Steroids[JOURNAL]
Sun
200 papers
Testosterone-TGF-β crosstalk modulates cell migration in human glioblastoma-derived cell lines.
Alemán OR, Quintero JC, Hernández-Lúa LN … +2 more , Espejel-Nuñez A, Camacho-Arroyo I
Steroids · 2026 · PMID 42119662 · Publisher ↗
Glioblastoma (GB) is the most aggressive brain tumor due to its extensive cellular migration. Although testosterone (T) and transforming growth factor-β (TGF-β) can regulate GB cell migration, the interaction between the...
Glioblastoma (GB) is the most aggressive brain tumor due to its extensive cellular migration. Although testosterone (T) and transforming growth factor-β (TGF-β) can regulate GB cell migration, the interaction between them in migration regulation in GB cells remains unclear. Here, we evaluated whether testosterone modulates TGF-β signaling to regulate cell migration in two human GB-derived cell lines. Androgen response elements (AREs) within the TGF-β gene were identified in-silico. The effects of T on TGF-β signaling were evaluated in U251 and T98G human GB-derived cell lines. TGF-β secretion was quantified by ELISA, and TGF-β/SMAD signaling activation after T stimulation was assessed by Western blot. Cell migration was analyzed by the scratch assay in the presence of SB431542, a TGF-β pathway inhibitor. Seven AREs were identified in the TGF-β gene. T increased TGF-β secretion in U251 but not in T98G cells. Consistently, T-induced SMAD activation was only observed in U251 cells. Inhibition of TGF-β signaling with SB431542 reduced T-stimulated migration exclusively in U251 cells. Our data demonstrate, for the first time, that T activates TGF-β signaling, promoting cell migration in U251 but not in T98G cells, highlighting cell line-specific heterogeneity in GB responses to the same hormonal stimulus.
Evaluation of serum Afamin and oxidative stress biomarkers in polycystic ovarian syndrome overweight women.
Hamad SS, Ahmed SN
Steroids · 2026 · PMID 42119661 · Publisher ↗
Afamin is a human vitamin E-binding glycoprotein that plays an essential role in protection against oxidative damage and disease. This study was conducted at Shahid Doctor Khalid Hospital in the Koya-Erbil Governorate. A...
Afamin is a human vitamin E-binding glycoprotein that plays an essential role in protection against oxidative damage and disease. This study was conducted at Shahid Doctor Khalid Hospital in the Koya-Erbil Governorate. A total of 120 women, aged 16 to 45 years, were enrolled comprising 90 overweight patients with polycystic ovary syndrome (PCOS) and 30 healthy participants without PCOS.The results showed that body mass index (BMI) was significantly higher in patients with PCOS compared to healthy participants, indicating that women with PCOS tend to be overweight. Severe acne, hirsutism and amenorrhea were markedly more prevalent in the PCOS group. This study clearly demonstrates that serum levels of Afamin, and 8-hydroxy-deoxyguanosine (8-OHdG) were significantly elevated in overweight patients with PCOS as compared to healthy individuals. In contrast, serum levels of vitamin E and glutathione peroxidase (GSH-PX) were significantly decreased in overweight patients with PCOS than in the control groups. Significant positive correlations were observed between BMI and Afamin, vitamin E and GSH-PX in overweight patients with PCOS, whereas a significant negative correlation was found between BMI with 8-OHdG. The mean levels of serum Total-Cholesterol (T-Chol), Triglyceride (TG), Low density lipoprotein (LDL), Very low density lipoprotein (VLDL) and Atherogenic index of plasma (AIP) are significantly increased in overweight patients with PCOS as compared to healthy groups, while the mean level of serum High density lipoprotein (HDL) was significantly decreased in overweight patients with PCOS as compared to healthy groups. Our study indicates a novel association between increased Afamin and 8-OHdG as a biomarker of oxidative stress resulting from the nucleoside or nucleotide pool in high BMI patients with PCOS. Elevated AIP levels and dyslipidemia identified as a useful biomarkers for predicting future cardiovascular disease (CVD) risk.
Raman spectroscopy-based metabolic fingerprinting of seminal plasma reveals distinct profiles among fertile men.
Gilany K, Jafarzadeh N, Hosseini E … +4 more , Bi Bi Fatemeh Nobakht MG, Henkel R, Amirjannati N, Tayanloo-Beik A
Steroids · 2026 May · PMID 42114664 · Publisher ↗
Traditional semen analysis provides valuable insights into male fertility but fails to capture the full biochemical complexity underlying sperm function. This study explored metabolic variability among fertile men using...
