Polycyclic Polyprenylated Acylphloroglucinols from Hypericum Hookerianum with their immunosuppressive activities

Phytochemical investigation of Hypericum hookerianum lead to nine new polycyclic polyprenylated acylphloroglucinols (PPAPs), hyperhookeriones A-I (1-9), alongside 11 known analogues (10-20). Structures were elucidated through NMR data analysis, conformation analysis, quantum calculations, and ECD spectra. The immunosuppressive activities of these compounds were evaluated in vitro. Compound 1 displayed moderate immunosuppressive activity against T-cell proliferation (IC₅₀ = 16.51 ± 5.32 μM), dose-dependently inhibiting pro-inflammatory cytokines IL-17 A, IL-6, IFN-γ. Further mechanistic studies revealed that compound 1 inhibits T-cell proliferation over activation by blocking IL-2 receptor signaling through reduction of JAK3 phosphorylation. This disruption attenuates phosphorylation of downstream effectors (STAT5, ERK1/2, and AKT), induces G₀/G₁ phase arrest, culminating in potent suppression of T-cell proliferation.