Pub Date : 2025-11-14DOI: 10.1016/j.steroids.2025.109717
Mercedes Perusquía
Dehydroepiandrosterone (DHEA) is the most abundant steroid hormone in primates; however, its levels decline with age in both men and women. Numerous studies have documented diverse biological activities of DHEA. This article reviews the current understanding of how DHEA regulates the contractile function of vascular and nonvascular smooth muscle (SM), specifically examining its relaxant properties mediated through nongenomic mechanisms. It summarizes both older and recent findings on DHEA and its role in regulating SM contractile activity. Moreover, it also discusses the potential mechanisms underlying its relaxation effects, including the structural–functional differences in the DHEA molecule and its ability to induce relaxation in various types of SM. Overall, DHEA introduces a novel aspect to the regulation of functional processes involved in SM contractile activity.
{"title":"Dehydroepiandrosterone impact on smooth muscle contractile activity by a nongenomic action","authors":"Mercedes Perusquía","doi":"10.1016/j.steroids.2025.109717","DOIUrl":"10.1016/j.steroids.2025.109717","url":null,"abstract":"<div><div>Dehydroepiandrosterone (DHEA) is the most abundant steroid hormone in primates; however, its levels decline with age in both men and women. Numerous studies have documented diverse biological activities of DHEA. This article reviews the current understanding of how DHEA regulates the contractile function of vascular and nonvascular smooth muscle (SM), specifically examining its relaxant properties mediated through nongenomic mechanisms. It summarizes both older and recent findings on DHEA and its role in regulating SM contractile activity. Moreover, it also discusses the potential mechanisms underlying its relaxation effects, including the structural–functional differences in the DHEA molecule and its ability to induce relaxation in various types of SM. Overall, DHEA introduces a novel aspect to the regulation of functional processes involved in SM contractile activity.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"225 ","pages":"Article 109717"},"PeriodicalIF":2.3,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145518585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-11DOI: 10.1016/j.steroids.2025.109716
Sophia Krombholz , Thomas Piper , Andreas Lagojda , Dirk Kühne , Mario Thevis
Advances in analytical techniques have markedly improved the detection of anabolic–androgenic steroids (AAS) in doping controls. This represents a major success for anti-doping efforts, but at the same times raises concerns about inadvertent exposure – not limited to oral ingestion, but also via dermal contact or mucosal absorption. Evaluating the plausibility of such scenarios can be complex, not least because these routes of drug intake can also be deliberately used for doping purposes. Analytical data on transdermal or mucosal absorption and elimination of AAS can be valuable here, particularly regarding the metabolite pattern in urine samples that might help to assess the route of drug delivery. This study investigated the urinary excretion profile of trenbolone and its metabolites after oral, transdermal and buccal administration in healthy male volunteers. Urine samples collected over a period of one week following the administration of 10 mg of trenbolone were analyzed by LC-HRMS, with regard to potential differences in the metabolite profile across the different routes of drug intake. Major trenbolone metabolites were detectable in the urine samples of all participants, however the detection windows varied strongly: Buccal resorption resulted in faster elimination, whereas transdermal application resulted in prolonged detectability, compared to oral administration. A cysteine-conjugated metabolite (M15-cys) was identified that showed higher abundances following transdermal and buccal administration, suggesting its potential as a marker for non-oral intake. In light of the growing importance of transdermal uptake of doping agents, these results provide valuable data for interpreting doping control findings, potentially also relevant for structurally related AAS.
