Steroids[JOURNAL]
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200 papers
Extraction of diosgenin using different techniques from fenugreek seeds- A review.
Kumar S, Praveen BM, Sudhakara A … +2 more , Sherugar P, Puttaiahgowda YM
Steroids · 2025 Feb · PMID 39647804 · Publisher ↗
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-inflamma...
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.
Relative fat mass (RFM) is linked to testosterone deficiency in adult males.
Wu M, Wang Z
Steroids · 2025 Feb · PMID 39638103 · Publisher ↗
PURPOSE: Relative fat mass (RFM) is a novel obesity assessment metric, and we aim to explore the relationship between RFM and testosterone deficiency in US adult males. METHODS: This study included data from adult males...
PURPOSE: Relative fat mass (RFM) is a novel obesity assessment metric, and we aim to explore the relationship between RFM and testosterone deficiency in US adult males. METHODS: This study included data from adult males aged 20-59 years from the NHANES 2013-2014 and 2015-2016 cycles. RFM was calculated using a linear equation based on height and waist circumference (WC). Testosterone deficiency was defined as a total serum testosterone level of less than 300 ng/dL. Logistic regression, subgroup analysis, and smooth curve fitting were employed to explore the relationship between RFM and the risk of testosterone deficiency. RESULTS: This study included 3243 participants, with 771 diagnosed with testosterone deficiency. Testosterone-deficient individuals exhibited significantly higher RFM levels compared to those with normal testosterone levels (31.23 ± 0.23 vs. 27.16 ± 0.19, P < 0.001). After adjusting for confounding variables, a positive correlation emerged between RFM and testosterone deficiency (OR = 1.16, 95 %CI = 1.11-1.22, P < 0.001). Smooth curve fitting further supported this relationship. Subgroup analysis did not identify any special populations. Receiver operating curve (ROC) analysis results indicated that RFM showed greater effectiveness compared to body mass index (BMI) and WC. CONCLUSIONS: Elevated RFM levels were found to be linked to the risk of testosterone deficiency. Further studies on RFM hold promise to evaluate and address testosterone deficiency.
Cardioprotective effects of S-equol, a soybean metabolite with estrogen activity, and role of the PI3K/Akt pathway in a male rat model of ischemic reperfusion.
Yamada M, Nakadate Y, Omiya K … +3 more , Oguchi T, Abe M, Matsukawa T
Steroids · 2025 Jan · PMID 39613131 · Publisher ↗
PURPOSE: S-equol, an isoflavone metabolite with high estrogenic activity, exhibits organ-protective effects via the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway. While estrogen has cardiopr...
PURPOSE: S-equol, an isoflavone metabolite with high estrogenic activity, exhibits organ-protective effects via the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway. While estrogen has cardioprotective effects against ischemia-reperfusion injury, whether S-equol shares this capability remains uncertain. This study aimed to assess the cardioprotective effects of S-equol on stunned myocardium using an isolated rat heart model and investigate the involvement of PI3K/Akt signaling pathway. METHODS: Male rat hearts were perfused using the Langendorff system and divided into four groups: 1) modified Krebs-Henseleit (KH) buffer containing 1 μmol/L S-equol (EQ); 2) KH buffer (Cont); 3) KH buffer supplemented with 1 μmol/L S-equol and 100 nmol/L wortmannin (a specific PI3K inhibitor) (EQW); or 4) KH buffer containing wortmannin (ContW). After stabilization, each group was perfused for 20 min before undergoing 7.5 min of no-flow ischemia, followed by 20 min reperfusion. The primary outcome was the maximum left ventricular derivative of pressure development (left ventricle [LV] dP/dt max)after 20 min of reperfusion. Myocardial Akt and glycogen synthase kinase-3 beta (GSK-3β) were assayed using western blotting. RESULTS: LV dP/dt max was greater in the EQ group than that in the Cont group after 15 and 20 min of reperfusion; however, this effect was attenuated in the presence of PI3K inhibitors. S-equol treatment increased Akt and suppressed GSK-3β expression in the EQ group compared to that in the Cont group. However, these effects were not observed in the presence of wortmannin. CONCLUSION: S-equol exerts a protective effect against myocardial ischemia-reperfusion injury, possibly by activating PI3K/Akt signaling.
PTX3 impairs granulosa cell function by promoting the secretion of inflammatory cytokines in M1 macrophages via the JAK pathway.
