连翘酯苷A通过抑制PXR介导的氧化应激减轻APAP诱发的小鼠肝损伤

doi:10.3969/j.issn.1674-7968.2026.04.011

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Abstract Excessive use of acetaminophen (APAP) can promote liver oxidative stress and cause liver damage. Forsythiaside A (FA), as the phenylethanol glycoside active component of the Chinese herb Forsythia, may have a hepatoprotective effect. To investigate the effect of FA on APAP-induced oxidative stress, C57BL/6 mice (Mus musculus) and alpha mouse liver 12 (AML12) cells were randomly divided into 4 groups: Blank control (NC), APAP-induced liver injury group (APAP), FA control group (FA), and FA treatment group (APAP+FA). Serum and cell supernatants were analyzed for alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity to determine the effective concentration of FA for treating APAP-induced liver injury. Levels of superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA), and hydrogen peroxide (H₂O₂) in mouse liver tissue were measured, and pathological changes in liver tissue were observed to explore the therapeutic effect of FA on APAP-induced liver injury. A pregnane X receptor (PXR) overexpression plasmid was constructed, and C57BL/6 mice and AML12 cells were divided into 5 groups: normal control (NC), APAP-induced liver injury (APAP), APAP+PXR overexpression (APAP+PXR(OE)), FA treatment (APAP+FA), and FA treatment with PXR overexpression (APAP+FA+PXR(OE)). The effects of FA on SOD activity, GSH, MDA, H₂O₂, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) content, PXR protein and gene expression levels, and liver pathology were observed, and a rescue experiment was designed to verify the potential mechanism. The results showed that FA significantly reduced ALT and AST activity, as well as MDA and H₂O₂ content in APAP model mice (P<0.05), increased SOD activity and GSH content (P<0.05), and improved liver tissue pathology. FA also significantly reduced MDA, H₂O₂ content, and TNF-α, IL-1β, IL-6 levels (P<0.05), and increased SOD activity and GSH content (P<0.05) by inhibiting PXR. In conclusion, FA ameliorated oxidative stress by inhibiting PXR, thereby exerting a protective effect against APAP-induced liver injury. This study provides new ideas for the treatment of drug-induced liver injury and a theoretical foundation for the hepatoprotective effect of FA through inhibiting PXR.

Key words： Forsythiaside A (FA) Pregnane X receptor (PXR) Acetaminophen (APAP) Liver injury Oxidative stress

Received: 24 January 2025

ZTFLH:

S859.7

Corresponding Authors: ^*wangmeng@gsau.edu.cn

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	GUO Fu-Hui
	PU Si-Si
	PAN Yang-Yang
	LIU Hui-Min
	ZHANG Jian-Hui
	ZHANG Qian
	WANG Li-Bin
	WANG Meng

Cite this article:

GUO Fu-Hui,PU Si-Si,PAN Yang-Yang, et al. Forsythiaside A Attenuates APAP-induced Liver Injury in Mus musculus by Inhibiting PXR-mediated Oxidative Stress[J]. 农业生物技术学报, 2026, 34(4): 812-822.

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https://journal05.magtech.org.cn/Jwk_ny/EN/10.3969/j.issn.1674-7968.2026.04.011 OR https://journal05.magtech.org.cn/Jwk_ny/EN/Y2026/V34/I4/812

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