Flavanones from Sorghum bicolor selectively inhibit COX-2: in-silico and in-vivo validation

Abstract

Abstract Background COX-2-specific inhibitors offer improved advantages over traditional NSAIDs. Plants are known to play critical roles in the discovery and developments of new pharmaceuticals. To the best of our knowledge, nothing has been reported so far on the selective inhibition of the cyclooxygenase by flavanones. The present study aims at evaluating the selective inhibition of COX-1 and/or COX-2 by flavanones from Sorghum bicolor. Results Flavanones demonstrate selective inhibition of COX-2 through the formation of hydrogen bonds. Eriodictyol forms two hydrogen bonds interactions (Tyr-371 and Ser-516) within the active site of COX-2, while it forms only one hydrogen bond (Met-521) with COX-1. Sorghum bicolor flavanone extract (SBFE) demonstrate hepatoprotective potentials by augmenting the antioxidant defense system of the liver and downregulate the expression of COX-2 while ineffective against COX-1. Histopathological analyses show that SBFE is effective in the prevention of HCl/ethanol-induced gastric injury in Wistar rats. Conclusions The side effects associated with current NSAIDs are as a result of selective inhibition of COX-1. Flavanones are potential selective inhibitors of COX-2. Sorghum bicolor flavanone extract (SBFE) demonstrates its anti-inflammatory potential through selective inhibition of COX-2. The virtual high throughput screening techniques adopted herein could help eradicate the corresponding rigors of identifying lead bioactive(s) components of plants. Graphical abstract

Keywords

• Molecular docking
• Virtual high throughput screening (vHTS)
• Eriodictyol
• Anti-inflammation
• Cyclooxygenase-1 (COX-1)
• Cyclooxygenase-2 (COX-2)