5α-Epoxyalantolactone from Inula macrophylla attenuates cognitive deficits in scopolamine-induced Alzheimer’s disease mice model

Abstract Alzheimer’s disease (AD) is a complex neurodegenerative condition. 5 α -epoxyalantolactone (5 α -EAL), a eudesmane-type sesquiterpene isolated from the herb of Inula macrophylla , has various pharmacological effects. This work supposed to investigate the improved impact of 5 α -EAL on cognitive impairment. 5 α -EAL inhibited the generation of nitric oxide (NO) in BV-2 cells stimulated with lipopolysaccharide (LPS) with an EC 50 of 6.2 μM. 5 α -EAL significantly reduced the production of prostaglandin E2 (PGE 2 ) and tumor necrosis factor-α (TNF-α), while also inhibiting the production of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) proteins. The ability of 5 α -EAL to penetrate the blood–brain barrier (BBB) was confirmed via a parallel artificial membrane permeation assay. Scopolamine (SCOP)-induced AD mice model was employed to assess the improved impacts of 5 α -EAL on cognitive impairment in vivo. After the mice were pretreated with 5 α -EAL (10 and 30 mg/kg per day, i.p. ) for 21 days, the behavioral experiments indicated that the administration of the 5 α -EAL could alleviate the cognitive and memory impairments. 5 α -EAL significantly reduced the AChE activity in the brain of SCOP-induced AD mice. In summary, these findings highlight the beneficial effects of the natural product 5 α -EAL as a potential bioactive compound for attenuating cognitive deficits in AD due to its pharmacological profile. Graphical Abstract