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Mediators Inflamm. 2019 May 27;2019:3041438. doi: 10.1155/2019/3041438. eCollection 2019.

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

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Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia.
Department of Pharmacology, Faculty of Medicine, Minia University, El-Minia 61511, Egypt.
Department of Pharmacology, Institute of Pharmacy, Nirma University, Ahmedabad, Gujarat 382 481, India.
Basic Health Sciences Department, Faculty of Medicine, Princess Nourah bint Abdulrahman University, Riyadh 11671, Saudi Arabia.
Department of Pharmaceutical Chemistry, Institute of Pharmacy, Nirma University, Ahmedabad, Gujarat 382 481, India.
Department of Pharmaceutics, Institute of Pharmacy, Nirma University, Ahmedabad, Gujarat 382 481, India.
Department of Biotechnology and Food Technology, Durban University of Technology, Durban 4000, South Africa.


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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