Traditional semen analysis provides valuable insights into male fertility but fails to capture the full biochemical complexity underlying sperm function. This study explored metabolic variability among fertile men using Raman spectroscopy to analyze the seminal plasma metabolome. In a cross-sectional design, semen samples were collected from 29 clinically fertile men (n = 29) and analyzed according to WHO guidelines. Metabolites were extracted using methanol/water (3:1), and Raman spectroscopy was applied to generate metabolic fingerprints of the seminal plasma. Multivariate statistical analyses, including Principal Component Analysis (PCA) and Orthogonal Partial Least Squares-Discriminant Analysis (OPLS-DA), revealed two distinct metabolic subgroups among fertile men. Significant differences were identified in key biochemical features such as phenylalanine, alcohols, alkanes, aldehydes, and amides. The OPLS-DA model demonstrated excellent classification performance (RX = 0.942, RY = 0.992, Q = 0.987), indicating robust subgroup separation and high predictive validity. These findings suggest that even within normozoospermic individuals, seminal plasma exhibits substantial metabolic heterogeneity. Raman-based metabolomic fingerprinting thus represents a promising complementary diagnostic tool to conventional semen analysis, offering deeper insight into male reproductive physiology and providing a foundation for future biomarker discovery in fertility research.
Veratrum-derived steroidal alkaloids: from scaffold to pharmacological leads.
Özüpek B, Pekacar S, Güverti ÖF … +2 more , Orhan DD, Patel V
Steroids · 2026 · PMID 42103199 · Publisher ↗
Veratrum species (Melanthiaceae) have a long history of medical usage throughout Europe, Asia, and North America. However, they are well-known for their toxicity. Their pharmacological significance stems from a number of...
Veratrum species (Melanthiaceae) have a long history of medical usage throughout Europe, Asia, and North America. However, they are well-known for their toxicity. Their pharmacological significance stems from a number of steroidal alkaloids with unique C-nor-d-homosteroidal and isosteroidal structures. This review provides an overview of the Veratrum-derived steroidal alkaloids. It focuses on their structural diversity, manufacturing processes, isolation methods, biological activity, and potential as new therapeutic leads. Nearly 185 steroidal alkaloids have been found in Veratrum species. They are usually classified as cevanine, veratramine, jervine, verazine, and solanidine. Improvements in chromatographic and spectroscopic technologies, particularly HPLC-MS/MS and multidimensional NMR, allow for a more detailed understanding of the structures of these complex substances and ensure quality control. Biosynthetic studies suggest that cholesterol is an important starting point for their synthesis, but various late-stage enzymatic processes remain unknown. Veratrum alkaloids have a diverse biological activity. Notably, they inhibit the Hedgehog/SMO pathway, as seen in cyclopamine and its derivatives, and impact voltage-gated sodium channels, such as veratridine. This emphasizes both their medicinal potential and hazardous hazards. Semi-synthetic alterations and research into the link between structure and activity have resulted in derivatives with increased potency, stability, and solubility, including prominent cyclopamine analogs such as patidegib. In conclusion, this review identifies Veratrum steroidal alkaloids as essential natural structures that link traditional medicine and modern drug research. It also emphasizes the importance of carefully evaluating their toxicity, as well as further research into their production and pharmacological properties, in order to realize their full therapeutic value.
Alteration of bile acid metabolism in mice under thermoneutral conditions.
Soma H, Yoshida R, Ishizuka S
Steroids · 2026 · PMID 42097261 · Publisher ↗
Metabolic responses in mice at thermoneutrality (TN; 30°C) closely reflect those in humans rather than at conventional ambient temperature (CT; 22°C). However, the effect of TN on bile acid (BA) metabolism remains unclea...
Metabolic responses in mice at thermoneutrality (TN; 30°C) closely reflect those in humans rather than at conventional ambient temperature (CT; 22°C). However, the effect of TN on bile acid (BA) metabolism remains unclear. In this study, mice were maintained at CT or TN for 6 weeks, and BA profiles were quantitatively assessed at several sites, including enterohepatic and systemic circulation. TN markedly increased feed efficiency, adipose tissue mass, and hepatic and circulating triglyceride levels. Moreover, the ratio of 12-hydroxylated to non-12-hydroxylated BAs was elevated in the liver, small intestinal contents, and feces in mice maintained at TN. The ratios of primary to secondary BAs and of conjugated to unconjugated BAs were consistently reduced across sites, suggesting enhanced microbiota-dependent BA metabolism at TN. Collectively, these findings indicate that TN shifts murine BA composition toward a more human-like profile, highlighting the significance of TN models in terms of BA metabolism.
