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Fulltext Timosaponin AIII promotes non-small-cell lung cancer ferroptosis through targeting and facilitating HSP90 mediated GPX4 ubiquitination and degradation

Zhou C, Yu T, Zhu R, Lu J, Ouyang X, Zhang Z, et al.

Int J Biol Sci, 2023;19(5):1471-1489.
PMID: 37056925 DOI: 10.7150/ijbs.77979

Timosaponin AIII (Tim-AIII), a steroid saponin, exhibits strong anticancer activity in a variety of cancers, especially breast cancer and liver cancer. However, the underlying mechanism of the effects of Tim-AIII-mediated anti-lung cancer effects remain obscure. In this study, we showed that Tim-AIII suppressed cell proliferation and migration, induced G2/M phase arrest and ultimately triggered cell death of non-small cell lung cancer (NSCLC) cell lines accompanied by the release of reactive oxygen species (ROS) and iron accumulation, malondialdehyde (MDA) production, and glutathione (GSH) depletion. Interestingly, we found that Tim-AIII-mediated cell death was reversed by ferroptosis inhibitor ferrostatin-1 (Fer-1). Meanwhile, the heat shock protein 90 (HSP90) was predicted and verified as the direct binding target of Tim-AIII by SwissTargetPrediction (STP) and surface plasmon resonance (SPR) assay. Further study showed that Tim-AIII promoted HSP90 expression and Tim-AIII induced cell death was blocked by the HSP90 inhibitor tanespimycin, indicating that HSP90 was the main target of Tim-AIII to further trigger intracellular events. Mechanical analysis revealed that the Tim-AIII-HSP90 complex further targeted and degraded glutathione peroxidase 4 (GPX4), and promoted the ubiquitination of GPX4, as shown by an immunoprecipitation, degradation and in vitro ubiquitination assay. In addition, Tim-AIII inhibited cell proliferation, induced cell death, led to ROS and iron accumulation, MDA production, GSH depletion, as well as GPX4 ubiquitination and degradation, were markedly abrogated when HSP90 was knockdown by HSP90-shRNA transfection. Importantly, Tim-AIII also showed a strong capacity of preventing tumor growth by promoting ferroptosis in a subcutaneous xenograft tumor model, whether C57BL/6J or BALB/c-nu/nu nude mice. Together, HSP90 was identified as a new target of Tim-AIII. Tim-AIII, by binding and forming a complex with HSP90, further targeted and degraded GPX4, ultimately induced ferroptosis in NSCLC. These findings provided solid evidence that Tim-AIII can serve as a potential candidate for NSCLC treatment.

Matched MeSH terms: Steroids/pharmacology
Fulltext Steroid therapy in obstructive airway diseases

Zainudin BMZ

Respirology, 1997 Mar;2(1):17-31.
PMID: 9424402 DOI: 10.1111/j.1440-1843.1997.tb00051.x

Asthma and chronic obstructive pulmonary disease (COPD) are two common illnesses that cause significant morbidity and mortality. Steroids are widely used in both conditions. They act through steroid or glucocorticoid receptors (GR) causing up or down regulation of protein synthesis resulting in an increase in lipocortin 1 and beta 2 adrenergic receptors, and decreased levels and activities of cytokines or cytokine receptors, which reduces the inflammatory process in the airways and decreases bronchial hyperreactivity. Consequently symptoms of airway obstruction are alleviated and lung function is improved. In asthma, steroids have been convincingly shown to be effective in the treatment of both acute exacerbations and chronic condition. In COPD, however, only a subset of patients seem to respond favourably to steroid therapy. Therapeutic trials are therefore recommended before committing to a long-term treatment in order to determine this subset of patients, as no markers of steroid responsiveness can be identified. The inhaled steroids currently available have a good safety profile with significant side effects occurring only occasionally. Such side effects are usually confined to the oropharynx, causing local irritation, candidiasis and dysphonia, which can be easily overcome. Biochemical abnormalities involving bone, adrenal, carbohydrate and lipid profiles have been noted with high doses of inhaled steroids; however, these have no significant clinical effects.

