Steroids[JOURNAL]
Sun
200 papers
Theoretical study of the pyridyl-cholestane formation pathway using DFT: A stepwise mechanistic approach.
Sharma K, Priyanka
Steroids · 2025 Apr · PMID 40032071 · Publisher ↗
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...
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.
New hydroxylated metabolite derived from the microbial biotransformation of 11α-acetoxyprogesterone by the endophytic fungus Phyllosticta sp. 16L1 and its cytotoxic activity.
Gazaem MAH, Othman WNNW, Shah SAA … +4 more , Salihu M, Zahari A, Sadiran SH, Salim F
Steroids · 2025 Apr · PMID 40024463 · Publisher ↗
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-aceto...
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 IC values ranging from 6.65 to 27.75 μM, while metabolite 3 displayed lower potency, with IC 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.
Design and discovery of novel heteroaryl substituted pregnenolone derivatives as potent anti-neuroinflammatory agents targeting LPS-stimulated BV-2 microglial cells.
Xu S, Fang L, Cai J … +4 more , Fang S, Zhu H, Lin F, Cai X
Steroids · 2025 Apr · PMID 40024462 · Publisher ↗
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 compou...
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 (IC = 2.05 μM). Compound 10b demonstrated significantly greater inhibitory effects than progesterone (prog) (IC = 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.
Analysis of genes implicated in non-obstructive azoospermia.
Wang J, Wang S, Wang M … +1 more , Yang J
Steroids · 2025 Apr · PMID 40020767 · Publisher ↗
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 investigati...
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.
Steroids from the mushroom Ganoderma shandongense and their AChE inhibitory activities.
Huo Y, Ma S, He X … +2 more , Wang Y, Yuan H
Steroids · 2025 Apr · PMID 39999915 · Publisher ↗
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 2-15). Their structures were determined via ext...
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 2-15). 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 (IC) 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.
Unraveling binding interactions between methasterone and bovine serum albumin (BSA): A spectroscopic and computational study.
Khurshid S, Rasheed S, Falke S … +1 more , Ahmad MS
Steroids · 2025 Mar · PMID 39983858 · Publisher ↗
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-stat...
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.
Effect of betulinic acid on MepA efflux pump inhibition in Staphylococcus aureus: Antibacterial and molecular study.
Pereira da Silva CA, Santos Araújo NJ, Morais Oliveira-Tintino CD … +9 more , Barbosa Filho JM, Alencar GG, de Araújo-Neto JB, Dos Santos JS, Soares JB, Domiciano CB, Silva DAE, Melo Coutinho HD, Andrade-Pinheiro JC
Steroids · 2025 Mar · PMID 39947505 · Publisher ↗
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 mo...
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.
Nandrolone decanoate induces heart injury via oxidative damage and mitochondrial apoptotic pathway by regulation of TLR4/NF-κB/NLRP3 axis in male rats: The rescue effect of N-acetylcysteine.
Amini H, Shirpoor A, Naderi R
Steroids · 2025 Feb · PMID 39894191 · Publisher ↗
Myocardial apoptosis is a leading cause of damage in cardiac tissues of nandrolone (ND) treatment. However, its molecular mechanism is not fully understood. This study aims to investigate the effect of ND with or without...
Myocardial apoptosis is a leading cause of damage in cardiac tissues of nandrolone (ND) treatment. However, its molecular mechanism is not fully understood. This study aims to investigate the effect of ND with or without N -acetylcysteine (NAC) treatment on oxidative damage and TLR4/NF-κB /NLRP3 signaling pathway in the heart of male rats. Eighteen male Wistar rats with a weight range of 220 ± 10 g were selected. They were divided into three groups (n = 6): control (C) group, ND group, NAC + ND group. After six weeks of treatment, the TUNEL staining indicated that ND increased the number of apoptotic cells in the hearts of male rats. The molecular analysis demonstrated that ND exposure resulted in increased protein levels of cytochrome c, c-Caspase-3/p-Caspase-3 ratio, p53, TLR4, NF-κB, NLRP3, and 8-OHdG with a concomitant up-regulation of LDH and CK-MB enzymes activity in the heart tissue compared to the C group. Our findings suggested that ND can cause damage to heart tissue via induction of DNA damage, apoptosis, and probably TLR4/NF-κB/NLRP3 signaling pathway plays a crucial role in this process. It also demonstrates that these negative effects of ND can be reduced by using NAC treatment as an antioxidant and anti-inflammatory agent.
