Natural Steroids Research Articles

Biologically Active Compounds in Stizolophus balsamita Inflorescences: Isolation, Phytochemical Characterization and Effects on the Skin Biophysical Parameters.

Three germacranolides, as well as five flavonoids, natural steroid and simple phenolic compounds, were isolated from the inflorescence of Stizolophus balsamita growing in Iran. The paper presents active compounds found for the first time in the inflorescence of this species. The flavonoids, simple phenolic compounds and natural steroids have been isolated for the first time in the genus Stizolophus. The MTT assay was employed to study in vitro cytotoxic effects of the taxifolin against human fibroblasts. We also evaluate the possible biological properties/cosmetic effects of Stizolophus balsamita extract and taxifolin on the human skin. Sixty healthy Caucasian adult females with no dermatological diseases were investigated. We evaluate the effects of S. balsamita extract and taxifolin on skin hydration and transepidermal water loss (TEWL). It was revealed that S. balsamita extract might decrease TEWL level and fixed the barrier function of the epidermis. The presence of bioactive phytochemical constituents in S. balsamita inflorescences makes them a valuable and safe source for creating new cosmetics and medicines.

Urinary phthalate metabolites and alternatives and serum sex steroid hormones among pre- and postmenopausal women from NHANES, 2013–16

BackgroundExposure to phthalates is ubiquitous across the United States. While phthalates have anti-androgenic effects in men, there is little research on their potential impacts on sex hormone concentrations in women and that also take into account menopausal status. MethodsCross-sectional data on urinary phthalate metabolites, serum sex hormones, and relevant covariates were obtained from the National Health and Nutrition Examination Survey 2013–14 and 2015–16. Women over the age of 20 who were not pregnant or breastfeeding and had not undergone oophorectomy were included (n = 698 premenopausal, n = 557 postmenopausal). Weighted multivariable linear and Tobit regression models stratified by menopausal status were fit with natural log-transformed phthalate concentrations and sex hormone outcomes adjusting for relevant covariates. ResultsPhthalate metabolites were associated with differences in sex hormone concentrations among postmenopausal women only. Di-2-ethylhexyl phthalate (DEHP) was associated with lower serum estradiol and bioavailable testosterone concentrations. Specifically, a doubling of DEHP concentrations was associated with 5.9% (95% Confidence Interval (CI): 0.2%, 11.3%) lower estradiol and 6.2% (95% CI: 0.0%, 12.1%) lower bioavailable testosterone concentrations. In contrast, 1,2-cyclohexane dicarboxylic acid di-isononyl ester (DINCH) was associated with higher free testosterone, bioavailable testosterone, and free androgen index. Finally, di-2-ethylhexyl terephthalate (DEHTP) was associated with a higher testosterone-to-estradiol ratio. None of these results retained statistical significance when adjusted for multiple comparisons. ConclusionsDEHP, DINCH, and DEHTP were associated with differences in serum sex hormone concentrations among postmenopausal women, highlighting the need for further research into the safety of these chemicals.

Occurrence and fate of androgens, progestogens and glucocorticoids in two swine farms with integrated wastewater treatment systems

