Alkaloids of Delphinium grandiflorum and their implication to H2O2-induced cardiomyocytes injury

Three new diterpenoid alkaloids (1?3), and eight known alkaloids (4?11) were isolated from the aerial parts of Delphinium grandiflorum. Grandifline A (1) represents an unprecedented diterpenoid alkaloid ring system featuring a C-7?N?C?17 hemiaminal moiety and a lactone fragment through the linkage of C-17?O?C?19 unit. And we named this newly-discovered class of rearranged C19-diterpenoid alkaloid scaffold as grandiflodines (B-12). Grandifline B (2) is the first naturally-occurring 7,17-secolycoctonine diterpenoid alkaloid with a C7?O?C?17 unit forming a hemiacetal. Their structures were elucidated via spectroscopic data and singlecrystal X-ray diffraction analysis. The protective effects of compounds 1?11 on H2O2-induced cardiomyocytes injury were assayed. And compounds 6 and 10 showed significant protective effects, with IC50 values of 1.881 ? 0.680 ?M and 1.904 ? 0.750 ?M, respectively. Further, compound 6 could reduce oxidative damage by inhibiting cell death via the AMPK/AKT/mTOR signaling pathway in H2O2-induced H9C2 cells.

Automated summary

Three new diterpenoid alkaloids and eight known alkaloids were isolated from Delphinium grandiflorum, with some compounds showing significant protective effects on H2O2-induced cardiomyocytes injury. Compound 6 was found to reduce oxidative damage by inhibiting cell death through the AMPK/AKT/mTOR signaling pathway in H2O2-induced H9C2 cells.