| ORIGINAL ARTICLES |
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5α-Epoxyalantolactone from Inula macrophylla attenuates cognitive deficits in scopolamine-induced Alzheimer’s disease mice model |
| Rui Ma1, Xu-Yao Feng2, Jiang-Jiang Tang2, Wei Ha1, Yan-Ping Shi1 |
1. CAS Key Laboratory of Chemistry of Northwestern Plant Resources, Key Laboratory for Natural Medicines of Gansu Province, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences (CAS), Lanzhou, 730000, People's Republic of China;
2. Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Chemistry & Pharmacy, Northwest A&F University, No. 3 Taicheng Road, Yangling, 712100, Shaanxi, China |
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Abstract Alzheimer’s disease (AD) is a complex neurodegenerative condition. 5α-epoxyalantolactone (5α-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 5α-EAL on cognitive impairment. 5α-EAL inhibited the generation of nitric oxide (NO) in BV-2 cells stimulated with lipopolysaccharide (LPS) with an EC50 of 6.2 μM. 5α-EAL significantly reduced the production of prostaglandin E2 (PGE2) 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 5α-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 5α-EAL on cognitive impairment in vivo. After the mice were pretreated with 5α-EAL (10 and 30 mg/kg per day, i.p.) for 21 days, the behavioral experiments indicated that the administration of the 5α-EAL could alleviate the cognitive and memory impairments. 5α-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 5α-EAL as a potential bioactive compound for attenuating cognitive deficits in AD due to its pharmacological profile.
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| Keywords
Alzheimer’s disease
5α-Epoxyalantolactone (5α-EAL)
Anti-neuroinflammation
Attenuates cognitive deficits
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| Fund:This work was financially supported by the National Key Research and Development Program of China (No. 2021YFE0103700), the National Natural Science Foundation of China (U21A20407, 22274163, and 22374160) and Shaanxi Fundamental Science Research Project for Chemistry and Biology (No. 23JHQ054). |
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Corresponding Authors:
Wei Ha,E-mail:hawei2012@licp.cas.cn;Yan-Ping Shi,E-mail:shiyp@licp.cas.cn
E-mail: hawei2012@licp.cas.cn;shiyp@licp.cas.cn
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Issue Date: 14 October 2024
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