Abstract:
The fruits of
Eucalyptus globulus Labill. are known to have a plenty of medicinal properties, such as anti-tumor, anti-inflammatory, and immunosuppressive activity. Our previous study found that the phloroglucinol-sesquiterpene adducts in the fruits of
E. globulus were immunosuppressive active constituents, especially Eucalyptin C (EuC). Phosphoinositide 3-kinases-
γ (PI3K
γ) plays a pivotal role in T cell mediated excessive immune responses. In this study, EuC was first discovered to be a novel selective PI3K
γ inhibitor with an IC
50 value of 0.9
μmol·L
−1 and selectivity over 40-fold towards the other PI3K isoforms. Molecular docking, molecular dynamics simulation, and cellular thermal shift assay showed that EuC bound to PI3K
γ. Furthermore, EuC suppressed the downstream of PI3K
γ to induce the apoptosis and inhibit the activation of primary spleen cells derived from allergic contact dermatitis mice. This work highlights the role of the fruits of
E. globulus as a source of bioactive plant with immunosuppressive activity.