Licochalcone A prevents cognitive decline in a lipopolysaccharide-induced neuroinflammation mice model

• DOI: 10.1186/s10020-025-01106-8
• Publication Date: 2025-02-11T01:23:11Z
• Authors: Marina Carrasco; Laura Guzman; Jordi Olloquequi; Amanda Cano; Ana Fortuna; Manuel Vazquez-Ca...; Ester Verdaguer; Carme Auladell; Miren Ettcheto; Antoni Camins
• Keywords: Cognitive Decline; SOD2

Abstract Inflammation plays a key role in the development of neurodegenerative disorders that are currently incurable. Licochalcone A (LCA) has been described as an emerging anti-inflammatory drug with multiple therapeutical properties could potentially prevent neurodegeneration. However, its neuroprotective mechanism remains unclear. Here, we investigated if LCA prevents cognitive decline induced by Lipopolysaccharide (LPS) and elucidated potential benefits. For that, 8-week-old C57BL6/J male mice were intraperitonially (i.p.) treated saline solution or (15 mg/kg/day, 3 times per week) for two weeks. The last day, single i.p injection LPS (1 mg/kg) was administered 24 h before sacrifice. results revealed significant reduction mRNA expression genes involved oxidative stress (S od1, Cat, Pkm, Pdha1, Ndyfv1, Uqcrb1, Cycs Cox4i1), metabolism (Slc2a1, Slc2a2, Prkaa1 Gsk3b) synapsis ( Bdnf, Nrxn3 Nlgn2) group compared to saline. These findings linked memory impairment depressive-like behavior observed this group. Interestingly, protected against alterations through effect, reducing gliosis regulating M1/M2 markers. Moreover, LCA-treated animals showed improvement antioxidant mechanisms, such citrate synthase activity SOD2. Additionally, demonstrated protection metabolic disturbances, downregulating GLUT4 P-AKT, enhanced synaptic-related proteins (P-CREB, BDNF, PSD95, DBN1 NLG3), leading all together dendritic spine preservation. In conclusion, our demonstrate treatment LPS-induced inflammation, enhancing response, protecting disruptions improving related mechanisms.