{"title":"The influence of the route of drug administration on the metabolic profile of trenbolone in doping control urine samples","authors":"Sophia Krombholz , Thomas Piper , Andreas Lagojda , Dirk Kühne , Mario Thevis","doi":"10.1016/j.steroids.2025.109716","DOIUrl":"10.1016/j.steroids.2025.109716","url":null,"abstract":"<div><div>Advances in analytical techniques have markedly improved the detection of anabolic–androgenic steroids (AAS) in doping controls. This represents a major success for anti-doping efforts, but at the same times raises concerns about inadvertent exposure – not limited to oral ingestion, but also via dermal contact or mucosal absorption. Evaluating the plausibility of such scenarios can be complex, not least because these routes of drug intake can also be deliberately used for doping purposes. Analytical data on transdermal or mucosal absorption and elimination of AAS can be valuable here, particularly regarding the metabolite pattern in urine samples that might help to assess the route of drug delivery. This study investigated the urinary excretion profile of trenbolone and its metabolites after oral, transdermal and buccal administration in healthy male volunteers. Urine samples collected over a period of one week following the administration of 10 <!--> <!-->mg of trenbolone were analyzed by LC-HRMS, with regard to potential differences in the metabolite profile across the different routes of drug intake. Major trenbolone metabolites were detectable in the urine samples of all participants, however the detection windows varied strongly: Buccal resorption resulted in faster elimination, whereas transdermal application resulted in prolonged detectability, compared to oral administration. A cysteine-conjugated metabolite (M15-cys) was identified that showed higher abundances following transdermal and buccal administration, suggesting its potential as a marker for non-oral intake. In light of the growing importance of transdermal uptake of doping agents, these results provide valuable data for interpreting doping control findings, potentially also relevant for structurally related AAS.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"225 ","pages":"Article 109716"},"PeriodicalIF":2.3,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145507019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-03DOI: 10.1016/j.steroids.2025.109684
Trevor M. Penning (Editor-in-Chief STEROIDS)
{"title":"Etienne Baulieu – In Memorial (1927–2025)","authors":"Trevor M. Penning (Editor-in-Chief STEROIDS)","doi":"10.1016/j.steroids.2025.109684","DOIUrl":"10.1016/j.steroids.2025.109684","url":null,"abstract":"","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"224 ","pages":"Article 109684"},"PeriodicalIF":2.3,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145517276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A fingernail clipping is expected to be a specimen suited for the detection of the medium-to-long term abnormal production of steroids. There are reports demonstrating that the concentration ratios of cortisol (F) to cortisone (E) and testosterone (T) to androstenedione (AD) in nails are significantly different from those in serum. However, the concentration ratios in the nails were determined with a small number of samples in some instances and differed from study to study, in addition to which, their gender differences remain poorly understood. Determining the differences in the concentration ratios between the nails and serum with a sufficient number of samples by gender and discussing a factor causing these differences will help for an accurate interpretation of the results in the nail-based steroid tests. In this study, we first developed and validated liquid chromatography/electrospray ionization-tandem mass spectrometry methods for determining the F/E and T/AD ratios in thumbnail clippings, then demonstrated that the F/E (in both sexes) and T/AD (in male) ratios in the nails were significantly lower than those in the serum reported in the literature. We found that steroids which are present at the higher concentrations in the nail than expected from their serum concentrations, such as E and AD, are bound to albumin at a high rate in the serum. As the affinities of corticoids and androgens to albumin are low (Ka, 103–104 M−1), we concluded that the albumin-bound fractions can be the sources of the nail-incorporated steroids as well as the free fractions.
