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17β-estradiol delays cardiac aging through suppressing the methylation of Beclin1 in a murine model 在小鼠模型中,17β-雌二醇通过抑制 Beclin1 的甲基化延缓心脏衰老。
IF 2.1 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-03-01 DOI: 10.1016/j.steroids.2025.109587
Lili Ye , Ruiyan Wang , Jun Zhao , Jingrong Chen , Feng Wang

Introduction

Cardiac endogenous senescence will gradually change and aggravate with age. Recent research showed that 17β-estradiol (17β-E2), an estrogen with numerous biological activities including the prevention of vascular senescence. However, how 17β-E2 against cardiac aging is still unknown. This work addressed the underlying mechanism with regard to Beclin1 and autophagy activity to better understand the anti-senescent effect of 17β-E2 on a well-established animal model of cardiac aging.

Material and methods

In this study, an aging model in female mice was established using d-galactose and ovariectomy. Cardiac function was evaluated by echocardiography, RNA-seq was performed to analyze the gene expression profiles of myocardial tissues from 17β-E2 treated mice. Additionally,The levels of Beclin1, LC3, P62, and ATG5 in myocardial tissues were assessed using qPCR and Western blotting. Methylation levels of the Beclin1 promoter region in myocardial tissues were determined by MSP and BSP.

Results

The findings demonstrated that cardiac aging mice treated with 17β-E2 had improved heart function. 17β-E2 restored EF(increase 1.25-fold) and FS(increase 1.2-fold) to near-normal levels. By RNA-sequencing and Gene Set Enrichment Analysis (GSEA) analysis, the autophagy signaling pathway was further enriched in the myocardial tissue of cardiac aging mice treated with 17β-E2, and we also discovered that 17β-E2 suppress the methylation of Beclin1 promoter region, which mediate the activation of autophagy signal.

Conclusions

Overall, our data showed that 17β-E2′s anti-senescent effect on cardiac aging mice was mediated by the crucial suppression of methylation in the Beclin1 promoter area and subsequent activation of the autophagy signal, which may present a possible therapeutic approach to prevent cardiac aging.
心脏内源性衰老会随着年龄的增长而逐渐改变和加剧。最近的研究表明,17β-雌二醇(17β-E2)是一种具有多种生物活性的雌激素,包括预防血管衰老。然而,17β-E2如何对抗心脏老化仍是未知的。为了更好地了解17β-E2在心脏衰老动物模型中的抗衰老作用,本研究探讨了Beclin1和自噬活性的潜在机制。材料与方法:本研究采用d-半乳糖和卵巢切除术建立雌性小鼠衰老模型。用超声心动图评价心脏功能,用RNA-seq分析17β-E2处理小鼠心肌组织的基因表达谱。采用qPCR和Western blotting检测心肌组织Beclin1、LC3、P62、ATG5的表达水平。心肌组织中Beclin1启动子区甲基化水平通过MSP和BSP检测。结果:心脏老化小鼠经17β-E2处理后,心脏功能得到改善。17β-E2恢复EF(增加1.25倍)和FS(增加1.2倍)至接近正常水平。通过rna测序和基因集富集分析(Gene Set Enrichment Analysis, GSEA)分析,我们发现17β-E2在心脏衰老小鼠心肌组织中进一步富集了自噬信号通路,并且我们还发现17β-E2抑制介导自噬信号激活的Beclin1启动子区甲基化。结论:总体而言,我们的数据表明,17β-E2对心脏衰老小鼠的抗衰老作用是通过关键的Beclin1启动子区甲基化抑制和随后的自噬信号激活介导的,这可能是一种可能的预防心脏衰老的治疗方法。
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引用次数: 0
Theoretical study of the pyridyl-cholestane formation pathway using DFT: A stepwise mechanistic approach 利用 DFT 对吡啶基-胆甾烷的形成途径进行理论研究:逐步机械方法。
IF 2.1 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-03-01 DOI: 10.1016/j.steroids.2025.109575
Kamlesh Sharma, Priyanka
The reaction mechanism of the formation of pyridyl-cholestane derivative 4 from a multi-component reaction involving cholestane-6-one, aromatic aldehyde, malononitrile, and ammonium acetate in presence of magnesium oxide nanoparticles (MgO NPs) as catalyst, was studied successfully by using DFT calculations. The mechanism involved condensation, cyclization, and aromatization steps which were investigated successfully theoretically. The theoretical calculations of physicochemical parameters, including Gibbs free energy, frontier molecular orbitals (FMOs), dipole moments, and hardness, of all the intermediates and transition states molecules. The study revealed the formation of key intermediates and transition states, with detailed analysis of their stability and electronic structures.