Chen Y, Luo X, Li Y … +4 more , Liu L, Liu Z, Tan Y, Chen Y
Steroids · 2025 Feb · PMID 39577792 · Publisher ↗
Polycystic Ovary Syndrome (PCOS) is an endocrine disorder syndrome among women in their reproductive years and is often linked to chronic inflammation. Pentraxin 3 (PTX3), a member of the pentraxin protein family, plays...
Polycystic Ovary Syndrome (PCOS) is an endocrine disorder syndrome among women in their reproductive years and is often linked to chronic inflammation. Pentraxin 3 (PTX3), a member of the pentraxin protein family, plays a key role in inflammation. In our study, we explored whether PTX3 influences granulosa cell function via its involvement in inflammation. Our analysis revealed elevated PTX3 concentrations in the follicular fluid and granulosa cells of patients with PCOS. Overexpression of PTX3 promoted apoptosis in the cultured murine granulosa cell line KK1 and inhibited the proliferation of these cells. Additionally, it suppressed the expression of luteinizing hormone receptor (LHR) and follicle-stimulating hormone receptor (FSHR), as well as those of key enzymes involved in steroid hormone synthesis, CYP19A1, and HSD3β, leading to reduced secretion of estradiol and progesterone. Moreover, both recombinant PTX3 protein and PTX3 secreted by granulosa cells (GCs) promoted the secretion of inflammatory cytokines IL-1β, IL-6, and TNF-α by M1 macrophages via the JAK pathway, which impaired the function of granulosa cells. This study may advance the understanding of cell-cell interactions in follicles and the inflammatory factors that contribute to PCOS pathophysiology.
Comparison of a chemiluminescence immunoassay with LC-MS/MS in the determination of the plasma aldosterone concentration in patients with impaired renal function.
Zeng Q, Li J, Yang Y … +7 more , He Y, Song Y, Hu J, Wang Y, Li Q, Yang S, Chongqing Primary Aldosteronism Study CONPASS Group
Steroids · 2025 Jan · PMID 39571878 · Publisher ↗
PURPOSE: Compared with chemiluminescence immunoassay (CLIA), the quantification of the plasma aldosterone concentration (PAC) via liquid chromatography-tandem mass spectrometry (LC-MS/MS) yields lower values. The extent...
PURPOSE: Compared with chemiluminescence immunoassay (CLIA), the quantification of the plasma aldosterone concentration (PAC) via liquid chromatography-tandem mass spectrometry (LC-MS/MS) yields lower values. The extent to which this difference is exacerbated by a reduced glomerular filtration rate (eGFR) is unclear. Therefore, this study aims to assess the impact of renal insufficiency on PAC as measured by CLIA using LC-MS/MS as the reference method. METHODS: In subjects with a normal or reduced estimated eGFR, the PAC was measured using both LC-MS/MS and two different CLIA kits (Mindray and Liaison). RESULTS: In total, 383 patients were included in our study. Among them, 71 subjects had eGFRs > 90 (Group one), 79 had eGFRs range from 60 to 89 (Group two), 108 had eGFR range from 30 to 59 (Group three), 51 had eGFRs range from 15 to 29 (Group four), and 74 had eGFRs < 15 (Group five) ml/min per 1.73 m. In all the subjects, PAC as measured by CLIA [68.2 (37.1-122.1) pg/ml for Mindray, 109.0 (68.1-170.0) pg/ml for Liaison] were significantly higher than those measured by LC-MS/MS [47.2 (22.9-88.7) pg/ml]. PAC as measured by CLIA was positively correlated with PAC as measured by LC-MS/MS, but the correlation coefficient gradually decreased as eGFR decreased. Between the LC-MS/MS and Liaison CLIA kits, the difference in PAC values increased with reduced eGFR in groups one through five (76.8 %, 69.2 %, 113.2 %, 152.2 %, and 476.2 % for groups one through five, respectively). However, this difference increased only in Group five with the Mindray CLIA kit (46.4 %, 48.1 %, 45.7 %, 45.0 %, and 74.9 % for groups one through five, respectively). CONCLUSION: CLIA progressively overestimated PAC as eGFR decreased, particularly with the Liaison method, indicating the need for caution when interpreting these measurements in patients with impaired renal function. In patients with impaired renal function, LC‒MS/MS measurements for PAC are preferable.
