C-13 Norisoprenoids and Eudesmanoids from Nelumbo nucifera Gaertn. Regulate the Lipid Metabolism via the AMPK/ACC/SREBP-1c Signaling Pathway.

Lotustine A (1), an undescribed C- norisoprenoid, along with 22 known analogues and two eudesmanoids, were isolated from the aerial parts of Nelumbo nucifera Gaertn. Among them, compounds 2, 15, 17, 21, 22, 24, 25 were isolated from N. nucifera leaves for the first time. Their structures, including absolute configurations, were elucidated by nuclear magnetic resonance, mass spectroscopy, and the modified Mosher's method. Compound 1 is the first example of C- norisoprenoid with a terminal double bond between C-5 and C-13. Moreover, the lipid-lowering activities of the isolates were evaluated, and the results showed that 2, 24 and 25 could remarkably decrease the levels of both total cholesterol and triglyceride in free fatty acids induced HepG2 cells at the concentration of 20 μM. The oil red staining assay further demonstrated the lipid-lowering effects of 2, 24 and 25. The western blot results indicated that compounds 2, 24 and 25 could regulate the lipid metabolism via the activation of the AMPK/ACC/SREBP-1c signaling pathway.