scholarly journals Modelling the glucocorticoid receptor and producing therapeutic agents with anti-inflammatory effects but reduced side-effects

2007 ◽  
Vol 92 (2) ◽  
pp. 299-309 ◽  
Author(s):  
Andrew McMaster ◽  
David William Ray
Keyword(s):  
Side Effects ◽  
Glucocorticoid Receptor ◽  
Therapeutic Agents ◽  
Anti Inflammatory

scholarly journals Computational and Biological Comparisons of Plant Steroids as Modulators of Inflammation through Interacting with Glucocorticoid Receptor

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Mohamed A. Morsy ◽  
Snehal S. Patel ◽  
Azza A. K. El-Sheikh ◽  
Jignasa K. Savjani ◽  
Anroop B. Nair ◽  
...  
Keyword(s):  
Side Effects ◽  
Glucocorticoid Receptor ◽  
Tumor Necrosis ◽  
Serum Levels ◽  
Withaferin A ◽  
Boswellic Acid ◽  
Cotton Pellet ◽  
Anti Inflammatory ◽  
Necrosis Factor

Despite the usefulness of glucocorticoids, they may cause hazardous side effects that limit their use. Searching for compounds that are as equally efficient as glucocorticoids, but with less side effects, the current study compared plant steroids, namely, glycyrrhetinic acid, guggulsterone, boswellic acid, withaferin A, and diosgenin with the classical glucocorticoid, fluticasone. This was approached both in silico using molecular docking against glucocorticoid receptor (GR) and in vivo in two different animal models. All tested compounds interacted with GR, but only boswellic acid and withaferin A showed docking results comparable to fluticasone, as well as similar in vivo anti-inflammatory effects, by significantly decreasing serum levels of interleukin-6 and tumor necrosis factor-α in cotton pellet-induced granuloma in rats. In addition, both compounds significantly decreased the percent of change in ear weight in croton oil-induced ear edema in mice and the granuloma weight in cotton pellet-induced granuloma in rats, to levels comparable to that of fluticasone. Both boswellic acid and withaferin A had no effect on adrenal index, but only withaferin A significantly increased the thymus index. In conclusion, boswellic acid may have comparable anti-inflammatory effects to fluticasone with fewer side effects.

scholarly journals A selective glucocorticoid receptor modulator attenuates lung inflammation and improves alveolarization in a neonatal rat model of bronchopulmonary dysplasia

2021 ◽  
Author(s):  
Shoichi Ishikawa ◽  
Tohru Ogihara ◽  
Shigeo Yamaoka ◽  
Jun Shinohara ◽  
Shigeru Kawabata ◽  
...  
Keyword(s):  
Side Effects ◽  
Glucocorticoid Receptor ◽  
Bronchopulmonary Dysplasia ◽  
Lung Inflammation ◽  
Inflammatory Cells ◽  
Mrna Levels ◽  
Compound A ◽  
Receptor Modulator ◽  
Anti Inflammatory ◽  
Tgf Β1

ABSTRACTBackgroundBronchopulmonary dysplasia (BPD) is a major problem for extremely preterm infants. Glucocorticoids effectively treat BPD; however, they have many side effects. Compound A (Cpd A) is a nonsteroidal Selective Glucocorticoid Receptor Modulator (SEGRM) that acts as a glucocorticoid receptor ligand without inducing the expression of glucocorticoid-response element-driven genes. Cpd A reportedly has anti-inflammatory properties with fewer side effects than glucocorticoids.MethodsUsing a bleomycin (Bleo)-induced BPD model, we evaluated the therapeutic effects of Cpd A. 0-day-old Sprague-Dawley rats were administered Bleo for 10 days and treated with dexamethasone (Dex) or Cpd A from day 0 to 13. We evaluated lung pathology by histology and the mRNA levels of interleukin (IL)-1β, transforming growth factor (TGF)-β1 and chemokines, CXCL1 and CCL2.ResultsBleo-treated mice had lungs with impaired alveolarization. Dex and Cpd A treatments improved the alveolar structure, attenuating the lung injury. Bleo-exposed lungs had increased inflammatory cells recruitment and inflammatory mediator mRNA levels. Cpd A treatment reduced inflammatory cells infiltration and CXCL1, CCL2 and TGF-β1 expression.ConclusionCpd A improved lung inflammation and alveolar maturation arrest, and restored histological and biochemical changes in a model of BPD. SEGRMs, including Cpd A, are promising candidates for the therapy of BPD.Impact Statement○What is the key message of your article?Compound A decreased lung inflammation and improved lung morphometric changes in Bleomycin-exposed lungs.○What does it add to the existing literature?Compound A has anti-inflammatory effects in an experimental model of BPD.○What is the impact?SEGRMs, including Cpd A, may be promising candidates for the therapy of BPD.

