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

Mohamed A Morsy,Jigar N Shah,Azza A K El-Sheikh,Jignasa K Savjani,Snehal S Patel,Katharigatta N Venugopala,Anroop B Nair

doi:10.1155/2019/3041438

Abstract

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.

Highlights

Glucocorticoids are indispensable pharmacological products employed in the treatment of various diseases, including cancers, autoimmune disorders, bronchial asthma, anaphylaxis, and adrenal insufficiency [1]
Using the enzyme-linked immunosorbent assay (ELISA) technique, our results showed that the rats challenged with cotton pellet-induced granuloma had significantly elevated levels of the proinflammatory markers, IL-6 and tumor necrosis factor-α (TNF-α), as compared to normal control group (Figures 3(a) and 3(b), respectively)
WA: positive control (PC) treated with withaferin A; PC-DG: PC treated with diosgenin; PC-FC: PC treated with fluticasone

Summary

Introduction

Glucocorticoids are indispensable pharmacological products employed in the treatment of various diseases, including cancers, autoimmune disorders, bronchial asthma, anaphylaxis, and adrenal insufficiency [1]. These drugs’ usage in treatment of diverse unrelated diseases arises from the abundance of their receptor, the glucocorticoid receptor (GR). Many pharmacological products were developed to take advantage of GR as a therapeutic target, including fluticasone that is considered a highly selective substrate of GR, with long duration of action reaching up to twenty-four hours due to its receptor fast association/slow dissociation properties [3]. Despite the high therapeutic efficacy of glucocorticoids in treating different disorders, they might cause several side effects, including the increased susceptibility to infections [4] and adrenal insufficiency [5].

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