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Magnolol upregulates CHRM1 to attenuate Amyloid-β-triggered neuronal injury through regulating the cAMP/PKA/CREB pathway

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Abstract

Alzheimer’s disease (AD) is a common neurodegenerative disease characterized by neuronal degeneration and hyperphosphorylated Tau. Magnolol is an active component isolated from Magnolia officinalis with potential neuroprotection activity. However, the function and mechanism of magnolol in AD progression is largely uncertain. In present study, the biomarkers related to AD and magnolol were predicted by bioinformatics analyses. The key biomarker levels were predicted by GSE5281 and GSE36980 using AlzData. Cell viability was detected by CCK-8 assay. mRNA and protein levels were examined by qRT-PCR and western blotting assays. Cell apoptosis was investigated by caspase-3 activity and flow cytometry analyses. The cAMP/PKA/CREB signaling was evaluated by ELISA and western blotting analyses. The results showed that CHRM1 was a key biomarker for magnolol against AD progression. Magnolol attenuated Aβ-induced viability inhibition, Tau hyperphosphorylation and apoptosis in SH-SY5Y cells by upregulating CHRM1. In addition, the cAMP signaling might be a potential pathway of CHRM1 in AD. Magnolol contributed to activation of the cAMP/PKA/CREB pathway through enhancing CHRM1 level. Inactivation of the cAMP/PKA/CREB signaling reversed the suppressive effect of magnolol on Tau hyperphosphorylation and apoptosis in Aβ-treated SH-SY5Y cells. As a conclusion, magnolol mitigated Aβ-induced Tau hyperphosphorylation and neuron apoptosis by upregulating CHRM1 and activating the cAMP/PKA/CREB pathway.

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The data and material presented in this manuscript are available from the corresponding author on reasonable request.

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Acknowledgements

I would like to thank Ms. Gemin Zhu, Yuan Fang, Xiaoli Cui, Ruihua Jia, and Xiaogang Kang, who have helped me during the writing, design, and experiment performance of this thesis.

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Author notes

  1. Gemin Zhu and Yuan Fang made equal contribution in this study.

Authors and Affiliations

  1. Department of Neurology, Xi’an Central Hospital of Xi’an Jiaotong University College of Medicine, Xi’an, 710003, People’s Republic of China

    Gemin Zhu

  2. Department of Neurosurgery, Xi’an No. 3 Hospital, The Affiliated Hospital of Northwest University, Xi’an, 710018, People’s Republic of China

    Yuan Fang

  3. Department of Neurology, Shaanxi Provincial People’s Hospital, No. 256 West Friendship Road, Xi’an, 710068, People’s Republic of China

    Xiaoli Cui, Ruihua Jia & Rui Zhao

  4. Department of Neurology, Xijing Hospital, Air Force Medical University, No. 15 Changle West Road, Xi’an, 710032, People’s Republic of China

    Xiaogang Kang

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  1. Gemin Zhu
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  3. Xiaoli Cui
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Contributions

GZ and YF designed and performed most of the experiments, GZ wrote the manuscript. XC and RJ involved in the performance of this experiment, XK and RZ made contributions to the study design and data analysis,

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Correspondence to Xiaogang Kang or Rui Zhao.

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Zhu, G., Fang, Y., Cui, X. et al. Magnolol upregulates CHRM1 to attenuate Amyloid-β-triggered neuronal injury through regulating the cAMP/PKA/CREB pathway. J Nat Med 76, 188–199 (2022). https://doi.org/10.1007/s11418-021-01574-2

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  • DOI: https://doi.org/10.1007/s11418-021-01574-2

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