Steroid hormones are endocrine-disrupting chemicals that can cause adverse effects even at trace levels. The information about steroid hormones in animal wastes is still very limited. Here we investigated the occurrence and fate of fourteen androgens, twenty-one progestogens, and five glucocorticoids in Farm Luo Cheng (LC) and Farm Shui Tai (ST) with integrated wastewater treatment systems (WTSs) in South China. These two integrated systems have four stages: primary treatment (primary sedimentation tank), secondary biological treatment (biogas digester and up-flow anaerobic sludge reaction bed (UASB)), third-stage disinfection process, and fourth-stage dilution and further biodegradation process (oxidation fish ponds/lagoons). A total of 31 target steroid hormones were detected in the wastewater of the two swine farms, with concentrations ranging from 0.12 ng/L (medroxyprogesterone acetate, MPA) to 11,200 ng/L (5α-dihydroprogesterone, 5α-DHP). A total of 22 target steroid hormones were detected in feces, of which 19 were detected in Farm LC and 17 in Farm ST. Some of these detected steroids were synthetic chemicals, which might be parent chemicals from exogenous addition or their metabolites, or transformation products from other natural steroids. The steroids excretion of sows in swine farms were estimated, with some steroids such as androstenedione (AED, 41.5 μg/d), epiandrosterone (EADR, 268 μg/d), progesterone (P, 661 μg/d), and 5α-DHP (982μg/d) having much higher values than those from human bodies. Both WTSs in the swine farms could effectively remove the target steroid hormones, with the removal rates of most targets exceeding 90%. In comparison, the anaerobic digester-A2/O (anaerobic-anoxic-oxic)-lagoon system performed better in removing steroids than the up-flow anaerobic sludge reaction bed (UASB)-two-stage series (A/O)2-oxidation fish ponds system. However, there were still 22 steroid hormones, including 14 synthetic ones detected in the effluent, with the risk quotients of most synthetic steroids exceeding 1, showing high risks to aquatic organisms. The findings from this study showed that there is a wide presence of steroid hormones, especially some synthetic steroids in animal wastes, posing potential ecological risks, and these steroids should be removed before discharge to the environment.

Histological Effect of Androgenic Anabolic Steroids on Liver

Abstract: Anabolic androgenic steroids (AAS) they are the synthetic type of the natural male sex hormone(testosterone), they are widespread used amongst athletes to enhance performance. Abuse of AAS is commonamongst players and it is usually accompanied by a many medically based complications. It was reportedthat hepatic problems include cholestasis, elevation of liver enzymes e.g. aminotransferases, as well as,benign hepatic adenomas, jaundice and to less extent of hepatocellular carcinoma was associated with theiruse.A total of (12) adult New Zealand rabbits (Oryctolagus cuniculus) male, aged one year was selected. 2control animals and 10 were treated with injections intramuscularly of the AAS, nandrolone decanoate(15 mg/kg) three times a week for 12 weeks. At the end of experiment the animals were sacrificed and theliver was dissected out and fixed using 10% buffered formalin-saline to prepare blocks for staining withhaematoxylin and eosin for histological examination using the light microscope.The liver of treated animals reveals that there are a mild to severe vascular congestion. There is swelling ofhepatocytes, and inflammatory cell infiltration. Perivascular fibrosis, cellular necrosis was observed in otherslides with sinusoidal congestions and extrabiliary bile pigments deposits.The benefit of AAS comes with unwanted side effects. The total volume of the hepatocytes and sinusoidswere increased in the studied animals. The total number of hepatocytes nuclei in experimental group alsoincreased. The damage of the liver cells or at least increased permeability of the hepatocellular membranewhich is noticed in the present work could explain the increment of plasma levels of liver enzymeswhich was studied by other researchers, as they notice an elevation liver enzymes activity such as alanineaminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AP), gamma glutamyltranspeptidase (GGT), and lactate dehydrogenase(LDH)..Patients and physicians must kept in mind that the sequelae of AAS abuse are life threatening. So peopleshould be aware about the complications of AAS use and a periodic examination of liver function and checkout should be done to those treated groups.

Monosex male formation of juvenile redclaw crayfish using natural steroid hormone from gamma sea cucumber and different doses of honey bee

In a new commercial commodity aquaculture, tropical freshwater crayfish Cherax quadricarinatus, it is known that female has a slower growth rate than male. One way to increase production rate is through monosex cultures comprising all-male population by using genital reversion technique. This biotechnology method can be applied by using hormones and natural products. The natural hormones extracted from gamma sea cucumber, Stichopus variegatus has bioactive substances including steroid compounds, while honey bee contains chrysin compounds that act as aromatase inhibitors. Therefore, the combination of both substances expected can increase in testosterone level and accelerate production in the male monosex population of juvenile crayfish. The purpose of the study is to determine the most effective dose of honey bee in masculinization of juvenile freshwater crayfish combined with 2 mg. L−1 steroid extract of gamma sea cucumber. Furthermore, a Completely Randomized Design (CRD) was designed in the experiment with five different dose of honey bee treatment and dipping method in 2 mg. L−1 steroid extract of gamma sea cucumber for 18 h. Each treatment with four replications. The highest male formation was found in the dose of 20 ml. L− 1 honey bee at 83.75% and the lowest was in control. The present of honey bee at different doses in 2 mg. L−1 of gamma steroid extract did not significantly give an effect on percentage of female, intersex formation, survival, and growth rate of juvenile redclaw crayfish.

