β-sitosterol,an important component in the fruits of Alpinia oxyphylla Miq.,prolongs lifespan of Caenorhabditis elegans by suppressing the ferroptosis pathway
LI Junyi
CHEN Siyuan
XIE Liyao
WANG Jin
CHENG Ao
ZHANG Shaowei
LIN Jiyu
FANG Zhihan
PAN Yirui
CUI Chonghe
CHEN Gengxin
ZHANG Chao
LI Li
Abstract：Objective To elucidate the anti-aging effect of β-sitosterol(BS),an important component in the fruits of Alpinia oxyphylla Miq.,in C.elegans and its regulatory effect on ETS-5 gene to modulate ferroptosis.Methods C.elegans treated with 10 µg/mL BS were monitored for survival time and changes in body length,motility,and reproductive function.The effect of ETS-5 gene knockdown on survival time of C.elegans was observed,and the changes in fat accumulation and lipid redox homeostasis in the transfected C.elegans were assessed using Oil Red O staining and by detecting MDA levels and the GSH/GSSG ratio.The mRNA expression levels of ferroptosis-related genes(FTN-1,GPX-1 and AAT-9)were detected using qPCR.The effects of BS treatment and ETS-5 knockdown on AAT-9 enzyme activity in C.elegans were examined.The effect of BS on nuclear localization of FEV(the human homolog of ETS-5)was validated in cultured human umbilical venous endothelial cells(HUVECs).Results Both BS treatment and ETS-5 knockdown significantly prolonged the lifespan,promoted lipid accumulation and reduced lipid peroxidation in C.elegans.ETS-5 knockdown resulted in upregulated expressions of the ferroptosis repressors GPX-1,AAT-9 and FTN-1 and increased the GSH/GSSG ratio in C.elegans.Conclusion BS inhibits ferroptosis in C.elegans by suppressing the expression of ETS-5 transcription factor and hence the activity of AAT-9 enzyme,a key gene for ferroptosis,which in turn prolongs the lifespan of C.elegans.
Keywords：β-sitosterolsenescenceferroptosisETS-5
Publication Date：2025-08-20
Online Publishing Date：2025-09-15(First online date of this platform, not the publication date of the document)
Pages：7( 1751-1757 )