Essential oil from seven homologous Zingiberaceae alleviates lipopolysaccharide-induced neuroinflammation: Integrated assessment of molecular mechanisms, gene regulation, and metabolite control

Excessive neuroinflammation may contribute to central nervous system disorders including multiple sclerosis, Alzheimer's disease, and Parkinson's disease. Zingiberaceae plants demonstrate documented sedative, analgesic, and anti-inflammatory properties. This study systematically investigated the therapeutic potential and mechanisms of essential oils (EOs) derived from seven Zingiberaceae species: Amomum tsaoko Crevost & Lem. (Amo), Zingiber officinale Roscoe (Zin), Alpinia officinarum Hance (AoH), Curcuma longa L. (Cur), Kaempferia galanga L. (Kae), Amomum villosum Lour. (AmV), and Alpinia oxyphylla Miq. (AoM). The findings provide scientific evidence for developing novel therapeutics targeting neuroinflammatory disorders. Primary phytochemical characterization was performed using microwave-assisted hydrodistillation coupled with gas chromatography-mass spectrometry (GC-MS) for qualitative and quantitative analysis. An LPS-induced neuroinflammation model was established in mice. Mechanistic investigations employed multimodal approaches including: Morris water maze experiment, immunohistochemistry, neuronal Nissl staining, transcriptomics, and metabolomics. The results revealed that all seven Zingiberaceae EOs significantly enhanced cognitive performance in mice with LPS-induced neuroinflammation, preserved neuronal architecture, upregulated Bcl-2 anti-apoptotic protein expression, and attenuated neuroinflammatory responses. Transcriptomic and metabolomic results indicated that the seven Zingiberaceae essential oils may have therapeutic effects on neuroinflammation by regulating signaling pathways such as MAPK, histidine metabolism, pantothenate and coenzyme A biosynthesis, phenylalanine metabolism and other metabolic pathways. • Essential oils from seven Zingiberaceae plants ameliorate learning and memory deficits in LPS-induced mice by protecting neurons. • These essential oils promote the expression of anti-apoptotic protein Bcl-2 in brain cells of mice with neuroinflammation, thus providing a protective effect. • Multiple neuroinflammatory signaling pathways and metabolic pathways are involved in the anti-neuroinflammatory mechanisms of the essential oils.