Lingguizhugan decoction protects PC12 cells against Aβ25-35-induced oxidative stress and neuroinflammation by modulating NF-κB/MAPK signaling pathways

Abstract

Ethnopharmacological relevanceAlzheimer's disease (AD) is recognized as one of the most prevalent neurodegenerative diseases. Lingguizhugan decoction (LGZGD) is a classical traditional Chinese medicine (TCM). Many studies have shown that LGZGD can alleviate the symptoms of AD. Aim of the studyThe aim of this study was to assess the neuroprotective effects of LGZGD and elucidate its molecular mechanism on Aβ25-35-induced PC12 cells. Materials and methodsPC12 cells were used MTT assays, ELISA, fluorescence probe analyses, Hoechst 33342 staining, immunofluorescent staining and western blot analyses were systematically conducted to evaluate the underlying mechanisms of LGZGD. ResultsIn Aβ25-35-induced PC12 cells, LGZGD remarkably increased cell viability, reduced the generation of TNF-α, IL-1β, IL-6, MDA and ROS, increased the activity of GSH-Px, inhibited cell apoptosis, downregulated the expression of Bax and cleaved caspase-3, and upregulated the expression of Bcl-2. Moreover, LGZGD modulated the NF-κB/MAPK signaling pathways by upregulating the levels of IκBα and phospho-ERK, while downregulating the levels of phospho-p65, phospho-IκBα, and phospho-p38. Furthermore, LGZGD repressed the nuclear translocation activity of NF-κB p65. Meanwhile, LGZGD increased the expression of phospho-GSK-3β and reversed the hyperphosphorylation of Tau proteins by inhibiting the activation of the ERK MAPK pathway. ConclusionsTaken together, the present study suggested that LGZGD may be a valuable drug candidate that can attenuate the neurotoxicity induced by Aβ25-35 by modulating the NF-κB/MAPK signaling pathways in PC12 cells.