Neuroprotective effects of Artemisia monosperma against LPS-induced neuroinflammation via TLR4 modulation and myeloperoxidase inhibition: metabolomic and molecular insights

Abstract Background Neuroinflammation substantially contributes to the progression of several neurodegenerative illnesses primarily triggered by activated microglia and the release of proinflammatory mediators. Artemisia monosperma , a medicinal herb rich in bioactive compounds, has been studied for its antioxidant and anti-inflammatory effects. This study aims to evaluate the neuroprotective effectiveness of A . monosperma against LPS-induced neuroinflammation in Neuro 2a cells, while also detailing its metabolic profile and antioxidant properties. Methodology The neuroprotective potential of A . monosperma methanolic extract has been assessed against LPS-induced neuroinflammation in Neuro 2a mouse neuroblastoma cells line through tracing TLR4 signaling and its related proteins, together with determining inflammatory cytokines and oxidative stress biomarkers. The Folin–Ciocalteu and aluminum chloride techniques were used to measure the extract total phenolics and flavonoid contents, respectively. The triple-time-of-flight tandem mass spectrometry (LC/triple-Q-TOF–MS/MS) coupled with reversed phase high-performance liquid chromatography was used to examine the metabolic profile of the plant. Results Artemisia monosperma contained total phenolic and flavonoid contents of 73.85 ± 4.55 μg GA E/mg and 22.38 ± 1.21 µg RE/mg, respectively. Significant antioxidant capacity (FRAP) was shown by A. monosperma extract (341.00 ± 6.34 μM eq/mg) in comparison with Trolox (6.57 ± 0.449 µg/mL). The radical-scavenging efficacy of DPPH (IC 50 values of 86.46 ± 2.77 µg/mL) was determined using Trolox as a standard drug. Analysis utilizing (LC-ESI-TOF–MS/MS) of A. monosperma extract revealed 48 hits, mostly polyphenols. Artemisia monosperma extract showed significant neuroprotective effect. This is accomplished by inhibiting TLR4, which reduces neuroinflammatory mediators and the oxidative stress caused by LPS in Neuro 2a mouse neuroblastoma cells. Molecular modeling study highlighted the bis-glycosidic flavones as the top-binding metabolites toward the human myeloperoxidase enzyme capable of competing with the enzyme natural substrate. Conclusion These results demonstrate that A. monosperma and/or its active components could be effective protective agents against neuroinflammatory disorders with potential molecular mechanistic activity toward the human myeloperoxidase enzyme, the key contributor to oxidative stress within inflammatory diseases including neurodegenerative conditions.