Novel compound heterozygous CYP17A1 mutations identified in a family with two siblings affected by 17α-hydroxylase/17,20-lyase deficiency.
He R, Xu L, Yang N … +6 more , Zhu S, Fan H, Zou J, Chen R, Qian L, Liu Y
Steroids · 2025 Feb · PMID 39874996 · Publisher ↗
BACKGROUND: 17α-Hydroxylase/17,20-lyase deficiency (17OHD) is a rare form of congenital adrenal hyperplasia (CAH), caused by mutations in the CYP17A1 gene. It typically manifests clinically as variable degree of hyperten...
BACKGROUND: 17α-Hydroxylase/17,20-lyase deficiency (17OHD) is a rare form of congenital adrenal hyperplasia (CAH), caused by mutations in the CYP17A1 gene. It typically manifests clinically as variable degree of hypertension, hypokalemia, and disorders of sexual development (DSD), which can include abnormal sexual differentiation in males and sexual infantilism in females. Over 100 mutations in CYP17A1 have been identified, with most cases involving missense mutations or small deletions. METHOD: This study examined the clinical features, biochemical profiles, and genetic background of two 46, XY siblings from the same family, both diagnosed with 17OHD-a scenario that is uncommonly seen in clinical practice. We performed a genetic analysis of the CYP17A1 gene in two generations of the family to confirm the diagnosis. RESULTS: Both patients are phenotypically female, presenting with hypertension, hypokalemia, primary amenorrhea, and absent secondary sexual characteristics. Genetic analysis revealed two novel compound heterozygous mutations in the CYP17A1 gene: R45WfsTer5 (a frameshift mutation) and L361P (a missense mutation). Neither variant is reported in the ClinVar database, and the frameshift mutation (R45WfsTer5) is newly identified. CONCLUSIONS: The discovery of these two novel CYP17A1 mutations expands the genetic spectrum of 17OHD and provides new insights into the genetic underpinnings of the disease. Personalized treatment plans are necessary, and the choice of glucocorticoids with stronger sodium retention effects may be required to manage hypertension and electrolyte imbalances in select patients.
Effect of estrogen on myocardial ischemia-reperfusion injury in male and female rats and related mechanism.
Chen S, Yang L, Xue J … +5 more , Tian X, Hu H, Gao Q, Feng R, Hao L
Steroids · 2025 Feb · PMID 39870188 · Publisher ↗
Due to the difference of estrogen levels in different phases of estrous cycle, it is necessary to exclude the influence of endogenous estrogen when studying the cardiovascular effects of estrogen and its analogues. In th...
Due to the difference of estrogen levels in different phases of estrous cycle, it is necessary to exclude the influence of endogenous estrogen when studying the cardiovascular effects of estrogen and its analogues. In this study, the ischemia/reperfusion (I/R) injury of isolated heart were investigated in female rats during different phases of estrous cycle with male rats as comparison. The results indicated that the estrogen content in blood of rats during metestrus and diestrus (MD) was lower than those during proestrus and estrous (PE). 17β-Estradiol (E2) at 10 M did not show significant effects on I/R injury in male rats and female rats during PE. However, E2 exerted an obviously protective effects against I/R injury on heart rate (HR), lactate dehydrogenase (LDH) and creatine kinase (CK) release in female rats during MD. Furthermore, E2 relieved I/R injury in female rats during MD by decreasing the infarct size and the expression level of p-CaMKII. The results suggested estrous cycles may influence on the extent of cardiac I/R injury due to the regulation of E2 on CaMKII expression level, providing an idea that the estrus cycle should be considered for animal model preparation and toxicity studies in estrogen and environmental hormone research.
