Steroids[JOURNAL]
Sun
200 papers
Microbial catalyzed derivatization of canrenone with Glomerella fusarioides, and Cunninghamella blakesleeana, and evaluation of aromatase inhibitory activity of the resulting metabolites.
Aziz A, Atia-Tul-Wahab, Farooq G … +5 more , Shaikh NN, Yousuf S, Zafar H, Ahmed Z, Choudhary MI
Steroids · 2026 Jan · PMID 41138989 · Publisher ↗
The purpose of this study was to identify potential aromatase inhibitors, which might play a role in preventing breast cancer. The fungal-catalyzed microbial transformation of an anti-mineralocorticoid, canrenone (1), wa...
The purpose of this study was to identify potential aromatase inhibitors, which might play a role in preventing breast cancer. The fungal-catalyzed microbial transformation of an anti-mineralocorticoid, canrenone (1), was catalyzed by Glomerella fusarioides, and Cunninghamella blakesleeana. Bioconversion of canrenone (1) with G. fusarioides provided a new polar metabolite 2, and two known metabolites 3 and 4, while C. blakesleana transformed compound 1 into two known polar metabolites 4, and 5. Modern spectroscopic techniques were employed to identify the structures of metabolites as 1-dehydro-11α-hydroxycanrenone (2), 1-dehydrocanrenone (3), 11α-hydroxycanrenone (4), and 11β-hydroxycanrenone (5). The SingleCrystal X-ray Diffraction (SCXRD) based structures of metabolites 2, and 3 are reported here for the first time. Canrenone (1) and the resulting metabolites 2-4 were evaluated for their human aromatase inhibitory activity. Compounds 1-4 showed the IC values of 0.288 ± 0.0392, 0.372 ± 0.002, 0.328 ± 0.0083, and 1.102 ± 0.099, µM comparable to the standard drug, exemestane (0.26 ± 0.011 µM). All transformed products were found non-cytotoxic to human fibroblast (BJ) cell line. Furthermore, the docking studies predicted the interaction of potential inhibitors with the active site residues of the enzyme via hydrogen bonding and other non-covalent interactions. Simulation studies predicted the formation of stable enzyme-inhibitor complexes with no or insignificant perturbation during the simulation time of 100 nsec. Hence, these inhibitors may serve as preliminary hits for drug discovery against ER+ breast cancer.
Soy isoflavone Daidzein resembling the vertebrate steroid structure exhibits neuroprotection via mitochondrial biogenesis in rotenone induced Parkinson's disease in preclinical model.
Peshattiwar V, Muke S, Kaikini A … +3 more , Bagle S, Dighe V, Sathaye S
Steroids · 2025 Dec · PMID 41115603 · Publisher ↗
Parkinson's disease (PD) ranks as the second most prevalent neurodegenerative disorder but is still devoid of neuroprotective treatment. Although approaches with disease modifying ability along with symptomatic relief ha...
Parkinson's disease (PD) ranks as the second most prevalent neurodegenerative disorder but is still devoid of neuroprotective treatment. Although approaches with disease modifying ability along with symptomatic relief has become an utmost necessity, the multifactorial nature of PD presents challenges for efficacy evaluation of potential test compound. This study attempts to address these issues by employing a rotenone induced PD model involving intranigral rotenone injection for evaluation of the neuroprotective efficacy of Daidzein (DZ) a soy isoflavone and a phytoestrogen. In this study, male Sprague Dawley rats after bilateral intranigral rotenone (12 μg) injection, were treated with DZ at a dose of 5, 10 and 20 mg/kg for 30 days. The neurobehavioral evaluation comprised of Rota-rod, Open field and Barnes maze test. The biochemical analysis constituting oxidative stress (Reduced glutathione, superoxide dismutase, catalase and lipid peroxidation), inflammation (TNF-α), mitochondrial alteration (complex I activity and biogenesis) was conducted on mid-brain tissue after 30 days of treatment. The Substantia nigra and striatum were subjected to immunohistochemical analysis (IHC) for TH positive neurons and Glial Fibrillary Acidic Protein. The analysis revealed significant improvement by daidzein in motor co-ordination and attenuation in cognitive deficits due to rotenone. The biochemical assessment exhibited significant decrement in oxidative stress as well as inflammation. DZ treatment also prevented complex I inhibition and promoted mitochondrial biogenesis eventually contributing to the neuroprotection apparent in IHC. Thus, the results strongly corroborate the neuroprotective potential of DZ against rotenone induced model of PD.
Potential of betulinic acid in the Antiformation and eradication of bacterial biofilms and pharmacokinetic and toxicological analysis.
Pereira da Silva CA, Santos Araújo NJ, do Socorro Costa M … +10 more , Pereira da Silva AR, Roque Paulo CL, de Araújo Neto JB, Barbosa Filho JM, de Freitas TS, Soares JB, Dos Santos JS, Bezerra Morais Braga MF, Melo Coutinho HD, Cosmo Andrade-Pinheiro J
Steroids · 2025 Dec · PMID 41110785 · Publisher ↗
Bacterial biofilms are complex, organized structures that adhere to surfaces, protected by a self-produced extracellular matrix. This conformation makes it difficult to eradicate infections with conventional treatments....
