β-sitosterol, an important component in the fruits of <i>Alpinia oxyphylla</i> Miq., prolongs lifespan of <i>Caenorhabditis elegans</i> by suppressing the ferroptosis pathway.

Junyi LI; Siyuan CHEN; Liyao XIE; Jin WANG; Ao CHENG; Shaowei ZHANG; Jiyu LIN; Zhihan FANG; Yirui PAN; Chonghe CUI; Gengxin CHEN; Chao ZHANG; Li LI

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β-sitosterol, an important component in the fruits of Alpinia oxyphylla Miq., prolongs lifespan of Caenorhabditis elegans by suppressing the ferroptosis pathway.

Author: Junyi LI ¹ ; Siyuan CHEN ² ; Liyao XIE ¹ ; Jin WANG ³ ; Ao CHENG ¹ ; Shaowei ZHANG ¹ ; Jiyu LIN ³ ; Zhihan FANG ³ ; Yirui PAN ³ ; Chonghe CUI ⁴ ; Gengxin CHEN ⁴ ; Chao ZHANG ³ ; Li LI ⁵
Author Information

1. First School of Clinical Medicine.
2. Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southern Medical University; Guangdong Provincial Key Laboratory of Single Cell Technology and Application, Guangzhou 510000, China.
3. Second School of Clinical Medicine, Southern Medical University, Guangzhou 510000, China.
4. School of Health, Guangdong Pharmaceutical University, Guangzhou 510006, China.
5. Department of Pathogenic Biology & Key Laboratory of Tropical Translational Medicine of Ministry of Education, School of Basic Medicine and Life Sciences, Hainan Medical University. Haikou 571199, China.
Publication Type:Journal Article
Keywords: ETS-5; ferroptosis; senescence; β-sitosterol
MeSH: Animals; Caenorhabditis elegans/physiology*; Ferroptosis/drug effects*; Alpinia/chemistry*; Sitosterols/pharmacology*; Longevity/drug effects*; Fruit/chemistry*; Humans
From: Journal of Southern Medical University 2025;45(8):1751-1757
CountryChina
Language:Chinese
Abstract: OBJECTIVES: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.
CONCLUSIONS: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.