Inhibition of ferroptosis by geniposide via activation of the SIRT3 signaling pathway to alleviate inflammatory injury in endothelial cells

Wen-Ting SUN; Miao-Miao ZHAO; Zhao-Ling SHI

doi:10.7499/j.issn.1008-8830.2507089

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Chinese Journal of Contemporary Pediatrics ›› 2026, Vol. 28 ›› Issue (4) : 486-492. DOI: 10.7499/j.issn.1008-8830.2507089

EXPERIMENTAL RESEARCH

Inhibition of ferroptosis by geniposide via activation of the SIRT3 signaling pathway to alleviate inflammatory injury in endothelial cells

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Abstract

Objective To study the effect and mechanism of geniposide (GE) on lipopolysaccharide (LPS)-induced inflammatory injury in human coronary artery endothelial cells (HCAECs). Methods HCAECs were randomly assigned to four groups: control (no treatment); model (LPS 20 ng/mL for 24 hours); GE (GE 30 μg/mL pretreatment for 12 hours, followed by LPS 20 ng/mL for 24 hours); and SIRT3 inhibitor (GE 40 μg/mL plus the SIRT3-specific inhibitor 3-TYP pretreatment for 12 hours, followed by LPS 20 ng/mL for 24 hours). Cell viability was assessed by CCK-8 assay. Lactate dehydrogenase (LDH) activity in culture medium and intracellular malondialdehyde (MDA), glutathione (GSH), and ferrous ion (Fe²⁺) levels were measured using commercial kits. Reactive oxygen species (ROS) were evaluated by DCFH-DA fluorescent probe method. Western blotting detected the protein expression of silent information regulator 3 (SIRT3), glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), and transferrin receptor 1 (TfR1). SIRT3 expression was examined by immunofluorescence staining. Results Compared with the control group, the model group showed decreased cell viability, GSH content, SIRT3 immunofluorescence intensity, and GPX4, SLC7A11, and SIRT3 protein expression (P<0.05), with increased LDH activity, TfR1 protein expression, and MDA, Fe²⁺, and ROS levels (P<0.05). Compared with the model group, the GE group exhibited increased cell viability, GSH content, SIRT3 immunofluorescence intensity, and GPX4, SLC7A11, and SIRT3 protein expression (P<0.05), and decreased LDH activity, TfR1 protein expression, and MDA, Fe²⁺, and ROS levels (P<0.05). Compared with the GE group, the SIRT3 inhibitor group showed reduced cell viability, GSH content, SIRT3 immunofluorescence intensity, and GPX4, SLC7A11, and SIRT3 protein expression (P<0.05), along with elevated LDH activity, TfR1 protein expression, and MDA, Fe²⁺, and ROS levels (P<0.05). Conclusions Geniposide alleviates LPS-induced inflammatory injury in HCAECs, and the mechanism may involve inhibition of ferroptosis and activation of SIRT3 signaling.

Key words

Geniposide / Silent information regulator 3 / Ferroptosis / Lipopolysaccharide / Human coronary artery endothelial cell

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Wen-Ting SUN , Miao-Miao ZHAO , Zhao-Ling SHI. Inhibition of ferroptosis by geniposide via activation of the SIRT3 signaling pathway to alleviate inflammatory injury in endothelial cells[J]. Chinese Journal of Contemporary Pediatrics. 2026, 28(4): 486-492 https://doi.org/10.7499/j.issn.1008-8830.2507089

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