Novel phenanthrene/bibenzyl trimers from the tubers of Bletilla striata attenuate neuroinflammation via inhibition of NF-κB signaling pathway

Five novel (9,10-dihydro) phenanthrene and bibenzyl trimers, as well as two previously identified biphenanthrenes and bibenzyls, were isolated from the tubers of Bletilla striata. Their structures were elucidated through comprehensive analyses of NMR and HRESIMS spectroscopic data. The absolute configurations of these compounds were determined by calculating rotational energy barriers and comparison of experimental and calculated ECD curves. Compounds 5b and 6 exhibited inhibitory effects on LPS-induced NO production in BV-2 cells, with IC₅₀ values of 12.59 ± 0.40 and 15.59 ± 0.83 μmol·L⁻¹, respectively. A mechanistic study suggested that these compounds may attenuate neuroinflammation by reducing the activation of the AKT/IκB/NF-κB signaling pathway. Additionally, compounds 3a, 6, and 7 demonstrated significant PTP1B inhibitory activities, with IC₅₀ values of 1.52 ± 0.34, 1.39 ± 0.11, and 1.78 ± 0.01 μmol·L⁻¹, respectively. Further investigation revealed that compound 3a might inhibit LPS-induced PTP1B overexpression and NF-κB activation, thereby mitigating the neuroinflammatory response in BV-2 cells.