Unraveling the impact of semaglutide in a diabetic rat model of testicular dysfunction: Insights into spermatogenesis pathways and miRNA-148a-5p.
Abdel-Wahab BA, El-Shoura EAM, Habeeb MS … +3 more , Aldabaan NA, Ahmed YH, Zaafar D
Steroids · 2025 Jan · PMID 39551458 · Publisher ↗
BACKGROUND: Diabetes has been a long-known risk factor for male sexual dysfunction, which may be caused by persistent hyperglycemia, oxidative stress, and spermatogenesis inhibition. This study explored the potential of...
BACKGROUND: Diabetes has been a long-known risk factor for male sexual dysfunction, which may be caused by persistent hyperglycemia, oxidative stress, and spermatogenesis inhibition. This study explored the potential of Semaglutide (Sem) to alleviate testicular dysfunction and spermatogenesis impairment in diabetic rats to understand the molecular mechanism of this protective effect. METHODOLOGY: A controlled experiment was conducted where 28 adult male rats were divided into four groups: control, Semaglutide, diabetic, and diabetes + Sem. Diabetes was induced using a single STZ dose (50 mg/kg, i.p.). At the same time, Sem was administered as a daily subcutaneous dose (25 nmol/kg) for four weeks after the confirmed diagnosis of diabetes. Several biochemical and histochemical analyses were performed in addition to mating behavior assessments. The estimation of spermatogenesis-related genes and proteins was conducted using PCR and western blotting techniques. RESULTS: revealed promising outcomes, wherein Sem treatment effectively mitigated diabetes-induced sexual and testicular dysfunction. Specifically, it regulated the disrupted redox balance, restored spermatogenesis gene and protein levels, modulated hormonal profiles, and mitigated testicular inflammation. CONCLUSION: Sem protects against diabetes-induced testicular and sexual impairments by influencing several pathways and restoring spermatogenesis-related genes and proteins. Future studies may involve a potential investigation of Sem translational applications in clinical settings for treating male infertility associated with diabetes.
Recent advances in the development of 17beta-hydroxysteroid dehydrogenase inhibitors.
Poirier D
Steroids · 2025 Jan · PMID 39532224 · Publisher ↗
The family of 17β-hydroxysteroid dehydrogenases (17β-HSDs) occupies a prominent place due to its number of isoforms, which carry out a bidirectional transformation (reduction of a steroid carbonyl to alcohol and oxidatio...
The family of 17β-hydroxysteroid dehydrogenases (17β-HSDs) occupies a prominent place due to its number of isoforms, which carry out a bidirectional transformation (reduction of a steroid carbonyl to alcohol and oxidation of a steroid alcohol to ketone) depending on the nature of the cofactor present. Involved in the activation or inactivation of key estrogens and androgens, 17β-HSDs are therefore therapeutic targets whose selective inhibition would make it possible to be considered for the treatment of several diseases, such as breast cancer, prostate cancer, endometriosis, Alzheimer's disease and osteoporosis. This review article is a continuation of those having reported the great diversity of inhibitors developed over the last years but focusses on inhibitors recently developed. Work to obtain more effective inhibitors that target the first known isoforms (types 1, 2, 3, 5 and 7) has continued, among others, but new inhibitors that target the isoforms more recently reported in the literature (types 10, 12, 13 and 14) are now being reported. Dual inhibitors of two enzymes (17β-HSD1 and steroid sulfatase) were also reported. These inhibitors were grouped according to the 17β-HSD type inhibited and their backbone (steroidal or non-steroidal) when necessary. They were also reported in chronological order and according to the research group.
Ascorbic acid Mitigates behavioural disturbances associated with letrozole-induced PCOS via switching-off JAK2/STAT5 and JAK2/ERK1/2 pathways in rat hippocampus.
Saad MA, Rastanawi AA, El-Sahar AE … +1 more , A Z El-Bahy A
Steroids · 2025 Jan · PMID 39528020 · Publisher ↗
PURPOSE: Polycystic ovary syndrome (PCOS) is an endocrine disorder with the highest prevalence among other disorders in sexually-active women. It is associated with broad-spectrum hormonal and metabolic disturbances with...
