Lingguizhugan decoction protects PC12 cells against Aβ25-35-induced oxidative stress and neuroinflammation by modulating NF-κB/MAPK signaling pathways. (28th June 2022)

• Record Type: Journal Article
• Authors: Han, Jing; Zhang, Haotian; Zhang, Yu; Zhang, Zan; Yu, Maomao; Wang, Sijie; Han, Fei
• Is Part Of: Journal of ethnopharmacology. Volume 292(2022)
• Publication Date: 2022-06-28
• Subjects: Lingguizhugan decoction -- Alzheimer's disease -- Amyloid beta peptide -- Tau hyperphosphorylation -- Nuclear factor-κB/mitogen-activated protein kinase (NF-κB/MAPK) signaling pathways; Ethnopharmacology -- Periodicals; Pharmacognosy -- Periodicals; Herbs -- Periodicals; Herbs -- Periodicals; Pharmacognosy -- Periodicals; Pharmacognosie -- Périodiques; Herbes -- Périodiques; 615.1
• DOI: 10.1016/j.jep.2022.115194
• Languages: English
• ISSNs: 0378-8741

Abstract

Abstract: 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 Aβ25-35 -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 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. Conclusions: Taken 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. Graphical abstract: Image 1