The reaction pathway begins with the formation of enamine I and α,β-unsaturated nitrile II, followed by Michael addition to produce intermediate B. The cyclization of A to intermediate B, which has the highest activation energy barrier was identified as slowest and the rate-determining step. The following steps, including cyclization (B to C) and proton transfer (C to D), exhibit progressively lower activation barriers and enhanced stability. Theoretical analysis indicates that the reaction is thermodynamically favorable, as the product is more stable than the initial reactants.
This study highlights the mechanistic insights contributing to the understanding of multi-component reactions in organic synthesis involved effectiveness of MgO NPs as a heterogeneous catalyst in enabling the efficient synthesis of pyridyl-cholestane derivative 4.
采用DFT计算方法,研究了在氧化镁纳米颗粒(MgO NPs)催化下,胆甾-6- 1、芳香醛、丙二腈、乙酸铵等多组分反应生成吡啶胆甾衍生物4的反应机理。反应机理包括缩合、环化和芳构化三个步骤,并在理论上进行了成功的研究。理论计算了所有中间态和过渡态分子的物理化学参数,包括吉布斯自由能、前沿分子轨道、偶极矩和硬度。该研究揭示了关键中间体和过渡态的形成,并详细分析了它们的稳定性和电子结构。该反应途径从形成烯胺I和α、β-不饱和腈II开始,然后经过Michael加成生成中间体B,其中A到中间体B的环化反应速度最慢,具有最高的活化能势垒。接下来的步骤,包括环化(B到C)和质子转移(C到D),表现出逐渐降低的激活障碍和增强的稳定性。理论分析表明,该反应在热力学上是有利的,因为产物比初始反应物更稳定。本研究强调了有助于理解有机合成中多组分反应的机理,包括MgO NPs作为多相催化剂在高效合成吡啶胆甾衍生物4中的有效性。
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引用次数: 0
New hydroxylated metabolite derived from the microbial biotransformation of 11α-acetoxyprogesterone by the endophytic fungus Phyllosticta sp. 16L1 and its cytotoxic activity 内生真菌Phyllosticta sp. 16L1对11α-乙酰氧基孕酮微生物转化的新羟基化代谢物及其细胞毒活性。
IF 2.1 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-02-28 DOI: 10.1016/j.steroids.2025.109584
Mufeda Ahmed Hazea Gazaem , Wan Nurul Nazneem Wan Othman , Syed Adnan Ali Shah , Mustapha Salihu , Azeana Zahari , Siti Hajar Sadiran , Fatimah Salim
Biotransformations catalysed by microbes are promising approach for producing a vast library of structurally diverse chemical molecules with applications in the pharmaceutical industry. The biotransformation of 11α-acetoxyprogesterone (1) by Phyllosticta sp. 16L1 has not been previously reported. In this study, the biotransformation of 11α-acetoxyprogesterone (1) was performed for the first time using the Phyllosticta sp. 16L1 strain. After an 8-day fermentation period, a new biotransformation metabolite, named as 11α-acetoxy-16α-hydroxyprogesterone (16α-hydroxy-3,20-dioxopregn-4-en-11α-yl acetate) (2) was isolated from the culture broth, along with its known isomer, 11α-acetoxy-15α-hydroxyprogesterone (3). The structure determination of the biotransformed products relied on comprehensive spectroscopic data, encompassing 1D and 2D-NMR, as well as LCMS analyses. The cytotoxic activity of the two biotransformed metabolites was assessed against selective human cancer cell lines, including hepatocellular carcinoma (HepG2), triple-negative breast cancer (MDA-MB-231), colorectal adenocarcinoma (Caco-2), and lung adenocarcinoma (A549). The results demonstrated that both metabolites 2 and 3 exhibited cytotoxic effects on the evaluated cell lines. Metabolite 2 showed stronger cytotoxic potential, with IC50 values ranging from 6.65 to 27.75 μM, while metabolite 3 displayed lower potency, with IC50 values between 38.20 and 162.53 μM. Notably, both metabolites exhibited minimal toxicity towards the normal liver Chang cells. Molecular docking studies were conducted to predict the binding modes and affinities of the metabolites against two targets (PDB: 5EM8 and 6V6O), both in 2D and 3D representations, with binding energies ranging from −8.5 to −7.2 kcal/mol. The results revealed that metabolites 2 and 3 interacted with key clinically significant amino acid residues, Lys745 and Met793, through conventional hydrogen bonding.
微生物催化的生物转化是一种很有前途的方法,可以产生大量结构多样的化学分子,并在制药工业中得到应用。Phyllosticta sp. 16L1对11α-乙酰氧基孕酮(1)的生物转化尚未见报道。本研究首次利用Phyllosticta sp. 16L1菌株进行了11α-乙酰氧基孕酮(1)的生物转化。经过8天的发酵,从培养液中分离出一种新的生物转化代谢物,命名为11α-乙酰氧基-16α-羟孕酮(16α-羟基-3,20-二氧opregn-4-烯-11α-乙酸酯)(2),以及其已知的异构体11α-乙酰氧基-15α-羟孕酮(3)。生物转化产物的结构测定依赖于综合光谱数据,包括1D和2d nmr,以及LCMS分析。两种生物转化代谢物的细胞毒活性被评估针对选择性人类癌细胞系,包括肝细胞癌(HepG2)、三阴性乳腺癌(MDA-MB-231)、结直肠癌(Caco-2)和肺腺癌(A549)。结果表明,代谢产物2和3对所评价的细胞系均表现出细胞毒性作用。代谢物2的IC50值在6.65 ~ 27.75 μM之间,代谢物3的IC50值在38.20 ~ 162.53 μM之间,代谢物3的IC50值较低。值得注意的是,这两种代谢物对正常肝细胞的毒性很小。通过分子对接研究,预测代谢产物与两个靶标(PDB: 5EM8和6v60)的结合模式和亲和力,以2D和3D形式表示,结合能范围为-8.5至-7.2 kcal/mol。结果显示,代谢产物2和3通过常规氢键与临床重要的氨基酸残基Lys745、Met793和Leu745相互作用。
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引用次数: 0
Design and discovery of novel heteroaryl substituted pregnenolone derivatives as potent anti-neuroinflammatory agents targeting LPS-stimulated BV-2 microglial cells 设计和发现新的杂芳基取代孕烯醇酮衍生物,作为有效的抗神经炎药物,靶向lps刺激的BV-2小胶质细胞
IF 2.1 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-02-28 DOI: 10.1016/j.steroids.2025.109588
Siqi Xu , Ling Fang , Jianfeng Cai , Shuopo Fang , Huide Zhu , Fei Lin , Xiaorui Cai
A new family of steroidal compounds based on a heteroaryl-4,5-dihydropyrazole thiazolinone core structure was designed and synthesized through structural modifications. The anti-neuroinflammatory activity of these compounds was evaluated in lipopolysaccharide (LPS)-stimulated murine microglial BV-2 cells in vitro. Among the synthesized compounds, 10b and 10d effectively inhibited nitric oxide (NO) production, with compound 10b emerging as the most potent anti-neuroinflammatory agent (IC50 = 2.05 μM). Compound 10b demonstrated significantly greater inhibitory effects than progesterone (prog) (IC50 = 3.23 μM) and reduced NO production in a concentration-dependent manner. Furthermore, compound 10b attenuated the release of pro-inflammatory mediators, including tumour necrosis factor (TNF)-α, interleukin-1β (IL-1β), interleukin-6 (IL-6), and prostaglandin E2 (PGE2). It also inhibited the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Mechanistic studies revealed that compound 10b significantly suppressed the transcriptional activity of nuclear factor kappa B (NF-κB) in activated microglial cells and prevented NF-κB p65 activation and IκBα degradation. These effects were likely mediated by the inhibition of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) signaling pathways. Additionally, molecular docking studies suggested that the anti-neuroinflammatory effects of compound 10b may result from its hydrophobic and hydrophilic interactions with iNOS and COX-2, supporting its proposed mechanism of action. In summary, these findings suggest that compound 10b exerts anti-neuroinflammatory effects in LPS-stimulated BV-2 microglial cells by modulating key inflammatory pathways, including NF-κB and MAPK signaling.
以杂芳基-4,5-二氢吡唑噻唑啉酮为核心结构,通过结构修饰,设计合成了一类新的甾体化合物。这些化合物的抗神经炎活性在体外脂多糖(LPS)刺激的小鼠小胶质BV-2细胞中进行了评估。在所合成的化合物中,化合物10b和10d能有效抑制一氧化氮(NO)的产生,其中化合物10b的抗神经炎作用最强(IC50 = 2.05 μM)。化合物10b的抑制作用显著高于孕酮prog (IC50 = 3.23 μM),并呈浓度依赖性地降低NO的生成。此外,化合物10b减少了促炎介质的释放,包括肿瘤坏死因子(TNF)-α、白细胞介素-1β (IL-1β)、白细胞介素-6 (IL-6)和前列腺素E2 (PGE2)。对诱导型一氧化氮合酶(iNOS)和环氧合酶-2 (COX-2)的表达也有抑制作用。机制研究表明,化合物10b可显著抑制活化小胶质细胞中核因子κB (NF-κB)的转录活性,抑制NF-κB p65的活化和i -κB α的降解。这些作用可能是通过抑制c-Jun n末端激酶(JNK)和细胞外信号调节激酶(ERK)信号通路介导的。此外,分子对接研究表明,化合物10b的抗神经炎症作用可能是由其与iNOS和COX-2的疏水和亲水相互作用引起的,支持了其作用机制。综上所述,这些发现表明化合物10b通过调节包括NF-κB和MAPK信号在内的关键炎症通路,在lps刺激的BV-2小胶质细胞中发挥抗神经炎症作用。
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引用次数: 0
Analysis of genes implicated in non-obstructive azoospermia 与非阻塞性无精子症相关的基因分析
IF 2.1 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-02-26 DOI: 10.1016/j.steroids.2025.109583
Junwei Wang , Shuhui Wang , Meng Wang , Jinfei Yang
Non-obstructive azoospermia (NOA) is the most common cause of male infertility, accounting for approximately 60 % of azoospermia cases. In recent years, gene mutations have emerged as the primary factor under investigation for the etiology of NOA. Therefore, finding the cause and pathogenesis of NOA at the genetic level has become one of the current research hotspots. Genetic analysis of NOA patients revealed that gene mutations primarily concentrate in protein-coding regions and non-coding RNAs, predominantly occurring in cases of non-obstructive azoospermia. Hence, understanding the relationship between these gene mutations and NOA can not only provide new ideas for treatment, but also provide a theoretical basis for revealing the pathogenesis of NOA. This article comprehensively reviews recent advancements in identifying genes that are intricately associated with azoospermia. These results will provide meaningful guidance for the future development of NOA-targeted therapeutic drugs.
