Investigating the Effect and Potential Mechanism of Rhamnetin 3-<i>O</i>-α-Rhamnoside on Acute Liver Injury In Vivo and In Vitro

<b>Background/Objectives</b>: Rhamnetin 3-<i>O</i>-α-rhamnoside (ARR) is a major flavonoid of the herb <i>Loranthus tanakae</i> Franch. & Sav., which has been used for treating liver diseases in China. However, the protective effect of ARR on the liver has not...

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Main Authors: Dandan Deng, Borong Zhao, Hong Yang, Songsong Wang, Ziying Geng, Jiangtao Zhou, Guane Yang, Liwen Han
Format: Article
Language:English
Published: MDPI AG 2025-01-01
Series:Pharmaceuticals
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Online Access:https://www.mdpi.com/1424-8247/18/1/116
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author Dandan Deng
Borong Zhao
Hong Yang
Songsong Wang
Ziying Geng
Jiangtao Zhou
Guane Yang
Liwen Han
author_facet Dandan Deng
Borong Zhao
Hong Yang
Songsong Wang
Ziying Geng
Jiangtao Zhou
Guane Yang
Liwen Han
author_sort Dandan Deng
collection DOAJ
description <b>Background/Objectives</b>: Rhamnetin 3-<i>O</i>-α-rhamnoside (ARR) is a major flavonoid of the herb <i>Loranthus tanakae</i> Franch. & Sav., which has been used for treating liver diseases in China. However, the protective effect of ARR on the liver has not been reported. <b>Methods</b>: Zebrafish larvae were used as a visual animal model, and liver injury was induced by thioacetamide (TAA) for an acute liver injury (ALI) model. The hepatoprotective activity of ARR was evaluated by assessing liver morphology, liver function indices, oxidative stress, and the mRNA expression levels of inflammation-related genes in the zebrafish model. Additionally, the ROS level, inflammatory factors, and protein expression related to the IKKβ/NF-κB signaling pathway were measured to investigate a potential mechanism of ARR in HepG2 cells. <b>Results</b>: ARR ameliorated TAA-induced growth retardation, reduced liver injury phenotypes, and decreased oxidative stress in the zebrafish. ARR was also able to lower ROS levels in HepG2 cells, effectively inhibit the overactivation of the IKKβ/NF-κB signaling pathway in pathological conditions, inhibit NF-κB p65 translocation from the cytoplasm to the nucleus, and reduce the release of intracellular inflammatory factors. <b>Conclusions</b>: ARR showed significant protective activity against TAA-induced liver injury in in vivo and in vitro models, and its potential mechanism was closely related to the IKKβ/NF-κB signaling pathway.
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spelling doaj-art-ae9403278d83469e9756b74fe99383a62025-01-24T13:45:27ZengMDPI AGPharmaceuticals1424-82472025-01-0118111610.3390/ph18010116Investigating the Effect and Potential Mechanism of Rhamnetin 3-<i>O</i>-α-Rhamnoside on Acute Liver Injury In Vivo and In VitroDandan Deng0Borong Zhao1Hong Yang2Songsong Wang3Ziying Geng4Jiangtao Zhou5Guane Yang6Liwen Han7School of Pharmaceutical Sciences, Shanxi Medical University, No. 56 South Xinjian Road, Taiyuan 030001, ChinaSchool of Pharmaceutical Sciences, Shanxi Medical University, No. 56 South Xinjian Road, Taiyuan 030001, ChinaSchool of Pharmaceutical Sciences, Shanxi Medical University, No. 56 South Xinjian Road, Taiyuan 030001, ChinaSchool of Pharmaceutical Sciences & Institute of Materia Medica, Shandong First Medical University & Shandong Academy of Medical Science, No. 6699 Qingdao Road, Jinan 250117, ChinaSchool of Pharmaceutical Sciences, Shanxi Medical University, No. 56 