Bioavailable fraction from the edible leaf of <i>Albizia lebbeck</i> (L.) Benth. inhibits neurotoxicity in human microglial HMC3 cells and promotes lifespan in <i>Caenorhabditis elegans</i>

Abstract Neurodegeneration is involved in the deterioration and death of cells in the central nervous system. Albizia lebbeck (L.) Benth. has exhibited antioxidant and health benefits. This study focused on the protective effect and underlying mechanism of the bioavailable fraction of A. lebbeck leaf (BAL) against toxicity of glutamate-induced endoplasmic reticulum (ER) stress and cell death in human microglial HMC3 cells, as well as evaluated the longevity and antioxidant effects of BAL in Caenorhabditis elegans. The BAL was obtained from the in vitro digestion of A. lebbeck leaf coupled with Caco-2 cells. Results showed that treating HMC3 cells with BAL attenuated glutamate-induced ER stress and apoptosis by decreasing the protein expressions of calpain1, caspase-12, Bax, cytochrome c, and cleaved caspase-9 while increasing the antiapoptotic Bcl-2. Additionally, LC–MS/MS results showed that BAL contained flavonoids and carotenoids such as quercetin-3β-D-glucoside, robinetin, vitexin, kaempferol, kuromanin, daidzein, tanshinon I, nootkatone, rutin, and luteolin. We further investigated molecular docking to illustrate these bioactive compounds on apoptosis-related mechanisms. The results demonstrated that luteolin, kaempferol, and nootkatone inhibited Bax, cytochrome c, and caspase-9 functions. We found that BAL also extended the lifespan of C. elegans and distinctly increased survival in response to juglone-induced oxidative stress. Interestingly, treating C. elegans with BAL could increase superoxide dismutase 3 expression, relating to the anti-stress response. These findings suggest that BAL possesses beneficial function in neuroprotection and longevity, supporting its potential for preventing age-related neurodegeneration.