Veronica persica ameliorates acetaminophen-induced murine hepatotoxicity via attenuating oxidative stress and inflammation

Excess acetaminophen (APAP) commonly causes severe acute liver injury (ALI), characterized by oxidative stress, pro-inflammatory responses, and hepatocyte damage. Veronica persica (VP) is a traditional medicine with antioxidant and anti-inflammatory properties. There is a paucity of information on i...

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Main Authors: Wei-shun Tian, Jing Zhao, Myung-Kon Kim, Hyun-Jin Tae, In-Shik Kim, Dongchoon Ahn, Hong Pil Hwang, Ming-xian Mao, Byung-Yong Park
Format: Article
Language:English
Published: Elsevier 2023-12-01
Series:Biomedicine & Pharmacotherapy
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0753332223016967
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author Wei-shun Tian
Jing Zhao
Myung-Kon Kim
Hyun-Jin Tae
In-Shik Kim
Dongchoon Ahn
Hong Pil Hwang
Ming-xian Mao
Byung-Yong Park
author_facet Wei-shun Tian
Jing Zhao
Myung-Kon Kim
Hyun-Jin Tae
In-Shik Kim
Dongchoon Ahn
Hong Pil Hwang
Ming-xian Mao
Byung-Yong Park
author_sort Wei-shun Tian
collection DOAJ
description Excess acetaminophen (APAP) commonly causes severe acute liver injury (ALI), characterized by oxidative stress, pro-inflammatory responses, and hepatocyte damage. Veronica persica (VP) is a traditional medicine with antioxidant and anti-inflammatory properties. There is a paucity of information on its medicinal value, especially its potential mechanisms for alleviating ALI. This study aimed to clarify the ameliorative effects and intracellular mechanisms of VP on APAP-induced ALI via attenuating oxidative stress and inflammation. Mice were given VP for 7 days before exposure to APAP (300 mg/kg). The HPLC and radical scavenging assay found that VP contains 12 phenolic acids and 6 flavonoids, as well as show robust antioxidant capacity. In the APAP-induced ALI model, pre-treatment with VP significantly reduces APAP-induced hepatotoxicity by observing improved hepatocyte pathological injury and further confirmed by serum biochemical indicator. Also, the reduction of TUNEL-positive regions and the regulation of Bcl-2-associated X protein indicated that VP attenuates hepatocytotoxicity. Moreover, VP pre-intervention inhibits the formation of liver pro-inflammatory cytokines, the expression of inflammatory response genes, and increases in myeloperoxidase (MPO) in APAP-exposed mice. The elevated reduced glutathione (GSH) levels and decreased oxidative stress markers indicate that VP reduces APAP-promoted oxidative stress. Further study revealed that VP inhibited the phosphorylation of NF-κB/STAT3 cascade, blocked ERK and JNK phosphorylation, and activated AMP-activated protein kinase (AMPK). To sum up, this study demonstrated that VP exists hepatoprotective abilities on APAP-induced ALI, primarily by suppressing the phosphorylation of NF-κB/STAT3 cascade and ERK-JNK and inducing AMPK activation to alleviate oxidative stress and inflammation.