Bacterial biofilms are complex, organized structures that adhere to surfaces, protected by a self-produced extracellular matrix. This conformation makes it difficult to eradicate infections with conventional treatments. In view of this, natural compounds have emerged as promising therapeutic alternatives. This study evaluated the potential of betulinic acid, a pentacyclic triterpene, in inhibiting the formation and eradication of bacterial biofilms, as well as predicting its pharmacokinetic properties and toxicity by means of in silico analyses. Six bacterial strains were tested. The crystal violet test was used to evaluate the antibiofilm activity, with chlorhexidine and the antibiotics norfloxacin, ampicillin and gentamicin as controls. The results showed that betulinic acid had moderate to good activity in inhibiting biofilm formation and a variable response in eradication, depending on the strain. In silico analyses indicated favorable physicochemical and pharmacokinetic properties, with emphasis on good intestinal absorption, oral bioavailability and absence of inhibition of cytochrome P450 enzymes, although potential toxicity risks were identified. These findings suggest that betulinic acid is a promising candidate for the development of new therapeutic strategies to combat infections associated with biofilms.
Exploring the relationship between endogenous steroids and nausea and vomiting in pregnancy: A longitudinal prospective study.
Benešová J, Hill M, Dlouhá D … +5 more , Roberts K, Ullmann J, Koliba P, Velíková M, Kaňková Š
Steroids · 2026 Jan · PMID 41110784 · Publisher ↗
Nausea and vomiting in pregnancy (NVP) affect approximately 70 % of women worldwide. It is thought to have an adaptive function in the first trimester, when it protects the mother and the fetus against potential dangers...
Nausea and vomiting in pregnancy (NVP) affect approximately 70 % of women worldwide. It is thought to have an adaptive function in the first trimester, when it protects the mother and the fetus against potential dangers from the diet. Proximate causes of NVP include hormonal changes during pregnancy. This longitudinal prospective study examined associations between various endogenous steroids and NVP. In the first and third trimester, pregnant women (N = 179) completed the Index of Nausea, Vomiting, and Retching questionnaire (92.1 % of women reported at least some symptoms of NVP in the first trimester and 37.4 % in the third trimester) and we analyzed their blood serum concentrations of 91 endogenous steroids. In the first trimester, NVP intensity was significantly positively associated with progesterone metabolites from the C21 5α/β-reduced steroid group (e.g., allopregnanolone sulfate) and with conjugated 5α-androstane-3α,17β-diol and conjugated 5α-androstane-3β,17β-diol. In the third trimester, we found significant negative associations between NVP and progesterone, conjugated testosterone, 7-oxo-DHEA, 5-androstene-3β,16α,17β-triol sulfate, some C21 Δ steroids (e.g., pregnenolone sulfate, 17-hydroxypregnenolone sulfate), and C21 5α/β-reduced steroids (such as allopregnanolone sulfate and conjugated pregnanolone). Our findings suggest that sulfated 3α-hydroxy-5α-steroids may contribute to NVP in early pregnancy by affecting brainstem regions involved in the vomiting reflex. In late pregnancy, higher levels of immunomodulatory androstanes and progesterone may reduce NVP severity via immune regulation and smooth muscle relaxation.
Nutrient manipulation regulates growth and steroidal alkaloid production in plant cultures of Solanum viarum Dunal.
Prasad A, Patel P, Niranjan A … +2 more , Saxena G, Chakrabarty D
Steroids · 2025 Dec · PMID 41106793 · Publisher ↗
Solanum viarum is a valuable medicinal plant native to India and widely distributed throughout Asia. It serves as a commercially viable raw source for the steroidal drug industry, being the richest natural source of an i...
Solanum viarum is a valuable medicinal plant native to India and widely distributed throughout Asia. It serves as a commercially viable raw source for the steroidal drug industry, being the richest natural source of an important steroidal alkaloid- solasodine. Enhancement of solasodine content in in vitro plant cultures is always a keen interest for tissue culturists for the research and development in pharmaceutical industries. In the present study, a multiple linear regression (MLR) model was employed to investigate the synergistic effects of key nutrient components in the growth medium (Mg, Ca, Fe, N, and sucrose) for optimized growth and solasodine production in in vitro plant cultures of S. viarum. All the cultures were harvested after 35, 45, and 55 days of the culture cycle. The three models were designed to predict growth index, solasodine content, and solasodine yield in the plant cultures. The designed model was further evaluated by performing a validation experiment using ten different experimental setups, which showed a greater similarity between the predicted and experimental datasets. The results of the model-based experimental set showed that 1.4 mM Mg, 2.9 mM Ca, 1.9 µM Fe, 41.9 mM Nitrogen, and 4 % (w/v) sucrose resulted in achieving maximum solasodine yield (108.82 mg/g DW) in the plant culture of S. viarum after 54 days of harvest. The proposed MLR model offers a robust and reliable approach for predicting the optimal concentrations of micro- and macronutrients to maximize growth and solasodine accumulation in in vitro cultures of Solanum viarum. This study establishes a strategic framework that can be leveraged to enhance biomass production and secondary metabolite yield, contributing significantly to the large-scale cultivation and pharmaceutical exploitation of this valuable medicinal plant.
Beta-Ecdysone protects osteocytes from excess glucocorticoids via Akt1-mediated regulation of Connexin43.
Xie A, Wang L, Zhang Y … +5 more , Zhang S, Cao J, Wang C, Wu H, Dai W
Steroids · 2025 Dec · PMID 41052694 · Publisher ↗
Glucocorticoid-induced osteoporosis (GIOP) is a leading cause of secondary osteoporosis (OP). β-Ecdysone (βEcd), a naturally occurring estrogen analog, was evaluated for its ability to mitigate the effects of glucocortic...