{"title":"Cortisol-to-cortisone and testosterone-to-androstenedione concentration ratios in nails: Their determination methods based on LC/MS/MS and differences from the serum concentration ratios in the literature","authors":"Himena Ishikawa, Sakurako Tanaka, Kenjiro Shibata, Tatsuya Higashi","doi":"10.1016/j.steroids.2025.109707","DOIUrl":"10.1016/j.steroids.2025.109707","url":null,"abstract":"<div><div>A fingernail clipping is expected to be a specimen suited for the detection of the medium-to-long term abnormal production of steroids. There are reports demonstrating that the concentration ratios of cortisol (F) to cortisone (E) and testosterone (T) to androstenedione (AD) in nails are significantly different from those in serum. However, the concentration ratios in the nails were determined with a small number of samples in some instances and differed from study to study, in addition to which, their gender differences remain poorly understood. Determining the differences in the concentration ratios between the nails and serum with a sufficient number of samples by gender and discussing a factor causing these differences will help for an accurate interpretation of the results in the nail-based steroid tests. In this study, we first developed and validated liquid chromatography/electrospray ionization-tandem mass spectrometry methods for determining the F/E and T/AD ratios in thumbnail clippings, then demonstrated that the F/E (in both sexes) and T/AD (in male) ratios in the nails were significantly lower than those in the serum reported in the literature. We found that steroids which are present at the higher concentrations in the nail than expected from their serum concentrations, such as E and AD, are bound to albumin at a high rate in the serum. As the affinities of corticoids and androgens to albumin are low (<em>Ka</em>, 10<sup>3</sup>–10<sup>4</sup> M<sup>−1</sup>), we concluded that the albumin-bound fractions can be the sources of the nail-incorporated steroids as well as the free fractions.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"225 ","pages":"Article 109707"},"PeriodicalIF":2.3,"publicationDate":"2025-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145442332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-28DOI: 10.1016/j.steroids.2025.109706
Maryia V. Barysevich , Volha V. Kazlova , Natalia M. Chaschina , Maxim D. Akalovich , Vitaly E. Syakhovich , Vladimir N. Zhabinskii , Vladimir A. Khripach
A concise synthesis of brassinolide and castasterone has been accomplished herein. The strategy relies on the addition of α−silyl substituted vinyl carbanions to steroidal C-22 aldehydes with pre-formed functionalities in the cyclic part. Commercially available brassinosteroids were used as a starting material. The key step of the present synthesis was the opening of the 23,24-epoxide with Me3Al in the presence of Ph3P as a Lewis base, which enhances the formation of a more nucleophilic alkylating agent. It was shown why the use of Me3Al is incompatible with the 3α,5-cyclo steroids, which are often employed as intermediates in the synthesis of brassinosteroids.
{"title":"α-Silyl substituted vinyl carbanions in the synthesis of brassinolide and castasterone","authors":"Maryia V. Barysevich , Volha V. Kazlova , Natalia M. Chaschina , Maxim D. Akalovich , Vitaly E. Syakhovich , Vladimir N. Zhabinskii , Vladimir A. Khripach","doi":"10.1016/j.steroids.2025.109706","DOIUrl":"10.1016/j.steroids.2025.109706","url":null,"abstract":"<div><div>A concise synthesis of brassinolide and castasterone has been accomplished herein. The strategy relies on the addition of α−silyl substituted vinyl carbanions to steroidal C-22 aldehydes with pre-formed functionalities in the cyclic part. Commercially available brassinosteroids were used as a starting material. The key step of the present synthesis was the opening of the 23,24-epoxide with Me<sub>3</sub>Al in the presence of Ph<sub>3</sub>P as a Lewis base, which enhances the formation of a more nucleophilic alkylating agent. It was shown why the use of Me<sub>3</sub>Al is incompatible with the 3α,5-cyclo steroids, which are often employed as intermediates in the synthesis of brassinosteroids.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"224 ","pages":"Article 109706"},"PeriodicalIF":2.3,"publicationDate":"2025-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145410151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-24DOI: 10.1016/j.steroids.2025.109705
Damião Sampaio de Sousa , Marcus Vinicius Ferreira da Silva , Aluísio Marques da Fonseca , Maria Mabelle Pereira Costa Paiva , Carminda Sandra Brito Salmito Vanderley , Gabrielle Silva Marinho
Alzheimer’s disease (AD) is the leading form of dementia in the world. It presents significant therapeutic challenges, especially in terms of the efficacy and safety of current cholinesterase inhibitors, such as AChE. To explore more effective therapeutic alternatives, this study investigated the potential of steroids derived from Spongia sp. as inhibitors of AChE and BuChE, utilizing in silico approaches. Six compounds (SP1-SP6) were subjected to pharmacokinetic property predictions (ADMET), metabolic stability evaluation, and molecular docking and molecular dynamics studies. The analyses indicated that compounds SP4-SP6 show greater polarity and metabolic stability in the hepatic microsomal system, while SP1-SP3 exhibit greater cell permeability and bioaccumulation potential. Among them, compound SP6 stood out for showing relevant interactions with active residues of BuChE, suggesting selectivity and structural compatibility with this enzyme. The results were reinforced by molecular dynamics simulations, which confirmed the stability of the SP6-BuChE complex, characterized by low structural deviations (RMSD), minimal residual fluctuations (RMSF), maintenance of hydrogen bonds, and a favorable binding free energy (MMGBSA). Thus, the steroids evaluated, especially SP6, have promising characteristics for modulating BuChE, with potential therapeutic application in AD. Additional experimental studies are needed to validate the efficacy and selectivity of these drugs. Additional experimental studies are needed to validate the efficacy and selectivity of these compounds in biological models.