PURPOSE: Polycystic ovary syndrome (PCOS) is an endocrine disorder with the highest prevalence among other disorders in sexually-active women. It is associated with broad-spectrum hormonal and metabolic disturbances with behavioural difficulties. Experimentally, letrozole administration causes similar findings. Ascorbic acid is powerful anti-oxidant; and its cellular levels decrease with "hyperglycemic and poor anti-oxidative" status, which is, a main hallmark of PCOS. Thus, ascorbic acid administration may prevent the induction of PCOS and its consequences. BASIC PROCEDURES: Forty female rats were divided into four groups (n = 10 in each): normal control (CTRL), ascorbic acid (ASC), letrozole (LTZ), and ascorbic acid + letrozole (ASC + LTZ) group. Behavioural tests (Y-maze spontaneous alteration, tail suspension test, forced swimming test) were performed. In serum, hormones (testosterone, estradiol, progesterone), glycemia (blood glucose, insulin and HOMA-IR) and oxidative stress (SOD activity, GSH) markers were measured. In hippocampus, inflammation and apoptosis indicators (p-JAK2, p-STAT5, p-ERK1/2, NF-κB, BAX, Bcl2, BAX/Bcl2 ratio) and neurotransmitters (DA, 5-HT, NE, BDNF) were determined. Lastly, ovary histopathological investigation was conducted to confirm PCOS induction. PRINCIPAL RESULTS: Letrozole induced PCOS with subsequent disturbances. Testosterone levels were augmented while estradiol and progesterone were declined. Fasting blood glucose, insulin, HOMA-IR and oxidative stress markers were elevated. The expression of p-JAK2, p-STAT5, p-ERK1/2, BAX and the levels of NF-κB were increased, but Bcl2 expression, monoamines and BDNF levels were lowered. Importantly, ASC restored the last mentioned parameters markedly. MAJOR CONCLUSIONS: Ascorbic acid mitigated the behavioural difficulties of PCOS possibly by switching-off JAK2/STAT5 and JAK2/ERK1/2 pathways in hippocampus along with its neurotransmission-improving, hormonal-normalizing, anti-hyperglycemic and anti-oxidative effects.
Patterns of corticosterone exposure affect the subcellular localisation of mineralocorticoid and glucocorticoid receptor complexes and gene expression.
Paul SN, De Visser A, Motta F … +4 more , Rivers CA, Pooley JR, Lightman SL, Meijer OC
Steroids · 2025 Feb · PMID 39490722 · Publisher ↗
Mineralocorticoid (MR) and glucocorticoid receptors (GR) act as transcription factors and major mediators of glucocorticoid signalling, with pivotal roles in regulating the stress response and hormonal signalling, mood,...
Mineralocorticoid (MR) and glucocorticoid receptors (GR) act as transcription factors and major mediators of glucocorticoid signalling, with pivotal roles in regulating the stress response and hormonal signalling, mood, cognition and memory. The MR and GR share many target genes, have a high degree of homology in their DNA binding (DBD) and ligand binding domain (LBD) but differ considerably in the N-terminal domain (NTD). Using Proximity Ligation Assay (PLA) we quantitatively assessed MR-GR complex subcellular localisation and transcriptional regulation in murine neuroblastoma (N2A) cells stimulated by constant or pulsatile corticosterone (CORT) patterns. We observe that continuous receptor activation by CORT caused localisation at the periphery of the cell nucleus. Truncation of the receptor Ligand Binding Domain (LBD) led to a stronger localisation of MR-GR complexes at the periphery of the cell nuclei. This was also observed for GR immunofluorescence (IF), while in cells expressing only MR or GR the mRNA response to pulsatile hormone treatment was substantially attenuated. However, there was no clearcut correlation between the spatial distribution of MR-GR complexes and the mRNA levels of target genes. Overall, our findings suggest that longer presence in the cell nucleus favors more peripheral nuclear localisation.
Sonogashira coupling-based synthesis and in vitro cytotoxic evaluation of C-2 alkynyl derivatives of withaferin A.
Ahmad Mir S, Firdous S, Shahid Maqbool M … +4 more , Hussain G, Yaqoob Bhat M, Malik FA, Khalid Yousuf S
Steroids · 2024 Dec · PMID 39486668 · Publisher ↗
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Testosterone replacement has a beneficial effect on the hemostatic system by altered gene expression of coagulation factors.
Vatandoost J, Yaghoubi-Nezhad A, Sadr AM … +2 more , Momeni-Moghaddam M, Hajjar T
Steroids · 2024 Dec · PMID 39486667 · Publisher ↗
This study aimed to investigate the effects of testosterone replacement therapy on hemostasis and some procoagulant gene expression in mice. 42 mice were randomly divided into two groups of non-orchiectomized (non-ORX) a...
