Metabolomics in combination with network pharmacology reveals the potential anti-neuroinflammatory mechanism of essential oils from four Curcuma species

In China, Curcuma plants have been widely used as traditional Chinese medicine in the treatment of inflammation-related diseases for thousands of years. This study aimed to investigate the anti-neuroinflammatory effect of essential oils (EOs) from four Curcuma species, including Curcuma longa L. (CL), Curcuma kwangsiensis S.G. Lee and C.F. Liang (CK), Curcuma zedoaria (Christm.) Roscoe (CZ) and Curcuma aro-matica Salisb. (CA), and to explore the underlying mechanisms using metabolomics and network pharmacology. A total of 49 chemical compositions were identified in EOs from four Curcuma species, and the main compounds included ar-turmerone (67.76%), curzerenone (2.33-50.43%), nootkatone (14.41%), curlone (12.93%), beta-Ele-mene (2.15-11.47%), curzerene (1.55-11.01%), 1,8-Cineole (11.00%) and humulene (1.89-10.99%). In the Morris water maze test, these EOs significantly improved cognitive impairment in LPS-induced mice. Treatment of these EOs protected neurons and inhibited microglia activation. Besides, a significant reduction of inflam-matory cytokines (IL-6, TNF-alpha, IL-1 beta and MCP-1) was detected in the brain tissue of mice. Based on the metabolomics of blood, 11 metabolites mainly associated with arachidonic acid metabolism, linoleic acid metabolism, and aminoacyl-tRNA biosynthesis were identified. Network pharmacology further validated these metabolic pathways and suggested that EOs may interfere with multiple neurodegenerative diseases and inflammation-related signaling pathways by modulating metabolic changes. In conclusion, this study demon-strates the inhibitory effect of four Curcuma EOs on neuroinflammation and suggests that they may be candidates for the treatment of neuroinflammation.