Improved synthesis and characterization of bile acid esters: Organogelation and supramolecular properties.
García-Méndez J, López-Torres A, Fernández-Herrera MA
Steroids · 2025 Feb · PMID 39793913 · Publisher ↗
Bile acid esters and their derivatives hold significant interest due to their applications in fields such as supramolecular chemistry, biomedicine, and nanomaterials. This study revisits the synthesis and characterizatio...
Bile acid esters and their derivatives hold significant interest due to their applications in fields such as supramolecular chemistry, biomedicine, and nanomaterials. This study revisits the synthesis and characterization of esters derived from cholic, deoxycholic, and lithocholic acids using short-chain alcohols in combination with microwave-assisted heating. The synthesized esters were analyzed for their potential as gel-forming agents, and their organogelation properties were evaluated. Microwave-assisted synthesis offers rapid and efficient esterification, leading to high yields with improved selectivity. The organogels were characterized through techniques such as differential scanning calorimetry (DSC) and scanning electron microscopy (SEM), revealing distinct structural and thermal properties. The study highlights the potential of these bile acid esters in materials science and supramolecular chemistry, contributing to the development of novel functional materials.
Pancreastatin inhibitor PSTi8 improves ovarian health in Letrozole-HFD induced PCOS rats by ameliorating metabolic and reproductive parameters.
Yadav S, Dadge S, Garg R … +4 more , Goand UK, Agarwal A, Chauhan D, Gayen JR
Steroids · 2025 Feb · PMID 39742935 · Publisher ↗
Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine and metabolic disorder associated with insulin resistance (IR) and hyperandrogenism. IR plays a crucial role in the etiology of PCOS. An insulin-sensitizing a...
Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine and metabolic disorder associated with insulin resistance (IR) and hyperandrogenism. IR plays a crucial role in the etiology of PCOS. An insulin-sensitizing agent like metformin is most commonly used as an off-label drug for the treatment of PCOS. PSTi8 (a pancreastatin inhibitor) is known as a promising therapeutic insulin-sensitizing agent for the treatment of IR in metabolic diseases. Thus, this study evaluates the insulin-sensitizing effects of PSTi8 compared to metformin on IR, hyperandrogenism, ovarian, and metabolic dysfunction in a PCOS model. To induce PCOS, rats were administered letrozole at a dose of 2 mg/kg via oral administration and fed a 60 % high-fat diet. Metformin and PSTi8 lowered serum insulin, testosterone, luteinizing hormone (LH) levels, and the LH/follicle-stimulating hormone ratio in the blood serum and improved steroidogenic gene expression in the PCOS ovaries. Both treatments increased the levels of sex hormone-binding globulin and estrogen hormone. Metformin and PSTi8 restore ovarian and uterine histomorphometry and improve the estrous cycle in PCOS rats. Metformin and PSTi8 treatments also improve blood glucose level and increase insulin sensitivity, inflammation, reactive oxygen species accumulation, lipid parameters, body weight, and fat mass in PCOS rats. This study revealed that PSTi8 is as helpful as metformin in decreasing hyperandrogenism by improving insulin sensitivity, free testosterone level and restoring disturbed reproductive and metabolic parameters in PCOS rats. PSTi8 has potential to serve as a therapeutic molecule for preventing IR induced by a western diet in PCOS.
The effect of resistance training and nandrolone decanoate administration on cardiac tissue in mice.
Atias Y, Ben-Zeev T, Levi C … +2 more , Binman L, Hoffman JR
Steroids · 2025 Feb · PMID 39742934 · Publisher ↗
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 re...
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 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.
Chronic treatment with nandrolone decanoate reduces left ventricular contractile response even when combined with strength training.
Ferreira LD, Aguilar BA, Bernal JVM … +5 more , Melo KY, Gerolim ME, Paixão TEV, Tiburcio DA, Souza HCD
Steroids · 2025 Feb · PMID 39736433 · Publisher ↗
INTRODUCTION: The use of anabolic steroids is widely adopted for aesthetic purposes and sports performance. In supraphysiological doses, they can impair various physiological systems. However, we know little about their...