非阻塞性无精子症(NOA)是男性不育的最常见原因,约占无精子症病例的60%。近年来,基因突变已成为NOA病因研究的主要因素。因此,在遗传水平上寻找NOA的病因和发病机制已成为当前的研究热点之一。NOA患者的遗传分析显示,基因突变主要集中在蛋白质编码区和非编码rna中,主要发生在非阻塞性无精子症病例中。因此,了解这些基因突变与NOA之间的关系不仅可以为治疗提供新的思路,而且可以为揭示NOA的发病机制提供理论依据。本文全面回顾了在鉴定与无精子症复杂相关的基因方面的最新进展。这些结果将为今后开发靶向noa治疗药物提供有意义的指导。
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引用次数: 0
Steroids from the mushroom Ganoderma shandongense and their AChE inhibitory activities 山东灵芝甾体及其乙酰胆碱酯酶抑制活性研究。
IF 2.1 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-02-23 DOI: 10.1016/j.steroids.2025.109574
Yaqin Huo , Shiyuan Ma , Xihan He , Yuxi Wang , Haisheng Yuan
Investigation of the solid culture of Ganoderma shandongense led to the isolation of 15 compounds, including one new steroid (compound 1) and fourteen known ones (compounds 215). Their structures were determined via extensive the nuclear magnetic resonance (NMR) spectroscopic analyses and quantum chemical calculations. Compounds 3, 9, and 14 exhibited inhibitory activities against acetylcholinesterase (AChE), with half maximal inhibitory concentration (IC50) values of 29.4, 29.4 and 33.2 µM, respectively. Furthermore, molecular docking studies were undertaken to elucidate the interaction mechanisms between the compounds and the amino acid residues of AChE.
对山东灵芝的固体培养进行了研究,共分离到15个化合物,其中1个为新化合物(化合物1),14个为已知化合物(化合物2 ~ 15)。通过广泛的核磁共振光谱分析和量子化学计算确定了它们的结构。化合物3、9和14对乙酰胆碱酯酶(AChE)具有抑制活性,半数最大抑制浓度(IC50)分别为29.4、29.4和33.2 µM。此外,还进行了分子对接研究,以阐明化合物与乙酰胆碱酯氨基酸残基之间的相互作用机制。
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引用次数: 0
Unraveling binding interactions between methasterone and bovine serum albumin (BSA): A spectroscopic and computational study 解开美沙酮和牛血清白蛋白(BSA)之间的结合相互作用:光谱和计算研究。
IF 2.1 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-02-19 DOI: 10.1016/j.steroids.2025.109573
Sahar Khurshid , Saima Rasheed , Sven Falke , Malik Shoaib Ahmad
In this study, binding interactions between methasterone and bovine serum albumin (BSA) were analyzed using spectroscopic techniques and molecular docking. UV absorption spectroscopy showed the formation of a ground-state complex between methasterone and bovine serum albumin (BSA). Thermodynamic parameters from fluorometric analysis indicated that the hydrogen bonding and van der Waal forces were the main interacting forces between the complex and the reaction was found to be spontaneous. Molecular docking further validated it. Nano differential scanning fluorimetry showed the protein was found to be more thermally stable in the presence of methasterone. Circular dichroism spectroscopy revealed slight reduction in the helicity after binding with methasterone suggesting conformational changes to promote binding. As no prior information exists on the binding interactions between methasterone and BSA, this study provides insights into methasterone-BSA interactions, which can serve as a foundation for future investigations into its pharmacological properties.