Matched MeSH terms: Steroids/adverse effects; Steroids/therapeutic use*
Fulltext Toxic keratouveitis secondary to Euphorbia lactea sap: a case report

Yihui Goh, Pooi Wah Lott, Sujaya Singh

Malaysian Journal of Medicine and Health Sciences, 2020;16(3):328-330.
MyJurnal

A 42-year-old gentleman presented with left eye pain after accidental contact with Euphorbia lactea sap while gar- dening. At presentation, left eye best-corrected visual acuity (BCVA) was 20/30. Ocular examination revealed left eye conjunctiva congestion and cornea abrasion. Eye symptoms and BCVA deteriorated over 12 hours. Cornea showed diffuse stromal oedema with presence of anterior uveitis. A diagnosis of toxic keratouveitis was made. He was treat- ed with intensive topical steroids, cycloplegics, lubricants, prophylactic antibiotics and oral non-steroidal anti-in- flammatory analgesic. Patient achieved complete resolution two weeks later. We aim to raise awareness among the ophthalmologists to detect and manage these injuries.

Matched MeSH terms: Steroids
Fulltext DARS-associated leukoencephalopathy can mimic a steroid-responsive neuroinflammatory disorder

Wolf NI, Toro C, Kister I, Latif KA, Leventer R, Pizzino A, et al.

Neurology, 2015 Jan 20;84(3):226-30.
PMID: 25527264 DOI: 10.1212/WNL.0000000000001157

To describe the expanding clinical spectrum of a recently described hereditary leukoencephalopathy, hypomyelination with brainstem and spinal cord involvement and leg spasticity, which is caused by mutations in the aspartyl tRNA-synthetase encoding gene DARS, including patients with an adolescent onset.

Matched MeSH terms: Steroids/therapeutic use*
Fulltext Treatment of MOG antibody associated disorders: results of an international survey

Whittam DH, Karthikeayan V, Gibbons E, Kneen R, Chandratre S, Ciccarelli O, et al.

J Neurol, 2020 Dec;267(12):3565-3577.
PMID: 32623595 DOI: 10.1007/s00415-020-10026-y

INTRODUCTION: While monophasic and relapsing forms of myelin oligodendrocyte glycoprotein antibody associated disorders (MOGAD) are increasingly diagnosed world-wide, consensus on management is yet to be developed.
OBJECTIVE: To survey the current global clinical practice of clinicians treating MOGAD.
METHOD: Neurologists worldwide with expertise in treating MOGAD participated in an online survey (February-April 2019).
RESULTS: Fifty-two responses were received (response rate 60.5%) from 86 invited experts, comprising adult (78.8%, 41/52) and paediatric (21.2%, 11/52) neurologists in 22 countries. All treat acute attacks with high dose corticosteroids. If recovery is incomplete, 71.2% (37/52) proceed next to plasma exchange (PE). 45.5% (5/11) of paediatric neurologists use IV immunoglobulin (IVIg) in preference to PE. Following an acute attack, 55.8% (29/52) of respondents typically continue corticosteroids for ≥ 3 months; though less commonly when treating children. After an index event, 60% (31/51) usually start steroid-sparing maintenance therapy (MT); after ≥ 2 attacks 92.3% (48/52) would start MT. Repeat MOG antibody status is used by 52.9% (27/51) to help decide on MT initiation. Commonly used first line MTs in adults are azathioprine (30.8%, 16/52), mycophenolate mofetil (25.0%, 13/52) and rituximab (17.3%, 9/52). In children, IVIg is the preferred first line MT (54.5%; 6/11). Treatment response is monitored by MRI (53.8%; 28/52), optical coherence tomography (23.1%; 12/52) and MOG antibody titres (36.5%; 19/52). Regardless of monitoring results, 25.0% (13/52) would not stop MT.
CONCLUSION: Current treatment of MOGAD is highly variable, indicating a need for consensus-based treatment guidelines, while awaiting definitive clinical trials.