INTRODUCTION: The use of anabolic steroids is widely adopted for aesthetic purposes and sports performance. In supraphysiological doses, they can impair various physiological systems. However, we know little about their effects on the heart, especially when combined with strength training. In this regard, we investigated the effects of nandrolone decanoate at supraphysiological doses, combined with strength training, on cardiac hemodynamic, morphological, and functional parameters using different approaches. METHODS: Male Wistar rats (N = 64, 18 weeks old) were divided into two groups (N = 32): vehicle-treated (VEH; peanut oil, 0.2 ml/kg) and nandrolone decanoate-treated (NAN, 5 mg/kg). Half of each group (N = 16) underwent strength training following a progressive load stair protocol three times per week for 12 weeks (T-VEH and T-NAN). All groups had their cardiac hemodynamic, morphological, and functional parameters recorded through two-dimensional echocardiography, while coronary perfusion pressure and left ventricular pressure (LVP) were measured using the Langendorff technique in isolated hearts. RESULTS: Both nandrolone decanoate-treated groups showed higher values of relative cardiac mass, interventricular septum thickness, and final diastolic and systolic diameters of the left ventricle compared to vehicle-treated groups (VEH and T-VEH). The NAN group exhibited reductions in coronary perfusion pressure, LVP, and maximum and minimum dP/dT compared to the VEH and T-VEH groups, while the T-NAN group showed reduced values for coronary perfusion pressure and LVP compared to the VEH group. CONCLUSIONS: Nandrolone decanoate treatment at supraphysiological doses reduced left ventricular performance. In turn, strength training appeared to provide minimal attenuation of these impairments.
Structural and functional characterization of genes and enzymes involved in withanolide biosynthesis in Physalis alkekengi L.
Gupta S, Akhoon BA, Sharma D … +3 more , Singh D, Kaul S, Dhar MK
Steroids · 2025 Feb · PMID 39722263 · Publisher ↗
Physalis alkekengi L. is recognized as a significant source of various secondary metabolites, particularly C steroidal lactones known as withanolides and physalins, renowned for their therapeutic properties with a rich h...
Physalis alkekengi L. is recognized as a significant source of various secondary metabolites, particularly C steroidal lactones known as withanolides and physalins, renowned for their therapeutic properties with a rich history in traditional medicine. In this study, we characterized the sequences of key downstream genes (PaFPPS, PaSQS, PaSQE, PaCAS, PaHYD1, and PaDWF5-1) involved in the biosynthesis of withanolides, marking the first characterization of these genes in P. alkekengi. Our findings revealed highly conserved amino acid sequences in P. alkekengi, with maximum similarity observed with Withania somnifera. Notably, essential domains crucial for enzyme function were preserved in P. alkekengi, indicating conserved enzyme activity. Comparative analysis of secondary structures, 3D topologies, and evolutionary studies supported ancestral homology. Investigations into the differential gene expression of these genes across seven tissues (young leaves, stems, roots, flowers, mature green fruit, breaker fruit, and red ripe fruit) highlighted higher expression levels in P. alkekengi leaves. These gene expression patterns were corroborated by phytochemical analyses using chromatographic techniques. High-Performance Liquid Chromatography (HPLC) confirmed the production of two key withanolides, withanolide A and withanone, in P. alkekengi, with maximum production observed in leaves and flowers. These findings suggest that P. alkekengi holds promise as an alternative to W. somnifera for large-scale industrial production of withanolides, particularly withanolide A. Using P. alkekengi eliminates the need to sacrifice the plant, which is typically required in traditional extraction methods from the roots of W. somnifera.
The advancement of structure, bioactivity, mechanism, and synthesis of bufotalin.
Chen N, Wu Y, Wei H … +2 more , Zhi S, Liu L
Steroids · 2025 Feb · PMID 39709107 · Publisher ↗
Toad venom, a family of toxic yet pharmacologically valuable biotoxins, has long been utilized in traditional medicine and holds significant promise in modern drug development. Bufotalin, a prominent bufotoxin, has demon...