This study aimed to investigate the effects of testosterone replacement therapy on hemostasis and some procoagulant gene expression in mice. 42 mice were randomly divided into two groups of non-orchiectomized (non-ORX) and orchiectomized (ORX) with three subgroups (n = 7) each, were subcutaneously administered with sesame oil (control), 2 and 20 mg/kg/week testosterone enanthate. Orchiectomized mice were allowed to recover for one week before treatment. On the 7th week of treatment, blood samples were collected for coagulation parameters analysis and measurement of plasma testosterone levels. Moreover, quantitative real-time PCR analysis was performed on liver samples to assess the expression of factor IX, factor X, and prothrombin genes. The results showed that supraphysiological doses (20 mg/kg) of testosterone significantly increased plasma testosterone levels in all groups, while physiological doses (2 mg/kg) only increased testosterone levels in non-ORX animals. Although testosterone administration had no effect on prothrombin time (PT) and activated partial thromboplastin time (aPTT), supraphysiological doses reduced bleeding time and clotting time. Furthermore, platelet count increased in a dose-dependent manner with testosterone enanthate treatment. The expression of coagulation factors was also decreased with supraphysiological doses of testosterone. In conclusion, testosterone had significant effects on primary hemostasis and common coagulation pathway, including increased platelet number and aggregation, decreased clotting time, and altered gene expression of coagulation factors.
Synthesis of 13β- and 13α-epimers of 3-hydroxy-17-hydroxymethylestra-1,3,5(10)-triene and considerations on their hormonal and antiproliferative potency.
Kuznetsov YV, Tserfas MO, Scherbakov AM … +5 more , Andreeva OE, Salnikova DI, Bozhenko EI, Zavarzin IV, Levina IS
Steroids · 2024 Dec · PMID 39486666 · Publisher ↗
Starting from 3-methoxyestra-1,3,5(10),16-tetraene-17-carbaldehydes of natural (13β) and epimeric (13α) series, a series of isomeric 3-hydroxy-17-hydroxymethylestra-1,3,5(10)-trienes, including those containing 16α,17α-a...
Starting from 3-methoxyestra-1,3,5(10),16-tetraene-17-carbaldehydes of natural (13β) and epimeric (13α) series, a series of isomeric 3-hydroxy-17-hydroxymethylestra-1,3,5(10)-trienes, including those containing 16α,17α-annulated cyclopropane and cyclohexane ring D', were prepared using the Corey-Chaykovsky and Diels-Alder reactions followed by reduction-demethylation with diisobutylaluminum hydride and hydrogenation. Target compounds showed antiproliferative effects on MCF-7 breast cancer cells to varying degrees superior to that on MCF-10A cells, in low micromolar concentrations. The ERα-mediated luciferase reporter gene assay demonstrated that obtained steroids without an additional carbocycle or with a cyclopropane 16α,17α-annulated carbocycle are effective ERα activators. In this test, steroids of the natural configuration showed high activity at both 10 nM and 100 nM concentrations, whereas 13α-steroids showed a strong dose-dependent effect, surpassing their natural counterparts at a concentration of 100 nM. The 13β-steroid bearing additional 16α,17α-cyclohexane ring had low activity in the test. A simple docking approach using AutoDock Vina was used as a test for a preliminary assessment of the estrogenicity of the compounds. The scope of its applicability and limitations were shown using examples of synthesized molecules.
Assessment of anti-cancer evaluation of new metabolites isolated from baked Sarcosphaera crassa: An edible poisonous mushroom.
Ullah Z, Öztürk M
Steroids · 2024 Dec · PMID 39477180 · Publisher ↗
The growing demand for wild mushrooms as functional foods has increased due to their pharmacological significance. Sarcosphaera crassa is a deadly poisonous mushroom consumed by people living in northern and eastern Euro...
