Diterpenoid alkaloids from Delphinium aemulans Nevski and their analgesic and ion channel inhibitory activities.

Six previously undescribed alkaloids, including four C19-diterpenoid alkaloids, aemulanines A-D, and two C18-diterpenoid alkaloids, aemulanines E-F, together with five known analogues, were isolated from the whole plant of Delphinium aemulans Nevski (Ranunculaceae). Their structures were established by comprehensive spectroscopic analysis, and the absolute configuration of aemulanine A was confirmed by single-crystal X-ray diffraction. Aemulanines A-C feature a rare C19-diterpenoid alkaloid skeleton with an opened B ring and an unusually rearranged D ring, while aemulanine E represents the first naturally occurring 7,17-secolycoctonine C18-diterpenoid alkaloid bearing a C-7-O-C-17 hemiacetal linkage. A plausible biosynthetic pathway for aemulanines A-C is proposed. In the acetic acid-induced writhing test in mice, aemulanines A and B exhibited notable analgesic activity, with 83.15% and 58.00% inhibition at 5 mg/kg, respectively. All previously undescribed isolates showed no significant inhibition of hERG or CaV3.1 ion channels, nor did they exhibit notable anti-inflammatory or cytotoxic activity against HeLa, HepG2, and HT-29 cell lines. Aemulanine A moderately inhibited KV channels (IC50 69.5 μM), while aemulanine B was much less potent (IC50 1600 μM). Aemulanine A additionally showed no activity against KV1.2, α7-nAChR, or the NLRP3 inflammasome.