Matched MeSH terms: Steroids
Phytochemistry, cytotoxicity and antiviral activity of Catharanthus roseus

Wahab NZA, Azizul A, Ibrahim N

Iran J Microbiol, 2020 Oct;12(5):460-465.
PMID: 33604002 DOI: 10.18502/ijm.v12i5.4608

Background and Objectives: Catharanthus roseus is generally used to treat many diseases in folklore remedies. The present study is aimed at determining phytochemical constituents, cytotoxicity and antiviral activities for crude extract of the plant.
Materials and Methods: The whole plant of C. roseus was extracted using methanol extraction method. Phytochemical qualitative screening was carried out for C. roseus extract according to standard procedures used to test for the presence of alkaloid, saponin, terpenoid and steroid. Cytotoxicity was assessed using 3-(4,5-dimethylthiazol-2,5-diphenyltetrazolium bromide (MTT) assay. Plaque reduction assays were carried out to evaluate the antiviral activity of C. roseus extract against herpes simplex virus type 1 (HSV-1). These include post-treatment, pre-treatment and virucidal assays.
Results: C. roseus extract contain secondary metabolites such as alkaloid, saponin and terpenoid but does not contain steroid. Cytotoxicity screening against Vero cells using MTT assay showed that the CC50 values for crude extract of C. roseus was 0.5 mg/mL. The extract prepared from C. roseus possesses phytochemical compound that was non-cytotoxic to the cell with potential antiviral activity. Plaque reduction assays against herpes simplex virus type 1 (HSV-1) showed that the selective indices (SI = CC50 / EC50) of C. roseus extract in post-treatment, pre-treatment and virucidal assays were 36, 20 and 4.7 respectively. The results revealed that the extract prepared from C. roseus possesses phytochemical compound that was non-cytotoxic to the cell with potential antiviral activity.
Conclusion: This study showed that C. roseus extract has promising potential to be explored as anti-HSV-1 agent regardless of the mode of treatment.

Matched MeSH terms: Steroids
Fulltext A Case Report of Steroid Withdrawal Syndrome

Wahab F, Rahman RA, Yaacob LH, Noor NM, Draman N

Korean J Fam Med, 2020 Sep;41(5):359-362.
PMID: 32961047 DOI: 10.4082/kjfm.18.0181

We report a case of steroid withdrawal syndrome in a 74-year-old woman who was suspected of having an occult exogenous Cushing's syndrome secondary to prolonged traditional complementary medicine use. She presented with non-specific symptoms of lethargy, malaise, and poor oral intake with weight loss for 1 month, and investigations showed suboptimal 9 AM cortisol level. She has responded well to steroid replacement.

Matched MeSH terms: Steroids
Steroids from Dysoxylum grande (Meliaceae) leaves

Wah LK, Abas F, Cordell GA, Ito H, Ismail IS

Steroids, 2013 Feb;78(2):210-9.
PMID: 23178158 DOI: 10.1016/j.steroids.2012.09.011

Seven new 23-oxo-cholestane derivatives named as grandol A (1), B (2), C (3), D (4), E (5), F (6), and G (7) were isolated from Dysoxylum grande leaves alongside with a new 3,4-secodammar-4(28)-en-3-oic acid derivative (8). The structures of the compounds were elucidated based on the interpretation of spectroscopic data, and their relative configurations were established by NOESY 2D NMR data. All of the isolates were tested for anti-acetylcholinesterase activity using thin layer chromatography (TLC)-bioautography with fast blue B salt. Only grandol A (1) and B (2) showed positive results, with clear discoloration at a concentration of 12.5 ppm. However, the obtained IC(50) values for grandol A and B, when using Ellman's method, were not significant (>200 μg/ml).

Matched MeSH terms: Steroids/isolation & purification*; Steroids/chemistry
Fulltext CORRELATION BETWEEN TPC AND TFC WITH ANTIOXIDANT ACTIVITY OF Piper sarmentosum EXTRACT AND ITS FORMULATION FOR COSMETIC PURPOSES

WAN ASIAH WAN SUKAIRI, LAILI CHE ROSE, ASNUZILAWATI ASARI, RAZIFAH MOHD RAZALI

UMT Journal of Undergraduate Research, 2021;3(2):51-60.
MyJurnal

This study investigates the characteristics of an antioxidant cream made from the methanol extract of Piper sarmentosum leaves, which is locally known as the wild betel or pokok kadok in Malay. The secondary metabolites of the leaves were subjected to phytochemical tests to detect the presence of natural compounds. Antioxidant activity was described by its total phenolic content (TPC) and total flavonoid content (TFC), which was assessed by 2,2-Diphenyl-1-picrylhydrazyl (DPPH) assay. A phase diagram was constructed to find a possible region to formulate an antioxidant cream. In phytochemical screening, the methanolic extract showed positive presence of alkaloids, flavonoids, steroids, terpenoids and tannins. In quantitative analysis of antioxidative components, besides having significantly higher TFC content compared with quercetin (P