{"title":"Selectivity, stability, and pharmacokinetic profiling of Spongia-derived steroids targeting AChE and BuChE for Alzheimer’s therapy","authors":"Damião Sampaio de Sousa , Marcus Vinicius Ferreira da Silva , Aluísio Marques da Fonseca , Maria Mabelle Pereira Costa Paiva , Carminda Sandra Brito Salmito Vanderley , Gabrielle Silva Marinho","doi":"10.1016/j.steroids.2025.109705","DOIUrl":"10.1016/j.steroids.2025.109705","url":null,"abstract":"<div><div>Alzheimer’s disease (AD) is the leading form of dementia in the world. It presents significant therapeutic challenges, especially in terms of the efficacy and safety of current cholinesterase inhibitors, such as AChE. To explore more effective therapeutic alternatives, this study investigated the potential of steroids derived from <em>Spongia</em> sp. as inhibitors of AChE and BuChE, utilizing in silico approaches. Six compounds (SP1-SP6) were subjected to pharmacokinetic property predictions (ADMET), metabolic stability evaluation, and molecular docking and molecular dynamics studies. The analyses indicated that compounds SP4-SP6 show greater polarity and metabolic stability in the hepatic microsomal system, while SP1-SP3 exhibit greater cell permeability and bioaccumulation potential. Among them, compound SP6 stood out for showing relevant interactions with active residues of BuChE, suggesting selectivity and structural compatibility with this enzyme. The results were reinforced by molecular dynamics simulations, which confirmed the stability of the SP6-BuChE complex, characterized by low structural deviations (RMSD), minimal residual fluctuations (RMSF), maintenance of hydrogen bonds, and a favorable binding free energy (MMGBSA). Thus, the steroids evaluated, especially SP6, have promising characteristics for modulating BuChE, with potential therapeutic application in AD. Additional experimental studies are needed to validate the efficacy and selectivity of these drugs. Additional experimental studies are needed to validate the efficacy and selectivity of these compounds in biological models.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"224 ","pages":"Article 109705"},"PeriodicalIF":2.3,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145418131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-23DOI: 10.1016/j.steroids.2025.109704
Ambreen Aziz , Atia-tul-Wahab , Ghulam Farooq , Nimra Naveed Shaikh , Sammer Yousuf , Humaira Zafar , Zaheer Ahmed , M. Iqbal Choudhary
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 IC50 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.