The growing demand for wild mushrooms as functional foods has increased due to their pharmacological significance. Sarcosphaera crassa is a deadly poisonous mushroom consumed by people living in northern and eastern Europe after being cooked adequately due to its significant properties. Herein, the baked Sarcosphaera crassa was studied for its ingredients. The cytotoxicity of hexane, acetone, and methanol extracts of baked Sarcosphaera crassa was investigated against MCF-7, HT-29, and HeLa cancer cell lines while toxicity against PDF fibroblast healthy cell lines using MTT assay. Acetone and methanol extracts of the baked mushroom exhibited significant cytotoxic activity. Further investigation of cytotoxic extracts afforded three new secondary metabolites, namely, (3β, 22E) ergosta-5, 22-dienyl 3-O-α-yl decanoate (Brassicasteryl decanoate) (1), bis (2- ethylpentadecyl) benzene-1,2-dicarboxylate (2), and (2S)-4-(aziridine-1-yl)-4-oxobutan-2-yl hexadecanoate (3), and six known compounds including ᴅ-sorbitol (4), 3β-ergosta-5,22-dien (5), two ergosterol-endoperoxides (6 and 7), nigerasterol A (8) and 5α,9α-epoksiergosta-7,22-dien, 3β,6α-diol (9). Among them, 2 exhibited effective cytotoxic activity against MCF-7 (IC: 33.45 ± 2.9 μg/mL) and HT-29 (IC: 45.53 ± 0.8 μg/mL) cancer cell lines. Compound 3 demonstrated high activity against HeLa (IC: 30.45 ± 0.35 μg/mL) and MCF-7 (IC: 33.55 ± 0.49 μg/mL) cancer cell lines, respectively. On the other hand, compound 1 demonstrated moderate cytotoxic activity against MCF-7 and HT-29 cancer cell lines. Besides, against PDF healthy cell lines, all extracts demonstrated lower toxicity. This discovery highlights the significance of Sarcosphaera crassa as a natural functional food reservoir.
Invalidating betulinic acid as a potential inhibitor against the main protease of SARS-CoV-2 via combined approaches.
Ye J, Xu T, Zhang R … +3 more , Liu X, Zhang C, Chen Y
Steroids · 2024 Dec · PMID 39424219 · Publisher ↗
In contrast to an earlier study reporting that betulinic acid is an inhibitor of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (Mpro), we demonstrated that beutilinic acid is not a potent...
In contrast to an earlier study reporting that betulinic acid is an inhibitor of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (Mpro), we demonstrated that beutilinic acid is not a potential Mpro inhibitor via combined approaches, including the fluorescence resonance energy transfer (FRET) assay, the fluorescence polarization (FP) assay, and the protease biosensor cleavage assay. Our results suggest that the addition of detergent to the assay buffers is essential for evaluating natural products as Mpro inhibitors. It is necessary to conduct comprehensive testing of Mpro inhibition via combined approaches for antiviral development.
Expression of pregnenolone-synthesizing enzymes CYP11A1 and CYP1B1 in the human, rat, and mouse brain.
Lin YC, Papadopoulos V
Steroids · 2024 Dec · PMID 39395524 · Publisher ↗
The central nervous system (CNS) is capable of synthesizing steroids for modulating essential functions such as neurotransmission, neuroplasticity, and neuroinflammation. These locally synthesized steroids, called neuros...
The central nervous system (CNS) is capable of synthesizing steroids for modulating essential functions such as neurotransmission, neuroplasticity, and neuroinflammation. These locally synthesized steroids, called neurosteroids, are produced through the conversion of cholesterol into the major steroid precursor pregnenolone, followed by downstream metabolism to form various steroids such as progesterone and allopregnanolone. Given that changes in neurosteroids are implicated in many neurological and psychiatric disorders, understanding the neurosteroidogenesis pathway is crucial. Recent studies have demonstrated an alternative pathway for the biosynthesis of pregnenolone, which is classically produced by CYP11A1 but was found instead to be made by CYP1B1 in human glial cells. However, numerous studies have demonstrated Cyp11a1 expression and activity in rodent brain tissue and brain cells. To elucidate whether species differences exist for the pregnenolone synthesis enzyme in human and rodent brains, we sought to directly compare the expression levels of CYP11A1 and CYP1B1 in human, rat, and mouse CNS tissues. We found that CYP1B1 mRNA expression was significantly higher than that of CYP11A1 in almost all CNS brain regions in human, rat, and mouse. The exception is in the mouse cerebral cortex, where Cyp11a1 RNA was more abundant than Cyp1b1. However, Cyp11a1 protein was clearly detectable in rodent CNS while completely undetectable in human brain. In contrast, the presence of CYP1B1 protein can be observed in both human and rodent brains. These results suggest that CYP1B1 is likely the dominant pregnenolone synthesis enzyme in the human brain, while rodent brains may use both Cyp11a1 and Cyp1b1.
