(-)-Epigallocatechin-3-gallate protects PC12 cells against corticosterone-induced neurotoxicity via the hedgehog signaling pathway

Feng,Sha; Liu,Jue; Cheng,Biao; Deng,Aiping; Zhang,Hong

doi:10.3892/etm.2018.5936

(-)-Epigallocatechin-3-gallate protects PC12 cells against corticosterone-induced neurotoxicity via the hedgehog signaling pathway

Authors:
- Sha Feng
- Jue Liu
- Biao Cheng
- Aiping Deng
- Hong Zhang
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Affiliations: Department of Pharmacy, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China, Department of Pharmacy, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430014, P.R. China
Published online on: March 8, 2018 https://doi.org/10.3892/etm.2018.5936
Pages: 4284-4290
Copyright: © Feng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

It has been acknowledged that environmental stress is a risk factor for developing mental disorders. Chronic stress may contribute to the hyperactivation of the hypothalamic‑pituitary‑adrenal (HPA) axis and a sustained rise in the levels of glucocorticoids (GCs). A high concentration of corticosterone (CORT) damages neuronal PC12 cells. It has been reported that (‑)‑Epigallocatechin‑3‑gallate (EGCG), a major component of green tea, exhibits neuroprotective activity. However, the protective effect of EGCG on neuronal cells injured by CORT remains to be elucidated. The present study aimed to identify the effects of EGCG on CORT‑injured neuronal PC12 cells and its associated mechanisms of action. CORT‑injured PC12 cells were pretreated with EGCG with or without cyclopamine. Cell viability was assessed using an MTT assay, changes in cell morphology were observed using phase‑contrast microscopy, cellular apoptosis was assessed by Hoechst 33342 staining, cell proliferation was measured using a cell counting kit‑8 assay, mRNA levels were measured by reverse transcription‑quantitative polymerase chain reaction and protein expression was assessed using western blot analysis. The current study demonstrated that exposure to high concentrations of CORT induced cytotoxicity and downregulated the Sonic hedgehog pathway (Shh) in PC12 cells. These effects were attenuated by EGCG. However, the EGCG‑mediated neuroprotective effects, as well as upregulation of the Shh pathway were all attenuated by the Shh signaling inhibitor cyclopamine. These results indicate that EGCG protects PC12 cells from CORT‑induced neurotoxicity via activation of the Shh signaling pathway.

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