Association between menopausal hormone therapy and risk of neurodegenerative diseases: Implications for precision hormone therapy.

IntroductionThe impact of menopausal hormone therapy (HT) on age‐associated Alzheimer's and neurodegenerative diseases (NDDs) remains unresolved. To determine the effect of HT, formulation, type, and duration on risk of NDDs, a retrospective analysis was performed using a 10‐year Humana claims dataset.MethodsStudy population included women aged 45 years or older with or without claim records of HT medications. Patients diagnosed with NDDs including Alzheimer's disease (AD), Parkinson's disease (PD), dementia, multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS) were identified. Relative risk (RR) ratios and 95% confidence intervals (CI) for combined NDDs, or AD, PD, dementia, MS, and ALS were determined. Cumulative hazard ratios were determined to investigate the association between HT and NDDs at different age groups.ResultsIn 379,352 women with or without claim records of HT, use of HT was associated with significantly reduced risk for combined NDDs (RR 0.42, 95% CI 0.40–0.43, P < 0.001). Average follow‐up time was 5.1 [2.3] years. Formulations containing natural steroids 17β‐estradiol and/or progesterone were associated with greater reduction in NDD risk. Oral‐ HT users showed significantly reduced RRs (0.42, 0.41–0.44, P < 0.001) for combined NDDs compared to non‐HT users. The RRs for transdermal‐HT users were significantly decreased for all‐cause dementia (0.73, 0.60–0.88, P = 0.001) and MS (0.55, 0.36–0.84, P = 0.005). Greatest reduction in risk of NDD, AD, and dementia emerged in patients aged 65 years or older. Further, the protective effect of long‐term therapy (>1 year) on combined NDDs, AD, PD, and dementia was greater compared to short‐term therapy (≤1 year).DiscussionHT was associated with reduced risk of all NDDs including AD and dementia, with greater duration of therapy and natural steroid formulations associated with greater efficacy. These findings advance precision HT to prevent NDDs including AD.

Natural steroid-based cationic copolymers cholesterol/diosgenin-r-PDMAEMAs and their pDNA nanoplexes: impact of steroid structures and hydrophobic/hydrophilic ratios on pDNA delivery.

Using natural-based lipids to construct biocompatible, controllable and efficient nanocarriers and elucidating their structure–function relationships, was regarded as an important area for creating sustainable biomaterials. Herein, we utilized two natural steroids: cholesterol and diosgenin (bearing different hydrophobic tails) as the building blocks, to synthesize a series of natural steroid-based cationic random copolymers PMA6Chol-r-PDMAEMA and PMA6Dios-r-PDMAEMA via RAFT polymerization. The results demonstrated that the steroid-r-PDMAEMA copolymers could efficiently bind pDNA (N/P < 3.0) and then form near-spherical shape (142–449 nm) and positively-charged (+11.5 to +19.6 mV) nanoparticles. The in vitro cytotoxicity and gene transfection efficiency greatly depend on the steroid hydrophobic tail structures and steroid/PDMAEMA block ratios. Optimum transfection efficiency of the (Chol-P1/pDNA and Dios-P3/pDNA) nanoplexes could reach to 18.1–31.2% of the PEI-25K/pDNA complex. Moreover, all of the steroid-r-PDMAEMA/Cy3-pDNA nanoplexes have an obvious “lysosome localization” effect, indicating the steroid structures do not remarkably influence the intracellular localization behaviors of these nanoplexes.

