Curcuma longa L. extract and residue prevent Alzheimer’s disease in mice by regulating microglia and TLR4/NF-κB signaling pathway

Abstract Background Curcuma longa L. (CL) is renowned for its various health benefits and has shown potential in alleviating Alzheimer’s disease (AD). The post-aqueous extraction residues (CLR) may retain valuable nutritional components. The research aimed to explore their chemical composition and neuroprotective mechanism against Aβ1-42-induced AD mice. Methods We employed UPLC-Q-Exactive/MS to characterize the chemical constituents of CL and CLR. An HPLC method was developed to quantify three predominant curcuminoids. To investigate their neuroprotective effects against Aβ1-42-induced AD mice, we assessed cognitive function using the Morris water maze and evaluated neuronal damage through histopathological examination. Molecular mechanisms were explored using immunofluorescence, ELISA, and qRT-PCR assays. Results The study unveiled 47 and 36 compounds in CL and CLR, respectively, and eight significant differential components. HPLC analysis revealed that CLR contained substantial curcuminoids. In Aβ1-42-induced AD mice, CL and CLR improved spatial learning and memory ability, ameliorated pathological alterations in the hippocampal region, and regulated overactivated microglia. Moreover, CL and CLR inhibited the TLR4/NF-κB inflammatory pathway. Conclusion CL and CLR exhibit the anti-AD effect by regulating microglia and suppressing the TLR4/NF-κB signaling pathway, which provides a scientific basis for future nutraceutical and pharmaceutical development.