Glucocorticoid-induced osteoporosis (GIOP) is a leading cause of secondary osteoporosis (OP). β-Ecdysone (βEcd), a naturally occurring estrogen analog, was evaluated for its ability to mitigate the effects of glucocorticoids (GCs) on osteocytes, the crucial cells in bone remodeling. In GIOP mouse model induced by dexamethasone (Dex), micro-CT, biomechanical testing, silver nitrate staining, and hematoxylin-eosin (HE) staining were employed, demonstrating that βEcd effectively attenuated Dex-induced decreases in bone mass and strength, and alleviated Dex induced reduction in osteocyte dendrite and viability. Network pharmacology analysis predicted that the therapeutic efficacy of βEcd against GIOP is mediated through the crucial targets such as protein kinase B (Akt1), with significant enrichment in pathways including apoptosis and phosphoinositide 3-kinase (PI3K)-Akt signaling. In vitro, the osteocyte-like MLO-Y4 cells were treated with 10 μM Dex for 48 h in the presence or absence of βEcd or the PI3K inhibitor LY294002 (LY). Crystal violet staining and connexin43 (CX43) immunofluorescence (IF) staining were employed, and western blot was used to assess the levels of Akt1, phospho (p)-Akt, CX43, p-CX43, and apoptosis-related factors. Hoechst staining and annexin V/PI apoptosis assays were also used to evaluate apoptosis. The results demonstrated that βEcd counteracted Dex-induced apoptosis by modulating Akt1 and CX43 expression in MLO-Y4 cells, while inhibition of Akt activity reversed these effects, suggesting that βEcd targets the Akt1 gene. The findings indicate that βEcd protects osteocytes from GC-induced apoptosis through Akt-mediated regulation of CX43, highlighting its potential as a therapeutic approach for the prevention and treatment of GIOP.
Kobochromone A, a polyphenol in Carex kobomugi, suppresses androgen signaling induced by 11-oxygenated androgens and enhances the efficacy of AKT inhibitors in triple-negative breast cancer cells.
Tanio M, Miyamoto Y, Saka T … +12 more , Kudo Y, Hayashi R, Kawano S, Yoshino Y, Abe N, Yamaguchi E, Arai Y, Kashiwagi H, Oyama M, Itoh A, Ikari A, Endo S
Steroids · 2025 Nov · PMID 41015102 · Publisher ↗
Breast cancer is the most common cancer in women, with triple-negative breast cancer (TNBC) accounting for approximately 20% of cases. TNBC lacks estrogen receptors (ER), progesterone receptors (PR), and epidermal growth...
Breast cancer is the most common cancer in women, with triple-negative breast cancer (TNBC) accounting for approximately 20% of cases. TNBC lacks estrogen receptors (ER), progesterone receptors (PR), and epidermal growth factor receptor 2 (HER2) expression, which makes targeted therapies ineffective. The luminal androgen receptor (LAR) subtype of TNBC expresses androgen receptor (AR), highlighting the need for treatment strategies that target androgen signaling. Recently, the role of 11-oxygenated androgens, in addition to conventional androgens such as testosterone and dihydrotestosterone, in androgen-related diseases in women has gained increased attention. In this study, we investigated the involvement of 11-oxygenated androgens in LAR TNBC and explored the anti-androgenic effects of Kobochromone A (KC-A), a natural compound derived from Carex kobomugi. KC-A inhibits the androgen-synthesizing enzyme dehydrogenase/reductase short-chain dehydrogenase/reductase family member 11 (DHRS11) and suppresses AR expression. Using the AR-positive TNBC cell line MDA-MB-453, we demonstrated that 11-oxygenated androgens activate androgen signaling and promote cell proliferation. KC-A significantly inhibited androgen signaling by reducing nuclear AR localization and decreasing transmembrane protease, serine 2, and c-Myc expression. Furthermore, KC-A synergistically enhanced antiproliferative effects of the AKT inhibitor capivasertib (Cap), promoted apoptosis, and further suppressed AR expression. The primary therapeutic mechanisms of KC-A were identified as its dual actions: inhibition of DHRS11 and suppression of AR expression. These findings suggest that KC-A, either alone or in combination with AKT inhibitors, may offer a promising therapeutic strategy for LAR TNBC by targeting androgen signaling. Further studies are needed to confirm the efficacy and safety of KC-A in clinical applications.
Steroidal scaffold dichotomy: pathogenic role of 7-ketocholesterol versus protective FXR-antagonistic actions of guggulsterone in metabolic regulation.
Sabarathinam S, Ganamurali N
Steroids · 2025 Nov · PMID 41005553 · Publisher ↗
Obesity-associated Dyslipidemia and inflammation are aggravated by the accumulation of toxic oxysterols, particularly 7-ketocholesterol (7-KC), which amplifies oxidative stress and metabolic dysfunction. The steroidal sc...
