Neuroprotective effects of bornyl acetate against okadaic acid–Induced cytotoxicity in pc12 cells via beclin-1-dependent autophagy pathway

Liping Huang; Xiaoqin Zhong; Zhongliu Zhou; NanBu Wang; MinZhen Deng

Articles

Abstract

Pharmacognosy Magazine,2022,18,80,962-968.

DOI:10.4103/pm.pm_565_21

Published:November 2022

Type:Original Article

Authors:

Author(s) affiliations:

Liping Huang¹, Xiaoqin Zhong², Zhongliu Zhou¹, NanBu Wang², MinZhen Deng³
¹School of Chemistry and Chemical Engineering, Western Guangdong Characteristic Biomedical Engineering Technology Research Center; Mangrove Institute, Lingnan Normal University, Zhanjiang 524048, China
²The First Clinical College of Guangzhou University of Chinese Medicine, 12 Jichang Road, Guangzhou, Guangdong 510405, P.R. China
³Department of Neurology, Guangdong Provincial Hospital of Chinese Medicine; Department of Neurology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine; Postdoctoral Research Station of Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, Guangdong 510120, P.R. China

Abstract:

Background: β-amyloid (Aβ) deposition and tau protein abnormality are the major pathogenesis of Alzheimer's disease (AD). Autophagy is contributed to eliminating the misfolded proteins or organelles and alleviated cellular injury. Our pre-experimental findings showed that bornyl acetate (BA), the main component of the volatile oil of Amomum villosum, has a neuroprotective effect in okadaic acid (OA)–induced PC12 cells. However, the protective mechanism of autophagy that BA relieves OA-induced cellular injury is still unclear. Objectives: The purpose of our experiment was to elucidate the mechanism of treatment of AD. Materials and Methods: To explore how BA has therapeutic effects on AD, a model of OA-induced PC12 cells was established. The OA modelling induction and BA treatment in cells were evaluated by LDH and CCK-8 methods; ELISA assay was used to detect the tau hyperphosphorylation (p-tau), Aβ₄₂ and β-secretase levels; The expression of p-Akt and p-mTOR were detected by western blot analysis; and immunohistochemical, immunofluorescence methods and western blot analysis were used to detect Beclin-1 expression. Autophagosomes in each group were observed by transmission electron microscopy (TEM). 175 nM OA for 48 hr was applied to OA modelling induction. Results: Compared to the control group, the OA-induced AD model cells displayed higher levels of p-tau, Aβ₄₂ and β-secretase (P < 0.01), suggesting that the AD model was successfully established. Compared to the OA model group alone, p-tau, Aβ₄₂ and β-secretase levels and autophagy promoter Beclin-1 expression decreased significantly in the BA group (P < 0.05), whereas p-Akt and p-mTOR increased (P < 0.01). Conclusion: BA exhibited a neuroprotection effect against OA-induced cellular injury in the AD model by suppressing the Beclin-1-dependent autophagy pathway, indicating that BA might be an appealing potential strategy to treat AD.