Genistein Promotes Anti-Heat Stress and Antioxidant Effects via the Coordinated Regulation of IIS, HSP, MAPK, DR, and Mitochondrial Pathways in Caenorhabditis elegans

To determine the anti-heat stress and antioxidant effects of genistein and the underlying mechanisms, lipofuscin, reactive oxygen species (ROS), and survival under stress were first detected inCaenorhabditis elegans (C. elegans); then the localization and quantification of the fluorescent protein was determined by detecting the fluorescently labeled protein mutant strain; in addition, the aging-related mRNAs were detected by applying real-time fluorescent quantitative PCR inC. elegans. The results indicate that genistein substantially extended the lifespan ofC. elegansunder oxidative stress and heat conditions; and remarkably reduced the accumulation of lipofuscin inC. elegansunder hydrogen peroxide (H2O2) and 35 °C stress conditions; in addition, it reduced the generation of ROS caused by H2O2and upregulated the expression ofdaf-16,ctl-1,hsf-1,hsp-16.2,sip-1,sek-1,pmk-1, andeat-2, whereas it downregulated the expression ofage-1anddaf-2inC. elegans;similarly, it upregulated the expression ofdaf-16,sod-3,ctl-1,hsf-1,hsp-16.2,sip-1,sek-1,pmk-1,jnk-1 skn-1, andeat-2, whereas it downregulated the expression ofage-1,daf-2,gst-4, andhsp-12.6inC. elegansat 35 °C; moreover, it increased the accumulation of HSP-16.2 and SKN-1 proteins in nematodes under 35 °C and H2O2conditions; however, it failed to prolong the survival time in the deleted mutant MQ130 nematodes under 35 °C and H2O2conditions. These results suggest that genistein promote anti-heat stress and antioxidant effects inC. elegansvia insulin/-insulin-like growth factor signaling (IIS), heat shock protein (HSP), mitogen-activated protein kinase (MAPK), dietary restriction (DR), and mitochondrial pathways.Keywords:genistein;anti-heat stress;antioxidant;Caenorhabditis elegans