Toad venom, a family of toxic yet pharmacologically valuable biotoxins, has long been utilized in traditional medicine and holds significant promise in modern drug development. Bufotalin, a prominent bufotoxin, has demonstrated potent cytotoxic properties through mechanisms such as apoptosis induction, cell cycle arrest, endoplasmic reticulum stress activation, and inhibition of metastasis by modulating key pathways including Akt, p53, and STAT3/EMT signaling-these multi-target mechanisms position bufotalin as a promising agent to combat multidrug resistance in cancer therapy. Additionally, advances in bufotalin synthesis, including chemical and biocatalytic methods, have streamlined production, with strategies such as C14α-hydroxylation and novel coupling techniques enhancing yield and reducing environmental impact. This review consolidates recent progress on bufotalin's structure, activity, cytotoxic mechanisms, and synthetic methodologies, offering a foundation for further development as an innovative chemotherapy agent.
Acetate abates adipose-ovarian endocrinometabolic disturbance in experimentally induced polycystic ovarian syndrome.
Olaniyi KS, Areloegbe SE, Ul Haq Shah MZ
Steroids · 2025 Feb · PMID 39706543 · Publisher ↗
BACKGROUND: Besides ovarian dysfunction and infertility, individuals with polycystic ovarian syndrome (PCOS) also present a number of systemic disturbances including functional derangements in the adipose tissue which po...
BACKGROUND: Besides ovarian dysfunction and infertility, individuals with polycystic ovarian syndrome (PCOS) also present a number of systemic disturbances including functional derangements in the adipose tissue which possibly aggravates the endocrinometabolic abnormality in PCOS. Epigenetic changes have been implicated in metabolic-related disorders including PCOS. However, its pathogenic involvement in adipose-ovarian dysfunction is unclear. Therefore, the present research was designed to investigate the impact of epigenetic regulator, particularly short chain fatty acids (SCFAs) on adipose-ovarian dysfunction in PCOS rat model. MATERIALS AND METHODS: Eight-weeks-old female Wistar rats were allotted into four groups of n = 5, namely control, sodium acetate (SACT), letrozole (LETZ), and LETZ + SACT. Letrozole (1 mg/kg; p.o.) was administered daily for 21 days to induce PCOS. Thereafter, the animals were treated daily with SACT (200 mg/kg; p.o.) for 6 weeks. RESULTS: Letrozole-induced PCOS rats were presented with androgen excess, insulin resistance/hyperinsulinemia, ovarian cystic follicles, increased levels of anti-Mullerian hormone, leptin, with a corresponding decrease in 17-β estradiol, and adiponectin. In addition, the LETZ group also showed dyslipidemia, decreased levels of adipose/ovarian sirtuin-1, adipose triglyceride, increased lipase activity as well as ovarian triglyceride, with corresponding increase in adipose/ovarian lipid peroxidation, caspase-6, TGF-β1, inflammatory response (TNF-α, NF-κB and MIF) and decreased GSH. Adipose/ovarian mitofusin 2 depletion was observed in LETZ group and this was accompanied by elevated HDAC2. Nevertheless, administration of acetate reversed these perturbations. CONCLUSION: Overall, the present results suggest that acetate ameliorates adipose-ovarian metabolic and endocrine disruptions that accompany PCOS, and these beneficial effects of acetate are associated with reduction of HDAC2 levels and elevation of mitofusin 2/sirtuin-1.
Synthesis of novel α-spinasterol derivatives and their inhibitory effects on CCL17 and CCL22 chemokine expression.
Moon H, Yoon H, Jung H … +2 more , Lee TH, Kim H
Steroids · 2025 Feb · PMID 39662716 · Publisher ↗
Natural α-spinasterol is well known for its various biological activities. In this study, we investigated the anti-inflammatory effects of newly synthesized α-spinasterol derivatives by tracking the expression of CCL17 a...