Matched MeSH terms: Steroids
Fulltext Editorial: Steroids and the Brain

Ubuka T, Trudeau VL, Parhar I

Front Endocrinol (Lausanne), 2020;11:366.
PMID: 32582033 DOI: 10.3389/fendo.2020.00366
Matched MeSH terms: Steroids/physiology*
Fulltext Status epilepticus as the initial presentation of antibody-negative Goodpasture's syndrome

Ting IP, Abdul Halim S, Adnan A, Jaafar H

BMJ Case Rep, 2017 Aug 01;2017.
PMID: 28765179 DOI: 10.1136/bcr-2017-219628

Goodpasture's syndrome is a rare pulmonary-renal disease. It is characterised by presence of auto-antibodies directed against the glomerular basement membrane (GBM) antigen. These antibodies that bind to the GBM antigens cause rapidly progressive glomerulonephritis. The alveolar basement membrane also contains similar antigen, leading to pulmonary haemorrhage in active disease. We report a case of a young man who initially presented with status epilepticus and later was found to have rapidly progressive glomerulonephritis with pulmonary haemorrhage. Serum anti-GBM antibody was negative but the renal biopsy confirmed the diagnosis by showing typical linear IgG along the GBM on immunofluorescent study. He was treated with plasmapheresis and high-dose steroid in combination with oral cyclophosphamide. His renal function normalised after treatment.

Matched MeSH terms: Steroids/administration & dosage; Steroids/therapeutic use
Fulltext CD80 Insights as Therapeutic Target in the Current and Future Treatment Options of Frequent-Relapse Minimal Change Disease

Teh YM, Lim SK, Jusoh N, Osman K, Mualif SA

Biomed Res Int, 2021;2021:6671552.
PMID: 33506028 DOI: 10.1155/2021/6671552

Minimal change disease (MCD) is the most common cause of idiopathic nephrotic syndrome in children, and it is well known for its multifactorial causes which are the manifestation of the disease. Proteinuria is an early consequence of podocyte injury and a typical sign of kidney disease. Steroid-sensitive patients react well with glucocorticoids, but there is a high chance of multiple relapses. CD80, also known as B7-1, is generally expressed on antigen-presenting cells (APCs) in steroid-sensitive MCD patients. Various glomerular disease models associated with proteinuria demonstrated that the detection of CD80 with the increase of urinary CD80 was strongly associated closely with frequent-relapse MCD patients. The role of CD80 in MCD became controversial because one contradicts finding. This review covers the treatment alternatives for MCD with the insight of CD80 as a potential therapeutic target. The promising effectiveness of CD20 (rituximab) antibody and CD80 inhibitor (abatacept) encourages further investigation of CD80 as a therapeutic target in frequent-relapse MCD patients. Therapeutic-based antibody towards CD80 (galiximab) had never been investigated in MCD or any kidney-related disease; hence, the role of CD80 is still undetermined. A new therapeutic approach towards MCD is essential to provide broader effective treatment options besides the general immunosuppressive agents with gruesome adverse effects.

Matched MeSH terms: Steroids
Fulltext Nocardia kroppenstedtii: a rare pathogen isolated from the spinal vertebral abscess of a patient on long-term immunosuppressive therapy

Tay ST, Wong PL, Chiu CK, Tang SN, Lee JL, Hamdan NW, et al.

Eur Rev Med Pharmacol Sci, 2021 01;25(2):605-608.
PMID: 33577013 DOI: 10.26355/eurrev_202101_24618

OBJECTIVE: Nocardia kroppenstedtii was isolated from the spinal vertebral abscess of a 78-year-old patient presenting with mid-thoracic pain and bilateral lower limb weakness and numbness. The patient was on long-term immunosuppressive therapy with steroids for underlying autoimmune hemolytic anemia. Investigations showed a T5 pathological fracture and vertebra plana with the erosion of the superior and inferior endplates. There was evidence of paraspinal collection from the T4-T6 vertebrae with an extension into the spinal canal. Analysis of Nocardia 16S rRNA (99.9%, 1395/1396 nt) and secA1 gene (99.5%, 429/431 nt) fragments showed the highest sequence similarity with Nocardia kroppenstedtii type strain (DQ157924), and next with Nocardia farcinica (Z36936). The patient was treated with intravenous carbapenem and oral trimethoprim-sulfamethoxazole for four weeks, followed by another six months of oral trimethoprim-sulfamethoxazole. Despite the improvement of neurological deficits, the patient required assistive devices to ambulate at discharge. This study reports the first isolation of N. kroppenstedtii from the spinal vertebral abscess of a patient from Asia. Infections caused by N. kroppenstedtii may be underdiagnosed as the bacterium can be misidentified as N. farcinica in the absence of molecular tests in the clinical laboratory.

