Neuroprotective effects of PRG on Aβ25-35-induced cytotoxicity through activation of the ERK1/2 signaling pathway

Zhiying Bian; Chenzhen Cao; Jie Ding; Liang Ding; Shuai Yu; Chuanxiang Zhang; Qian Liu; Lihao Zhu; Jing Li; Yongqing Zhang; Yuhong Liu

doi:10.1016/j.jep.2023.116550

Neuroprotective effects of PRG on Aβ_25-35-induced cytotoxicity through activation of the ERK1/2 signaling pathway

J Ethnopharmacol. 2023 Sep 15:313:116550. doi: 10.1016/j.jep.2023.116550. Epub 2023 Apr 28.

Authors

Zhiying Bian¹, Chenzhen Cao², Jie Ding¹, Liang Ding¹, Shuai Yu¹, Chuanxiang Zhang¹, Qian Liu¹, Lihao Zhu³, Jing Li⁴, Yongqing Zhang⁵, Yuhong Liu⁶

Affiliations

¹ Shandong University of Traditional Chinese Medicine, Jinan, 250355, China.
² Shandong University of Traditional Chinese Medicine, Jinan, 250355, China; Health Surveillance Section, Junan County Center for Disease Control and Prevention, Linyi, 276600, China.
³ Sishui Siheyuan Culture and Tourism Development Company, Ltd, Sishui, 273200, China.
⁴ Shandong University of Traditional Chinese Medicine, Jinan, 250355, China. Electronic address: 05000089@sdutcm.edu.cn.
⁵ Shandong University of Traditional Chinese Medicine, Jinan, 250355, China. Electronic address: 60030002@sdutcm.edu.cn.
⁶ Shandong University of Traditional Chinese Medicine, Jinan, 250355, China. Electronic address: yhliu@sdutcm.edu.cn.

PMID: 37120057
DOI: 10.1016/j.jep.2023.116550

Abstract

Ethnopharmacological relevance: Phylloporia ribis (Schumach:Fr.)Ryvarden is a genus of needle Phellinus medicinal fungi, parasitic on the living rhizomes of hawthorn and pear trees. As a traditional Chinese medicine, Phylloporia ribis was used in folklore for long-term illness, weakness and memory loss in old age. Previous studies have shown that polysaccharides from Phylloporia ribis (PRG) significantly promoted synaptic growth in PC12 cells in a dose-dependent manner, exhibiting "NGF"-like neurotrophic activity. Aβ_25-35 damage to PC12 cells produced neurotoxicity and decreased cell survival, and PRG reduced the apoptosis rate, suggesting that PRG has neuroprotective effects. The studies confirmed that PRG had the potential to be a neuroprotective agent, but its neuroprotective mechanism remained unclear.

Aim of the study: We aimed to elucidate the neuroprotective effects of PRG in an Aβ_25-35-induced Alzheimer's disease (AD) model.

Materials and methods: Highly-differentiated PC12 cells were treated with Aβ_25-35 (AD model) and PRG, and were assessed for cellular apoptosis, inflammatory factors, oxidative stress, and kinase phosphorylation.

Results: The results showed that the PRG groups effectively inhibited the neurotoxicity, mainly manifested by inhibiting mitochondrial oxidative stress, attenuating neuroinflammatory responses, and improving mitochondrial energy metabolism, eventually resulting in higher cell survival. The expression of p-ERK, p-CREB and BDNF proteins was increased in the PRG groups compared to the model group, which confirmed that PRG reversed the inhibition of the ERK pathway.

Conclusion: We provide evidence for neuroprotection conferred by PRG and its mechanism by inhibiting ERK1/2 hyper-phosphorylation, prevention of mitochondrial stress, and subsequent prevention of apoptosis. The study highlights PRG as a promising candidate with neuroprotective effects, the potential of which can be harnessed for identifying novel therapeutic targets.

Keywords: Alzheimer's disease; Aβ(25–35); ERK1/2; PC12 cells; Phylloporia ribis; Polysaccharide.

MeSH terms

Alzheimer Disease* / drug therapy
Amyloid beta-Peptides / metabolism
Amyloid beta-Peptides / toxicity
Animals
Apoptosis
Cell Survival
Humans
MAP Kinase Signaling System
Neuroprotective Agents* / pharmacology
Neuroprotective Agents* / therapeutic use
Neurotoxicity Syndromes*
PC12 Cells
Peptide Fragments / metabolism
Rats
Signal Transduction

Substances

Neuroprotective Agents
Amyloid beta-Peptides
Peptide Fragments

Supplementary concepts

Phylloporia ribis