Natural α-spinasterol is well known for its various biological activities. In this study, we investigated the anti-inflammatory effects of newly synthesized α-spinasterol derivatives by tracking the expression of CCL17 and CCL22 chemokines, which serve as biomarkers for immune cell trafficking in skin inflammation. Initially, the 3-epimer of α-spinasterol, which results from inversion of stereochemistry at the C-3 position of α-spinasterol, was synthesized using the Mitsunobu reaction. Subsequently, new compounds were synthesized by introducing azido, amino, and amide groups at the C-3 position of α-spinasterol or 3-epi-α-spinasterol. The anti-inflammatory activity of these compounds was evaluated by examining their inhibitory effects on the mRNA expression of CCL17 and CCL22. Among these derivatives, 3α-8, 3α-12b, and 3α-12c exhibited potential anti-inflammatory activity in vitro, compared to α-spinasterol. Furthermore, compound 3α-8 showed even greater activity than 3α-12b and 3α-12c, underscoring its potential as a highly effective agent. These results suggest that the newly synthesized α-spinasterol derivatives hold promise as candidates for skin inflammation therapeutics.
Understanding the role of hormones in pediatric growth: Insights from a double-debiased machine learning approach.
Deng Y, Yang N, Wang J … +1 more , Tu T
Steroids · 2025 Feb · PMID 39653159 · Publisher ↗
This study investigates the causal relationships between hormone levels and growth and development of children, focusing specifically on height disparities in cases of dwarfism. Besides utilizing double-debiased machine...
This study investigates the causal relationships between hormone levels and growth and development of children, focusing specifically on height disparities in cases of dwarfism. Besides utilizing double-debiased machine learning approach, the study integrates three alternative causal inference methods: partialing-out lasso linear regression, cross-fit partialing-out lasso linear regression, and post-double selection LASSO. These machine learning techniques are pivotal in identifying causal effects within observational data. The findings reveal a positive correlation between luteinizing hormone (LH) levels and adolescent height, while follicle-stimulating hormone (FSH) and the LH/FSH ratio show inverse correlations. The study underscores the significant role of hormone levels, particularly LH, in determining height, offering valuable insights that could guide future interventions or treatments for children and adolescents with dwarfism.
Allosteric communications between domains of nuclear receptors.
Rastinejad F
Steroids · 2025 Feb · PMID 39653158 · Publisher ↗
Nuclear receptors (NRs) regulate gene expression in response to hormonal signals, influencing diverse physiological processes and diseases. Structural and dynamics investigations based on X-ray crystallography, cryo-elec...
Nuclear receptors (NRs) regulate gene expression in response to hormonal signals, influencing diverse physiological processes and diseases. Structural and dynamics investigations based on X-ray crystallography, cryo-electron microscopy (cryo-EM), hydrogen-deuterium exchange mass spectrometry, and molecular dynamics simulations, have significantly deepened our understanding of the conformational states, dynamics, and interdomain interactions of multi-domain NRs. Structural studies have examined heterodimeric complexes such as peroxisome proliferator-activated receptor gamma (PPAR-γ) with retinoid X receptor alpha (RXRα), liver X receptor beta (LXRβ) with RXRα, and retinoic acid receptor beta (RARβ) with RXRα, as well as homodimers like hepatic nuclear factor 4 alpha (HNF-4α), androgen receptor (AR), and glucocorticoid receptor (GR). These investigations highlight critical allosteric communication between ligand-binding domains (LBDs) and DNA-binding domains (DBDs), emphasizing the roles of flexible hinge regions and N-terminal segments in adapting to diverse DNA configurations. Both non-steroid receptor heterodimers and homodimers exhibit robust interdomain connections that mediate allosteric signaling. For instance, AR demonstrates three distinct conformational states that underscore its dynamic behavior, while GR exhibits unique ligand-dependent domain interactions shaping receptor signaling. The collective findings so far suggest a conserved mechanism of cross-domain communication across the NR family. Supported by complementary biophysical, spectroscopic, mutagenesis, and computational studies, this body of research has elucidated the nature of domain-domain interfaces and their pivotal roles in regulating the transcriptional activity of steroid and non-steroid receptors.
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