Biotransformation of progesterone by Aspergillus welwitschiae CCMB 674 yields a novel metabolite 11α,21-dihydroxyprogesterone, alongside three known compounds.
Dutra LP, Oliveira MN, Dias de Souza ML … +4 more , Duarte LP, de Pádua RM, Góes-Neto A, Vidal DM
Steroids · 2026 · PMID 42070679 · Publisher ↗
Fungal biotransformation represents a sustainable strategy for the selective functionalization of steroid frameworks, particularly in the synthesis of corticosteroid intermediates. These molecules posses a pregnane-type...
Fungal biotransformation represents a sustainable strategy for the selective functionalization of steroid frameworks, particularly in the synthesis of corticosteroid intermediates. These molecules posses a pregnane-type skeleton making progesterone an attractive model substrate for evaluating the biocatalytic potential of microorganisms. Among industrially relevant fungi, Aspergillus niger is widely employed for enzyme and food additive producer. The related species, Aspergillus welwitschiae, has recently been investigated for enzyme production. However, it has never been evaluated as biocatalyst. Thus, in this study, the biocatalytic activity of Aspergillus welwitschiae CCMB 674 toward progesterone was investigated under submerged fermentation conditions. After a 96 h pre-fermentation period, cultures were incubated with progesterone (1 g·L) for 168 h. Metabolites were extracted, purified, and characterized using spectroscopic and spectrometric techniques, including 1D and 2D NMR, FT-IR, GC-MS, and HRMS. The biotransformation yielded 11α-hydroxyprogesterone (20%) as the major product, together with 11α,15β-dihydroxyprogesterone (2%), 6β,11α-dihydroxyprogesterone (1%), and a previously undescribed metabolite, 11α,21-dihydroxyprogesterone (0.4%). Kinetic analysis revealed the continuous accumulation of the major product, reaching 260 mg·L after 168 h. These findings highlight A. welwitschiae as a promising biocatalyst for selective steroid hydroxylation.
ELISA-based validation of differentially expressed Fibrinogen, S100A9, SERPINA3 and SERPINA6 proteins in Polycystic Ovary Syndrome (PCOS).
Fatima S, Kori JA, Vankwani S … +2 more , Mirza MR, Rehman R
Steroids · 2026 · PMID 42034305 · Publisher ↗
BACKGROUND AND OBJECTIVES: Polycystic ovary syndrome (PCOS) remains difficult to diagnose reliably, especially when clinical decisions rely heavily on ovarian morphology, which is often mis-interpreted. To address the ne...
BACKGROUND AND OBJECTIVES: Polycystic ovary syndrome (PCOS) remains difficult to diagnose reliably, especially when clinical decisions rely heavily on ovarian morphology, which is often mis-interpreted. To address the need for more objective molecular indicators, we validated four serum proteins highlighted in earlier nLC-MS/MS based proteomic work, namely; Fibrinogen, S100A9, SERPINA3 and SERPINA6. The objective was to analyse differential expression of these proteins and evaluate the diagnostic performance by using ROC curves. METHODOLOGY: Blood samples were collected from Endocrinology clinic, Aga Khan University Hospital and further categorized into 2 groups of cases (44 infertile PCOS and 44 healthy control fertile females). Enzyme-Linked Immunosorbent Assay (ELISA) technique was used to validate proteins. SPSS (IBM SPSS 21) was used for statistical analysis whereas, GraphPad statistical software (v.8.02) was used to generate ROC curves. RESULTS: Both PCOS and healthy control sample groups showed non-significant differences in age and BMI while significant difference was observed in FSH, LH and AMH levels. ELISA showed the similar pattern of expression profiling as mass spectrometric data. Fibrinogen and SERPINA6 concentrations were significantly higher in women with PCOS (p-value < 0.05), whereas S100A9 and SERPINA3 protein expression levels were significantly lower (p-value < 0.05) as compared to healthy control group. In addition, ROC curve analyses showed AUC (Area Under the Curve) value of all proteins ranging from 0.639 to 0.725 showing acceptable discrimination potential of the these differentially expressed proteins with Fibrinogen (AUC = 0.707) and SERPINA3 (AUC = 0.725) showing good discrimination efficiency. CONCLUSION: In conclusion, these serum proteins may serve as a diagnostic tool for the detection PCOS.
