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葛根素通过调节药物转运体及Nrf2/NF-κB/Bcl-2信号通路改善黄独诱导的肝损伤。

Puerarin improves Dioscorea bulbifera L.-induced liver injury by regulating drug transporters and the Nrf2/NF-κB/Bcl-2 signaling pathway.

作者信息

Wang Xin, Zhang Yuhan, Zhu Hongzhe, Shi Leilei, Shi Yong, Cao Shanshan, Liu Jiping, Xie Yundong

机构信息

Department of Pharmacology, Shaanxi University of Chinese Medicine, No. 1 Middle Section of Century Avenue, Xianyang, 712046, People's Republic of China.

Key Laboratory of Pharmacodynamic Mechanism and Material Basis of Traditional Chinese Medicine, Shaanxi Administration of Traditional Chinese Medicine, Xianyang, 712046, People's Republic of China.

出版信息

J Pharm Pharmacol. 2024 Dec 2;76(12):1620-1633. doi: 10.1093/jpp/rgae123.

Abstract

PURPOSE

Investigate the protective effect and mechanism of Puerarin (PU) against Dioscorea bulbifera L. (DB)-induced liver injury.

MATERIALS AND METHODS

The protective effect of PU against DB-induced liver injury was evaluated by the present animal experiment, which assessed the pathological changes in the liver of mice and detected Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Alkaline phosphatase (AKP), as well as inflammation and oxidative stress-related indexes. Finally, the transcription and expression of related proteins were detected using western blot and quantitative reverse transcription (PCR) techniques.

RESULTS

PU significantly increased body weight, reduced liver index, and attenuated pathological changes in the liver compared to the DB group. It also decreased levels of AST, ALT, AKP, tumor necrosis factor-α, interleukin-1β, and malondialdehyde while increasing interleukin-10 levels and superoxide dismutase activity. Additionally, it upregulated inhibitor of NF-κB (IκB-α), B-cell lymphoma-2 (Bcl-2), Nuclear respiratory factor 2 (Nrf2), and Heme oxygenase 1 (HO-1) expression while down-regulating p-NF-κB p65 and bcl2-associated x (Bax) expression in the liver. Furthermore, PU upregulated protein and gene expression levels of Multidrug resistance-associated protein2, bile salt export pump, p-glycoprotein, and UDP-glucuronyltransferase 1A1 (UGT1A1) as well.

CONCLUSION

PU mitigates DB-induced liver injury by regulating the expression of drug transporters and modulating the Nrf2/NF-κB/Bcl-2 signaling pathway.

摘要

目的

研究葛根素(PU)对黄独(DB)所致肝损伤的保护作用及机制。

材料与方法

通过本动物实验评估PU对DB所致肝损伤的保护作用,该实验评估了小鼠肝脏的病理变化,并检测了丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、碱性磷酸酶(AKP)以及炎症和氧化应激相关指标。最后,采用蛋白质印迹法和定量逆转录(PCR)技术检测相关蛋白的转录和表达。

结果

与DB组相比,PU显著增加体重,降低肝脏指数,并减轻肝脏病理变化。它还降低了AST、ALT、AKP、肿瘤坏死因子-α、白细胞介素-1β和丙二醛水平,同时提高了白细胞介素-10水平和超氧化物歧化酶活性。此外,它上调了肝脏中核因子κB抑制蛋白(IκB-α)、B细胞淋巴瘤-2(Bcl-2)、核呼吸因子2(Nrf2)和血红素加氧酶1(HO-1)的表达,同时下调了磷酸化核因子κB p65和bcl2相关X蛋白(Bax)的表达。此外,PU还上调了多药耐药相关蛋白2、胆盐输出泵、P-糖蛋白和尿苷二磷酸葡萄糖醛酸基转移酶1A1(UGT1A1)的蛋白和基因表达水平。

结论

PU通过调节药物转运体的表达和调控Nrf2/NF-κB/Bcl-2信号通路减轻DB所致的肝损伤。

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