营养物质和毒素,表明它们参与了许多生物过程。具体来说,在男性中,TRs主要存在于睾丸和附睾,在那里它们有助于激素的产生、精子的发生和精子的成熟。在女性中,这些受体存在于卵巢、子宫和子宫肌层,在排卵、月经周期调节和胚胎着床中起着至关重要的作用。关于TRs的研究有很多被遗漏的领域,这些领域要求填补目前对它们在生殖中的作用的理解的空白。本文旨在全面概述口外TRs在生殖健康中的新作用,重点介绍其在各种生殖过程中的生理和病理生理意义。此外,还考虑了对新的药物干预措施的关注,以管理男性和女性的受孕和避孕。
{"title":"Unleashing the pharmacological potential of taste receptors in reproductive processes beyond their gustatory role","authors":"Nourhan Magdy ,&nbsp;Noha F. Abdelkader ,&nbsp;Hala F. Zaki ,&nbsp;Ahmed S. Kamel","doi":"10.1016/j.steroids.2025.109603","DOIUrl":"10.1016/j.steroids.2025.109603","url":null,"abstract":"<div><div>Traditionally, taste receptors (TRs) have been understood to reside within the taste buds on the tongue, serving as initiators for different taste perceptions. However, recent research has expanded our understanding, revealing that TRs are found throughout the body and perform a wide range of functions beyond taste perception as non-tasting functions. These receptors, along with their genetic variations, have been linked to various human health conditions. They are activated by an array of substances, including hormones, nutrients, and toxins, indicating their involvement in numerous biological processes. Specifically, in males, TRs are notably present in the testes and epididymis, where they contribute to the hormonal production, spermatogenesis, and sperm maturation. In females, these receptors are found in the ovaries, uterus, and myometrium, playing crucial roles in ovulation, menstrual cycle regulation, and embryo implantation. There are a lot of missed areas regarding TRs research that imposes to fulfill the gaps in the current understanding of their role in reproduction. This review aims to provide a comprehensive overview of the emerging roles of extraoral TRs in reproductive health, highlighting their physiological and pathophysiological significance in various reproductive processes. As well, grabbing the attention towards the release of new pharmacological interventions to manage conception and contraception in male and female was considered.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"217 ","pages":"Article 109603"},"PeriodicalIF":2.1,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143724183","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
BSS-4, a diosgenin analogue, reduces carrageenan-induced paw inflammation in rat 薯蓣皂苷元类似物BSS-4可减轻卡拉胶诱导的大鼠足部炎症。
IF 2.1 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-03-22 DOI: 10.1016/j.steroids.2025.109602
Marisol Casimiro-Rosas , Irving Parra , Jesús Sandoval-Ramírez , María A. Fernández Herrera , Yousef Tizabi , Isabel Martínez-García , Liliana Mendieta
Inflammation is an adaptive response that ensures the survival of the organism in the face of injuries or trauma primarily via the immune system. However, overactivation of this process can be detrimental to the point of fatality. To overcome this overactivation, immunosuppressant agents such as steroids and non-steroidal anti-inflammatory drugs (NSAIDs) are used. Given the limitations of these drugs, including their side effects, an urgent need for development of potent and safer anti-inflammatory drugs is evident. Diosgenin, a steroidal saponin (a glycoside found in plants) and its analog, BSS-4 are gaining ground in this respect. Our objective in this study was to determine the effectiveness of BSS-4 in an established model of inflammation and provide clues on its mechanism of action. Carrageenan (Carr)-induced paw edema was used to evaluate the effectiveness of two doses of BSS-4 (0.5 and 1 mg/kg administered intraperitoneally) in adult male Wistar rats. Plantar edema was induced by subcutaneous injection of 50 µL of carrageenan (1 %) into the plantar aponeurosis of the right paw. Inflammatory cytokine markers, tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β) were quantified in this paw region using immunohistochemical assays. BSS-4 at 0.5 mg/kg dose, significantly reduced the paw edema up to three hours after administration. Concomitantly, TNF-α and IL-1β immunostaining were significantly reduced. BSS-4 also preserved the tissue architecture as assessed by hematoxylin and eosin (H&E) staining. These results indicate that BSS-4 can impart potent anti-inflammatory effects as well as reductions in TNF-α and IL-1β in an inflammatory rat model.