Current advances in phytosterol free forms and esters: Classification, biosynthesis, chemistry, and detection.
Khallouki F, Zennouhi W, Hajji L … +6 more , Bourhia M, Benbacer L, El Bouhali B, Rezig L, Poirot M, Lizard G
Steroids · 2024 Dec · PMID 39378976 · Publisher ↗
Phytosterols are plant sterols that are important secondary plant metabolites with significant pharmacological properties. Their presence in the plant kingdom concerns many unrelated botanical families such as oleageneou...
Phytosterols are plant sterols that are important secondary plant metabolites with significant pharmacological properties. Their presence in the plant kingdom concerns many unrelated botanical families such as oleageneous plants and cereals. The structures of phytosterols evoke those of cholesterol. These molecules are composed of a sterane ring, also known as perhydrocyclopentanophenanthrene, along with a methyl or ethyl group at C-24 in their side chains, a hydroxyl group at C-3 on ring A, and one or two double bonds in the B ring. Phytosterols display different oxidation degrees at the sterane ring and at the side chain as well as varying numbers of carbons with complex stereochemistries. Fats and water solubilities of phytosterols have been achieved by physical, chemical and enzymatic esterifications to favor their bioavailability and to improve the sensory quality of food, and the efficiency of pharmaceutic and cosmetic products. This review aims to provide comprehensive information starting from the definition and structural classification of phytosterols, and exposes an update of their biogenic relationships. Next, the synthesis of phytosterol esters and their applications as well as their effective roles as hormone precursors are discussed. Finally, a concise exploration of the latest advancements in phytosterol / oxyphytosterols analysis techniques is provided, with a particular focus on modern hyphenated techniques.
A sustainable approach towards extraction of diosgenin from fenugreek seeds using polystyrene/divinyl benzene resin.
Kumar S, Praveen BM, Sudhakara A
Steroids · 2024 Dec · PMID 39357783 · Publisher ↗
Diosgenin, a bioactive molecule; is one of the deeply explored saponin with a wide spectrum of benefits against various ailments. The extraction and yield enhancement of diosgenin from a wide range of naturally occurring...
Diosgenin, a bioactive molecule; is one of the deeply explored saponin with a wide spectrum of benefits against various ailments. The extraction and yield enhancement of diosgenin from a wide range of naturally occurring medicinal products has always been a challenging task for its commercial usage. The current research work envisages the use of a novel resin to maximize the yield of diosgenin. The extracted diosgenin was characterized using modern techniques. The current method qualifies for the extraction of diosgenin at a large scale making it a commercially viable technique.
An efficient regioconvergent synthesis of 3-aza-obeticholic acid.
Harris LD, Aponte RAL, Jiao W … +5 more , Cameron SA, Weymouth-Wilson A, Furneaux RH, Compton BJ, Luxenburger A
Steroids · 2024 Dec · PMID 39322098 · Publisher ↗
Bile acids (BAs) are steroidal molecules that play important roles in nutrient absorption, distribution, and excretion. They also act on specific receptors implicated in various metabolic and inflammatory diseases demons...
Bile acids (BAs) are steroidal molecules that play important roles in nutrient absorption, distribution, and excretion. They also act on specific receptors implicated in various metabolic and inflammatory diseases demonstrating their importance as potential drug candidates. Accordingly, there has been a concerted effort to develop new BA derivatives to probe structure-activity relationships with the goal of discovering BA analogues with enhanced pharmacological properties. Among the many steroidal derivatisations reported, the formation of endocyclic azasteroids appeals due to their potential to deliver altered biological responses with minimal change to the steroidal superstructure. Here, we report the synthesis of 3-aza-obeticholic acid (6) via a regioconvergent route. Ammoniolysis of lactones, formed from an m-CPBA-mediated Baeyer-Villiger reaction on a 3-keto-OCA derivative, furnished protected intermediate amido-alcohols which were separately elaborated to amino-alcohols via Hofmann degradation with BAIB. Upon individual N-Boc-protection, these underwent annulation to the 3-aza-A-ring when subjected to either mesylation or a Dess-Martin oxidation/hydrogenation sequence. Global deprotection of the 3-aza-intermediate delivered 3-aza-OCA in ten steps and an overall yield of up to 19%.