Dioscin Improves Pyroptosis in LPS-Induced Mice Mastitis by Activating AMPK/Nrf2 and Inhibiting the NF-κB Signaling Pathway.

Dioscin, a natural steroid saponin, has been shown to have anti-inflammatory effects, but its protective mechanism against mastitis is still unknown. NLRP3 inflammasome and pyroptosis play important roles in the pathogenesis of many inflammatory diseases, including mastitis. The purpose of this study was to explore the effect of dioscin on lipopolysaccharide- (LPS-) induced mastitis in vivo and in vitro and its mechanism of action. In vivo experiments, dioscin can reduce the inflammatory lesions and neutrophil motility in mammary tissue. Moreover, dioscin also can reduce the production of proinflammatory factors such as interleukin-1 beta (IL-1β) and inhibit the activation of NLRP3 inflammasome in LPS-induced mice mastitis. In vitro experiments, the results showed that dioscin inhibited the inflammatory response and the activation of NLRP3 inflammasome, but the survival rate of mouse mammary epithelial cells (mMECs) induced by LPS+ATP is increased. Subsequently, the experiment convinces that dioscin can reduce LPS+ATP-induced mMEC pyroptosis by adding Ac-DEVD-CHO (a caspase-3 inhibitor). Further mechanistic studies demonstrate that dioscin can activate AMPK/Nrf2 to inhibit NLRP3/GSDMD-induced mMEC pyroptosis. In summary, this paper reveals a novel function of dioscin on mMEC pyroptosis and provides a new potential therapy of dioscin for the treatment and prevention of mastitis.

Phenylhydrazone and Quinazoline Derivatives from the Cold-Seep-Derived Fungus Penicillium oxalicum

Three new phenylhydrazones, penoxahydrazones A–C (compounds 1–3), and two new quinazolines, penoxazolones A (compound 4) and B (compound 5), with unique linkages were isolated from the fungus Penicillium oxalicum obtained from the deep sea cold seep. Their structures and relative configurations were assigned by analysis of 1D/2D NMR and mass spectroscopic data, and the absolute configurations of 1, 4, and 5 were established on the basis of X-ray crystallography or ECD calculations. Compound 1 represents the first natural phenylhydrazone-bearing steroid, while compounds 2 and 3 are rarely occurring phenylhydrazone tautomers. Compounds 4 and 5 are enantiomers that feature quinazoline and cinnamic acid units. Some isolates exhibited inhibition of several marine phytoplankton species and marine-derived bacteria.

Inhibition of SARS-CoV-2 by Highly Potent Broad-Spectrum Anti-Coronaviral Tylophorine-Based Derivatives.

Tylophorine-based compounds and natural cardiotonic steroids (cardenolides and bufadienolides) are two classes of transmissible gastroenteritis coronavirus inhibitors, targeting viral RNA and host cell factors, respectively. We tested both types of compounds against two types of coronaviruses, to compare and contrast their antiviral properties, and with view to their further therapeutic development. Examples of both types of compounds potently inhibited the replication of both feline infectious peritonitis virus and human coronavirus OC43 with EC50 values of up to 8 and 16 nM, respectively. Strikingly, the tylophorine-based compounds tested inhibited viral yields of HCoV-OC43 to a much greater extent (7–8 log magnitudes of p.f.u./ml) than the cardiotonic steroids (about 2–3 log magnitudes of p.f.u./ml), as determined by end point assays. Based on these results, three tylophorine-based compounds were further examined for their anti-viral activities on two other human coronaviruses, HCoV-229E and SARS-CoV-2. These three tylophorine-based compounds inhibited HCoV-229E with EC50 values of up to 6.5 nM, inhibited viral yields of HCoV-229E by 6–7 log magnitudes of p.f.u./ml, and were also found to inhibit SARS-CoV-2 with EC50 values of up to 2.5–14 nM. In conclusion, tylophorine-based compounds are potent, broad-spectrum inhibitors of coronaviruses including SARS-CoV-2, and could be used for the treatment of COVID-19.

