Development of novel herbal compound combinations targeting neuroinflammation : network pharmacology, molecular docking and experimental verification

Abstract

This study aimed to develop a novel herbal compound combination to attenuate neuroinflammation with a synergistic approach in vitro. Two novel herbal compound combinations targeting neuroinflammation with a synergistic approach have been identified through a series of studies using network pharmacology, molecular docking, and in vitro experimental verification. The major research findings are shown as follows: 1) AN-SG and BA-SG synergistically inhibited pro-inflammatory mediators, NO, IL-6 and TNF-a in LPS-induced mono-cultured microglial N11 cells; 2) The observed synergy of AN-SG and BA-SG was associated with downregulation of phosphor-MAPKp38/MAPKp38, iNOS and NF-?B p65 nuclear translocation. 3) AN-SG and BA-SG exhibited enhanced anti-neuroinflammatory activities than their individual component in the neuroinflammation tri-culture model and subsequently restored the endothelial tight junction, protected the neuronal survival and reduced p-tau expression. Chapter 3 constructed the compound-gene targets-signaling pathway networks, which highlight the hub gene targets and KEGG pathways for eight selected phytochemicals against neuroinflammation. The top five gene targets included MAPK14, MAPK8, NOS3, EGFR and SRC, and the top KEGG pathway was the MAPK signaling pathway. The molecular docking partly verified the network pharmacology results that demonstrated good bind affinities of all phytochemicals with MAPK14 and NOS3. In Chapter 4, two herbal-compound combinations, AN-SG and BA-SG, were found to exhibit synergistic effects (CI

Date of Award	2023
Original language	English