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

doi:10.1007/s13659-024-00462-y

Natural Products and Bioprospecting ›› 2024, Vol. 14 ›› Issue (5): 39-39.DOI: 10.1007/s13659-024-00462-y

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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

Received:2024-05-23 Online:2024-10-14 Published:2024-10-24
Contact: Wei Ha,E-mail:hawei2012@licp.cas.cn;Yan-Ping Shi,E-mail:shiyp@licp.cas.cn
Supported by:
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).

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

通讯作者: Wei Ha,E-mail:hawei2012@licp.cas.cn;Yan-Ping Shi,E-mail:shiyp@licp.cas.cn
基金资助:
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).

Abstract

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.

Key words: Alzheimer’s disease, 5α-Epoxyalantolactone (5α-EAL), Anti-neuroinflammation, Attenuates cognitive deficits

摘要： 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.

关键词: Alzheimer’s disease, 5α-Epoxyalantolactone (5α-EAL), Anti-neuroinflammation, Attenuates cognitive deficits

Rui Ma, Xu-Yao Feng, Jiang-Jiang Tang, Wei Ha, Yan-Ping Shi. 5α-Epoxyalantolactone from Inula macrophylla attenuates cognitive deficits in scopolamine-induced Alzheimer’s disease mice model[J]. Natural Products and Bioprospecting, 2024, 14(5): 39-39.

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

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

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