Obesity-associated Dyslipidemia and inflammation are aggravated by the accumulation of toxic oxysterols, particularly 7-ketocholesterol (7-KC), which amplifies oxidative stress and metabolic dysfunction. The steroidal scaffold is a central determinant of whether such molecules exert protective or pathogenic effects. This review highlights the dichotomy between 7-KC, a cytotoxic oxysterol, and Guggulsterone, a Phytosteroids with therapeutic potential. Guggulsterone retains the tetracyclic steroid backbone, enabling it to mimic endogenous sterols while functioning as a farnesoid X receptor (FXR) antagonist. By relieving FXR-mediated suppression of CYP7A1, Guggulsterone enhances bile acid synthesis, promotes cholesterol clearance, and improves lipid profiles. Additionally, its structural features confer anti-inflammatory activity via NF-κB inhibition, contrasting with the pro-oxidant nature of 7-KC. The concept of steroid scaffold mimicry underscores the potential of Phytosteroids as blueprints for drug design, offering a path toward innovative therapies for obesity-linked metabolic disorders.
Duration of vitamin D supplementation modulates the association between cardiovascular disease and high-sensitivity C-reactive protein across body mass index strata.
Koufakis T, Georgiadis T, Kourti A … +6 more , Thisiadou K, Karalazou P, Kokkinos A, Doumas M, Kotsa K, Makedou K
Steroids · 2025 Nov · PMID 40998142 · Publisher ↗
BACKGROUND: Cardiovascular disease (CVD) and higher body mass index (BMI) are linked to chronic low-grade inflammation. It is unclear whether vitamin D modifies the association between CVD and inflammatory biomarkers uni...
BACKGROUND: Cardiovascular disease (CVD) and higher body mass index (BMI) are linked to chronic low-grade inflammation. It is unclear whether vitamin D modifies the association between CVD and inflammatory biomarkers uniformly across BMI strata. We therefore tested whether vitamin D status and supplementation modify the CVD-biomarker association and whether any modification differs by BMI category. METHODS: In a cross-sectional cohort of adults free of acute infection (N = 88; 20 with normal BMI, 34 with overweight, and 34 with obesity), four inflammatory biomarkers were assessed: high-sensitivity C-reactive protein (hs-CRP), presepsin, ferritin, and β-defensin-2. Outcomes were modeled on the natural-log scale with age and sex as covariates. We tested the interaction between BMI and CVD and evaluated whether vitamin D variables [25(OH)D concentrations, supplementation status, supplementation duration, sufficiency category] modified the CVD-biomarker relationship, including prespecified three-way interactions among CVD, vitamin D, and BMI. RESULTS: No interaction between BMI and CVD was detected for any biomarker. For hs-CRP, a significant three-way interaction among CVD, vitamin D supplementation duration, and BMI was observed (p = 0.008) and was robust to sensitivity analyses [duration capped at three or six months; additional adjustment for 25(OH)D and supplementation status]. With longer supplementation, the CVD-hs-CRP difference widened in the moderate-BMI category and attenuated in the higher-BMI category. Other biomarkers showed no comparable interactions. CONCLUSION: Vitamin D exposure-particularly supplementation duration-may modulate CVD-related inflammation in a BMI-dependent manner. Replication in larger studies is warranted.
Design, synthesis and characterization of novel cholesterol derivatives: Anti-cancer activity, ADMET profiling and DFT insights.
Verma A, Rawat P, Shukla S … +6 more , Singh RP, Gupta P, Parveen S, Banerjee M, Sethi A, Singh SK
Steroids · 2025 Nov · PMID 40962243 · Publisher ↗
In the present work, Steglich esterification and Mizoroki-Heck reaction have been carried out for the synthesis of novel cholesterol derivatives. The synthesized derivatives 2, 3, 4, 5 and 6 were purified through column...
In the present work, Steglich esterification and Mizoroki-Heck reaction have been carried out for the synthesis of novel cholesterol derivatives. The synthesized derivatives 2, 3, 4, 5 and 6 were purified through column chromatography and characterized by H, C NMR, FT-IR spectroscopy, and mass spectrometry. The geometries of all the compounds were optimized in the ground state by the density function theory at the B3LYP/6-31G(d,p) level. The in vitro evaluation of compounds 2 (IC 17), 3 (IC 11), 4 (IC 14) and 6 (IC 20) for their anti-cancer activity against SiHa cells demonstrated an increased apoptotic activity in comparison to the parent compound 1 (IC 24) i.e. cholesterol. The Molecular docking studies were carried out against two proteins bearing the protein data bank (PDB) ID 2B9D and 1R9W to investigate the inhibitory action of the derivatives. The result of molecular docking showed appreciable interactions of 2, 3, 4, 5 and 6 with the selected proteins as compared to 1. The in vitro and molecular docking studies show that the synthesized molecules can prove to be better anti-cancer agents on other cancer cells also. The computational analysis data and the experimental data were in conformation with each other. ADMET analysis was carried out using the admetSAR database and Swiss ADME.
Mineralocorticoid receptor antagonism of vamorolone: Evidence from LIONHEART and VISION-DMD clinical trials.
de Vera A, Clemens PR, Dang UJ … +12 more , Dutreix C, Gresko E, Guglieri M, Hagerty L, Hasham S, Damsker J, Hathout Y, Linden A, Berglund A, Tobin R, Wahbi K, Hoffman EP
Steroids · 2025 Nov · PMID 40957504 · Publisher ↗
The effect of vamorolone, the first dissociative corticosteroid for Duchenne muscular dystrophy (DMD), at the mineralocorticoid receptor (MR) was investigated in the Phase 1 mechanistic LIONHEART study and using serum sa...
