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

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, boswelli...

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Main Authors: Mohamed A. Morsy, Snehal S. Patel, Azza A. K. El-Sheikh, Jignasa K. Savjani, Anroop B. Nair, Jigar N. Shah, Katharigatta N. Venugopala
Format: Article
Language:English
Published: Wiley 2019-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2019/3041438
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author Mohamed A. Morsy
Snehal S. Patel
Azza A. K. El-Sheikh
Jignasa K. Savjani
Anroop B. Nair
Jigar N. Shah
Katharigatta N. Venugopala
author_facet Mohamed A. Morsy
Snehal S. Patel
Azza A. K. El-Sheikh
Jignasa K. Savjani
Anroop B. Nair
Jigar N. Shah
Katharigatta N. Venugopala
author_sort Mohamed A. Morsy
collection DOAJ
description 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.
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spelling doaj-art-69de5f7462984aaeb6ee4a29a916a30d2025-02-03T06:08:09ZengWileyMediators of Inflammation0962-93511466-18612019-01-01201910.1155/2019/30414383041438Computational and Biological Comparisons of Plant Steroids as Modulators of Inflammation through Interacting with Glucocorticoid ReceptorMohamed A. Morsy0Snehal S. Patel1Azza A. K. El-Sheikh2Jignasa K. Savjani3Anroop B. Nair4Jigar N. Shah5Katharigatta N. Venugopala6Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi ArabiaDepartment of Pharmacology, Institute of Pharmacy, Nirma University, Ahmedabad, Gujarat 382 481, IndiaDepartment of Pharmacology, Faculty of Medicine, Minia University, El-Minia 61511, EgyptDepartment of Pharmaceutical Chemistry, Institute of Pharmacy, Nirma University, Ahmedabad, Gujarat 382 481, IndiaDepartment of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi ArabiaDepartment of Pharmaceutics, Institute of Pharmacy, Nirma University, Ahmedabad, Gujarat 382 481, IndiaDepartment of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi ArabiaDespite 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.http://dx.doi.org/10.1155/2019/3041438
spellingShingle Mohamed A. Morsy
Snehal S. Patel
Azza A. K. El-Sheikh
Jignasa K. Savjani
Anroop B. Nair
Jigar N. Shah
Katharigatta N. Venugopala
Computational and Biological Comparisons of Plant Steroids as Modulators of Inflammation through Interacting with Glucocorticoid Receptor
Mediators of Inflammation
title Computational and Biological Comparisons of Plant Steroids as Modulators of Inflammation through Interacting with Glucocorticoid Receptor
title_full Computational and Biological Comparisons of Plant Steroids as Modulators of Inflammation through Interacting with Glucocorticoid Receptor
title_fullStr Computational and Biological Comparisons of Plant Steroids as Modulators of Inflammation through Interacting with Glucocorticoid Receptor
title_full_unstemmed Computational and Biological Comparisons of Plant Steroids as Modulators of Inflammation through Interacting with Glucocorticoid Receptor
title_short Computational and Biological Comparisons of Plant Steroids as Modulators of Inflammation through Interacting with Glucocorticoid Receptor
title_sort computational and biological comparisons of plant steroids as modulators of inflammation through interacting with glucocorticoid receptor
url http://dx.doi.org/10.1155/2019/3041438
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