Bis-MPA Janus dendrimers-prednisone conjugates against human breast cancer cells.
Barajas-Mendoza I, Espinosa-Hernández A, Martínez-Klimova E … +2 more , Ramírez-Ápan T, Martínez-García M
Steroids · 2026 · PMID 41990959 · Publisher ↗
In this paper, we report the synthesis of Janus dendrimers using 2,2-bis(hydroxymethyl)propionic acid (bis-MPA) polyester dendrons with an azide and an alkyne group. The Janus dendrimers were obtained via azide-alkyne cl...
In this paper, we report the synthesis of Janus dendrimers using 2,2-bis(hydroxymethyl)propionic acid (bis-MPA) polyester dendrons with an azide and an alkyne group. The Janus dendrimers were obtained via azide-alkyne click reaction. The dendron and Janus dendrimers are shown to be selective against K-562 and MFC-7 cell lines. We found that the cytotoxic activity and selectivity against cancer cells of Janus prednisone-dendrimers depend on the functional groups in the dendritic arms. The conjugated dendrimer with OH as terminal groups was lower in activity against K-562 (IC 38.98 ± 0.1 μM) than the Janus dendrimer with acetonide groups (IC 28.87 ± 0.3 μM). Also, it was observed that the presence of the acetonide groups resulted in increased selectivity and cytotoxicity activity against MFC-7 (IC 24.18 ± 0.4 μM). All the compounds studied showed no activity against normal cells. Our results suggest that polyethylene glycol and polyesters attached with prednisone in the dendrimer increase the bioavailability of the Janus dendrimer as an anticancer drug.
Nitrogen-Containing Steroidal Alkaloids and the Gut Microbiome: A Steroid-Xenobiotic Axis Perspective for Drug Discovery and Therapeutic Modulation.
Ganamurali N, Sabarathinam S, Narasimhan MK … +1 more , S ES
Steroids · 2026 · PMID 41967658 · Publisher ↗
Drug metabolism has traditionally emphasized hepatic pathways; however, the gut microbiome introduces a parallel system of biochemical modification that profoundly affects drug efficacy, safety, and variability. This rev...
Drug metabolism has traditionally emphasized hepatic pathways; however, the gut microbiome introduces a parallel system of biochemical modification that profoundly affects drug efficacy, safety, and variability. This review integrates the emerging steroid-xenobiotic-microbiome axis, emphasizing nitrogen-containing steroidal alkaloids (NSAs) as pivotal modulators. These compounds, combining a hydrophobic steroidal scaffold with nitrogen-based polarity, exhibit unique bioactivities through microbial biotransformation. Gut microbes enzymatically modify steroids and xenobiotics via reduction, deconjugation, and oxidation, shaping pharmacokinetics and receptor signaling. Conversely, steroidal scaffolds regulate microbial enzyme expression, forming reciprocal metabolic feedback. Case studies on digoxin, solanine, and veratramine illustrate this interplay. Understanding how nitrogen incorporation governs structure activity relationships and microbial interactions offers a new avenues for precision pharmacology, biomarker discovery, and rational drug design. This integrated perspective bridges medicinal chemistry, microbiome science, and steroid pharmacology to develop next generation therapeutics guided by host-microbe metabolic crosstalk.
Absent nocturnal cortisol decline in Pheochromocytoma: A retrospective study.
Sun Y, Kometani M, Aiga K … +5 more , Mai X, Konishi S, Kadono M, Gondoh Y, Yoneda T
Steroids · 2026 · PMID 41935676 · Publisher ↗
Pheochromocytoma is a catecholamine-producing tumor that may exhibit atypical hormonal profiles. Emerging evidence suggests an association with cortisol dysregulation in the absence of overt Cushing syndrome; however, sy...