本研究利用光谱技术和分子对接技术分析了美沙酮与牛血清白蛋白(BSA)的结合相互作用。紫外吸收光谱显示美沙酮与牛血清白蛋白(BSA)之间形成基态配合物。荧光分析的热力学参数表明,氢键和范德华力是配合物之间的主要相互作用力,反应是自发的。分子对接进一步验证了这一点。纳米差示扫描荧光法显示,该蛋白在美沙酮存在下更热稳定。圆二色光谱显示,与美沙酮结合后,螺旋度略有降低,表明构象变化促进了结合。由于目前尚无关于美沙酮与牛血清白蛋白结合相互作用的相关信息,本研究为进一步研究美沙酮与牛血清白蛋白的相互作用提供了新的视角,为进一步研究其药理特性奠定了基础。
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引用次数: 0
Effect of betulinic acid on MepA efflux pump inhibition in Staphylococcus aureus: Antibacterial and molecular study 白桦酸对金黄色葡萄球菌MepA外排泵抑制作用的抑菌及分子研究。
IF 2.1 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-02-11 DOI: 10.1016/j.steroids.2025.109572
Camila Aparecida Pereira da Silva , Nara juliana Santos Araújo , Cícera Datiane Morais Oliveira-Tintino , José Maria Barbosa Filho , Gabriel Gonçalves Alencar , José Bezerra de Araújo-Neto , Josefa Sayonara dos Santos , Juliete Bezerra Soares , Carolina Bandeira Domiciano , Davi Antas e Silva , Henrique Douglas Melo Coutinho , Jacqueline Cosmo Andrade-Pinheiro
Infections caused by pathogenic bacteria have been responsible for a significant number of deaths in recent decades. Invasive infections caused by Staphylococcus aureus are highly prevalent and have high morbidity and mortality rates. Faced with the increase in multidrug-resistant bacteria, a promising strategy is the development of adjuvant molecules that enhance the effects of antibiotics, such as efflux pump inhibitors. Betulinic acid (BA) is a pentacyclic triterpene of the lupane type, found in various plant species, which has shown various pharmacological activities, including antibacterial potential. This study investigated the inhibitory action of BA on the MepA efflux pump in strains of Staphylococcus aureus K2068, as well as carrying out fluorescence and membrane permeability tests. The minimum inhibitory concentrations (MIC) were determined using the broth microdilution method. Subsequently, their effects on efflux pump-mediated antibiotic resistance were evaluated by reducing the MIC of the antibiotic and ethidium bromide (EtBr), while fluorimetry and permeability potential tests were carried out using the SYTOX Green fluorescence method. BA did not show intrinsic antibacterial activity, however it showed synergistic effects when associated with the antibiotics ciprofloxacin and ethidium bromide, inducing a reduction in MIC and indicating inhibitory effects on the MepA efflux pump. BA also induced a significant increase in fluorescence and demonstrated the ability to permeabilize the bacterial membrane. The results obtained show that BA has a high potential to act as an efflux pump inhibitor and could help in the treatment of resistant bacterial infections.
近几十年来,由致病菌引起的感染造成了大量死亡。金黄色葡萄球菌引起的侵袭性感染非常普遍,发病率和死亡率都很高。面对耐多药细菌的增加,一种有希望的策略是开发增强抗生素作用的佐剂分子,如外排泵抑制剂。白桦酸(Betulinic acid, BA)是一种狼烷型的五环三萜,存在于多种植物中,具有多种药理活性,包括抗菌潜力。本研究考察了BA对金黄色葡萄球菌K2068菌株MepA外排泵的抑制作用,并进行了荧光和膜透性试验。采用肉汤微量稀释法测定最低抑菌浓度(MIC)。随后,通过降低抗生素和溴化乙啶(EtBr)的MIC来评估它们对外排泵介导的抗生素耐药性的影响,同时使用SYTOX绿色荧光法进行荧光法和渗透电位测试。BA不表现出固有的抗菌活性,但与抗生素环丙沙星和溴化乙锭联用时表现出协同作用,诱导MIC降低,对MepA外排泵有抑制作用。BA也诱导了荧光的显著增加,并证明了渗透细菌膜的能力。结果表明,BA具有很高的作为外排泵抑制剂的潜力,可以帮助治疗耐药细菌感染。
{"title":"Effect of betulinic acid on MepA efflux pump inhibition in Staphylococcus aureus: Antibacterial and molecular study","authors":"Camila Aparecida Pereira da Silva ,&nbsp;Nara juliana Santos Araújo ,&nbsp;Cícera Datiane Morais Oliveira-Tintino ,&nbsp;José Maria Barbosa Filho ,&nbsp;Gabriel Gonçalves Alencar ,&nbsp;José Bezerra de Araújo-Neto ,&nbsp;Josefa Sayonara dos Santos ,&nbsp;Juliete Bezerra Soares ,&nbsp;Carolina Bandeira Domiciano ,&nbsp;Davi Antas e Silva ,&nbsp;Henrique Douglas Melo Coutinho ,&nbsp;Jacqueline Cosmo