炎症是一种适应性反应,主要通过免疫系统确保生物体在面对损伤或创伤时的生存。然而,这个过程的过度激活可能是有害的,甚至是致命的。为了克服这种过度激活,免疫抑制剂如类固醇和非甾体抗炎药(NSAIDs)被使用。鉴于这些药物的局限性,包括它们的副作用,开发更有效和更安全的抗炎药物的迫切需要是显而易见的。薯蓣皂苷元,一种甾体皂苷(一种在植物中发现的糖苷)及其类似物BSS-4在这方面正在取得进展。我们的研究目的是确定BSS-4在已建立的炎症模型中的有效性,并为其作用机制提供线索。采用卡拉胶(Carrageenan, Carr)诱导的足跖水肿来评价两种剂量BSS-4(0.5和1 mg/kg腹腔注射)对成年雄性Wistar大鼠的有效性。右足跖腱膜皮下注射50 µL卡拉胶(1 %)诱导足底水肿。用免疫组织化学方法定量检测足部炎症细胞因子标志物、肿瘤坏死因子α (TNF-α)和白细胞介素-1β (IL-1β)。0.5 mg/kg剂量的BSS-4在给药后3小时显著减少足跖水肿。同时,TNF-α和IL-1β免疫染色明显降低。苏木精和伊红(H&E)染色显示,BSS-4也保留了组织结构。这些结果表明,BSS-4在炎症大鼠模型中具有有效的抗炎作用,并能降低TNF-α和IL-1β。
{"title":"BSS-4, a diosgenin analogue, reduces carrageenan-induced paw inflammation in rat","authors":"Marisol Casimiro-Rosas ,&nbsp;Irving Parra ,&nbsp;Jesús Sandoval-Ramírez ,&nbsp;María A. Fernández Herrera ,&nbsp;Yousef Tizabi ,&nbsp;Isabel Martínez-García ,&nbsp;Liliana Mendieta","doi":"10.1016/j.steroids.2025.109602","DOIUrl":"10.1016/j.steroids.2025.109602","url":null,"abstract":"<div><div>Inflammation is an adaptive response that ensures the survival of the organism in the face of injuries or trauma primarily via the immune system. However, overactivation of this process can be detrimental to the point of fatality. To overcome this overactivation, immunosuppressant agents such as steroids and non-steroidal anti-inflammatory drugs (NSAIDs) are used. Given the limitations of these drugs, including their side effects, an urgent need for development of potent and safer anti-inflammatory drugs is evident. Diosgenin, a steroidal saponin (a glycoside found in plants) and its analog, BSS-4 are gaining ground in this respect. Our objective in this study was to determine the effectiveness of BSS-4 in an established model of inflammation and provide clues on its mechanism of action. Carrageenan (Carr)-induced paw edema was used to evaluate the effectiveness of two doses of BSS-4 (0.5 and 1 mg/kg administered intraperitoneally) in adult male Wistar rats. Plantar edema was induced by subcutaneous injection of 50 µL of carrageenan (1 %) into the plantar aponeurosis of the right paw. Inflammatory cytokine markers, tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β) were quantified in this paw region using immunohistochemical assays. BSS-4 at 0.5 mg/kg dose, significantly reduced the paw edema up to three hours after administration. Concomitantly, TNF-α and IL-1β immunostaining were significantly reduced. BSS-4 also preserved the tissue architecture as assessed by hematoxylin and eosin (H&amp;E) staining. These results indicate that BSS-4 can impart potent anti-inflammatory effects as well as reductions in TNF-α and IL-1β in an inflammatory rat model.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"217 ","pages":"Article 109602"},"PeriodicalIF":2.1,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143693390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Target-specific high-throughput screening of anti-inflammatory phytosteroids for autoimmune diseases: A molecular docking-dynamics simulation approach 靶向特异性抗炎植物类固醇对自身免疫性疾病的高通量筛选:分子对接动力学模拟方法
IF 2.1 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-03-20 DOI: 10.1016/j.steroids.2025.109601
Alaka Sahoo , Sudhir Kumar Paidesetty , Maitreyee Panda
Without proper pathophysiology and recommended therapy, synthetic steroids are widely used as a first-line option for the management of autoimmune diseases. However, their prolonged use often leads to severe side effects such as osteoporosis, hypertension, cardiovascular, gastrointestinal complications, etc. To search for potential and safer therapeutic options, the present study aims to explore the potency and drug-ability profiles of anti-inflammatory phytosteroids (PSs). In a target-specific approach, we have selected three key molecular targets: glucocorticoid receptor/GR (PDB ID: 4P6W), cyclooxygenase-2/COX2 (PDB ID: 5F1A), and inducible nitric oxide synthase/iNOS (PDB ID: 4NOS) for a docking study of 167) selected PSs. The drug-chemistry profiles (physicochemical, toxicity, pharmacokinetic, drug-ability, etc.) of PSs were also assessed using various bioinformatics and chemoinformatics tools. The above assessment suggested that withaminilide B (PS46) is a lead candidate with higher drug-ability properties. Further, the drug stability and kinetic behaviour of the lead with the GR target ‘GR-withaminilide B’ in comparison with the control drug, ‘GR-triamcinolone acetonide’ docking complex, were studied through molecular dynamics (MD) simulation at 200 nanosecond with free energy calculation (MM/PBSA). Overall findings suggested that PSs exhibit distinct drug-ability profiles based on their functional attachments with a steroidal core moiety, where withaminilide B is a lead PSs among all to be used as alternative/ complementary candidates expected with limited adverse effects. Further experimentation is essential before mainstream application, but the study provided a platform to select drug-able candidates with a higher chance of experimental success and accelerate the drug discovery process within limited resources.