South Xinjian Road, Taiyuan 030001, ChinaSchool of Pharmaceutical Sciences, Shanxi Medical University, No. 56 South Xinjian Road, Taiyuan 030001, ChinaSchool of Pharmaceutical Sciences, Shanxi Medical University, No. 56 South Xinjian Road, Taiyuan 030001, ChinaSchool of Pharmaceutical Sciences & Institute of Materia Medica, Shandong First Medical University & Shandong Academy of Medical Science, No. 6699 Qingdao Road, Jinan 250117, China<b>Background/Objectives</b>: Rhamnetin 3-<i>O</i>-α-rhamnoside (ARR) is a major flavonoid of the herb <i>Loranthus tanakae</i> Franch. & Sav., which has been used for treating liver diseases in China. However, the protective effect of ARR on the liver has not been reported. <b>Methods</b>: Zebrafish larvae were used as a visual animal model, and liver injury was induced by thioacetamide (TAA) for an acute liver injury (ALI) model. The hepatoprotective activity of ARR was evaluated by assessing liver morphology, liver function indices, oxidative stress, and the mRNA expression levels of inflammation-related genes in the zebrafish model. Additionally, the ROS level, inflammatory factors, and protein expression related to the IKKβ/NF-κB signaling pathway were measured to investigate a potential mechanism of ARR in HepG2 cells. <b>Results</b>: ARR ameliorated TAA-induced growth retardation, reduced liver injury phenotypes, and decreased oxidative stress in the zebrafish. ARR was also able to lower ROS levels in HepG2 cells, effectively inhibit the overactivation of the IKKβ/NF-κB signaling pathway in pathological conditions, inhibit NF-κB p65 translocation from the cytoplasm to the nucleus, and reduce the release of intracellular inflammatory factors. <b>Conclusions</b>: ARR showed significant protective activity against TAA-induced liver injury in in vivo and in vitro models, and its potential mechanism was closely related to the IKKβ/NF-κB signaling pathway.https://www.mdpi.com/1424-8247/18/1/116rhamnetin 3-<i>O</i>-α-rhamnosideacute liver injuryzebrafishIKKβ/NF-κB signaling pathwaynuclear translocationthioacetamide
spellingShingle Dandan Deng
Borong Zhao
Hong Yang
Songsong Wang
Ziying Geng
Jiangtao Zhou
Guane Yang
Liwen Han
Investigating the Effect and Potential Mechanism of Rhamnetin 3-<i>O</i>-α-Rhamnoside on Acute Liver Injury In Vivo and In Vitro
Pharmaceuticals
rhamnetin 3-<i>O</i>-α-rhamnoside
acute liver injury
zebrafish
IKKβ/NF-κB signaling pathway
nuclear translocation
thioacetamide
title Investigating the Effect and Potential Mechanism of Rhamnetin 3-<i>O</i>-α-Rhamnoside on Acute Liver Injury In Vivo and In Vitro
title_full Investigating the Effect and Potential Mechanism of Rhamnetin 3-<i>O</i>-α-Rhamnoside on Acute Liver Injury In Vivo and In Vitro
title_fullStr Investigating the Effect and Potential Mechanism of Rhamnetin 3-<i>O</i>-α-Rhamnoside on Acute Liver Injury In Vivo and In Vitro
title_full_unstemmed Investigating the Effect and Potential Mechanism of Rhamnetin 3-<i>O</i>-α-Rhamnoside on Acute Liver Injury In Vivo and In Vitro
title_short Investigating the Effect and Potential Mechanism of Rhamnetin 3-<i>O</i>-α-Rhamnoside on Acute Liver Injury In Vivo and In Vitro
title_sort investigating the effect and potential mechanism of rhamnetin 3 i o i α rhamnoside on acute liver injury in vivo and in vitro
topic rhamnetin 3-<i>O</i>-α-rhamnoside
acute liver injury
zebrafish
IKKβ/NF-κB signaling pathway
nuclear translocation
thioacetamide
url https://www.mdpi.com/1424-8247/18/1/116
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