Tigliane and rhamnofolane glycosides from Euphorbia wallichii prevent oxidative stress-induced neuronal death in PC-12 cells.

[Display omitted] • Twelve new tigliane/rhamnofolane glycosides were isolated from Euphorbia wallichii. • The aglycones of 1 – 5 represent a rare class of 13-deoxygenated tiglianes. • The aglycones of 8 – 12 represent the first examples of 4-deoxygenated rhamnofolanes. • Euphorwallside C (3) was identified as a promising neuroprotective agent. • 3 inhibit ROS accumulation and restore the MMP via Nrf2 signaling pathway. Tigliane and rhamnofolane diterpenoids bearing glycosyl substituents are rarely found in nature. In the current study, seven new tigliane glycosides, euphorwallsides A − G (1 – 7), and five new rhamnofolane glycosides, euphorwallsides H − L (8 – 12), were isolated from the whole plants of Euphorbia wallichii. Their structures were elucidated by a combination of spectroscopic, computational, and chemical means. The aglycones of 1 – 5 represent a rare class of 13-deoxygenated tiglianes, while those of 8 – 12 represent the first examples of 4-deoxygenated rhamnofolanes. 2 , 3 , 5 , 7 , 8 , and 12 showed significant neuroprotective effects on sodium nitroprusside (SNP)-induced neuronal death in pheochromocytoma cell line PC-12 at 10 μM, being more active than the clinical drug, edaravone. Mechanistic study revealed that the most active compound, 3 , could inhibit reactive oxygen species (ROS) accumulation and restore the mitochondrial membrane potential via modulating the Nrf2 signaling pathway in PC-12 cells. [ABSTRACT FROM AUTHOR]