These findings suggest that viscosine shows antipyretic properties by reducing the concentration of prostaglandin E<sub>2</sub> 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.
In conclusion, our in silico approach leads to the selection of a compound that presents the chemical features to inhibit mPGES-1 and reduces fever induced by LPS.
Furthermore, injection of a virus vector expressing microsomal prostaglandin E synthase-1 (mPGES-1) into the median preoptic nucleus of fever-refractive mPGES-1 knock-out mice, resulted in a temperature elevation in response to LPS.
The febrile response is triggered by prostaglandin E2 synthesis mediated by induced expression of the enzymes cyclooxygenase-2 (COX-2) and microsomal prostaglandin E synthase 1 (mPGES-1).
Studies, mainly from disruption of the mPGES-1 gene in mice, indicate key roles of mPGES-1-generated PGE(2) in female reproduction and in pathological conditions such as inflammation, pain, fever, anorexia, atherosclerosis, stroke, and tumorigenesis.