The effect of vamorolone, the first dissociative corticosteroid for Duchenne muscular dystrophy (DMD), at the mineralocorticoid receptor (MR) was investigated in the Phase 1 mechanistic LIONHEART study and using serum samples from boys with DMD in the pivotal VISION-DMD trial. In LIONHEART, 30 healthy adult males were randomized 1:1:1 to vamorolone 20 mg/kg, eplerenone 200 mg, or no treatment arms. A fludrocortisone challenge was administered between -9 h and 24 h after treatment. The LIONHEART primary outcome was urinary Na/K ratio; additional outcomes were pharmacokinetics, urine Na and K concentrations, and safety. In VISION-DMD, boys with DMD aged 4-7 years were treated with vamorolone 2 or 6 mg/kg/d for 48 weeks or with prednisone 0.75 mg/kg/d or placebo for 24 weeks followed by vamorolone 2 or 6 mg/kg/d for 20 weeks following a 4-week washout. Serum sample analysis from VISION-DMD used the SomaScan® 7 K assay. In LIONHEART, vamorolone reversed the decrease in urinary Na/K ratio induced by fludrocortisone, confirming vamorolone MR antagonism. The maximum MRA effect of vamorolone was observed at 4-6 h post dose and was detectable until approximately 10 h post dose. Vamorolone reversed fludrocortisone induced Na retention with no evidence of decreased potassium excretion. Vamorolone 20 mg/kg was well tolerated, and results were consistent with known PK parameters. The VISION-DMD results showed vamorolone-specific increases in renin serum levels, as well as klotho, and calcium carrier proteins fetuin A and B, consistent with an MR antagonist effect. The available data confirm the MR antagonistic effect of vamorolone in humans. LIONHEART: NCT06649409; VISION-DMD: NCT03439670.
Quercetin-cyclodextrin combination effects on cytochrome P450 genes, oxidative stress and ovarian function in PCOS rats.
Taghipour F, Samadian H, Dalirfardouei R … +3 more , Asl SS, Barati N, Artimani T
Steroids · 2025 Nov · PMID 40945696 · Publisher ↗
This study investigates the effect of the quercetin/cyclodextrin (Que/β-CD) complex on oxidative stress, cytochrome P450 gene expression, and ovarian tissue structure in a rat polycystic ovary syndrome (PCOS) model. The...
This study investigates the effect of the quercetin/cyclodextrin (Que/β-CD) complex on oxidative stress, cytochrome P450 gene expression, and ovarian tissue structure in a rat polycystic ovary syndrome (PCOS) model. The Que/β-CD complexes were synthesized using the solvent evaporation method and characterized via scanning electron microscope (SEM) imaging and fourier transform infrared (FTIR) spectroscopy. Thirty female Wistar rats (6 weeks old, 160-180 g) with regular estrous cycles were randomly divided into six experimental groups: control, PCOS, PCOS treated with Que, PCOS adminstrated the β-CD, PCOS recivied metformin, and PCOS given Que/β-CD complex. Following model induction and treatments, tissue and gene expression analyses were performed. Characterization confirmed the successful synthesis of Que/β-CD complex. PCOS rats showed increased weight and higher number of atretic follicles compared to the controls (p < 0.01), which were effectively decreased after Que/β-CD treatment. Additionally, PCOS rats had reduced corpora lutea and CYP19A expression levels (p < 0.01), which were enhanced after Que/β-CD administration. Elevated CYP11A and CYP17A gene expression in PCOS rats markedly diminished with Que/β-CD treatment, indicating an improvement in disease symptoms. Oxidant levels, higher in PCOS rats (p < 0.01), meaningfully decreased after treatment with metformin, Que, or Que/β-CD (p < 0.0001, p < 0.001, and p < 0.001, respectively). Overall, Que/β-CD treatment in the PCOS model resulted in to a significant decrease in body and ovary weights, number of cysts, atretic follicles, and oxidative stress markers, accompanied by a notable increase in corpora lutea, CYP19A expression, and antioxidant activity. These findings highlight Que/β-CD's therapeutic potential in managing PCOS symptoms.
Synthesis and preliminary biological evaluation of novel steroidal compounds as antibacterial agents.
Esposito A, Stabile M, Migliaccio A … +3 more , De Gregorio E, D'Errico S, Guaragna A
Steroids · 2025 Nov · PMID 40925475 · Publisher ↗
Antimicrobial resistance is currently one of the most serious and alarming threats to human health; therefore, the identification of novel antimicrobial agents is a compelling need. Recently, we identified the heterocycl...
Antimicrobial resistance is currently one of the most serious and alarming threats to human health; therefore, the identification of novel antimicrobial agents is a compelling need. Recently, we identified the heterocyclic steroid PYED-1 as a novel promising antibacterial and antibiofilm agent. In an effort to broaden the repertoire of active compounds and elucidate the structural features responsible for their antibacterial activity, two novel derivatives of PYED-1 have been conceived herein. The target compounds have been readily obtained in few steps and with very good yields. The antibacterial activity has been evaluated against S. aureus and A. baumannii strains, as examples of Gram-positive and -negative bacteria, by the broth microdilution method, while hemolysis assay has been used for the assessment of cytotoxicity. One of the two derivatives was able to inhibit the growth of S. aureus strains with lower MIC values (8 µg/mL) compared with those of PYED-1 (16 µg/mL) without showing hemolytic effect suggesting therefore a favorable safety profile. Overall, this study provides further indications on the functional groups required for the antibacterial activity of these novel steroidal derivatives.
