Elesestriterpenoid A, an Unprecedented 5/7/6/6/5 Carbon Skeleton with Neuroprotective Activity from Leaves of Eleutherococcus sessiliflorus

One undescribed triterpenoid and four novel triterpenoid saponins, elesestriterpenoids A-E (1-5) were isolated from the leaves of Eleutherococcus sessiliflorus (Rupr. & Maxim.) S. Y. Hu. Their chemical structures were determined using spectroscopic data analysis, with their corresponding absolute configurations measured using single-crystal X-ray diffraction, electronic circular dichroism calculations, and DP4+ technologies. Notably, elesestriterpenoid A (1) represents the first reported lupane-type triterpenoid with a 5/7/6/6/5-fused ring system from nature, and elesestriterpenoids B-E (2-5) feature an unprecedented 7/6/6/5-fused carbon skeleton. The neuroprotective potential of these isolates was evaluated using an in vitro model of oxidative stress in l-glutamate-induced HT22 mouse hippocampal neuron cells. The results revealed significant neuroprotective activity for compounds 1, 3, and 4. Particularly noteworthy, compound 1 demonstrated pronounced efficacy in mitigating oxidative damage through modulation of the Keap1/Nrf2/HO-1 signaling pathway in HT22 cells, indicating its potential for treating nerve injuries.