Worenine Prevents Solar Ultraviolet–Induced Sunburn by Inhibiting JNK2

Excessive solar ultraviolet (SUV) radiation often causes dermatitis, photoaging, and even skin cancer. In the pathological processes of SUV-induced sunburn, JNK is activated by phosphorylation, and it in turn phosphorylates its downstream transcription factors, such as ATF2 and c-jun. The transcript...

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Main Authors: Juanjuan Xiao, Hui Lu, Tengfei Ma, Xiaofang Ni, Teding Chang, Man Liu, Nijie Li, Peijiang Lu, Changshu Ke, Qin Tian, Ling Zou, Fei Wang, Wei Wang, Lu Zhang, Ping Yuan, Lin Liu, Jianmin Zhang, Fei Shi, Qiuhong Duan, Feng Zhu
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-07-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2022.881042/full
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author Juanjuan Xiao
Juanjuan Xiao
Hui Lu
Hui Lu
Tengfei Ma
Xiaofang Ni
Teding Chang
Man Liu
Nijie Li
Peijiang Lu
Changshu Ke
Qin Tian
Ling Zou
Fei Wang
Wei Wang
Lu Zhang
Ping Yuan
Lin Liu
Jianmin Zhang
Fei Shi
Qiuhong Duan
Feng Zhu
Feng Zhu
Feng Zhu
Feng Zhu
author_facet Juanjuan Xiao
Juanjuan Xiao
Hui Lu
Hui Lu
Tengfei Ma
Xiaofang Ni
Teding Chang
Man Liu
Nijie Li
Peijiang Lu
Changshu Ke
Qin Tian
Ling Zou
Fei Wang
Wei Wang
Lu Zhang
Ping Yuan
Lin Liu
Jianmin Zhang
Fei Shi
Qiuhong Duan
Feng Zhu
Feng Zhu
Feng Zhu
Feng Zhu
author_sort Juanjuan Xiao
collection DOAJ
description Excessive solar ultraviolet (SUV) radiation often causes dermatitis, photoaging, and even skin cancer. In the pathological processes of SUV-induced sunburn, JNK is activated by phosphorylation, and it in turn phosphorylates its downstream transcription factors, such as ATF2 and c-jun. The transcription factors further regulate the expression of pro-inflammatory genes, such as IL-6 and TNF-α, which ultimately leads to dermatitis. Therefore, inhibiting JNK may be a strategy to prevent dermatitis. In this study, we screened for worenine as a potential drug candidate for inhibiting sunburn. We determined that worenine inhibited the JNK-ATF2/c-jun signaling pathway and the secretion of IL-6 and TNF-α in cell culture and in vivo, confirming the role of worenine in inhibiting sunburn. Furthermore, we determined that worenine bound and inhibited JNK2 activity in vitro through the MST, kinase, and in vitro kinase assays. Therefore, worenine might be a promising drug candidate for the prevention and treatment of SUV-induced sunburn.
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spelling doaj.art-24134b29180d4992bffef8021c37ed802022-12-22T00:50:43ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-07-011310.3389/fphar.2022.881042881042Worenine Prevents Solar Ultraviolet–Induced Sunburn by Inhibiting JNK2Juanjuan Xiao0Juanjuan Xiao1Hui Lu2Hui Lu3Tengfei Ma4Xiaofang Ni5Teding Chang6Man Liu7Nijie Li8Peijiang Lu9Changshu Ke10Qin Tian11Ling Zou12Fei Wang13Wei Wang14Lu Zhang15Ping Yuan16Lin Liu17Jianmin Zhang18Fei Shi19Qiuhong Duan20Feng Zhu21Feng Zhu22Feng Zhu23Feng Zhu24Cancer Research Institute, The Affiliated Hospital of Guilin Medical University, Guilin, ChinaGuangxi Health Commission Key Laboratory of Novel Onco-Kinases in Target Therapy, The Affiliated Hospital of Guilin Medical University, Guilin, ChinaWuhan Children’s Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Biochemistry and Molecular Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Biochemistry and Molecular Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaWuhan Children’s Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaSecond Clinical College, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaSecond Clinical College, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaSecond Clinical College, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaSecond Clinical College, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Biochemistry and Molecular Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Biochemistry and Molecular Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Biochemistry and Molecular Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Biochemistry and Molecular Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Biochemistry and Molecular Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Biochemistry and Molecular Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Biochemistry and Molecular Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Biochemistry and Molecular Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Dermatology, The General Hospital of Air Force, Beijing, ChinaDepartment of Biochemistry and Molecular Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaCancer Research Institute, The Affiliated Hospital of Guilin Medical University, Guilin, ChinaGuangxi Health Commission Key Laboratory of Novel Onco-Kinases in Target Therapy, The Affiliated Hospital of Guilin Medical University, Guilin, ChinaDepartment of Biochemistry and Molecular Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaGuangxi Key Laboratory of Molecular Medicine in Liver Injury and Repair, The Affiliated Hospital of Guilin Medical University, Guilin, ChinaExcessive solar ultraviolet (SUV) radiation often causes dermatitis, photoaging, and even skin cancer. In the pathological processes of SUV-induced sunburn, JNK is activated by phosphorylation, and it in turn phosphorylates its downstream transcription factors, such as ATF2 and c-jun. The transcription factors further regulate the expression of pro-inflammatory genes, such as IL-6 and TNF-α, which ultimately leads to dermatitis. Therefore, inhibiting JNK may be a strategy to prevent dermatitis. In this study, we screened for worenine as a potential drug candidate for inhibiting sunburn. We determined that worenine inhibited the JNK-ATF2/c-jun signaling pathway and the secretion of IL-6 and TNF-α in cell culture and in vivo, confirming the role of worenine in inhibiting sunburn. Furthermore, we determined that worenine bound and inhibited JNK2 activity in vitro through the MST, kinase, and in vitro kinase assays. Therefore, worenine might be a promising drug candidate for the prevention and treatment of SUV-induced sunburn.https://www.frontiersin.org/articles/10.3389/fphar.2022.881042/fullTCMtraditional Chinese medicineworenineJNK2SUVsunburn
spellingShingle Juanjuan Xiao
Juanjuan Xiao
Hui Lu
Hui Lu
Tengfei Ma
Xiaofang Ni
Teding Chang
Man Liu
Nijie Li
Peijiang Lu
Changshu Ke
Qin Tian
Ling Zou
Fei Wang
Wei Wang
Lu Zhang
Ping Yuan
Lin Liu
Jianmin Zhang
Fei Shi
Qiuhong Duan
Feng Zhu
Feng Zhu
Feng Zhu
Feng Zhu
Worenine Prevents Solar Ultraviolet–Induced Sunburn by Inhibiting JNK2
Frontiers in Pharmacology
TCM
traditional Chinese medicine
worenine
JNK2
SUV
sunburn
title Worenine Prevents Solar Ultraviolet–Induced Sunburn by Inhibiting JNK2
title_full Worenine Prevents Solar Ultraviolet–Induced Sunburn by Inhibiting JNK2
title_fullStr Worenine Prevents Solar Ultraviolet–Induced Sunburn by Inhibiting JNK2
title_full_unstemmed Worenine Prevents Solar Ultraviolet–Induced Sunburn by Inhibiting JNK2
title_short Worenine Prevents Solar Ultraviolet–Induced Sunburn by Inhibiting JNK2
title_sort worenine prevents solar ultraviolet induced sunburn by inhibiting jnk2
topic TCM
traditional Chinese medicine
worenine
JNK2
SUV
sunburn
url https://www.frontiersin.org/articles/10.3389/fphar.2022.881042/full
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