Saebias A-G, eudesmane sesquiterpenes from Salvia plebeia with potential for Alzheimer's disease prevention via anti-neuroinflammatory and neuroprotective effects.

Saebias A-G (1-7), seven previously undescribed eudesmane sesquiterpenoids compounds and seventeen known compounds were isolated from Salvia plebeia R.Br. Among them, compound 1 is a unique C16-type eudesmane sesquiterpenoid featuring a 6/6/5-membered scaffold, 2-3 are nor-eudesmane sesquiterpenoids and 5 contains a rare 6/6/3/5 tetracyclic skeleton. Their structures including absolute configurations were elucidated by extensive spectroscopic methods, single-crystal X-ray crystallographic and ECD calculation. All compounds were evaluated for their inhibitory effect on nitric oxide (NO) production induced by lipopolysaccharide (LPS) in BV-2 cells and neuroprotective effect induced by H2O2 in PC12 cells. The results showed that four compounds exhibited significant NO inhibitory effects, with IC50 values ranging from 0.76 to 3.72 μM. Among them, compound 2 showed significant inhibitory effect, which significantly suppressed the production of IL-6, IL-1β, and iNOS in a concentration-dependent manner. The PC12 cells damage induced by H2O2 was attenuated by compounds 2, 10, 11, 13, 15, and 23. Moreover, compounds 2 and 11 delayed H2O2 induced damage, stabilized reactive oxygen species (ROS), mitochondrial membrane potential (MMP) and apoptosis expression levels. Notably, compound 2 exerted dual anti-neuroinflammatory and neuroprotective activities, and its multi-target pharmacological profile makes it a promising candidate for the prevention and treatment of Alzheimer's disease. These studies provide new potential neuroprotective agents for the prevention and treatment of neurodegenerative diseases.