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

IF 2.8 4区 医学 Q2 PHARMACOLOGY & PHARMACY Journal of Pharmacy and Pharmacology Pub Date : 2024-10-07 DOI:10.1093/jpp/rgae123
Xin Wang, Yuhan Zhang, Hongzhe Zhu, Leilei Shi, Yong Shi, Shanshan Cao, Jiping Liu, Yundong Xie
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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.

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葛根素通过调节药物转运体和Nrf2/NF-κB/Bcl-2信号通路改善薯蓣皂苷诱导的肝损伤
目的:研究葛根素(Puerarin,PU)对薯蓣(Dioscorea bulbifera L.,DB)诱导的肝损伤的保护作用及其机制:本动物实验评估了葛根素对DB诱导的肝损伤的保护作用,评估了小鼠肝脏的病理变化,检测了丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、碱性磷酸酶(AKP)以及炎症和氧化应激相关指标。最后,利用 Western 印迹和定量反转录(PCR)技术检测了相关蛋白质的转录和表达:结果:与 DB 组相比,PU 能明显增加体重,降低肝脏指数,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 和丙二醛的水平,同时提高了白细胞介素-10 的水平和超氧化物歧化酶的活性。此外,它还能上调肝脏中 NF-κB 抑制剂(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 p-NF-κB p65 和 bcl2 相关 x(Bax)的表达。此外,聚氨酯还能上调多药耐药性相关蛋白2、胆盐输出泵、p-糖蛋白和UDP-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Nrf2/NF-κB/Bcl-2信号通路,减轻了DB诱导的肝损伤。
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来源期刊
CiteScore
6.60
自引率
0.00%
发文量
91
审稿时长
3 months
期刊介绍: JPP keeps pace with new research on how drug action may be optimized by new technologies, and attention is given to understanding and improving drug interactions in the body. At the same time, the journal maintains its established and well-respected core strengths in areas such as pharmaceutics and drug delivery, experimental and clinical pharmacology, biopharmaceutics and drug disposition, and drugs from natural sources. JPP publishes at least one special issue on a topical theme each year.
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