Chenopodium album L. herb attenuates inflammation by modulating multiple signaling pathways in zebrafish: Network pharmacology analysis, transcriptomics analysis and experimental verification

Abstract

Chenopodium album L., is a folk potherb as well as a traditional herbal medicine, which valued for its rich material ingredients and pharmacological effects. However, its pharmacological substance basis and potential molecular mechanisms of the anti-inflammatory effect have still not been fully elucidated. The present study aims to investigate its active fractions, material basis and action mechanism of C. album to cure inflammation. First of all, C. album was extracted by 95 % ethanol, and was separated to four fractions via macroporous resin. Then we confirmed the typically anti-inflammatory active fraction CA-A with the best anti-inflammatory effect by CuSO₄-induced inflammatory zebrafish model. Subsequently, the main components of CA-A were identified as amino acids and their derivatives and saccharides by UPLC-Q-TOF-MS. And the comprehensive evaluation of anti-inflammatory effect for CA-A indicated that CA-A inhibited inflammatory cells migration in zebrafish with a dose-dependent manner, and promote the up-regulation of IL-10 and the down-regulation of TNF-α and IL-1β. Eventually, network pharmacology and transcriptomic analysis, together with RT-qPCR verification revealed that CA-A suppressed inflammation progression by down-regulating PI3K/AKT, MAPK, and NF-κB signaling pathways and up-regulating PPAR signaling pathway. These findings offered guidance for its potential applications of C. album and provide a novel foundation for development of CA-A as functional food to inhibit inflammation.