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槲皮素7-鼠李糖苷通过改善胆汁排泄和抑制炎症反应，对α-萘异硫氰酸酯（ANIT）诱导的胆汁淤积性肝炎大鼠起到保护作用。

Quercetin 7-rhamnoside protects against alpha-naphthylisothiocyanate (ANIT)-induced in cholestatic hepatitis rats by improving biliary excretion and inhibiting inflammatory responses.

作者信息

Jin Hong-Liu, Liu Xiao-Jia, Feng Xiao-Ying, Zhu Wen-Ting, Feng Sen-Ling, Cao Li-Ping, Yuan Zhong-Wen

机构信息

Department of Pharmacy, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, China.

出版信息

Front Pharmacol. 2023 Jan 9;13:1116257. doi: 10.3389/fphar.2022.1116257. eCollection 2022.

DOI:10.3389/fphar.2022.1116257
PMID:36699093
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9868710/
Abstract

To explore the pharmacological effects and molecular mechanism of quercetin 7-rhamnoside (Q7R) in the treatment of cholestatic hepatitis induced by alpha-naphthylisothiocyanate (ANIT). ANIT-induced cholestatic hepatitis rat model was used to investigate the hepatoprotective effects of three different doses of Q7R (1.25 mg/kg; 2.5 mg/kg; 5 mg/kg). Serum biochemical indices were detected using commercial kits. H&E and masson staining were used to observe hepatic tissue damage and collagen deposition in hepatocytes. The metabolism of bile acid-related substances was detected HPLC-MS/MS by 5-(diisopropylamino) amylamine (DIAAA) derivative method. Hepatocyte injury, cholestasis, and inflammation were detected at the mRNA and protein levels using reverse transcription-polymerase chain reaction (RT-PCR) and western blotting, respectively. Q7R can decrease the level of CYP7A1, and increase FXR, CYP27A1 so then improving abnormal bile acid secretion. Furthermore, Q7R can also ameliorating inflammation by reduce TNF-α, IL-1β, PTGS1, PTGS2, NCOA2, NF-κB level. Therefore, Q7R had an effective therapeutic effect on ANIT-induced cholestatic hepatitis, improving abnormal bile acid secretion, and inhibiting inflammatory responses. The results demonstrated that Q7R treat cholestatic hepatitis by regulating bile acid secretion and alleviating inflammation.

摘要

探讨槲皮素7-鼠李糖苷（Q7R）治疗α-萘异硫氰酸酯（ANIT）诱导的胆汁淤积性肝炎的药理作用及分子机制。采用ANIT诱导的胆汁淤积性肝炎大鼠模型，研究三种不同剂量的Q7R（1.25mg/kg；2.5mg/kg；5mg/kg）的肝脏保护作用。使用商业试剂盒检测血清生化指标。采用苏木精-伊红（H&E）染色和马松染色观察肝组织损伤及肝细胞内胶原沉积情况。采用5-（二异丙基氨基）戊胺（DIAAA）衍生化法，通过高效液相色谱-串联质谱（HPLC-MS/MS）检测胆汁酸相关物质的代谢情况。分别采用逆转录-聚合酶链反应（RT-PCR）和蛋白质印迹法在mRNA和蛋白质水平检测肝细胞损伤、胆汁淤积及炎症情况。Q7R可降低CYP7A1水平，升高法尼醇X受体（FXR）、CYP27A1水平，从而改善胆汁酸分泌异常。此外，Q7R还可通过降低肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）、前列腺素内过氧化物合酶1（PTGS1）、前列腺素内过氧化物合酶2（PTGS2）、核受体辅激活因子2（NCOA2）、核因子κB（NF-κB）水平来减轻炎症。因此，Q7R对ANIT诱导的胆汁淤积性肝炎具有有效的治疗作用，可改善胆汁酸分泌异常并抑制炎症反应。结果表明，Q7R通过调节胆汁酸分泌和减轻炎症来治疗胆汁淤积性肝炎。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db6c/9868710/dafa0645c411/fphar-13-1116257-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db6c/9868710/7726b9dbee2f/fphar-13-1116257-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db6c/9868710/4666cc22e2ac/fphar-13-1116257-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db6c/9868710/f38197b3baf5/fphar-13-1116257-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db6c/9868710/59995dbd5807/fphar-13-1116257-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db6c/9868710/482c76af4d55/fphar-13-1116257-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db6c/9868710/2fea6d6435ed/fphar-13-1116257-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db6c/9868710/dafa0645c411/fphar-13-1116257-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db6c/9868710/7726b9dbee2f/fphar-13-1116257-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db6c/9868710/4666cc22e2ac/fphar-13-1116257-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db6c/9868710/f38197b3baf5/fphar-13-1116257-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db6c/9868710/59995dbd5807/fphar-13-1116257-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db6c/9868710/482c76af4d55/fphar-13-1116257-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db6c/9868710/2fea6d6435ed/fphar-13-1116257-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db6c/9868710/dafa0645c411/fphar-13-1116257-g007.jpg

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[2]
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本文引用的文献

[1]
Transcriptome and Gut Microbiota Profiling Analysis of ANIT-Induced Cholestasis and the Effects of Da-Huang-Xiao-Shi Decoction Intervention.

Microbiol Spectr. 2022-12-21

[2]
Hyjapones A-D, trimethylated acyphloroglucinol meroterpenoids from Hypericum japonicum thunb. With anti-inflammatory activity.

Phytochemistry. 2022-10

[3]
Combination of resveratrol and luteolin ameliorates α-naphthylisothiocyanate-induced cholestasis by regulating the bile acid homeostasis and suppressing oxidative stress.

Food Funct. 2022-7-4

[4]
Intrahepatic cholestasis induced by α-naphthylisothiocyanate can cause gut-liver axis disorders.

Environ Toxicol Pharmacol. 2021-8

[5]
A Network Pharmacology Study of the Molecular Mechanisms of Hypericum japonicum in the Treatment of Cholestatic Hepatitis with Validation in an Alpha-Naphthylisothiocyanate (ANIT) Hepatotoxicity Rat Model.

Med Sci Monit. 2021-3-3

[6]
Metabolism pathways of arachidonic acids: mechanisms and potential therapeutic targets.

Signal Transduct Target Ther. 2021-2-26

[7]
Ginsenoside Rg1 alleviates ANIT-induced intrahepatic cholestasis in rats via activating farnesoid X receptor and regulating transporters and metabolic enzymes.

Chem Biol Interact. 2020-3-18

[8]
Picroside II protects against cholestatic liver injury possibly through activation of farnesoid X receptor.

Phytomedicine. 2019-12-16

[9]
Isorhamnetin Inhibits Liver Fibrosis by Reducing Autophagy and Inhibiting Extracellular Matrix Formation via the TGF-1/Smad3 and TGF-1/p38 MAPK Pathways.

Mediators Inflamm. 2019-7-31

[10]
LC-MS and HR-MS characterization of secondary metabolites from Hypericum japonicum Thunb. ex Murray from Nepalese Himalayan region and assessment of cytotoxic effect and inhibition of NF-κB and AP-1 transcription factors in vitro.

J Pharm Biomed Anal. 2019-7-2

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