Physalin A attenuates inflammation through down-regulating c-Jun NH2 kinase phosphorylation/Activator Protein 1 activation and up-regulating the antioxidant activity

Yu-Hsien Lin; Ya-Hsin Hsiao; Ka-Lok Ng; Yueh-Hsiung Kuo; Yun-Ping Lim; Wen-Tsong Hsieh

doi:10.1016/j.taap.2020.115115

Physalin A attenuates inflammation through down-regulating c-Jun NH2 kinase phosphorylation/Activator Protein 1 activation and up-regulating the antioxidant activity

Toxicol Appl Pharmacol. 2020 Sep 1:402:115115. doi: 10.1016/j.taap.2020.115115. Epub 2020 Jul 4.

Authors

Yu-Hsien Lin¹, Ya-Hsin Hsiao², Ka-Lok Ng³, Yueh-Hsiung Kuo⁴, Yun-Ping Lim⁵, Wen-Tsong Hsieh⁶

Affiliations

¹ Department of Pharmacology, China Medical University, Taichung 40402, Taiwan, ROC; School of Pharmacy, College of Pharmacy, China Medical University, No. 91, Hsueh-Shih Road, Taichung 40402, Taiwan, ROC.
² Department of Pharmacology, China Medical University, Taichung 40402, Taiwan, ROC.
³ Department of Bioinformatics and Medical Engineering, Asia University, Taichung 41354, Taiwan, ROC; Department of Medical Research, China Medical University Hospital, China Medical University, 40402, Taiwan, ROC.
⁴ Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung 40402, Taiwan, ROC; Department of Biotechnology, Asia University, Taichung 40402, Taiwan, ROC; Chinese Medicine Research Center, China Medical University, Taichung 40402, Taiwan, ROC.
⁵ School of Pharmacy, College of Pharmacy, China Medical University, No. 91, Hsueh-Shih Road, Taichung 40402, Taiwan, ROC.
⁶ Department of Pharmacology, China Medical University, Taichung 40402, Taiwan, ROC; Chinese Medicine Research Center, China Medical University, Taichung 40402, Taiwan, ROC; Drug Development Center, China Medical University, Taichung 40402, Taiwan, ROC. Electronic address: wthsieh@mail.cmu.edu.tw.

PMID: 32634518
DOI: 10.1016/j.taap.2020.115115

Abstract

Physalin A (PA), a withanolide, was isolated from Physalis angulata L. In this study, it is shown that PA can inhibit the production of inflammatory cytokines such as PGE₂, NO, IL-1β, IL-6, and TNF-α in LPS-induced RAW 264.7 cells. Furthermore, the results indicated that PA suppressed the IκB/NF-κB and JNK/ AP-1 inflammatory signaling pathways and inhibited the levels of pro-inflammatory factors iNOS and COX-2 in LPS-stimulated RAW 264.7 cells. In the carrageenan-induced mouse hind paw edema study, PA was shown to inhibit the production of inflammatory mediators such as NO, MDA, and TNF-α production. Conversely, the antioxidant factor levels of SOD, CAT, and GPx were all increased by the treated PA. According to the data, we are suggesting that the anti-inflammatory effects of PA may be through the suppressions of the JNK/AP-1 and IκB/NF-κB signaling pathways and up-regulation of the anti-oxidative activity.

Keywords: Anti-inflammatory effect; Anti-oxidative activity; IκB/NF-κB; JNK/AP-1; Physalin A; Physalis angulata.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antioxidants / chemistry
Antioxidants / pharmacology
Carrageenan / toxicity
Cell Survival / drug effects
Down-Regulation / drug effects
Gene Expression Regulation / drug effects
I-kappa B Proteins / genetics
I-kappa B Proteins / metabolism
Inflammation / drug therapy*
Inflammation / metabolism*
JNK Mitogen-Activated Protein Kinases / genetics
JNK Mitogen-Activated Protein Kinases / metabolism*
Male
Malondialdehyde
Mice
Mice, Inbred ICR
Molecular Structure
NF-kappa B / genetics
NF-kappa B / metabolism
Physalis / chemistry
RAW 264.7 Cells
Random Allocation
Transcription Factor AP-1 / genetics
Transcription Factor AP-1 / metabolism*
Withanolides / chemistry
Withanolides / pharmacology*

Substances

Antioxidants
I-kappa B Proteins
NF-kappa B
Transcription Factor AP-1
Withanolides
physalin A
Malondialdehyde
Carrageenan
JNK Mitogen-Activated Protein Kinases