Abstract
Aberrant microglial activation drives neuroinflammation and neurodegeneration in Alzheimer's disease (AD). The present study is aimed at investigating whether the herbal formula Qi-Fu-Yin (QFY) could inhibit the inflammatory activation of cultured BV-2 microglia. A network pharmacology approach was employed to predict the active compounds of QFY, protein targets, and affected pathways. The representative pathways and molecular functions of the targets were analyzed by Gene Ontology (GO) and pathway enrichment. A total of 145 active compounds were selected from seven herbal ingredients of QFY. Targets (e.g., MAPT, APP, ACHE, iNOS, and COX-2) were predicted for the selected active compounds based on the relevance to AD and inflammation. As a validation, fractions were sequentially prepared by aqueous extraction, ethanolic precipitation, and HPLC separation, and assayed for downregulating two key proinflammatory biomarkers iNOS and COX-2 in lipopolysaccharide- (LPS-) challenged BV-2 cells by the Western blotting technique. Moreover, the compounds of QFY in 90% ethanol downregulated iNOS in BV-2 cells but showed no activity against COX-2 induction. Among the herbal ingredients of QFY, Angelicae Sinensis Radix and Ginseng Radix et Rhizoma contributed to the selective inhibition of iNOS induction. Furthermore, chemical analysis identified ginsenosides, especially Rg3, as antineuroinflammatory compounds. The herbal formula QFY may ameliorate neuroinflammation via downregulating iNOS in microglia.
Highlights
Alzheimer’s disease (AD) is the major neurodegenerative cause of progressive dementia in the elderly [1]
Based on the pharmacokinetic or physiochemical properties, 126 active compounds were obtained while another 19 compounds were added by searching the PubMed database for the implications in the treatment of AD
The active compounds were further classified by the Medical Subject Headings (MeSH) classification system and text mining
Summary
Alzheimer’s disease (AD) is the major neurodegenerative cause of progressive dementia in the elderly [1]. Some controversial results showed that these agents barely prevented the progression of AD and could cause adverse effects [4]. Neurotoxic peptide Aβ activates microglia and exacerbates neuroinflammation, leading to Oxidative Medicine and Cellular Longevity the onset and progression of AD [5, 6]. The overexpression of proinflammatory enzymes such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX2) jeopardizes the survival of neurons in brains [7]. Excessive nitric oxide in the brain induced oxidative damage in neurons and led to the activation of apoptosis [8]. Effective inhibition of neuroinflammation represents a key strategy for the management of AD, but the in vivo efficacies of antineuroinflammatory and microglia-targeting agents remain uncertain [9]
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