scholarly journals Ginsenoside Rg1 Acts as a Selective Glucocorticoid Receptor Agonist with Anti-Inflammatory Action without Affecting Tissue Regeneration in Zebrafish Larvae

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1107
Author(s):  
Min He ◽  
Mahmoud Halima ◽  
Yufei Xie ◽  
Marcel J. M. Schaaf ◽  
Annemarie H. Meijer ◽  
...  
Keyword(s):  
Side Effects ◽  
Glucocorticoid Receptor ◽  
Tissue Regeneration ◽  
Drug Effects ◽  
Structural Similarity ◽  
Ginsenoside Rg1 ◽  
Zebrafish Larvae ◽  
Wide Range ◽  
Ability To Regenerate ◽  
Anti Inflammatory

Glucocorticoids are effective anti-inflammatory drugs, but their clinical use is complicated due to the wide range of side effects they induce. Patients requiring glucocorticoid therapy would benefit from more selective glucocorticoid receptor (GR) agonists, capable of attenuating the immune response without causing these side effects. Ginsenosides, such as the compound Rg1, are natural plant compounds with structural similarity to classical glucocorticoids and well-documented anti-inflammatory effects. Here, we have investigated the activity of the ginsenoside Rg1 using a zebrafish larval model, in which amputation of the tail fin allows us to assess drug effects on inflammation, while the ability to regenerate the wounded tissue serves as a readout for side effects. We found that Rg1 attenuates neutrophilic inflammation at the amputation site, similarly to a classical glucocorticoid, beclomethasone. Mutation of the Gr abolishes this anti-inflammatory effect of Rg1. Rg1 and beclomethasone differentially modulate gene expression, suggesting that Rg1 induces transrepression, but not transactivation, activity of Gr. Interestingly, we found no effect of Rg1 on tissue regeneration, whereas beclomethasone inhibits tissue regeneration entirely. We conclude that Rg1 is a promising candidate for development as a selective glucocorticoid drug, and that zebrafish larvae provide a useful model system for screening of such GR agonists.

scholarly journals Selective Glucocorticoid Receptor Modulator: A Novel Class of Anti-inflammatory Compounds

2020 ◽  
pp. 55-66
Author(s):  
Mujahid A. Alsulaimani ◽  
Mahmoud Alsulaimani
Keyword(s):  
Side Effects ◽  
Glucocorticoid Receptor ◽  
Beneficial Effect ◽  
Target Genes ◽  
The Other ◽  
Physiological Effects ◽  
Receptor Modulator ◽  
Wide Range ◽  
Anti Inflammatory ◽  
High Degree

Background: Glucocorticoids exert a wide range of physiological effects. They  effectively control various inflammatory and autoimmune diseases and play an important role in organ transplantation. Glucocorticoids are associated with unfavorable side effects that restrict their utilization. The most undesirable side effects are related to the transactivation of target genes. On the other hand, the transrepression of the genes is also responsible for the anti-inflammatory and immunomodulator of glucocorticoids. Principal Findings: The separation between these two processes through alteration in glucocorticoid receptor resulting in a compound with similar GCs benefit activity with fewer side effects. This review will discuss the molecular mechanism and summarizes the most common compounds and their beneficial effect in preclinical experiments. Conclusion: Several compounds that possess this feature are tested in preclinical experiments with promising results. These compounds are expected to be a better alternative to GCs drugs in the management of different diseases with a high degree of effectiveness.

scholarly journals The glucocorticoid receptor in inflammatory processes: transrepression is not enough

