Uncovering the quality markers and mechanisms of Gastrodia elata against LPS-induced neuroinflammation via network pharmacology and experimental verification

ETHNOPHARMACOLOGICAL RELEVANCE: Gastrodia elata Blume (TM), a renowned traditional Chinese medicinal herb, has long been clinically used for the treatment of dizziness, stroke and other cerebrovascular diseases. Modern pharmacological investigations have confirmed that its neuroprotective effects are closely associated with the amelioration of neuroinflammation. Nevertheless, the underlying anti-neuroinflammatory mechanisms and quality markers (Q-marker) of TM remain to be further elucidated. AIM OF THE STUDY: To identify the Q-marker and mechanisms of TM anti-neuroinflammation based on network pharmacology and experimental verification. MATERIALS AND METHODS: Integrated chemical composition analysis and network pharmacology predict Q-Marker and mechanisms of TM in alleviating neuroinflammation, verified by in vivo and in vitro experiments. RESULTS: Gastrodin (GAS) and p-hydroxybenzyl alcohol (HBA) were identified as the efficacy Q-marker of TM for ameliorating neuroinflammation. The in vitro and in vivo experimental results demonstrated that TM, GAS and HBA all could regulate the polarization shift of microglia from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype, inhibit the release of TNF-α, IL-6 and IL-1β, reduce neuronal apoptosis, and alleviate inflammatory injuries in BALB/c mice and BV2 microglial cells. Furthermore, Western blot assay confirmed that the underlying molecular mechanism of the anti-neuroinflammatory efficacy exerted by TM, GAS and HBA might be mediated by inhibiting the Src/NF-κB signaling pathway. CONCLUSIONS: GAS and HBA as the key Q-marker responsible for the anti-neuroinflammatory activity of TM, primarily by inhibiting of the Src/NF-κB signaling pathway.