The Phenylpropionamide Extract of Hemp (Cannabis Sativa L.) Seed Improves Learning Memory Ability and Survival Rate by Attenuating Microglia Activation  and Reducing Amyloid Deposition Via the Sirt1-Amad10 Pathway in App/Ps1 Mice

38 Pages Posted: 23 Jun 2023

See all articles by Mei Yang

Mei Yang

Shandong University

Siqing Bu

Shandong University

Jianbo Ji

Shandong University - Department of Pharmaceutics

Jieyue Sun

Shandong University

Yue Zhang

Shandong University

Xiaoyan Hu

Shandong University

Jiaozhen Zhang

Shandong University

Hongxiang Lou

Shandong University

Peihong Fan

Shandong University

Abstract

Background: Fructus cannabis (Hemp seed), the dried and mature fruit of Cannabis sativa L., was reported effects against Alzheimer’s disease (AD) in different experimental models. However, either chemical composition or the action of mechanisms was not clear. Our previous work isolated and identified diverse phenylpropionamides such as cannabisin A-F, caffeoyltyramine and feryroyltyramine from hemp seed, which showed antioxidant and anti-neuroinflammatory activity in cells models.P

urpose: To study the anti-AD effect and mechanism of the total phenylpropionamides (TPA) extract from hemp seed using APPswe/PS1dE9 mice model.Methods: TPA extract was prepared via extraction and column chromatography techniques, then analyzed and measured using HPLC, HPLC-ESIMS and Folin method. The extract was administered by gavage to APPswe/PS1dE9 mice. The learning memory ability of mice were examined using new object recognition test and water maze adoption. H&E staining was used to observe the morphology of neuronal cells in the hippocampal region of brain tissue; ELISA was used to measure the content of IL-1β, TNF-а, IL-6, superoxide dismutase (SOD), malondialdehyde (MDA) in the brain tissue; the deposition of Aβ protein was measured by immunohistochemistry and Western blotting; the activation of microglia was measured by immunofluorescence and Western blotting. The expression of APP, PS1, SIRT1, and ADAM10 proteins was measured by Western blotting.

Results: Folin method showed the total phenylpropionamide content was 238.03 μg Caffeic acid equivalent /mg TPA. HPLC and HPLC-MS showed the contents of N-trans-caffeoyltyramine, cannabisin A and B were 20.16 μg/mg, 32.16μg/mg and 214.35μg/mg, respectively, in TPA extract. TPA treatment significantly increased the survival rate of APP/PS1 mice, improved the learning and memory ability, reversed the neural cell damage in the hippocampal region, and reduced Aβ deposition and the activation of microglia in brain tissue. Meanwhile, the administration decreased the neuroinflammatory factors TNF-α, IL-6, IL-1β expression, increased antioxidant enzyme SOD activity, and attenuated MDA expression. Western blotting showed that TPA administration increased SIRT1 and ADAM10 protein expression and decreased APP and PS1 protein expression.

Conclusion: TPA improved learning memory capacity, increased survival, attenuated neuroinflammation, oxidative stress, microglia activation and hippocampal apoptosis, and could reduce amyloid deposition via the SIRT1-AMAD10 pathway in APP/PS1 mice.

Note:
Funding Information: The authors gratefully acknowledge the financial support provided by the National Natural Science Foundation of China (No.82073984).

Declaration of Interests: The authors declare no conflicts of interest.

Ethical Approval Statement: Aall animal experiments were approved by the Animal Experimentation Committee of the College of Pharmacy, Shandong University (No.20006, approval date: 31 March, 2020)

Keywords: hemp seed, phenylpropionamides, APP/PS1 mice, sirt1, ADAM10, Aβ protein

Suggested Citation

Yang, Mei and Bu, Siqing and Ji, Jianbo and Sun, Jieyue and Zhang, Yue and Hu, Xiaoyan and Zhang, Jiaozhen and Lou, Hongxiang and Fan, Peihong, The Phenylpropionamide Extract of Hemp (Cannabis Sativa L.) Seed Improves Learning Memory Ability and Survival Rate by Attenuating Microglia Activation  and Reducing Amyloid Deposition Via the Sirt1-Amad10 Pathway in App/Ps1 Mice. Available at SSRN: https://ssrn.com/abstract=4474684 or http://dx.doi.org/10.2139/ssrn.4474684

Mei Yang

Shandong University ( email )

27 Shanda Nanlu
South Rd.
Jinan, SD 250100
China

Siqing Bu

Shandong University ( email )

27 Shanda Nanlu
South Rd.
Jinan, SD 250100
China

Jianbo Ji

Shandong University - Department of Pharmaceutics ( email )

Jieyue Sun

Shandong University ( email )

27 Shanda Nanlu
South Rd.
Jinan, SD 250100
China

Yue Zhang

Shandong University ( email )

27 Shanda Nanlu
South Rd.
Jinan, SD 250100
China

Xiaoyan Hu

Shandong University ( email )

27 Shanda Nanlu
South Rd.
Jinan, SD 250100
China

Jiaozhen Zhang

Shandong University ( email )

27 Shanda Nanlu
South Rd.
Jinan, SD 250100
China

Hongxiang Lou

Shandong University ( email )

Peihong Fan (Contact Author)

Shandong University ( email )

27 Shanda Nanlu
South Rd.
Jinan, SD 250100
China

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