2015 ◽  
Vol 396 (11) ◽  
pp. 1223-1231 ◽  
Author(s):  
Sabine Hübner ◽  
Lien Dejager ◽  
Claude Libert ◽  
Jan P. Tuckermann
Keyword(s):  
Side Effects ◽  
Glucocorticoid Receptor ◽  
Term Treatment ◽  
Disease Models ◽  
Side Effect Profile ◽  
Inflammatory Mechanism ◽  
Long Term Treatment ◽  
Inflammatory Processes ◽  
Anti Inflammatory

Abstract Glucocorticoids (GCs) are the most commonly used anti-inflammatory agents to treat inflammatory and immune diseases. However, steroid therapies are accompanied by severe side-effects during long-term treatment. The dogma that transrepression of genes, by tethering of the glucocorticoid receptor (GR) to DNA-bound pro-inflammatory transcription factors, is the main anti-inflammatory mechanism, is now challenged. Recent discoveries using conditional GR mutant mice and genomic approaches reveal that transactivation of anti-inflammatory acting genes is essential to suppress many inflammatory disease models. This novel view radically changes the concept to design selective acting GR ligands with a reduced side-effect profile.

A Brief Review on the Development of Novel Potentially Active Azetidin-2-ones Against Cancer

2020 ◽  
Vol 24 (5) ◽  
pp. 473-486 ◽  
Author(s):  
Ligia S. da Silveira Pinto ◽  
Thatyana R. Alves Vasconcelos ◽  
Claudia Regina B. Gomes ◽  
Marcus Vinícius N. de Souza
Keyword(s):  
Side Effects ◽  
Anticancer Agents ◽  
Heterocyclic Compounds ◽  
Biological Activities ◽  
Present Review ◽  
Pharmacological Properties ◽  
Important Group ◽  
Wide Range ◽  
Anti Inflammatory

Azetidin-2-ones (β-lactams) and its derivatives are an important group of heterocyclic compounds that exhibit a wide range of pharmacological properties such as antibacterial, anticancer, anti-diabetic, anti-inflammatory and anticonvulsant. Efforts have been made over the years to develop novel congeners with superior biological activities and minimal potential for undesirable side effects. The present review aimed to highlight some recent discoveries (2013-2019) on the development of novel azetidin-2-one-based compounds as potential anticancer agents.

Nanotechnological Innovations Enhancing the Topical Therapeutic Efficacy of Quercetin: A Succinct Review

2020 ◽  
Vol 17 (4) ◽  
pp. 270-278
Author(s):  
Maha Nasr ◽  
Rawan Al-Karaki
Keyword(s):  
Side Effects ◽  
Therapeutic Efficacy ◽  
Skin Permeation ◽  
Skin Penetration ◽  
Topical Delivery ◽  
Natural Compounds ◽  
Therapeutic Activity ◽  
Dermatological Diseases ◽  
Anti Inflammatory ◽  
Topical Applications

Nanotechnology is currently a hot topic in dermatology and nutraceutical/cosmeceutical delivery, owing to the advantages it provides in terms of enhancing the skin permeation of drugs, as well as increasing their therapeutic efficacy in the treatment of different dermatological diseases. There is also a great interest in the topical delivery of nutraceuticals; which are natural compounds with both therapeutic and cosmetic benefits, in order to overcome the side effects of topically applied chemical drugs. Quercetin is a key nutraceutical with topical antioxidant and anti-inflammatory properties which was reported to be effective in the treatment of different dermatological diseases, however, its topical therapeutic activity is hindered by its poor skin penetration. This review highlights the topical applications of quercetin, and summarizes the nanocarrier-based solutions to its percutaneous delivery challenges.

Anti-inflammatory Glycosylated Flavonoids as Therapeutic Agents for Treatment of Diabetes-Impaired Wounds

2015 ◽  
Vol 15 (23) ◽  
pp. 2456-2463 ◽  
Author(s):  
Marilena Antunes-Ricardo ◽  
Janet Gutierrez-Uribe ◽  
Sergio Serna-Saldivar
Keyword(s):  
Therapeutic Agents ◽  
Treatment Of Diabetes ◽  
Anti Inflammatory
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