Naringin ameliorates liver fibrosis in zebrafish by modulating IDO1-mediated lipid metabolism and inflammatory infiltration

Liver fibrosis (LF) is an important reparative process in response to acute or chronic hepatic injury, which has the potential to advance towards cirrhosis and hepatocellular carcinoma. Dietary naringin consumption contributes to protection against LF in animal studies, while the exact protective me...

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Veröffentlicht in:Food & function 2023-11, Vol.14 (23), p.1347-1361
Hauptverfasser: Qin, Meng-chen, Li, Jun-jie, Zheng, Yan-tao, Li, Yun-jia, Zhang, Yu-xue, Ou, Rou-xuan, He, Wei-yi, Zhao, Jia-min, Liu, Su-tong, Liu, Ming-hao, Lin, Hai-yan, Gao, Lei
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container_end_page 1361
container_issue 23
container_start_page 1347
container_title Food & function
container_volume 14
creator Qin, Meng-chen
Li, Jun-jie
Zheng, Yan-tao
Li, Yun-jia
Zhang, Yu-xue
Ou, Rou-xuan
He, Wei-yi
Zhao, Jia-min
Liu, Su-tong
Liu, Ming-hao
Lin, Hai-yan
Gao, Lei
description Liver fibrosis (LF) is an important reparative process in response to acute or chronic hepatic injury, which has the potential to advance towards cirrhosis and hepatocellular carcinoma. Dietary naringin consumption contributes to protection against LF in animal studies, while the exact protective mechanism of naringin remains unclear. This study aimed to investigate the molecular mechanisms behind the potential protective effect of naringin against TAA-induced LF in zebrafish. In this study, we utilized zebrafish to create the LF model and investigate the therapeutic mechanism of naringin. Firstly, we evaluated the changes in hepatic fibrosis and lipid accumulation in the liver following naringin treatment with oil red O, Nile red, and Sirius red and immunohistochemistry. In addition, we employed an ROS probe to directly measure oxidative stress and monitor inflammatory cell migration in a zebrafish transgenic line. Morpholino was used in the knockdown of IDO1 in order to verify its vital role in LF. Our findings demonstrated that naringin exhibited anti-inflammatory and anti-fibrotic action in conjunction with a reversal in lipid accumulation, oxidative stress and suppression of macrophage infiltration and activation of hepatic stellate cells. Furthermore, the results showed that the antifibrotic effect of naringin was removed upon IDO1 knockdown, proving that naringin exerts a protective effect by regulating IDO1. Naringin demonstrates remarkable protective effects against LF, effectively counteracting inflammation and hepatic steatosis in zebrafish liver. These findings suggest that naringin may function as an effective IDO1 inhibitor, holding the potential for clinical translation as a therapeutic agent for the treatment of LF. Liver fibrosis (LF) is an important reparative process in response to acute or chronic hepatic injury, which has the potential to advance towards cirrhosis and hepatocellular carcinoma.
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Dietary naringin consumption contributes to protection against LF in animal studies, while the exact protective mechanism of naringin remains unclear. This study aimed to investigate the molecular mechanisms behind the potential protective effect of naringin against TAA-induced LF in zebrafish. In this study, we utilized zebrafish to create the LF model and investigate the therapeutic mechanism of naringin. Firstly, we evaluated the changes in hepatic fibrosis and lipid accumulation in the liver following naringin treatment with oil red O, Nile red, and Sirius red and immunohistochemistry. In addition, we employed an ROS probe to directly measure oxidative stress and monitor inflammatory cell migration in a zebrafish transgenic line. Morpholino was used in the knockdown of IDO1 in order to verify its vital role in LF. Our findings demonstrated that naringin exhibited anti-inflammatory and anti-fibrotic action in conjunction with a reversal in lipid accumulation, oxidative stress and suppression of macrophage infiltration and activation of hepatic stellate cells. Furthermore, the results showed that the antifibrotic effect of naringin was removed upon IDO1 knockdown, proving that naringin exerts a protective effect by regulating IDO1. Naringin demonstrates remarkable protective effects against LF, effectively counteracting inflammation and hepatic steatosis in zebrafish liver. These findings suggest that naringin may function as an effective IDO1 inhibitor, holding the potential for clinical translation as a therapeutic agent for the treatment of LF. Liver fibrosis (LF) is an important reparative process in response to acute or chronic hepatic injury, which has the potential to advance towards cirrhosis and hepatocellular carcinoma.