Matched MeSH terms: Steroids/therapeutic use
Fulltext Childhood-Onset Systemic Lupus Erythematosus: Southeast Asian Perspectives

Tang SP, Lim SC, Arkachaisri T

J Clin Med, 2021 Feb 03;10(4).
PMID: 33546120 DOI: 10.3390/jcm10040559

Childhood onset systemic lupus erythematosus is a rare disease that is more common amongst Southeast Asian children compared to the West. It is typified by a peripubertal onset and a female preponderance, which increases with advancing age. Organs commonly involved at diagnosis include haematological, renal, and mucocutaneous. Fever, malar rash, and cutaneous vasculitis are common. Lupus nephritis is typically proliferative especially Class IV and contributes to both disease activity and damage. Antinuclear antibody and anti-dsDNA positivity are both prevalent in this region. Disease activity is higher than Western cohorts at onset but responds to therapy reducing to low disease activity by six months. However, organ damage occurs early and continues to accumulate over the time, a consequence of both active disease (neurological and renal systems) and steroid-related complications especially in the eye (cataract and glaucoma) and musculoskeletal systems (avascular necrosis). Infections remain the leading cause of death and mortality in this region is highly variable contributed by the heterogeneity in social economic status, healthcare access, and availability of paediatric rheumatology expertise in the region.

Matched MeSH terms: Steroids
Dengue maculopathy: a case report

Tan SY, Kumar G, Surrun SK, Ong YY

Travel Med Infect Dis, 2007 Jan;5(1):62-3.
PMID: 17161325

Dengue fever is endemic in many countries of South East Asia. In spite of the occasional epidemics, dengue maculopathy remains a rare entity.

Matched MeSH terms: Steroids/therapeutic use
Ab-Externo Implantation of XEN Gel Stent for Refractory Steroid-Induced Glaucoma After Lamellar Keratoplasty

Tan SY, Md Din N, Mohd Khialdin S, Wan Abdul Halim WH, Tang SF

Cureus, 2021 Feb 12;13(2):e13320.
PMID: 33738163 DOI: 10.7759/cureus.13320

The hazy corneal donor-recipient interface after corneal transplant may cause difficulties when implanting the XEN gel stent via ab-interno approach. We aim to describe XEN gel stent implantation via ab-externo approach in refractory steroid-induced glaucoma after corneal lamellar keratoplasty. Under local anaesthesia, the XEN injector needle was inserted 7 mm behind the limbus with the bevel facing up, directly beneath the conjunctiva and advanced to the marked 2.5 mm scleral entry wound. The needle then pierced the sclera until the needle tip was just visible in the anterior chamber (AC). The slider was pushed until the tip of the XEN stent was seen in the AC. The needle was slowly withdrawn while still pushing the slider to complete stent deployment. Subconjunctival Mitomycin C 0.01% (30 µg/0.3 mL) was then injected posterior to the bleb. Three eyes of three patients with steroid-induced glaucoma after lamellar keratoplasty underwent XEN gel stent implantation via ab-externo approach placed at the superotemporal quadrant. Pre-operatively, all patients had uncontrolled IOP between 30-45 mmHg despite maximum medications and selective laser trabeculoplasty. After XEN gel stent implantation, IOP ranged between 10-17 mmHg with one or two topical antiglaucoma at 12 months. Complications include hypotony maculopathy, stent migration and hyphaema, all of which were successfully managed. Corneal graft remained clear at 12 months. XEN gel stent implantation via ab-externo approach is able to achieve good intraocular pressure (IOP) control without compromising cornea graft in patients with steroid-induced glaucoma after lamellar keratoplasty at 12 months.