Andrade-Pinheiro","doi":"10.1016/j.steroids.2025.109572","DOIUrl":"10.1016/j.steroids.2025.109572","url":null,"abstract":"<div><div>Infections caused by pathogenic bacteria have been responsible for a significant number of deaths in recent decades. Invasive infections caused by <em>Staphylococcus aureus</em> are highly prevalent and have high morbidity and mortality rates. Faced with the increase in multidrug-resistant bacteria, a promising strategy is the development of adjuvant molecules that enhance the effects of antibiotics, such as efflux pump inhibitors. Betulinic acid (BA) is a pentacyclic triterpene of the lupane type, found in various plant species, which has shown various pharmacological activities, including antibacterial potential. This study investigated the inhibitory action of BA on the MepA efflux pump in strains of <em>Staphylococcus aureus</em> K2068, as well as carrying out fluorescence and membrane permeability tests. The minimum inhibitory concentrations (MIC) were determined using the broth microdilution method. Subsequently, their effects on efflux pump-mediated antibiotic resistance were evaluated by reducing the MIC of the antibiotic and ethidium bromide (EtBr), while fluorimetry and permeability potential tests were carried out using the SYTOX Green fluorescence method. BA did not show intrinsic antibacterial activity, however it showed synergistic effects when associated with the antibiotics ciprofloxacin and ethidium bromide, inducing a reduction in MIC and indicating inhibitory effects on the MepA efflux pump. BA also induced a significant increase in fluorescence and demonstrated the ability to permeabilize the bacterial membrane. The results obtained show that BA has a high potential to act as an efflux pump inhibitor and could help in the treatment of resistant bacterial infections.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"215 ","pages":"Article 109572"},"PeriodicalIF":2.1,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143415358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Extraction of diosgenin using different techniques from fenugreek seeds- A review 用不同技术从葫芦巴种子中提取薯蓣皂甙--综述。
IF 2.1 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-02-01 DOI: 10.1016/j.steroids.2024.109543
Sharavan Kumar , B.M. Praveen , Aralihalli Sudhakara , Prajwal Sherugar , Yashoda Malgar Puttaiahgowda
Diosgenin, falls under the category of steroidal saponin present in fenugreek seeds (Trigonella foenum-graecum) in the amount of 0.2–09%. This compound possesses certain pharmacological characteristics like anti-inflammatory, anti-cancer, anti-oxidant etc., that render it a desirable component in the medicinal and nutraceutical industries. Various methods such as, conventional solvent extraction, green extraction methods like Soxhlet extraction, microwave-assisted extraction (MAE), maceration methods, ultrasound-assisted extraction (UAE) and supercritical fluid extraction methods are employed to extract diosgenin from fenugreek seeds. Fundamentals such as solvent choice, pre-treatment techniques, and optimization parameters, affect the diosgenin extraction process. Furthermore, the quantification of diosgenin is governed by analytical methods(chromatography and spectroscopy), underscoring the significance of standardizing diosgenin levels to set the stage for upcoming pharmacological research. However there have been very negligible resources which focuses on conventional and novel techniques for extraction of diosgenin from Fenugreek seeds. This review aims to provide combined insights into the diverse methodologies employed for diosgenin extraction from fenugreek seeds and their implications in pharmaceutical research.
