Although the anti-inflammatory effect of the Hypericum extracts was attributed mainly to the inhibitory action of quercetin upon the signal transduction pathway, recent experiments reveal an important role of hyperforin, demonstrating an inhibitory effect upon the lymphocyte reaction at the level of the epidermal cells and upon the T-lymphocyte proliferation [16]. Hyperforin also interferes with prostanoid generation in biological systems, particularly with key enzymes participating in prostaglandin (PG) E2 biosynthesis, i.e., cyclooxygenases (COX)-1/2 and microsomal PGE2 synthase (mPGES)-1 which play key roles in inflammation and tumorigenesis [17]. On the other hand, hyperforin is one of the natural compounds with a strong inhibitory effect upon cyclooxygenase-1 (COX-1) and lipoxygenase-5 (LOX-5) [18]. This dual mechanism offers the rational basis for the traditional use of St. John’s wort in inflammatory dermal disorders.