没有适当的病理生理学和推荐的治疗方法,合成类固醇被广泛用作治疗自身免疫性疾病的一线选择。然而,它们的长期使用往往导致严重的副作用,如骨质疏松症、高血压、心血管、胃肠道并发症等。为了寻找潜在的和更安全的治疗选择,本研究旨在探索抗炎植物类固醇(PSs)的效力和药物能力概况。在靶向特异性方法中,我们选择了三个关键分子靶点:糖皮质激素受体/GR (PDB ID: 4P6W),环氧化酶-2/COX2 (PDB ID: 5F1A)和诱导型一氧化氮合酶/iNOS (PDB ID: 4NOS),用于167个选定的PSs的对接研究。利用多种生物信息学和化学信息学工具对PSs的药物化学特征(物理化学、毒性、药代动力学、药物能力等)进行了评估。上述评价表明,withaminilide B (PS46)是具有较高药性的主要候选药物。此外,通过分子动力学(MD)模拟,在200 ns下计算自由能(MM/PBSA),研究了铅与GR靶点“GR-withaminilide B”和对照药物“GR-曲安奈德”对接配合物的药物稳定性和动力学行为。总体研究结果表明,基于其与甾体核心部分的功能附着物,PSs表现出不同的药物能力特征,其中withaminilide B是所有PSs中首选的替代/补充候选药物,预期副作用有限。在主流应用之前,进一步的实验是必不可少的,但该研究提供了一个平台,可以选择具有更高实验成功机会的候选药物,并在有限的资源内加速药物发现过程。
{"title":"Target-specific high-throughput screening of anti-inflammatory phytosteroids for autoimmune diseases: A molecular docking-dynamics simulation approach","authors":"Alaka Sahoo ,&nbsp;Sudhir Kumar Paidesetty ,&nbsp;Maitreyee Panda","doi":"10.1016/j.steroids.2025.109601","DOIUrl":"10.1016/j.steroids.2025.109601","url":null,"abstract":"<div><div>Without proper pathophysiology and recommended therapy, synthetic steroids are widely used as a first-line option for the management of autoimmune diseases. However, their prolonged use often leads to severe side effects such as osteoporosis, hypertension, cardiovascular, gastrointestinal complications, etc. To search for potential and safer therapeutic options, the present study aims to explore the potency and drug-ability profiles of anti-inflammatory phytosteroids (PSs). In a target-specific approach, we have selected three key molecular targets: glucocorticoid receptor/GR (PDB ID: 4P6W), cyclooxygenase-2/COX2 (PDB ID: 5F1A), and inducible nitric oxide synthase/iNOS (PDB ID: 4NOS) for a docking study of 167) selected PSs. The drug-chemistry profiles (physicochemical, toxicity, pharmacokinetic, drug-ability, etc.) of PSs were also assessed using various bioinformatics and chemoinformatics tools. The above assessment suggested that withaminilide B (PS46) is a lead candidate with higher drug-ability properties. Further, the drug stability and kinetic behaviour of the lead with the GR target ‘GR-withaminilide B’ in comparison with the control drug, ‘GR-triamcinolone acetonide’ docking complex, were studied through molecular dynamics (MD) simulation at 200 nanosecond with free energy calculation (MM/PBSA). Overall findings suggested that PSs exhibit distinct drug-ability profiles based on their functional attachments with a steroidal core moiety, where withaminilide B is a lead PSs among all to be used as alternative/ complementary candidates expected with limited adverse effects. Further experimentation is essential before mainstream application, but the study provided a platform to select drug-able candidates with a higher chance of experimental success and accelerate the drug discovery process within limited resources.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"217 ","pages":"Article 109601"},"PeriodicalIF":2.1,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143693394","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