Pheochromocytoma is a catecholamine-producing tumor that may exhibit atypical hormonal profiles. Emerging evidence suggests an association with cortisol dysregulation in the absence of overt Cushing syndrome; however, systematic cortisol evaluation is not routinely performed. This study investigated the prevalence and clinical characteristics of absent nocturnal cortisol decline in pheochromocytoma. This retrospective study included 53 patients with histologically confirmed pheochromocytoma treated between 2011 and 2024. All eligible patients diagnosed during the study period were included. Among them, 22 had paired morning (8:00 AM) and midnight serum cortisol measurements for analysis of nocturnal cortisol decline. Adrenocorticotropic hormone (ACTH) and the 1-mg dexamethasone suppression test (DST) were assessed when available. Patients were stratified by midnight cortisol level (≥1.8 µg/dL vs < 1.8 µg/dL). Among the 22 patients, 18 (82%) had elevated midnight cortisol, indicating absent nocturnal decline (mean midnight, 5.1 µg/dL; mean morning, 13.7 µg/dL). The elevated group (n = 18) was older than the normal group (n = 4) (median, 64 vs 43 years). Metabolic comorbidities were more frequent in the elevated group, including diabetes (50% vs. 25%), dyslipidemia (61% vs. 25%), and cardiovascular disease (44% vs. 0%). DST was performed in 10 patients and showed adequate suppression in 7 of 8 patients with paired cortisol measurements, arguing against autonomous cortisol secretion. No patients had clinical features of overt Cushing syndrome. Absent nocturnal cortisol decline was common and may reflect a pseudo-Cushing state associated with catecholamine excess. These findings support further evaluation of cortisol regulation and its clinical implications.
Synthesis of 2-aryl/alkylaminomethyl 17-sulfamate/17-methyl estratrienes and their in vitro cytotoxicity in human cancer cell cultures.
Balaiah E, Agneswaran R, Dhatchana Moorthy N … +3 more , Panchapakesan G, Prabhu A, Mohanakrishnan AK
Steroids · 2026 · PMID 41905481 · Publisher ↗
2-Methoxyestradiol (2-ME), a natural metabolite of 17β-estradiol, exhibits potent anticancer activity by inhibiting tubulin polymerization and modulating steroid sulfatase (STS). However, its rapid metabolism limits its...
2-Methoxyestradiol (2-ME), a natural metabolite of 17β-estradiol, exhibits potent anticancer activity by inhibiting tubulin polymerization and modulating steroid sulfatase (STS). However, its rapid metabolism limits its clinical usefulness. To overcome these issues, we designed a new series of 2-aryl/alkylaminomethyl estratriene analogues with sulfamate groups at C‑3 and/or C‑17, serving as hybrid agents that disrupt microtubules and modulate STS, derived from the 2-ME pharmacophore. We used a stepwise transformation of estrone to access C‑2 aminomethyl frameworks, followed by regioselective sulfamoylation to create mono‑ (C‑17 or C‑3) and bis‑sulfamoylated derivatives, including 17‑sulfamates 8a-h, 3,17‑bis-sulfamates 11a-c, 3‑sulfamates 18a,b, and 25. These compounds were tested for their antiproliferative activity against HCT‑116 (colon) and MCF‑7 (breast) cancer cell lines. Notably, mono C‑17 sulfamoylated analogues with small lipophilic C‑2 amines, such as cyclopropyl 8a and 4‑chlorophenyl 8e, exhibited the most potent activity (GI < 3 μM), outperforming both 3‑sulfamates and 3,17‑bis-sulfamates. Structure-activity relationship analysis revealed that excessive polarity from bis‑sulfamoylation and bulky C‑2 amines reduces activity, while compact lipophilic or halogenated C‑2 substituents enhance the balance of electronic effects, steric compatibility, and permeability. Compared to literature on 2-ME sulfamates, our results show a distinct regioselectivity profile, with the 2‑aminomethyl scaffold favouring C‑17 sulfamoyation for maximum activity. This study offers the potential to develop estratriene-based anticancer agents with improved pharmacokinetic profiles.
Bileomic identification and quantification of bile acids in rat kidney by UPLC-MS/MS.
Gaikwad NW
Steroids · 2026 Jun · PMID 41856445 · Publisher ↗
BACKGROUND: Bile acids (BAs) act as endocrine-like signals governing metabolic, inflammatory, oncologic, neurodegenerative, hepatic, and renal processes as well as cellular homeostasis. Despite renal expression of the BA...