Vitamin D potentiation of metformin hepatoprotective activities: Concurrent targeting of carbohydrate enzymatic pathways and PCSK9/AGEs-regulated oxidative stress mechanisms in type 2 diabetic male Wistar rats.
Abdulrahim HA, Odetayo AF, Amosa MB … +11 more , Olumoye JO, Hassan WA, Ebadan IA, Yusuf KY, Abodunrin GT, Adefolarin SO, Ajibare AJ, Olatunji T, Abdussalam T, Okesina KB, Olayaki LA
Steroids · 2025 Nov · PMID 40921316 · Publisher ↗
BACKGROUND: Emerging evidence indicates that metformin-based combination therapy may offer better glycemic control and improved tolerability compared to diabetes monotherapy. Building on this, vitamin D was considered a...
BACKGROUND: Emerging evidence indicates that metformin-based combination therapy may offer better glycemic control and improved tolerability compared to diabetes monotherapy. Building on this, vitamin D was considered a potential adjunct to metformin for managing type 2 diabetes. Although vitamin D is primarily recognized for its role in calcium regulation, it also appears to influence glucose metabolism and other non-skeletal functions. Therefore, this study was designed to evaluate the hepatoprotective effects of vitamin D and metformin in diabetic rats. METHODOLOGY: Thirty (30) male Wistar rats were randomized into five treatment groups as follows: control, diabetes (DM) untreated, DM treated with vitamin D (25 µg/kg), DM treated with metformin (180 mg/kg), and DM treated with both vitamin D (25 µg/kg) and metformin (180 mg/kg). All treatments were via the oral route and lasted for 28 days. RESULTS: Vitamin D and/or metformin improved glucose and lipid imbalances caused by diabetes. These benefits were linked to enhanced activity of key liver enzymes involved in glucose metabolism, including hexokinase, phosphofructokinase, pyruvate kinase, glucose-6-phosphate dehydrogenase, G-6-phosphatase, and lactate dehydrogenase. Additionally, treatment with vitamin D and/or metformin counteracted diabetes-induced increases in pro-oxidant levels, restored both enzymatic and non-enzymatic antioxidant defenses, and reduced inflammation. This oxido-inflammatory response appeared to be connected to oxidative signaling mediated by proprotein convertase subtilisin/kexin type 9 (PCSK9), highlighting a potential mechanism underlying the protective effects of these therapies. CONCLUSION: Vitamin D enhanced the antidiabetic effects of metformin by further improving the activity of carbohydrate-metabolizing enzymes and modulating PCSK9-mediated oxidative signaling. This suggests that vitamin D can boost metformin's efficacy in regulating glucose-lipid metabolism and reducing oxidative stress in diabetes.
Are dexamethasone implants a safe and effective breakthrough in uveitis treatment? A systematic review and meta-analysis.
Chen KY, Chan HC, Chan CM
Steroids · 2025 Nov · PMID 40829733 · Publisher ↗
BACKGROUND: Uveitis encompasses inflammatory conditions affecting the iris, ciliary body, and choroid. Its management relied on corticosteroids, immunosuppressive agents, and, more recently, biologic therapies. The devel...
BACKGROUND: Uveitis encompasses inflammatory conditions affecting the iris, ciliary body, and choroid. Its management relied on corticosteroids, immunosuppressive agents, and, more recently, biologic therapies. The development of sustained-release intravitreal corticosteroid delivery systems, like dexamethasone intravitreal implants, has revolutionized the treatment of posterior uveitis. OBJECTIVES: To critically appraise the evidence of the safety and efficacy of dexamethasone implants in managing Uveitis. METHODS: A systematic review of the safety and efficacy of dexamethasone implants in managing Uveitis was conducted. A comprehensive and systematic electronic database search was conducted in Scopus, PubMed, Cochrane Library, ScienceDirect, Google Scholar, and Wiley Online Library for studies published from their inception to the present date. Modified PICOS criteria were used to screen and select the eligible studies from the potential articles retrieved from the database search. Studies were considered if they included patients with uveitis. A comprehensive risk of bias assessment was conducted using the Newcastle Ottawa Scale (NOS) for cohort studies, the Risk of Bias in Non-Randomized Studies (ROBINS-I) tool for non-randomized trials, the risk of bias visualization tool (ROB 2.0) tool for RCTs, and the National Institutes of Health (NIH) quality assessment tool for Interventional case-series. Data were then procedurally extracted and analyzed. RESULTS: The study selection process identified 29 studies, including 1,086 eyes. Dexamethasone implant significantly reduced central retinal/macular thickness at all time points: 150.4 μm at 1 month (p < 0.001), 200.8 μm at 3 months (p < 0.001), and 225.5 μm at 6-24 months (p < 0.001). Inflammation control was achieved in 80.8 % of cases (p < 0.001). Visual acuity improvements were modest at 6 months (p = 0.078) but significant long-term (p < 0.001). However, the dexamethasone implant resulted in cataract formation (p = 0.010), with a recurrence rate of 0.501 (p = 0.968). CONCLUSION: Dexamethasone implants offer clinically significant benefits, resulting in substantial reductions in central retinal thickness, improvements in visual acuity, and effective control of inflammation in patients with uveitis.
Salivary 1,25(OH)D & cortisol as biomarkers of anxiety, depression, and periodontitis: a comparative cross-sectional study.