Matched MeSH terms: Steroids
Fulltext Clinical practice with steroid therapy for Duchenne muscular dystrophy: An expert survey in Asia and Oceania

Takeuchi F, Nakamura H, Yonemoto N, Komaki H, Rosales RL, Kornberg AJ, et al.

Brain Dev, 2020 Mar;42(3):277-288.
PMID: 31980267 DOI: 10.1016/j.braindev.2019.12.005

BACKGROUND: Several studies on clinical practice for Duchenne muscular dystrophy (DMD) have been conducted in Western countries. However, there have been only a few similar studies in Asia and Oceania. Here, we investigate the steroid therapy-related clinical practice for DMD among the local experts. In 2015, we conducted a DMD expert survey in Asia and Oceania to acquire information regarding patients with DMD and to assess current clinical practice with the cooperation of Asian and Oceanian Myology Centre, a neuromuscular disease research network.
RESULTS: We obtained survey responses from 87 out of 148 clinicians (62%) from 13 countries and regions. In China, 1385 DMD patients were followed-up by 5 respondent neurologists, and 84% were between 0 and 9 years of age (15% were 10-19 years, 1% > 19 years). While in Japan, 1032 patients were followed-up by 20 clinicians, and the age distribution was similar between the 3 groups (27% were 0-9 years, 35% were 10-19 years, 38% were >19 years). Most respondent clinicians (91%) were aware of DMD standard of care recommendations. Daily prednisolone/prednisone administration was used most frequently at initiation (N = 45, 64%). Inconsistent opinion on steroid therapy after loss of ambulation and medication for bone protection was observed.
CONCLUSIONS: Rare disease research infrastructures have been underdeveloped in many of Asian and Oceanian countries. In this situation, our results show the snapshots of current medical situation and clinical practice in DMD. For further epidemiological studies, expansion of DMD registries is necessary.

Matched MeSH terms: Steroids/therapeutic use*
Fulltext Bee bread mitigates downregulation of steroidogenic genes, decreased spermatogenesis, and epididymal oxidative stress in male rats fed with high-fat diet

Suleiman JB, Abu Bakar AB, Noor MM, Nna VU, Othman ZA, Zakaria Z, et al.

Am J Physiol Endocrinol Metab, 2021 Sep 01;321(3):E351-E366.
PMID: 34229480 DOI: 10.1152/ajpendo.00093.2021

The pituitary-gonadal axis plays an important role in steroidogenesis and spermatogenesis, and by extension, fertility. The aim of this study was to investigate the protective role of bee bread, a natural bee product, against obesity-induced decreases in steroidogenesis and spermatogenesis. Thirty-two adult male Sprague-Dawley rats weighing between 200 and 300 g were divided into four groups (n = 8/group), namely: normal control (NC), high-fat diet (HFD), HFD plus bee bread administered concurrently for 12 wk (HFD + B), HFD plus orlistat administered concurrently for 12 wk (HFD + O) groups. Bee bread (0.5 g/kg) or orlistat (10 mg/kg/day) was suspended in distilled water and given by oral gavage daily for 12 wk. Levels of follicle-stimulating hormone, luteinizing hormone, testosterone, and adiponectin, as well as sperm count, motility, viability, normal morphology, and epididymal antioxidants decreased, whereas levels of leptin, malondialdehyde, and sperm nDNA fragmentation increased significantly in the HFD group relative to the NC group. There were significant decreases in the testicular mRNA transcript levels of androgen receptor, luteinizing hormone receptor, steroidogenic acute regulatory protein, cytochrome P450 enzyme, 3β-hydroxysteroid dehydrogenase (HSD) and 17β-HSD in the testes of the HFD group. Furthermore, mount, intromission and ejaculatory latencies increased, and penile cGMP level decreased significantly in the HFD group. Supplementation with bee bread significantly reduced leptin level and increased adiponectin level, enhanced sperm parameters and reduced sperm nDNA fragmentation, upregulated the levels of steroidogenic genes and proteins in HFD-induced obese male rats. Bee bread improved steroidogenesis and spermatogenesis by upregulating steroidogenic genes. Therefore, bee bread may be considered as a potential supplementation to protect against infertility in overweight men or men with obesity.NEW & NOTEWORTHY The high-fat diet utilized in the present study induced obesity in the male rats. Bee bread supplementation mitigated impaired steroidogenesis, spermatogenesis, mating behavior, and fertility potential by counteracting the downregulation of steroidogenic genes, thus increasing testosterone levels and suppressing epididymal oxidative stress. These benefits may be due to the abundance of phenolic and flavonoid compounds in bee bread.