Evaluation of structural features of anabolic-androgenic steroids: entanglement for organ-specific toxicity.
Sinha A, Deb VK, Datta A … +3 more , Yadav S, Phulkar A, Adhikari S
Steroids · 2024 Dec · PMID 39322097 · Publisher ↗
Anabolic-androgenic steroids (AASs), more correctly termed "steroidal androgens", are a broad category of compounds including both synthetic derivatives and endogenously produced androgens like testosterone, which have l...
Anabolic-androgenic steroids (AASs), more correctly termed "steroidal androgens", are a broad category of compounds including both synthetic derivatives and endogenously produced androgens like testosterone, which have long been employed as performance-enhancing substances, primarily among recreational athletes and some professionals. While their short-term effects on muscle physiology are well-documented, the long-term health consequences remain inadequately understood. A key finding is the disruption of hormone production, leading to reversible and irreversible changes, particularly with prolonged use. While debate exists over the prevalence of adverse effects, studies suggest a spectrum of somatic and psychiatric consequences, highlighting the need for improved understanding and prevention strategies. AASs are not only affect muscle structure but also influence mood, behavior, and body image, potentially exacerbating substance dependence and psychological distress. Liver alterations are a prominent concern, with oxidative stress implicated in AAS-induced hepatotoxicity. Reproductive complications, including gonadal atrophy and infertility, are common, alongside virilization and feminization effects in both genders. Cardiovascular effects are particularly worrisome, with AASs implicated in hypertension, dyslipidemia, and increased thrombotic risk, contributing to cardiovascular morbidity and mortality. Moreover, AASs may enhance cancer risks, potentially accelerating carcinogenesis in various tissues, including the prostate. The review emphasizes the need for comprehensive public health initiatives to mitigate harm, including harm minimization strategies, routine health screenings, and targeted interventions for AAS users. Understanding the complex interplay of biological mechanisms and systemic effects is crucial for informing clinical management and preventive measures. This review also examines the biological impact of AASs on human muscles, detailing mechanisms of action, chemistry, and associated health risks such as liver damage, cardiovascular disease, and endocrine dysfunction.
SPRY4 regulates ERK1/2 phosphorylation to affect oxidative stress and steroidogenesis in polycystic ovary syndrome.
Pan Y, Yang C, Sun Y … +4 more , Zhang S, Xue T, Li F, Fu D
Steroids · 2024 Dec · PMID 39313103 · Publisher ↗
Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder in women of childbearing age. The role of Sprouty RTK Signaling Antagonist 4 (SPRY4) in ovarian function in PCOS was investigated herein, focusing on its...
Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder in women of childbearing age. The role of Sprouty RTK Signaling Antagonist 4 (SPRY4) in ovarian function in PCOS was investigated herein, focusing on its regulation of ERK1/2 phosphorylation. PCOS models were established in mice using dehydroepiandrosterone (DHEA). The expression levels of SPRY4 in ovarian tissues were analyzed through RT-qPCR and immunohistochemistry. SPRY4 knockdown was achieved via lentivirus, and its effects on endocrine function, ovarian morphology, oxidative stress, and ERK1/2 phosphorylation were evaluated. Afterwards, granulosa cells were isolated and treated with DHEA and ERK2 agonist tert-Butylhydroquinone. The impacts of ERK2 activation on the regulation of SPRY4 knockdown were assessed using ELISA, fluorescent probes, western blotting, and biochemical assays. SPRY4 knockdown normalized the estrous cycle, reduced serum levels of testosterone, anti-Müllerian hormone, and luteinizing hormone/follicle-stimulating hormone ratio, and improved ovarian morphology. Additionally, SPRY4 knockdown alleviated oxidative stress by decreasing reactive oxygen species and malondialdehyde levels while increasing superoxide dismutase activity. It also restored steroidogenic enzyme expression, which were disrupted by DHEA induction. In vitro, SPRY4 knockdown enhanced granulosa cell viability and reduced ERK1/2 phosphorylation, with tert-Butylhydroquinone reversing these effects and restoring oxidative stress and steroidogenesis disruptions. Together, SPRY4 modulates ERK1/2 phosphorylation to influence oxidative stress and steroidogenesis in PCOS. Targeting SPRY4 may provide novel therapeutic avenues for improving ovarian function and managing PCOS.
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