薯蓣皂苷元属于甾体皂苷类,存在于葫芦巴种子(Trigonella foenum-graecum)中,含量为0.2-09%。这种化合物具有一定的药理特性,如抗炎、抗癌、抗氧化等,使其成为医药和营养保健行业的理想成分。胡芦巴种子中薯蓣皂苷元的提取方法有传统的溶剂提取、索氏提取等绿色提取法、微波辅助提取法、浸渍法、超声辅助提取法、超临界流体提取法等。溶剂选择、预处理工艺、优化参数等基本因素影响薯蓣皂苷元的提取过程。此外,薯蓣皂苷元的定量是由分析方法(色谱和光谱)控制的,强调了标准化薯蓣皂苷元水平的重要性,为即将到来的药理学研究奠定了基础。然而,从胡芦巴种子中提取薯蓣皂苷元的传统技术和新技术的研究很少。本文综述了胡芦巴种子中薯蓣皂苷元的提取方法及其在药物研究中的应用。
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引用次数: 0
The effect of resistance training and nandrolone decanoate administration on cardiac tissue in mice 抗阻训练与癸酸诺龙对小鼠心脏组织的影响。
IF 2.1 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-02-01 DOI: 10.1016/j.steroids.2024.109559
Yechiel Atias, Tavor Ben-Zeev, Chagai Levi, Lior Binman, Jay R. Hoffman
Purpose: This study examined the effect of resistance training (RT) by itself and in combination with supraphysiological administration of nandrolone decanoate (ND) on the inflammatory, apoptotic, and oxidative stress response in cardiac tissue. The effect of the training and androgen intervention on adiponectin expression, a potential cardio protectant was also examined. Methods: Forty male C57Bl/6J mice, 3 months of age were randomized into four groups (n = 10 per group). Two groups of animals performed a 3-day per week RT program for 7-weeks, while the other two groups remained sedentary (SED). The RT and SED animals were further randomized into an androgen group (RTA and SEDA, respectively) or a sham group (RTS and SEDS, respectively). Animals in the RTA and SEDA groups received 38-mg·kg−1 injected once per week. Mice from RTS and SEDS received sham injections. Results: Main effects for group indicated that RT resulted in significant elevations in NFκβ (p < 0.001), glutamine peroxidase (GPX) (p = 0.007) and adiponectin (p < 0.001). Main effects for treatment indicated that ND administration resulted in greater elevations in NFκβ (p = 0.01) and TNF-α (p = 0.017). In addition, TNF-α expression was greater in RTA compared to RETS (p = 0.006) and the adiponectin response in RTA was greater (p’s < 0.05) than all other groups. A significant correlation was noted between average training volume during the RT program and GPX expression (r = 0.716, p < 0.001). Conclusion: Results indicate that RT and ND administration can increase markers of apoptosis and inflammation. Elevations in adiponectin expression suggest that it may act as a compensatory mechanism supporting cardiovascular health.
目的:本研究探讨抗阻训练(RT)单独及联合经生理给药十酸诺龙(ND)对心脏组织炎症、凋亡和氧化应激反应的影响。训练和雄激素干预对脂联素表达的影响,一种潜在的心脏保护剂也被检查。方法:选取3 月龄雄性C57Bl/6J小鼠40只,随机分为4组,每组 = 10只。两组动物每周进行3天的RT计划,持续7周,而另外两组保持久坐(SED)。RT和SED动物进一步随机分为雄激素组(分别为RTA和SEDA)或假组(分别为RTS和SEDS)。RTA组和SEDA组每周1次注射38 mg·kg-1。RTS和SEDS小鼠接受假注射。结果:各组主要效应显示,RT组nf - κβ显著升高(p )。结论:RT和ND均可增加细胞凋亡和炎症标志物。脂联素表达的升高表明它可能作为一种支持心血管健康的代偿机制。
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