Rafique S, Ahmed S, Noushad S
Steroids · 2025 Oct · PMID 40816638 · Publisher ↗
PURPOSE: This study examines the correlation between salivary levels of 1,25(OH)D (calcitriol) and cortisol in healthy individuals and patients with anxiety and depression, both with and without periodontitis. The innova...
PURPOSE: This study examines the correlation between salivary levels of 1,25(OH)D (calcitriol) and cortisol in healthy individuals and patients with anxiety and depression, both with and without periodontitis. The innovative evaluation of salivary 1,25(OH)D, which is impervious to seasonal fluctuations, could facilitate the early identification and prevention of psychiatric and oral conditions by utilizing salivary biomarkers derived from the oral environment. METHODS: This comparative cross-sectional study involved 152 participants from the Department of Periodontology at Jinnah Medical and Dental College, Karachi, Pakistan. Anxiety and depression were evaluated with the Aga Khan University Anxiety and Depression Scale, while periodontitis was assessed via clinical attachment loss and probing pocket depth. Salivary 1,25(OH)D and cortisol levels were quantified with an Enzyme-Linked-Immunosorbent-Assay (ELISA). The statistical evaluation encompassed one-way ANOVA, Kruskal-Wallis tests, post hoc comparisons, and correlation and regression analyses. RESULTS: The mean 1,25(OH)D levels were significantly lower in patients with anxiety and depression (AD) and those with both anxiety, depression, and periodontitis (ADP) (130.78 ± 8.52 pmol/L and 33.44 ± 26.17 pmol/L) compared to healthy controls (HC) (220.92 ± 11.63 pmol/L, p < 0.05), demonstrating a strong negative correlation (AD: r = -0.936, p < 0.05, ADP: r = -0.932, p < 0.05). Conversely, cortisol levels were significantly higher in case groups (AD: 6.41 ± 0.54 nmol/L, ADP: 7.8 ± 1.09 nmol/L) than in healthy controls (4.22 ± 0.61 nmol/L, p < 0.05), showing a strong positive correlation (AD: r = 0.922, p < 0.05, ADP: r = 0.496, p < 0.002). Regression analysis identified cortisol and 1,25(OH)D as significant predictors of anxiety, depression, and periodontitis (p < 0.05). CONCLUSION: Salivary 1,25(OH)D and cortisol serve as potential non-invasive markers for the early detection of anxiety, depression, and periodontitis.
Biotransformation of 22-hydroxy-23,24-bisnorchol-4-ene-3-one by Gibberella fujikuroi CICC 40272-A to discover novel C22 steroid derivatives.
He R, Cui W, Song M … +11 more , Song Y, Guo X, Liu X, Cui Y, Zheng X, Wang X, Zhou Y, Han J, Zhang G, Wang F, Xu W
Steroids · 2025 Oct · PMID 40783027 · Publisher ↗
The microbial transformation of steroids offers a sustainable and selective approach to synthesize pharmacologically valuable derivatives. This study investigated the biotransformation of 22-hydroxy-23,24-bisnorchol-4-en...
The microbial transformation of steroids offers a sustainable and selective approach to synthesize pharmacologically valuable derivatives. This study investigated the biotransformation of 22-hydroxy-23,24-bisnorchol-4-ene-3-one (4-HBC) by Gibberella fujikuroi CICC 40272-A to produce novel C22 steroid derivatives. Among seven screened fungal strains, G. fujikuroi exhibited superior regio- and stereo-selective hydroxylation activity. High performance liquid chromatography (HPLC) and thin layer chromatography (TLC) analyses revealed the formation of a major metabolite, identified as 7β,11α-dihydroxy-23,24-bisnorchol-4-ene-3-one (7β,11α-diOH-HBC) via NMR and MS, confirming the introduction of two hydroxyl groups at positions 7β and 11α. Optimization of fermentation conditions through single-factor and orthogonal experiments demonstrated that a medium containing 50 g/L galactose, 10 g/L NaNO, and pH 5.5, combined with 3 % inoculum, 1 g/L 4-HBC, and 96 h transformation time, achieved a maximum transformation rate of 65.88 %. Methanol (2 % v/v) was identified as the optimal cosolvent, enhancing substrate solubility while minimizing cytotoxicity. The study highlights G. fujikuroi CICC 40272-A as an effective biocatalyst for stereoselective steroid hydroxylation, providing an efficient and eco-friendly strategy to produce 7β,11α-diOH-HBC. These findings advance the application of microbial systems in pharmaceutical synthesis, emphasizing their potential to replace energy-intensive chemical processes in steroid derivative production.
Targeted metabolomics in PCOS mice identifies hippuric acid as a therapeutic metabolite.
Lan H, Meng B, Li J … +4 more , Duan C, Liu S, Qu P, Qin H
Steroids · 2025 Oct · PMID 40774621 · Publisher ↗
Polycystic ovary syndrome (PCOS) represents a complex endocrine disorder with profound detrimental effects on women's reproductive and metabolic health, yet the absence of specific pharmacotherapeutic interventions has r...
