Cleome amblyocarpa Barr. and Murb. from the family Cleomaceae is used in folk medicine as it has analgesic, anti-inflammatory, antibacterial and antioxidant activities.

Cornulacin, a new isoflavone, was isolated from Cornulaca monacantha with structural elucidation and cytotoxicity against ovarian A2780 cancer through apoptosis induction.

The COVID-19 pandemic has spread throughout the whole globe, so it is imperative that all available resources be used to treat this scourge.

Natural medicines with neuroprotective, antioxidative, and anti-inflammatory characteristics may act as promising neuroprotective agents against neurodegenerative disorders. This study aims to determine the essential components of the methanolic extract of Cornulaca monacantha, and to explore their neuroprotection against lipopolysaccharides (LPS)-induced neuroinflammation in Neuro-2a mouse neuroblastoma cells, and also to investigate the possible underlying molecular mechanism through tracing the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. LC-ESI-TOF-MS/MS was conducted for metabolomic profiling, together with the determination of bioactive compounds. The MTT assay was performed to select an appropriate cytoprotective dose for further analyses. Then, the cells were divided into three groups: control, LPS, and LPS + C. monacantha extract. Inflammatory cytokines, gene expression of Nrf2-related genes, and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α)-mediated mitochondrial adaptation were also detected. Protein–protein interaction (PPI) network analysis and gene ontology (GO) enrichment analysis based on biological process were also performed. C. monacantha crude extract showed meaningful contents of flavonoids and phenolic compounds, together with other 49 additional hits detected by LC-ESI-TOF-MS/MS. It also showed a significant antioxidant capacity by 2,2-diphenyl-1-picrylhydrazyl hydrate (DPPH) and ferric reducing antioxidant power (FRAP) assays. The extract also exhibited a significant decline in the level of inflammatory biomarkers, along with modulation of the Nrf2 signaling pathway. C. monacantha showed beneficial phytochemical composition, which may be responsible for the neuroprotective effect that might be mediated through modulation of Nrf2 expression and related genes, together with the anti-inflammatory capability. Other molecular pathways were found to be interconnected with the Nrf2 pathway, as revealed by PPI and GO, which may act as further molecular targets in neuroinflammation.