The antipyretic potential
of viscosine, a natural product isolated from the medicinal plant
Dodonaea viscosa
, was investigated using yeast-induced
pyrexia rat model, and its structure–activity relationship
was investigated through molecular docking analyses with the target
enzymes cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), and microsomal
prostaglandin E synthase-1 (mPGES-1). The in vivo antipyretic experiments
showed a progressive dose-dependent reduction in body temperatures
of the hyperthermic test animals when injected with viscosine. Comparison
of docking analyses with target enzymes showed strongest bonding interactions
(binding energy −17.34 kcal/mol) of viscosine with the active-site
pocket of mPGES-1. These findings suggest that viscosine shows antipyretic
properties by reducing the concentration of prostaglandin E
2
in brain through its mPGES-1 inhibitory action and make it a potential
lead compound for developing effective and safer antipyretic drugs
for treating fever and related pathological conditions.