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spelling doaj.art-bc12d9c460094aa1b8095a33ab21aaea2023-12-05T04:14:43ZengElsevierBiomedicine & Pharmacotherapy0753-33222023-12-01169115898Veronica persica ameliorates acetaminophen-induced murine hepatotoxicity via attenuating oxidative stress and inflammationWei-shun Tian0Jing Zhao1Myung-Kon Kim2Hyun-Jin Tae3In-Shik Kim4Dongchoon Ahn5Hong Pil Hwang6Ming-xian Mao7Byung-Yong Park8College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, Henan, People’s Republic of China; College of Veterinary Medicine and Institute of Animal Transplantation, Jeonbuk National University, Iksan, Jeollabuk-do 54596, Republic of KoreaCollege of Animal Science and Technology, Henan University of Science and Technology, Luoyang, Henan, People’s Republic of ChinaDepartment of Food Science and Technology, Jeonbuk National University, Jeonju 54896, Republic of KoreaCollege of Veterinary Medicine and Institute of Animal Transplantation, Jeonbuk National University, Iksan, Jeollabuk-do 54596, Republic of KoreaCollege of Veterinary Medicine and Institute of Animal Transplantation, Jeonbuk National University, Iksan, Jeollabuk-do 54596, Republic of KoreaCollege of Veterinary Medicine and Institute of Animal Transplantation, Jeonbuk National University, Iksan, Jeollabuk-do 54596, Republic of KoreaDepartment of Surgery of Jeonbuk National University Medical School and Hospital, Jeonju 54896, Republic of KoreaCollege of Animal Science and Technology, Henan University of Science and Technology, Luoyang, Henan, People’s Republic of ChinaCollege of Veterinary Medicine and Institute of Animal Transplantation, Jeonbuk National University, Iksan, Jeollabuk-do 54596, Republic of Korea; Corresponding author.Excess acetaminophen (APAP) commonly causes severe acute liver injury (ALI), characterized by oxidative stress, pro-inflammatory responses, and hepatocyte damage. Veronica persica (VP) is a traditional medicine with antioxidant and anti-inflammatory properties. There is a paucity of information on its medicinal value, especially its potential mechanisms for alleviating ALI. This study aimed to clarify the ameliorative effects and intracellular mechanisms of VP on APAP-induced ALI via attenuating oxidative stress and inflammation. Mice were given VP for 7 days before exposure to APAP (300 mg/kg). The HPLC and radical scavenging assay found that VP contains 12 phenolic acids and 6 flavonoids, as well as show robust antioxidant capacity. In the APAP-induced ALI model, pre-treatment with VP significantly reduces APAP-induced hepatotoxicity by observing improved hepatocyte pathological injury and further confirmed by serum biochemical indicator. Also, the reduction of TUNEL-positive regions and the regulation of Bcl-2-associated X protein indicated that VP attenuates hepatocytotoxicity. Moreover, VP pre-intervention inhibits the formation of liver pro-inflammatory cytokines, the expression of inflammatory response genes, and increases in myeloperoxidase (MPO) in APAP-exposed mice. The elevated reduced glutathione (GSH) levels and decreased oxidative stress markers indicate that VP reduces APAP-promoted oxidative stress. Further study revealed that VP inhibited the phosphorylation of NF-κB/STAT3 cascade, blocked ERK and JNK phosphorylation, and activated AMP-activated protein kinase (AMPK). To sum up, this study demonstrated that VP exists hepatoprotective abilities on APAP-induced ALI, primarily by suppressing the phosphorylation of NF-κB/STAT3 cascade and ERK-JNK and inducing AMPK activation to alleviate oxidative stress and inflammation.http://www.sciencedirect.com/science/article/pii/S0753332223016967Veronica persica (VP)Acetaminophen (APAP)Acute liver injury (ALI)Oxidative stressERK-JNKAMPK
spellingShingle Wei-shun Tian
Jing Zhao
Myung-Kon Kim
Hyun-Jin Tae
In-Shik Kim
Dongchoon Ahn
Hong Pil Hwang
Ming-xian Mao
Byung-Yong Park
Veronica persica ameliorates acetaminophen-induced murine hepatotoxicity via attenuating oxidative stress and inflammation
Biomedicine & Pharmacotherapy
Veronica persica (VP)
Acetaminophen (APAP)
Acute liver injury (ALI)
Oxidative stress
ERK-JNK
AMPK
title Veronica persica ameliorates acetaminophen-induced murine hepatotoxicity via attenuating oxidative stress and inflammation
title_full Veronica persica ameliorates acetaminophen-induced murine hepatotoxicity via attenuating oxidative stress and inflammation
title_fullStr Veronica persica ameliorates acetaminophen-induced murine hepatotoxicity via attenuating oxidative stress and inflammation
title_full_unstemmed Veronica persica ameliorates acetaminophen-induced murine hepatotoxicity via attenuating oxidative stress and inflammation
title_short Veronica persica ameliorates acetaminophen-induced murine hepatotoxicity via attenuating oxidative stress and inflammation
title_sort veronica persica ameliorates acetaminophen induced murine hepatotoxicity via attenuating oxidative stress and inflammation
topic Veronica persica (VP)
Acetaminophen (APAP)
Acute liver injury (ALI)
Oxidative stress
ERK-JNK
AMPK
url http://www.sciencedirect.com/science/article/pii/S0753332223016967
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