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

Ethnopharmacological relevance: Alzheimer'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 study: The aim of this study was to assess the neuroprotective effects of LGZGD and elucidate its molecular mechanism on A ss 25-35-induced PC12 cells. Materials and methods: PC12 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. Results: In A ss 25-35-induced PC12 cells, LGZGD remarkably increased cell viability, reduced the generation of TNFa, IL-1 ss, 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-.B/MAPK signaling pathways by upregulating the levels of I.Ba and phospho-ERK, while downregulating the levels of phospho-p65, phospho-I.Ba, and phospho-p38. Furthermore, LGZGD repressed the nuclear translocation activity of NF-.B p65. Meanwhile, LGZGD increased the expression of phospho-GSK-3 ss and reversed the hyperphosphorylation of Tau proteins by inhibiting the activation of the ERK MAPK pathway. Conclusions: Taken together, the present study suggested that LGZGD may be a valuable drug candidate that can attenuate the neurotoxicity induced by A ss 25- 35 by modulating the NF-.B/MAPK signaling pathways in PC12 cells.

Automated summary

This study evaluated the neuroprotective effects of Lingguizhugan decoction (LGZGD) on Aβ25-35-induced PC12 cells and elucidated its molecular mechanism. The results showed that LGZGD increased cell viability, reduced inflammatory factors, inhibited cell apoptosis, and modulated the NF-κB/MAPK signaling pathways. Therefore, LGZGD may be a valuable drug candidate for attenuating Aβ25-35-induced neurotoxicity.