Fig. 1.

COX and POX reactions are catalyzed by coxibs and quercetin-like natural plant compounds, respectively. COX-2 catalyzes arachidonic acid conversion to PGG₂ by the COX activity site. The POX activity site of COX-2 reduces PGG₂ to PGH₂. Downstream prostaglandin products are formed from PGH₂ via different synthases. The COX activity site of COX-2 but not the POXsite is inhibited by COX-2–selective inhibitors called coxibs. The labels of coxibs must carry a “black box” warning due to adverse cardiovascular events. Quercetin-like natural plant compounds decrease the risk of cardiovascular disease and serve as activators and cofactors of COX-2 to reduce the cardiotoxicity of coxibs by binding to the POX site