Reevaluation of the contributions of reactive intermediates to the photochemical transformation of 17β-estradiol in sewage effluent

Photodegradation of the natural steroid 17β-estradiol (E2), an endocrine-disrupting hormone that has been widely detected in aquatic environments, was investigated in wastewater effluents at various pH ranges under simulated solar irradiation. The rate of E2 degradation in the sewage effluents was stable at pH 6.0-7.0 but suddenly increased from pH 8.0-10.0. The second-order reaction rate constants of E2 with 3EfOM* and CO3•− were measured to increase 11.0-fold and 18.0-fold from pH 6.0 to 10.0, respectively. Two main reasons are proposed for this sharp increase. First, the change in the ionization state of E2 made it susceptible to oxidation by triplet-state effluent organic matter (3EfOM*) and carbonate radicals (CO3•−). Second, the steady-state concentration of CO3•− increased with increasing pH. Indirect photolysis was suggested to be the main degradation pathway in the sewage effluents, and 3EfOM* was proposed to play a major role at pH 8.0-9.0, while CO3•− played a significant role at pH 10.0. In this study, EfOM was shown for the first time to inhibit the oxidation of E2 initiated by 3EfOM* and CO3•−. Thus, we suggest that EfOM plays a dual role in the photodegradation of E2: EfOM can not only be activated as 3EfOM* to degrade E2 but also can inhibit the degradation of E2 by reducing the E2 oxidation intermediate back to E2. The estrogenic activity of the photodegradation products was also studied. The in vitro estrogenic activity of E2 solutions decreased approximately as fast as the E2 photodegradation occurred in the effluent water at various pH values, suggesting that solar photodegradation in sewage effluents reduces the risk of endocrine disruption in waters impacted by E2 and subject to continuing inputs. The results of this study are important for predicting the environmental fate of endocrine-disrupting chemicals and developing methods for their removal from aquatic environments.

HMGB-1/RAGE signaling inhibition by dioscin attenuates hippocampal neuron damage induced by oxygen-glucose deprivation/reperfusion.

Cerebral ischemia is one of the most common clinical diseases characterized by high morbidity and mortality. Neurocyte apoptosis and a cascade of inflammatory signals following cerebral ischemia-reperfusion injury (IRI) may contribute to secondary brain damage, resulting in severe neurological damage. It has been reported that dioscin, a natural steroid saponin, exerts anti-inflammatory properties against different diseases. The present study aimed to investigate the role of dioscin in oxygen-glucose deprivation/reperfusion (OGD/R) induction in hippocampal cells in vitro and in vivo. For the in vitro study, hippocampal cells were collected from rat embryos of gestational age of E18. The oxygen-glucose deprivation model in primary hippocampal neurons was used to mimic cerebral IRI in vitro. To select the optimum dioscin concentration and acting time, cell viability was evaluated by a Cell Counting Kit-8 (CCK-8) assay. Neurons subjected to OGD/R were treated with dioscin and the inflammatory cytokines, high mobility group box chromosomal protein 1 (HMGB-1)/receptor for advanced glycation end products (RAGE) signaling molecules and apoptosis-associated genes were determined. The intracellular reactive oxygen species (ROS) generation was detected. Furthermore, the effects of dioscin on the antioxidant defense mechanisms were evaluated by measuring the activity of glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT) and the glutathione (GSH)/glutathione disulphide (GSSG) ratio. In addition, OGD/R-induced cells were transfected with pcDNA3.1-HMGB-1 and treated with dioscin, and the neuronal cell apoptosis rate was determined using a terminal deoxynucleotidyl transferase-mediated 2-deoxyuridine 5-triphosphate-biotin nick-end labeling (TUNEL) assay. The mRNA and protein expression levels of the inflammatory factors were measured using real-time quantitative polymerase chain reaction (RT-qPCR) and western blot analysis, respectively. For the in vivo investigation, the oxidation and anti-oxidation system in rat hippocampal tissue was evaluated by detecting the expression of the aforementioned oxidative stress-associated proteins, 3-NT as well as 8-oxo-deoxyguanosine (8-OHdG). In the hippocampal region, the apoptotic rate was determined using a TUNEL assay. The results demonstrated that dioscin at a dose of 400 ng/ml significantly reversed the increase in the expression levels of the inflammatory factors and attenuated those of apoptotic cytokines induced by OGD/R. Additionally, dioscin notably reversed the OGD/R-mediated activation of the HMGB-1/RAGE signaling pathway in vitro and in vivo. Cell treatment with dioscin significantly attenuated ROS production and increased the activity of antioxidant enzymes. Additionally, increasing the expression of HMGB-1 inhibited the protective effects of dioscin on cell apoptosis in the OGD/R-induced neurons. Furthermore, HMGB-1 overexpression reversed the antiapoptotic and anti-inflammatory effects of dioscin on neurons. The results of the present study indicated that dioscin exerted anti-inflammatory, antiapoptotic and antioxidant effects via the HMGB-1/RAGE signaling pathway. These results suggest a novel perspective of the protective effects of dioscin as a prospective remedial factor for IRI.