</description><identifier>ISSN: 2042-6496</identifier><identifier>EISSN: 2042-650X</identifier><identifier>DOI: 10.1039/d3fo03858k</identifier><language>eng</language><publisher>Cambridge: Royal Society of Chemistry</publisher><subject>Accumulation ; Cell activation ; Cirrhosis ; Danio rerio ; Diet ; Fatty liver ; Fibrosis ; Hepatocellular carcinoma ; Immunohistochemistry ; Infiltration ; Inflammation ; Leukocyte migration ; Lipid metabolism ; Lipids ; Liver ; Macrophages ; Molecular modelling ; Oxidative stress ; Pharmacology ; Steatosis ; Stellate cells ; Zebrafish</subject><ispartof>Food &amp; function, 2023-11, Vol.14 (23), p.1347-1361</ispartof><rights>Copyright Royal Society of Chemistry 2023</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c314t-683db722392c6e966db73d3f772733b207b90267bfb9da0772cedb95261b87873</citedby><cites>FETCH-LOGICAL-c314t-683db722392c6e966db73d3f772733b207b90267bfb9da0772cedb95261b87873</cites><orcidid>0000-0001-9030-390X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,781,785,27929,27930</link.rule.ids></links><search><creatorcontrib>Qin, Meng-chen</creatorcontrib><creatorcontrib>Li, Jun-jie</creatorcontrib><creatorcontrib>Zheng, Yan-tao</creatorcontrib><creatorcontrib>Li, Yun-jia</creatorcontrib><creatorcontrib>Zhang, Yu-xue</creatorcontrib><creatorcontrib>Ou, Rou-xuan</creatorcontrib><creatorcontrib>He, Wei-yi</creatorcontrib><creatorcontrib>Zhao, Jia-min</creatorcontrib><creatorcontrib>Liu, Su-tong</creatorcontrib><creatorcontrib>Liu, Ming-hao</creatorcontrib><creatorcontrib>Lin, Hai-yan</creatorcontrib><creatorcontrib>Gao, Lei</creatorcontrib><title>Naringin ameliorates liver fibrosis in zebrafish by modulating IDO1-mediated lipid metabolism and inflammatory infiltration</title><title>Food &amp; function</title><description>Liver fibrosis (LF) is an important reparative process in response to acute or chronic hepatic injury, which has the potential to advance towards cirrhosis and hepatocellular carcinoma. 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Liver fibrosis (LF) is an important reparative process in response to acute or chronic hepatic injury, which has the potential to advance towards cirrhosis and hepatocellular carcinoma.</description><subject>Accumulation</subject><subject>Cell activation</subject><subject>Cirrhosis</subject><subject>Danio rerio</subject><subject>Diet</subject><subject>Fatty liver</subject><subject>Fibrosis</subject><subject>Hepatocellular carcinoma</subject><subject>Immunohistochemistry</subject><subject>Infiltration</subject><subject>Inflammation</subject><subject>Leukocyte migration</subject><subject>Lipid metabolism</subject><subject>Lipids</subject><subject>Liver</subject><subject>Macrophages</subject><subject>Molecular modelling</subject><subject>Oxidative stress</subject><subject>Pharmacology</subject><subject>Steatosis</subject><subject>Stellate cells</subject><subject>Zebrafish</subject><issn>2042-6496</issn><issn>2042-650X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><recordid>eNpdkctLAzEQxhdRsKgX70LAiwir2aTN4yj1icVeFLwtySarqcmmJluh-s87tT7AXJLJ_L5JZr6i2K_wSYWpPDW0jZiKkXjZKAYED0nJRvhx8-c8lGy72Mt5hmFRKYUUg-LjTiXXPbkOqWC9i0n1NiPv3mxCrdMpZpcRZN-tTqp1-RnpJQrRLLzqQYduzqdVGaxxoDOgmzuDgu2Vjt7lgFRnQN16FYLqY1quAud7eMXFbrfYapXPdu973ykeLi_ux9flZHp1Mz6blA2thn3JBDWaE0IlaZiVjEFEoVfOCadUE8y1xIRx3WppFIbrxhotR4RVWnDB6U5xtK47T_F1YXNfB5cb673qbFzkmgjBRlCXrNDDf-gsLlIHvwNKwmy5lEOgjtdUA_PJybb1PLmg0rKucL2yoj6nl9MvK24BPljDKTe_3J9V9BNuOIbM</recordid><startdate>20231127</startdate><enddate>20231127</enddate><creator>Qin, Meng-chen</creator><creator>Li, Jun-jie</creator><creator>Zheng, Yan-tao</creator><creator>Li, Yun-jia</creator><creator>Zhang, Yu-xue</creator><creator>Ou, Rou-xuan</creator><creator>He, Wei-yi</creator><creator>Zhao, Jia-min</creator><creator>Liu, Su-tong</creator><creator>Liu, Ming-hao</creator><creator>Lin, Hai-yan</creator><creator>Gao, Lei</creator><general>Royal Society of