Characterization of β-Sitosterol for Potential Selective GR Modulation

Background: Although glucocorticoids (GCs) are characterized as powerful agents to treat inflammatory afflictions, they are accompanied by metabolic side effects which limit their usage. β-Sitosterol, as a minor component found in extraction of vegetable oil, was reported to have anti-inflammatory effects in RAW 264.7 cells. Objective: To test whether β-sitosterol has an effect to dissociate transrepression from transactivation as a selective novel GR binder, this work evaluated the dissociated characteristics of β-sitosterol. Methods: The probable binding interaction between β-sitosterol and GR was explored by molecular docking. The GR transcriptional activity of β-sitosterol was assessed in the reporter gene assay. The ability of β-sitosterol to modulate the transactivation and transrepression of GR was evaluated by real-time quantitative PCR analysis. Results and Discussion: In the present study, β-sitosterol treatment cannot induce GR-mediated transactivation. β-Sitosterol exerted a potential to inhibited the expression of GR target transrepressed gene without activating the expression of GR transactivation dependent gene. Molecular docking demonstrated that β-Sitosterol was able to bind the ligand binding domain of GR but unable to induce GR activation. Conclusion: This work offers evidence that β-sitosterol may serve as a selective GR modulator.