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

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


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.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / therapeutic use
  • Croton Oil / toxicity
  • Diosgenin / therapeutic use
  • Ear Diseases / blood
  • Ear Diseases / chemically induced
  • Ear Diseases / drug therapy*
  • Ear Diseases / metabolism*
  • Edema / blood
  • Edema / chemically induced
  • Edema / drug therapy
  • Edema / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Glycyrrhetinic Acid / therapeutic use
  • Inflammation / chemically induced
  • Inflammation / drug therapy*
  • Inflammation / immunology
  • Inflammation / metabolism*
  • Interleukin-6 / blood
  • Mice
  • Molecular Docking Simulation
  • Phytosterols / therapeutic use*
  • Pregnenediones / therapeutic use
  • Rats
  • Receptors, Glucocorticoid / metabolism*
  • Software
  • Thymus Gland / drug effects
  • Thymus Gland / metabolism
  • Triterpenes / therapeutic use
  • Tumor Necrosis Factor-alpha / blood
  • Withanolides / therapeutic use


  • Anti-Inflammatory Agents
  • Interleukin-6
  • Phytosterols
  • Pregnenediones
  • Receptors, Glucocorticoid
  • Triterpenes
  • Tumor Necrosis Factor-alpha
  • Withanolides
  • boswellic acid
  • Croton Oil
  • pregna-4,17-diene-3,16-dione
  • Diosgenin
  • withaferin A
  • Glycyrrhetinic Acid