Among the eleven phosphodiesterases (PDEs) superfamily
categorized by human genome encoding, PDE4 enzyme
serves as a key effector in degrading cAMP to 5′-AMP mainly
in immune and inflammatory cells in which the accumulation
of cAMP could negatively regulate the inflammatory
responses such as the release of cytokine by T cells. Hence,
PDE4 has been investigated as a target for the treatment of
several diseases, such as chronic obstructive pulmonary
disease (COPD) and asthma [10–13]. Furthermore, PDE4 has
also been identified as a target for anti-aging, reducing
stroke risk, and treatment of memory loss associated with
Alzheimer's disease [11,14–16], which makes it an active
area of research. Recently, our search demonstrated that
resveratrol, which ubiquitously exists in plants, can ameliorate
aging-related metabolic phenotypes by inhibiting PDE3
and PDE4 [14], and thus serves as a calorie restriction
mimetic with potential anti-aging properties. Moracin M
can be viewed as an analogue of resveratrol, extracted from
the Chinese herbal medicine Morus alba L. for the treatment
of asthma, was also identified to be a selective PDE4 inhibitor
by our group [11].