BACKGROUND: Bile acids (BAs) act as endocrine-like signals governing metabolic, inflammatory, oncologic, neurodegenerative, hepatic, and renal processes as well as cellular homeostasis. Despite renal expression of the BA receptors FXR and TGR5, direct demonstration of BAs in kidney tissue has remained elusive. OBJECTIVE: To provide the first comprehensive identification and quantification of BAs in rat kidney using a mass spectrometry-based bileomics approach. METHODS: Kidneys from female Wistar rats (n = 6) were profiled by ultra‑performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) with Multiple Reaction Monitoring for BA panel. Data were processed in TargetLynx and analyzed by unsupervised principal component analysis (PCA) to compare kidney with urine. RESULTS: Approximately 20 BAs were identified in kidney tissue. The composition was dominated by amidated species (69.4%), followed by non‑amidated (30.4%) and trace glycine-conjugated species (∼0.1%). Taurine conjugation predominated over glycine. CA, TCA, and T‑β‑MCA were the most abundant species. PCA revealed a distinct kidney BA profile compared with urine, ruling out contamination and confirming tissue‑resident BAs. CONCLUSIONS: This is the detailed report of a kidney tissue bileome. The distinct BA signature suggests active transport, metabolism, and signaling functions in kidney and provides a foundation for mechanistic studies of BA‑mediated renal physiology and disease.
High androgen might increase the resistance of granulosa cells to ferroptosis by decreasing ROS and mitoROS, increasing GSH/GSSG ratio, and downregulating DHCR7 in PCOS.
Acar BC, Berkel C
Steroids · 2026 Jun · PMID 41839401 · Publisher ↗
Abstract loading — click title to view on PubMed.
Polyhydroxylated steroids from the Vietnamese starfish Luidia maculata.
Hanh TTH, Vien LT, Ngoc NT … +4 more , Cuong NX, Ha DV, Nam NH, Minh CV
Steroids · 2026 Jun · PMID 41794352 · Publisher ↗
Applying various chromatographic separations, six polyhydroxylated steroids including four new ones, maculasteroids A-D (1-4), were isolated from the Vietnamese starfish Luidia maculata. Their structures were elucidated...
Applying various chromatographic separations, six polyhydroxylated steroids including four new ones, maculasteroids A-D (1-4), were isolated from the Vietnamese starfish Luidia maculata. Their structures were elucidated by detailed analysis of 1D, 2D NMR and HR QTOF mass spectra. The 3β,5,6β,7α,15α,16β-hexol 15-sulfate (1 and 2) and 2β,3β,5,6β,7α,15α,16β-heptol 15-sulfate (3) steroid cores were reported for the first time in polyhydroxylated steroids to date. In addition, the best antiproliferative activity among the isolated compounds was recorded for 5α-cholestane-3β,5,6β,7α,15α,16β,26-heptol (5) on all five cell lines SK-LU-1 (lung carcinoma), HepG2 (hepatocarcinoma), MCF7 (breast carcinoma), LNCaP (prostate carcinoma), and KB (carcinoma in the mouth) and 5α-cholestane-3β,6β,7α,15α,16β,26-hexol (6) on LNCaP and KB cell lines with IC values ranging from 10.40 ± 0.38 to 19.91 ± 1.22 µM.
Amentoflavone alleviates nonylphenol-induced testicular damage through regulating Nrf-2/Keap-1, steroidogenic, hormonal, and histological profile in albino rats.
Hamza A, Batool M, Salar MZ … +1 more , Hamdi H
Steroids · 2026 May · PMID 41747952 · Publisher ↗
This study was conducted to assess the palliative role of amentoflavone (AMF) against nonylphenol (NP) induced testicular dysfunction. Male albino rats (n = 48) were separated into 4 equal groups, control group, NP treat...
This study was conducted to assess the palliative role of amentoflavone (AMF) against nonylphenol (NP) induced testicular dysfunction. Male albino rats (n = 48) were separated into 4 equal groups, control group, NP treated group, NP + AMF co-treated group and only AMF treated group. The trial was conducted for 56 days. NP exposure lowered the expressions of Nrf-2 and upregulated Keap-1 expression. NP administration significantly (P < 0.05) decreased the activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), heme oxygensae-1 (HO-1) and glutathione reductase (GSR), while increasing ROS and MDA levels. In addition, a considerable (P < 0.05) escalation was seen in dead spermatozoa number, deformities in sperm tail, head and midpiece in NP administrated rats. Moreover, the expressions of steroidogenic enzymes were downregulated, whereas inflammatory markers were escalated in NP exposed rats. Furthermore, the expressions of apoptotic markers were considerably (P < 0.05) increased and on the other hand anti-apoptotic marker expressions were downregulated. A significant (P < 0.05) decrease in the hormonal level was also observed in NP exposed group. Moreover, the histopathological assessment demonstrated that NP significantly (P < 0.05) impaired the testicular tissues. However, AMF + NP co-treatment significantly alleviated these testicular impairments. This study demonstrates that AMF displays a considerable potential to attenuate testicular damage due to its anti-apoptotic, anti-oxidant anti-inflammatory and pro-steroidogenic nature. To the best of our knowledge, this is the first study that presents the protective effects of AMF against NP induced testicular dysfunction via modulating Nrf-2/Keap-1 axis and restoring steroidogenesis.