Polycystic ovary syndrome (PCOS) represents a complex endocrine disorder with profound detrimental effects on women's reproductive and metabolic health, yet the absence of specific pharmacotherapeutic interventions has resulted in a significant therapeutic gap. To elucidate the metabolic alterations in PCOS, we conducted a comprehensive targeted metabolomics analysis of plasma samples from healthy control mice and PCOS model mice, examining a panel of 197 metabolites spanning diverse metabolic classes. Our analysis revealed substantial metabolic differences between the groups, with organic acids, amino acids, and fatty acids emerging as the most abundant metabolite classes in both cohorts. Among the 197 metabolites analyzed, 86 demonstrated a Variable Importance in Projection (VIP) score > 1, with univariate analysis confirming 76 distinct metabolites showing significant alterations. Notably, the PCOS group exhibited marked increases in metabolites such as tartaric acid and docosapentaenoic acid, while hippuric acid showed the most pronounced reduction. Pathway enrichment analysis identified significant perturbations in key metabolic pathways, including amino acid metabolism, fatty acid oxidation, and the urea cycle in PCOS mice. The exogenous administration of hippuric acid led to a significant amelioration of ovarian pathology in PCOS mice, highlighting its promising therapeutic potential. These findings provide crucial insights into the altered metabolic landscape of PCOS, identifying potential biomarkers and therapeutic targets, with particular emphasis on the promising therapeutic role of hippuric acid in mitigating PCOS pathology, thereby offering a valuable avenue for further investigation and clinical translation.
Protective effects of coenzyme Q10 against trihexyphenidyl-induced testicular oxidative damage: modulation of antioxidant enzymes, inflammatory markers, hormonal and steroidogenic pathways in rats.
Okeleji LO, Hamed MA, Jegede AI … +2 more , Oyovwi MO, Ajayi AF
Steroids · 2025 Oct · PMID 40749881 · Publisher ↗
BACKGROUND: Trihexyphenidyl is clinically effective for Parkinson's disease and antipsychotic-induced extrapyramidal symptoms. However, its abuse potential and adverse effects on male reproductive health are significant...
BACKGROUND: Trihexyphenidyl is clinically effective for Parkinson's disease and antipsychotic-induced extrapyramidal symptoms. However, its abuse potential and adverse effects on male reproductive health are significant concerns. Coenzyme Q10 (CoQ10), a potent antioxidant, is known to protect reproductive tissues from injury. This study investigated the protective effects of CoQ10 against trihexyphenidyl-induced testicular damage in male Wistar rats. METHODS: Twenty male Wistar rats (160-180 g) were randomly allocated into four groups (n = 5/group): control (Tween 80), trihexyphenidyl (1.5 mg/kg), CoQ10 (10 mg/kg), and trihexyphenidyl + CoQ10. Treatments were administered orally for 60 days. Testicular tissue biomarkers and serum hormone levels were analyzed. RESULTS: Trihexyphenidyl treatment significantly reduced relative paired epididymal and testicular weights, along with serum levels of Follicle Stimulating Hormone (FSH), Luteinizing Hormone, and Testosterone. It also decreased the activity of steroidogenic enzymes (3β-HSD, 17β-HSD) and antioxidant enzymes (SOD, GPx, Catalase) compared to controls. Conversely, trihexyphenidyl increased markers of oxidative stress (MDA, 8-OHdG), inflammation (TNF-α, MPO, IL-1β), apoptosis (caspase-3), and altered lactate/pyruvate levels, accompanied by significant histopathological damage. Co-administration of CoQ10 with trihexyphenidyl significantly attenuated these detrimental effects, restoring biochemical parameters and improving testicular architecture. CONCLUSION: Coenzyme Q10 effectively protects against trihexyphenidyl-induced testicular toxicity by mitigating oxidative stress, inflammation, and apoptosis, while preserving steroidogenic enzyme activity and hormonal balance. These findings highlight CoQ10's potential as a therapeutic agent to counteract the reproductive side effects of trihexyphenidyl.
Endocannabinoid and steroid hormone levels during and after pregnancy in fingernail samples from mothers and their infants.
Voegel CD, Murari M, La Marca-Ghaemmaghami P … +3 more , Kraemer T, Binz TM, Restin T
Steroids · 2025 Oct · PMID 40730314 · Publisher ↗
Stress exposure and protective biological factors such as steroid hormones and endocannabinoids (eCBs) play a crucial role in pregnancy and birth outcomes. The keratinized nail matrix is a convenient medium for long-term...
Stress exposure and protective biological factors such as steroid hormones and endocannabinoids (eCBs) play a crucial role in pregnancy and birth outcomes. The keratinized nail matrix is a convenient medium for long-term hormone monitoring. However, data on changes in steroid hormone and eCB concentrations in human fingernails during pregnancy and the postpartum period remain limited. The aim of this longitudinal pilot study is to explore such changes in the fingernails of pregnant women and their infants. The study also seeks to identify optimal sampling time points for future research and to explore the feasibility of fingernail analysis as a non-invasive sampling method in perinatal stress research. A pilot study was conducted with five mothers and four corresponding infants. Nail samples were collected repeatedly at several time points during pregnancy and postpartum, while the newborns' first six nail clippings were analyzed. Using liquid chromatography-tandem mass spectrometry (LC-MS/MS), five steroid hormones (cortisone, cortisol, androstenedione, testosterone, progesterone) and four eCBs (2-arachidonylglycerol, (2-AG), anandamide (AEA), oleoylethanolamide (OEA), palmitoylethanolamide (PEA)) were quantified. Progesterone levels in maternal nail samples increased during pregnancy, peaking around the time of delivery, while cortisol and cortisone levels started to increase in the third trimester. In contrast, eCB concentrations were lower in the third trimester compared to the second. These findings encourage further research on the use of nail samples as a promising tool for the retrospective assessment of hormonal changes and stress markers during pregnancy and the postpartum period.
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