Roles of brassinosteroids in plant growth and abiotic stress response

Brassinosteroids (BRs) are widely used class of natural steroidal plant hormones. BRs take part in the regulation of growth and development of plants, maintaining BRs homeostasis, and allowing adaptation to environmental changes through the life cycle. They also play an important role in abiotic stress responses such as drought, salinity, high temperature, low temperature and heavy metal stresses. Through the signal transduction pathway, BRs interact with a variety of transcription factors via a series of phosphorylation cascades to regulate the expression of BR target genes. Thus, they regulate the various growth and development processes of plants. BRs crosstalk with different hormones to regulate plant physiology and development. This review primarily introduces the signaling pathways of BRs, their role in regulating plant growth and development, abiotic stresses, and their interaction with other plant hormones at the transcriptional and post-transcriptional levels. Our review of this topic will provide a complete reference for the study and utilization of BRs in the future.

A review on steroid dimers: 2011–2019

The first review article on steroid dimers by Li and Dias in 1997, followed by the second review and a book on steroid dimers by Nahar and Sarker in 2007 and 2012, respectively, covered steroid dimers reported until the end of 2010. Since then, there have been considerable amounts of research carried out on steroid dimers, prompting the need for another comprehensive review on this topic. Therefore, this present review appraises the literature published during the period 2011–2019 on various aspects of steroid dimers, including isolation from natural sources, synthesis and applications. A structured and systematic literature search was performed, using the key words: steroid dimer, steroidal dimer, dimeric steroid, bis-steroid, bis-steroidal conjugates, molecular umbrella, cephalostatins, ritterazines and crellastatins. Several databases like Web of Knowledge, Science Direct, PubMed and Google Scholar were consulted. During the period covered in this review, well over 200 new synthetic steroidal dimers, ring A-ring A connection being the major group, have been reported, only one natural steroid dimer has been isolated, and potential applications of steroid dimers in the treatment of cancers and tumors, and microbial infections have been indicated.

An Update of the Occurrence of Organic Contaminants of Emerging Concern in the Canary Islands (Spain)

Nowadays, activities associated with industries, cities, and leisure generate a number of different wastes, including many chemical pollutants that enter the environment and negatively affect the wildlife. Some of them are emerging organic contaminants (EOCs), which include UV filters and stabilizers, antineoplastic agents, and natural and synthetic steroid hormones, among others. It is well demonstrated that the presence of this kind of contaminants may produce adverse effects in aquatic environments and also in marine organisms. Even though the Canary Islands (Spain) are one of the most biodiverse parts of the temperature regions of the world, little is known about the presence of these substances in the environment and organisms in the archipelago. For that purpose, the objective of this work was to evaluate the presence of some UV filters, cytostatic compounds, and hormones in water (wastewater and seawater), sediments, and marine organisms. Moreover, we evaluated conventional and natural wastewater treatment plants (WWTPs) to study the removal efficiencies of these target compounds. UV filters and stabilizers were found in all the analysed samples and were the only target family found in seawater (with UV-329 appearing at all the locations at concentrations between 67.5 and 859 ng L−1). Some cytostatic compounds were detected in hospital wastewater at concentrations between 375.8 and 1851 ng L−1, but not in the analysis of sludge or fish samples. Hormones were detected in wastewater, sludge, and fish samples, and their removal in the natural treatment system (over 76% for all the hormones) allowed to prove it as an efficient technology for the elimination of these EOCs from urban wastewaters in small communities.