Kaempferol ameliorates PCOS by alleviating metabolic and endocrine abnormalities as well as oxidative stress.
Nejabati HR, Roshangar L
Steroids · 2026 May · PMID 41747951 · Publisher ↗
Polycystic ovary syndrome (PCOS) is an endocrine irregularity aligned with enhanced androgen levels, insulin resistance (IR), dyslipidemia, ovulation disorders, and infertility. For decades, natural active ingredients fr...
Polycystic ovary syndrome (PCOS) is an endocrine irregularity aligned with enhanced androgen levels, insulin resistance (IR), dyslipidemia, ovulation disorders, and infertility. For decades, natural active ingredients from plants have been utilized as pharmaceuticals to treat a wide range of reproductive system disorders. Most importantly, their effects are achieved either through targeting enzymes, hormones, and/or eliminating reactive oxygen species (ROS) in ovarian cells. Kaempferol (KPF) is a natural flavonol belonging to the flavonoid family and has various medicinal features like anti-inflammatory, antioxidative, anticancer, antimicrobial, and cardioprotective properties. Recently, studies have investigated the medicinal impact of various plant extracts containing high concentrations of KPF in animal models of PCOS. The results of these studies show that this flavonol can boost the metabolic and hormonal abnormalities of rat with PCOS. In this research paper, for the first time, the molecular effects of KPF on improving metabolic and hormonal as well as oxidative stress parameters of PCOS rats were investigated. In this study, 30 Sprague-Dawley rats were arbitrarily studied in four groups: control, letrozole-induced PCOS, KPF, KPF+ metformin (MET). The blood species, adipose and ovarian tissues were prepared to investigate the therapeutic impacts of KPF on PCOS rats. Our results pointed out that the examined therapeutic factors effectively alleviated HA, IR as well as oxidative stress in PCOS rats and improved the browning of adipose tissue in these animals. To the best of our knowledge, this report is the first that indicates the favorable effects of KPF on steroidogenesis, insulin resistance and oxidative stress-related genes in rats with PCOS. Our findings showed that it successfully regulates the mentioned abnormalities in generated animal model. Therefore, these data point out that KPF can be a novel medicinal alternative for women with PCOS.
Corrigendum to "In silico analysis of Moringaceae derived potential drug-like compounds against Newcastle disease virus" [Steroids 219 (2025) 109628].
Mustafa MH, Rehman FU, Ali M … +9 more , Javed M, Ahmad N, Shafique T, Zidan A, Bahadur A, Iqbal S, Mahmood S, Farouk AE, Jafri I
Steroids · 2026 Apr · PMID 41629168 · Publisher ↗
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Steroidal alkaloids: Exploring new therapeutic frontiers in cardiovascular diseases.
Bapat M, Barve K
Steroids · 2026 Apr · PMID 41619896 · Publisher ↗
Cardiovascular diseases (CVDs) still remain one of the leading causes of mortality worldwide, requiring novel therapeutic approaches. Steroidal alkaloids, a unique class of naturally bioactive compounds, have showcased p...
Cardiovascular diseases (CVDs) still remain one of the leading causes of mortality worldwide, requiring novel therapeutic approaches. Steroidal alkaloids, a unique class of naturally bioactive compounds, have showcased promising pharmacological qualities in cardiovascular health. This review article explores the structural classification, pharmacokinetics, and pharmacodynamics properties of such alkaloids, emphasizing their potential therapeutic effects in CVDs. Key cardiovascular activities of these alkaloids include antihypertensive, vasodilatory, antiarrhythmic, and lipid-lowering effects, primarily mediated through receptor interactions, ion channel modulation, and enzyme inhibition. Clinical and preclinical research studies provide preliminary proof of efficacy, though significant research gaps still remain, including very clinical trials and incomplete mechanistic understanding. Furthermore, safety concerns regarding dose-response relationships, toxicity, and drug interactions must be addressed before clinical translation. Novel trends such as, targeted delivery systems, synthetic derivatives and multi-targeted approaches throw light upon the future potential of alkaloids in cardiovascular therapy. This review establishes the need for well-designed clinical trials and structure-activity relationship (SAR) studies to optimize these molecules for cardiovascular drug development. Further research studies integrating omics technologies and exploring the role of steroidal alkaloids in rare cardiovascular disorders could increase their therapeutic applicability.
