Hydroxysafflor yellow A ameliorates alcohol-induced liver injury through PI3K/Akt and STAT3/NF-κB signaling pathways

PI3K/AKT/mTOR通路 蛋白激酶B 车站3 信号转导 肝损伤 化学 NF-κB 药理学 癌症研究 细胞生物学 医学 生物 生物化学
作者
Wenxuan Wang,Min Liu,Xianglei Fu,Man Qi,Furong Zhu,Furong Fan,Yuanchuang Wang,Kaiyue Zhang,Shenghui Chu
出处
期刊:Phytomedicine [Elsevier]
卷期号:132: 155814-155814 被引量:1
标识
DOI:10.1016/j.phymed.2024.155814
摘要

Alcohol-associated liver disease (ALD) is a prevalent liver ailment. It has escalated into a significant public health issue, imposing substantial burdens on medical, economic, and social domains. Currently, oxidative stress, inflammation, and apoptosis are recognized as crucial culprits in improving ALD. Consequently, mitigating these issues has emerged as a promising avenue for enhancing ALD. Hydroxysafflor yellow A (HSYA) is the main ingredient in safflower, showing excellent antioxidative stress, anti-inflammatory, and anti-apoptosis traits. However, there are limited investigations into the mechanisms by which HSYA ameliorates ALD PURPOSE: We investigated whether HSYA, a significant constituent of Asteraceae safflower, exerts antioxidant stress and attenuates inflammation and anti-apoptotic effects through PI3K/Akt and STAT3/NF-κB pathways, thereby ameliorating ALD METHODS: We established two experimental models: an ethanol-induced liver damage mouse model in vivo and a HepG2 cell alcohol injury model in vitro RESULTS: The results demonstrated that HSYA effectively ameliorated liver tissue damage, reduced levels of ALT, AST, LDL-C, TG, TC, and MDA, enhanced HDL-C levels, SOD and GSH activities, reduced ROS accumulation in cells, and activated the Nrf2 pathway, a transcription factor involved in antioxidant defense. By regulating the PI3K/Akt and STAT3/NF-κB pathways, HSYA exhibits notable antioxidative stress, anti-inflammatory, and anti-apoptotic effects, effectively impeding ALD's advancement. To further confirm the regulatory effect of HSYA on PI3K/Akt and downstream signaling pathways, the PI3K activator 740 Y-P was used and was found to reverse the downregulation of PI3K by HSYA CONCLUSION: This study supports the effectiveness of HSYA in reducing ALD by regulating the PI3K/Akt and STAT3/NF-κB pathways, indicating its potential medicinal value.
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