| Summary: | 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 in <i>Caenorhabditis elegans (C. elegans</i>); 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 in <i>C. elegans</i>. The results indicate that genistein substantially extended the lifespan of <i>C. elegans</i> under oxidative stress and heat conditions; and remarkably reduced the accumulation of lipofuscin in <i>C. elegans</i> under hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) and 35 °C stress conditions; in addition, it reduced the generation of ROS caused by H<sub>2</sub>O<sub>2</sub> and upregulated the expression of <i>daf-16</i>, <i>ctl-1</i>, <i>hsf-1</i>, <i>hsp-16.2</i>, <i>sip-1</i>, <i>sek-1</i>, <i>pmk-1</i>, and <i>eat-2</i>, whereas it downregulated the expression of <i>age-1</i> and <i>daf-2</i> in <i>C. elegans;</i> similarly, it upregulated the expression of <i>daf-16</i>, <i>sod-3</i>, <i>ctl-1</i>, <i>hsf-1</i>, <i>hsp-16.2</i>, <i>sip-1</i>, <i>sek-1</i>, <i>pmk-1</i>, <i>jnk-1 skn-1</i>, and <i>eat-2</i>, whereas it downregulated the expression of <i>age-1</i>, <i>daf-2</i>, <i>gst-4</i>, and <i>hsp-12.6</i> in <i>C. elegans</i> at 35 °C; moreover, it increased the accumulation of HSP-16.2 and SKN-1 proteins in nematodes under 35 °C and H<sub>2</sub>O<sub>2</sub> conditions; however, it failed to prolong the survival time in the deleted mutant MQ130 nematodes under 35 °C and H<sub>2</sub>O<sub>2</sub> conditions. These results suggest that genistein promote anti-heat stress and antioxidant effects in <i>C. elegans</i> via insulin/-insulin-like growth factor signaling (IIS), heat shock protein (HSP), mitogen-activated protein kinase (MAPK), dietary restriction (DR), and mitochondrial pathways.
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