Diterpenoid alkaloids from Delphinium forrestii var. viride and their anti-inflammation activity

Six undescribed diterpenoid alkaloids including five C-19-diterpenoid alkaloids forrestlines A-E, and one C-20-diterpenoid alkaloid forrestline F, together with nine known alkaloids have been isolated from the whole herbs of Delphinium forrestii var. vride. Their structures were elucidated by spectroscopic data, and their inhibitory activities on NO production stimulated by LPS in RAW264.7 macrophage cells were determined. Then, forrestline F, with the strongest inhibitory activity (IC50 of 9.57 +/- 1.43 mu M), was selected to study its possible anti-inflammatory mechanism. ELISA results showed that forrestline F suppressed inflammatory cytokines, including interleukin-1 beta (IL-1 beta), tumor necrosisfactor-alpha (TNF-alpha), and interleukin-6 (IL-6). Moreover, forrestline F could down-regulate LPS-induced expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) by western blotting assay. It also inhibited expression of phosphorylation of MAPKs (including p-p38, p-ERK and p-JNK), and NF-kappa B p65, and decreased ROS accumulation by upregulating the expression of HO-1 expression via nuclear translocation of Nrf2. In conclusion, forrestline F showed anti-inflammatory effect by inhibiting NF-kappa B/MAPK and Nrf2/HO-1 signaling pathway. Therefore, forrestline F could be a promising molecule for the development of anti-inflammatory agents in the future.

Automated summary

Six new diterpenoid alkaloids were isolated from Delphinium forrestii var. vride, with forrestline F showing the strongest anti-inflammatory activity. It acted through multiple mechanisms by suppressing inflammatory cytokines, modulating NF-kappa B/MAPK and Nrf2/HO-1 signaling pathways.