{"title":"Microbial catalyzed derivatization of canrenone with Glomerella fusarioides, and Cunninghamella blakesleeana, and evaluation of aromatase inhibitory activity of the resulting metabolites","authors":"Ambreen Aziz , Atia-tul-Wahab , Ghulam Farooq , Nimra Naveed Shaikh , Sammer Yousuf , Humaira Zafar , Zaheer Ahmed , M. Iqbal Choudhary","doi":"10.1016/j.steroids.2025.109704","DOIUrl":"10.1016/j.steroids.2025.109704","url":null,"abstract":"<div><div>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 (<strong>1</strong>), was catalyzed by <em>Glomerella fusarioides</em>, and <em>Cunninghamella blakesleeana</em>. Bioconversion of canrenone (<strong>1</strong>) with <em>G. fusarioides</em> provided a new polar metabolite <strong>2</strong>, and two known metabolites <strong>3</strong> and <strong>4</strong>, while <em>C. blakesleana</em> transformed compound <strong>1</strong> into two known polar metabolites <strong>4</strong>, and <strong>5</strong>. Modern spectroscopic techniques were employed to identify the structures of metabolites as 1-dehydro-11<em>α</em>-hydroxycanrenone (<strong>2</strong>), 1-dehydrocanrenone (<strong>3</strong>), 11<em>α</em>-hydroxycanrenone (<strong>4</strong>), and 11<em>β</em>-hydroxycanrenone (<strong>5</strong>). The SingleCrystal X-ray Diffraction (SCXRD) based structures of metabolites <strong>2</strong>, and <strong>3</strong> are reported here for the first time. Canrenone (<strong>1</strong>) and the resulting metabolites <strong>2</strong>–<strong>4</strong> were evaluated for their human aromatase inhibitory activity. Compounds <strong>1</strong>–<strong>4</strong> showed the IC<sub>50</sub> 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 <em>via</em> 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.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"225 ","pages":"Article 109704"},"PeriodicalIF":2.3,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145370468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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.
{"title":"Soy isoflavone Daidzein resembling the vertebrate steroid structure exhibits neuroprotection via mitochondrial biogenesis in rotenone induced Parkinson’s disease in preclinical model","authors":"Vaibhavi Peshattiwar , Suraj Muke , Aakruti Kaikini , Sneha Bagle , Vikas Dighe , Sadhana Sathaye","doi":"10.1016/j.steroids.2025.109703","DOIUrl":"10.1016/j.steroids.2025.109703","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"224 ","pages":"Article 109703"},"PeriodicalIF":2.3,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145337455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-17DOI: 10.1016/j.steroids.2025.109702
Camila Aparecida Pereira da Silva , Nara Juliana Santos Araújo , Maria do Socorro Costa , Ana Raquel Pereira da Silva , Cícera Laura Roque Paulo , José Bezerra de Araújo Neto , José Maria Barbosa Filho , Thiago Sampaio de Freitas , Juliete Bezerra Soares , Josefa Sayonara dos Santos , Maria Flaviana Bezerra Morais Braga , Henrique Douglas Melo Coutinho , Jacqueline Cosmo Andrade-Pinheiro
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.
{"title":"Potential of betulinic acid in the Antiformation and eradication of bacterial biofilms and pharmacokinetic and toxicological analysis","authors":"Camila Aparecida Pereira da Silva , Nara Juliana Santos Araújo , Maria do Socorro Costa , Ana Raquel Pereira da Silva , Cícera Laura Roque Paulo , José Bezerra de Araújo Neto , José Maria Barbosa Filho , Thiago Sampaio de Freitas , Juliete Bezerra Soares , Josefa Sayonara dos Santos , Maria Flaviana Bezerra Morais Braga , Henrique Douglas Melo Coutinho , Jacqueline Cosmo Andrade-Pinheiro","doi":"10.1016/j.steroids.2025.109702","DOIUrl":"10.1016/j.steroids.2025.109702","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"224 ","pages":"Article 109702"},"PeriodicalIF":2.3,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145329857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-17DOI: 10.1016/j.steroids.2025.109701
Jana Benešová , Martin Hill , Daniela Dlouhá , Kateřina Roberts , Jana Ullmann , Peter Koliba , Marta Velíková , Šárka Kaňková
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 Δ5 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.
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