Matched MeSH terms: Steroids/metabolism*
Evaluation of the possible role of glucose, carnitine, coenzyme Q10 and steroids in the treatment of Reye's syndrome using the margosa oil animal model

Sinniah D, Sinniah R, Baskaran G, Pathmanathan R, Yamashita F, Yoshino M

Acta Paediatr Jpn, 1990 Aug;32(4):462-8.
PMID: 2288230

Glucose and steroids have been used in the treatment of children with Reye's syndrome, while carnitine and coenzyme Q10 have been the subject of some recent studies which suggest that these agents may have a role in the treatment of Reye's syndrome and Reye-like syndrome due to margosa oil poisoning. Because of the paucity of causes of Reye's syndrome seen at any one centre, the clinical variability of the disease, and limited knowledge of definite aetiologic factors, controlled clinical trials are not easy to carry out or to interpret in human cases. These caveats were overcome by evaluation of these four treatment modalities in an established margosa-oil-induced animal model of Reye's syndrome. Effectiveness of the treatment modalities was determined from clinical response and histopathologic parameters (grading of light microscopic fatty changes and ultrastructural changes in the hepatocytes). Results show that carnitine per se produces a small improvement in survival, but statistically, more significant benefit is seen with glucose administration. Carnitine plus 10% dextrose appears to produce better results. Evaluation of coenzyme Q10 and carnitine on histopathologic parameters in the liver after a sublethal dose of margosa oil showed no obvious ameliorating effect on liver pathology. Steroids (dexamethasone/methylprednisolone) had no beneficial effects in reducing mortality, affecting glycogen storage or lipid accumulation. Changes in the mitochondria, ribosomes and endoplasmic reticulum were unaltered from the groups treated with margosa oil alone. While glucose and carnitine supplements appear to be beneficial, the other modes of therapy do not seem to hold much promise in the treatment of Reye-like syndrome in the margosa-oil-induced animal model.

Matched MeSH terms: Steroids/therapeutic use*
In-vitro and in-silico anti-HSV-1 activity of a marine steroid from the jellyfish Cassiopea andromeda venom

Shamsian S, Nabipour I, Mohebbi G, Baghban N, Zare M, Zandi K, et al.

Microb Pathog, 2024 Jan;186:106486.
PMID: 38056601 DOI: 10.1016/j.micpath.2023.106486

In this study, we investigated the potential in vitro anti-HSV-1 activities of the Cassiopea andromeda jellyfish tentacle extract (TE) and its fractions, as well as computational work on the thymidine kinase (TK) inhibitory activity of the identified secondary metabolites. The LD50, secondary metabolite identification, preparative and analytical chromatography, and in silico TK assessment were performed using the Spearman-Karber, GC-MS, silica gel column chromatography, RP-HPLC, LC-MS, and docking methods, respectively. The antiviral activity of TE and the two purified compounds Ca2 and Ca7 against HSV-1 in Vero cells was evaluated by MTT and RT-PCR assays. The LD50 (IV, mouse) values of TE, Ca2, and Ca7 were 104.0 ± 4, 5120 ± 14, and 197.0 ± 7 (μg/kg), respectively. They exhibited extremely effective antiviral activity against HSV-1. The CC50 and MNTD of TE, Ca2, and Ca7 were (125, 62.5), (25, 12.5), and (50, 3.125) μg/ml, respectively. GC-MS analysis of the tentacle extract revealed seven structurally distinct chemical compositions. Four of the seven compounds had a steroid structure. According to the docking results, all compounds showed binding affinity to the active sites of both thymidine kinase chains. Among them, the steroid compound Pregn-5-ene-3,11-dione, 17,20:20,21 bis [methylenebis(oxy)]-, cyclic 3-(1,2-ethane diyl acetal) (Ca2) exhibited the highest affinity for both enzyme chains, surpassing that of standard acyclovir. In silico data confirmed the experimental results. We conclude that the oxosteroid Ca2 may act as a potent agent against HSV-1.

Matched MeSH terms: Steroids/pharmacology

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