Chemistry</general><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>7T7</scope><scope>7TO</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-9030-390X</orcidid></search><sort><creationdate>20231127</creationdate><title>Naringin ameliorates liver fibrosis in zebrafish by modulating IDO1-mediated lipid metabolism and inflammatory infiltration</title><author>Qin, Meng-chen ; Li, Jun-jie ; Zheng, Yan-tao ; Li, Yun-jia ; Zhang, Yu-xue ; Ou, Rou-xuan ; He, Wei-yi ; Zhao, Jia-min ; Liu, Su-tong ; Liu, Ming-hao ; Lin, Hai-yan ; Gao, Lei</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c314t-683db722392c6e966db73d3f772733b207b90267bfb9da0772cedb95261b87873</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Accumulation</topic><topic>Cell activation</topic><topic>Cirrhosis</topic><topic>Danio rerio</topic><topic>Diet</topic><topic>Fatty liver</topic><topic>Fibrosis</topic><topic>Hepatocellular carcinoma</topic><topic>Immunohistochemistry</topic><topic>Infiltration</topic><topic>Inflammation</topic><topic>Leukocyte migration</topic><topic>Lipid metabolism</topic><topic>Lipids</topic><topic>Liver</topic><topic>Macrophages</topic><topic>Molecular modelling</topic><topic>Oxidative stress</topic><topic>Pharmacology</topic><topic>Steatosis</topic><topic>Stellate cells</topic><topic>Zebrafish</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Qin, Meng-chen</creatorcontrib><creatorcontrib>Li, Jun-jie</creatorcontrib><creatorcontrib>Zheng, Yan-tao</creatorcontrib><creatorcontrib>Li, Yun-jia</creatorcontrib><creatorcontrib>Zhang, Yu-xue</creatorcontrib><creatorcontrib>Ou, Rou-xuan</creatorcontrib><creatorcontrib>He, Wei-yi</creatorcontrib><creatorcontrib>Zhao, Jia-min</creatorcontrib><creatorcontrib>Liu, Su-tong</creatorcontrib><creatorcontrib>Liu, Ming-hao</creatorcontrib><creatorcontrib>Lin, Hai-yan</creatorcontrib><creatorcontrib>Gao, Lei</creatorcontrib><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Food &amp; 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Dietary naringin consumption contributes to protection against LF in animal studies, while the exact protective mechanism of naringin remains unclear. This study aimed to investigate the molecular mechanisms behind the potential protective effect of naringin against TAA-induced LF in zebrafish. In this study, we utilized zebrafish to create the LF model and investigate the therapeutic mechanism of naringin. Firstly, we evaluated the changes in hepatic fibrosis and lipid accumulation in the liver following naringin treatment with oil red O, Nile red, and Sirius red and immunohistochemistry. In addition, we employed an ROS probe to directly measure oxidative stress and monitor inflammatory cell migration in a zebrafish transgenic line. Morpholino was used in the knockdown of IDO1 in order to verify its vital role in LF. Our findings demonstrated that naringin exhibited anti-inflammatory and anti-fibrotic action in conjunction with a reversal in lipid accumulation, oxidative stress and suppression of macrophage infiltration and activation of hepatic stellate cells. Furthermore, the results showed that the antifibrotic effect of naringin was removed upon IDO1 knockdown, proving that naringin exerts a protective effect by regulating IDO1. Naringin demonstrates remarkable protective effects against LF, effectively counteracting inflammation and hepatic steatosis in zebrafish liver. These findings suggest that naringin may function as an effective IDO1 inhibitor, holding the potential for clinical translation as a therapeutic agent for the treatment of LF. Liver fibrosis (LF) is an important reparative process in response to acute or chronic hepatic injury, which has the potential to advance towards cirrhosis and hepatocellular carcinoma.</abstract><cop>Cambridge</cop><pub>Royal Society of Chemistry</pub><doi>10.1039/d3fo03858k</doi><tpages>15</tpages><orcidid>https://orcid.org/0000-0001-9030-390X</orcidid></addata></record>
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source Royal Society Of Chemistry Journals
subjects Accumulation
Cell activation
Cirrhosis
Danio rerio
Diet
Fatty liver
Fibrosis
Hepatocellular carcinoma
Immunohistochemistry
Infiltration
Inflammation
Leukocyte migration
Lipid metabolism
Lipids
Liver
Macrophages
Molecular modelling
Oxidative stress
Pharmacology
Steatosis
Stellate cells
Zebrafish
title Naringin ameliorates liver fibrosis in zebrafish by modulating IDO1-mediated lipid metabolism and inflammatory infiltration
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