Conversion of Estrone to 17β-Estradiol: A Potential Confounding Factor in Assessing Risks of Environmental Estrogens to Fish.

Feminization of male fish and the role of endocrine-active chemicals in this phenomenon has been an area of intense study for many years. Estrone (E1), a natural steroid, is found in aquatic environments sometimes at high concentrations relative to the estrogenic steroids 17β-estradiol (E2) and 17α-ethynylestradiol. However, E1 has been less thoroughly studied than E2 or 17α-ethynylestradiol due in part to a relatively lower potency in metabolically limited estrogen receptor (ER) binding/activation assays. Recent evidence suggests that in vivo biotransformation of E1 to E2 may occur in fathead minnows (Pimephales promelas) residing in environments with high concentrations of E1, such as near wastewater treatment plants. The enzymes likely responsible for this biotransformation, 17β-hydroxysteroid dehydrogenases (17βHSDs), have been well characterized in mammals but to a lesser extent in fish species. In the present study, a novel systematic analysis of amino acid sequence data from the National Center for Biotechnology Information database demonstrated that multiple 17βHSD isoforms are conserved across different fish species. Experimentally, we showed that metabolically active hepatic cytosolic preparations from 2 commercially important salmonid species, rainbow trout and lake trout, biotransformed E1 to E2 to a degree sufficient to alter results of competitive ER binding assays. These results from in silico and in vitro analyses indicate that E1 and biotransformation may play a significant role in adverse effects on development and reproduction of a variety of fish species in contaminated aquatic environments. Environ Toxicol Chem 2020;39:2028-2040. Published 2020. This article is a US Government work and is in the public domain in the USA.

Separation and HPLC Characterization of Active Natural Steroids in a Standardized Extract from the Serratula coronata Herb with Antiseborrheic Dermatitis Activity.

Phytoecdysteroids are natural compounds with therapeutic benefits in both humans and animals. The effectiveness of natural products with health potential is based on the activities and potencies of their active ingredients. In this study, dominant ecdysteroids—ajugasterone C, 20-hydroxyecdysone and polypodine B—from the Serratula coronata (S. coronata) herb were separated by column chromatography, identified by spectroscopic data and quantified by high-performance liquid chromatography with a diode array detector (HPLC-DAD). The obtained concentration of ecdysteroids (approximately 23%) in the S. coronatae herb extract enhances the possibility of their use in pharmaceutical and cosmetic products with high levels of phytoecdysteroids. Moreover, this study has shown a positive effect of ecdysteroids-containing cream on changes in quality of life and a beneficial effect in reducing the symptoms of seborrheic dermatitis. It has been demonstrated that the application of the cream with phytoecdysteroids resulted in a statistically significant alleviation of symptoms (p < 0.05), especially in terms of itching, pain or burning sensations in the affected areas in comparison to previous symptoms.

Dioscin Attenuates Interleukin 1β (IL-1β)-Induced Catabolism and Apoptosis via Modulating the Toll-Like Receptor 4 (TLR4)/Nuclear Factor kappa B (NF-κB) Signaling in Human Nucleus Pulposus Cells.