LCA and 3-oxo-LCA mitigate dietary oxysterols-induced loss of barrier function in intestinal epithelial cells.
Reghu G, Fathima A, Swaminathan N … +2 more , Sakhuja R, Jamma T
Steroids · 2026 Apr · PMID 41616898 · Publisher ↗
Loss of intestinal barrier integrity is a hallmark of many intestinal inflammations and associated diseases, including inflammatory bowel disease (IBD) and colorectal cancer (CRC). One of the primary factors contributing...
Loss of intestinal barrier integrity is a hallmark of many intestinal inflammations and associated diseases, including inflammatory bowel disease (IBD) and colorectal cancer (CRC). One of the primary factors contributing to intestinal epithelial barrier damage is a diet high in cholesterol. The non-enzymatically oxidized forms of dietary cholesterol, collectively known as oxysterols, have recently gained attention as mediators of various inflammatory conditions. In addition, oxysterols have been found to cause intestinal barrier damage via the loss of tight junction protein expression and promote inflammation. Secondary bile acids of host-gut microbial origin, and several other gut-microbiota-derived metabolites, are known to modulate intestinal inflammation. Here, we have studied the roles of two secondary bile acids in restoring barrier integrity and reducing the extent of dietary oxysterol-induced damage in intestinal epithelial cells. We found that oxysterols exert their damaging effects by inducing matrix metalloproteinases (MMP-2 and MMP-9) and activating NF-κB, which is coupled with the production of pro-inflammatory cytokines and chemokines (CCL2, CCL5, & IL-8). Additionally, we also show that the secondary bile acids lithocholic acid (LCA) and dehydrolithocholic acid (3-oxo-LCA) counteract dietary oxysterol-induced loss of barrier function (TEER & FITC-dextran flux). Overall, these findings provide supportive evidence for the potential role for secondary bile acids in maintaining barrier integrity and modulating inflammation in intestinal epithelial cells exposed to dietary oxysterols in vitro.
N-acetyl-cysteine alleviates nandrolone decanoate-induced hippocampal cell apoptosis in rats via reversing protein expressions of S1P1, Akt and FOXO3a signaling pathway.
Shirpoor A, Zarrini Z, Naderi R
Steroids · 2026 Apr · PMID 41616897 · Publisher ↗
Illicit use of nandrolone can result in apoptosis in the hippocampus tissue but the underlying mechanism is unknown. The present study evaluated the role of S1P1/Akt/FOXO3a pathway in hippocampus cell apoptosis following...
Illicit use of nandrolone can result in apoptosis in the hippocampus tissue but the underlying mechanism is unknown. The present study evaluated the role of S1P1/Akt/FOXO3a pathway in hippocampus cell apoptosis following exposure to nandrolone decanoate either alone or in combination with N-acetyl-cysteine. Twenty-four male Wistar rats were randomly divided into three groups (n = 8): control, nandrolone (10 mg/kg; intramuscularly; three times per week), and nandrolone + N-acetyl-cysteine (150 mg/kg; intraperitoneally). After six weeks of treatment, the number of apoptotic cells was significantly increased in the nandrolone treated group compared with the control group. Compared to control group, nandrolone group showed significant upregulation of NOX2, iNOS, 8-OHdG, P-FOXO3a/FOXO3a and lactate dehydrogenase (LDH) protein expression in rat hippocampus cells. Conversely, the protein expressions of P-Akt/Akt and S1P1 were significantly downregulated in hippocampus tissue of rats treated with nandrolone compared with control rats. Co-administration of N-acetyl-cysteine with nandrolone significantly reduced the apoptotic index and reversed the expressions of S1P1, P-Akt/Akt and P-FOXO3a/FOXO3a in the hippocampus neurons compared with the nandrolone group. These findings suggest that S1P1/Akt/FOXO3a signaling pathway may at least in part play an important role in the progression of apoptosis induced by nandrolone exposure, providing new insights into the pathogenesis and potential treatment of nandrolone-induced hippocampal damage.
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