BackgroundNucleus pulposus (NP) cell dysfunction and apoptosis contribute to disc degeneration. Dioscin, a natural steroid saponin, has been demonstrated to have anti-inflammatory, antiapoptotic, and antioxidative effects in various diseases. However, little is known about the roles of dioscin in intervertebral disc degeneration.Material/MethodsTo evaluate the roles of dioscin in disc degeneration and its specific mechanism, human NP cells were incubated with IL-1β and various concentrations of dioscin. Cell viability, extracellular matrix protein expression, catabolic factors, degree of apoptosis, inflammatory factors, and related signaling pathways were evaluated by western blotting, fluorescence immunostaining, TUNEL staining, and reverse transcription PCR.ResultsDioscin inhibited IL-1β-activated apoptotic signaling and catabolic activity in NP cells. Dioscin suppressed TLR4/NF-0κB signaling, and attenuated the level of inflammatory mediators (IL-6, TNF-α) in IL-1β-stimulated human NP cells.ConclusionsOur work provides the first evidence that dioscin attenuates IL-1β-activated inflammation and catabolic activity in human NP cells through inhibiting the TLR4/NF-κB pathway, indicating that dioscin is a new potential candidate for clinical therapy to attenuate disc degeneration.

Occurrence and distribution of natural and synthetic progestins, androgens, and estrogens in soils from agricultural production areas in China

The occurrence of biologically potent sex hormones in agricultural soils is of growing concern due to their ability to disrupt the endocrine systems of aquatic organisms after being transported to surface waters via runoff. This study, therefore, examined the large-scale occurrence of 34 natural and synthetic sex hormones (13 progestins, 16 androgens, and 5 estrogens) in soils from 7 provinces and 1 municipality in China. The target sex hormones were detected in 99.3% of the soil samples, indicating their widespread occurrence in most agricultural areas. Additionally, seven synthetic progestins were detected in soils for the first time. The total concentration of the 34 sex hormones (Σsex hormones) in the sampled soils ranged from below the method detection limit to 23.7 ng/g (mean of 4.72 ± 4.07 ng/g), with androgens and progestins being the most dominant hormone groups. Significant correlations were observed among the concentrations of Σestrogens, Σandrogens, and Σprogestins (r = 0.117–0.433, p < 0.001), suggesting similar sources of sex hormones. The mean concentration of Σsex hormones varied considerably across the selected provinces/municipality. Notably, the annual slaughter of poultry and swine (R2 = 0.75–0.88), female population (R2 = 0.57–0.58), and soil organic carbon content (R2 = 0.20–0.55) in each province were significantly correlated with the concentrations or mean concentrations of Σsex hormones, Σestrogens, or Σprogestins. This finding implies that these parameters contributed to the occurrence and distribution of sex hormones in the studied soils. Finally, risk quotients for some sex hormones exceeded 0.01, indicating medium or high risks to agroecosystems. This study highlights the importance of designing an optimal manure fertilization strategy in order to mitigate the risks posed by sex hormones in agroecosystems.

A photochemical dehydrogenative strategy for aniline synthesis.

Chemical reactions that reliably join two molecular fragments together (cross-couplings) are essential to the discovery and manufacture of pharmaceuticals and agrochemicals1,2. The introduction of amines onto functionalized aromatics at specific and pre-determined positions (ortho versus meta versus para) is currently achievable only in transition-metal-catalysed processes and requires halogen- or boron-containing substrates3-6. The introduction of these groups around the aromatic unit is dictated by the intrinsic reactivity profile of the method (electrophilic halogenation or C-H borylation) so selective targeting of all positions is often not possible. Here we report a non-canonical cross-coupling approach for the construction of anilines, exploiting saturated cyclohexanones as aryl electrophile surrogates. Condensation between amines and carbonyls, a process that frequently occurs innature andis often used by (bio-)organic chemists7, enables a predetermined and site-selective carbon-nitrogen (C-N) bond formation, while a photoredox- and cobalt-based catalytic system progressively desaturates the cyclohexene ring en route to the aniline. Given that functionalized cyclohexanones are readily accessible with complete regiocontrol using thewell established carbonyl reactivity, this approach bypasses some of the frequent selectivity issues of aromatic chemistry. We demonstrate the utility of this C-N coupling protocol by preparing commercial medicines and by the late-stage amination-aromatization of natural products, steroids and terpene feedstocks.