Norbergenin prevents LPS-induced inflammatory responses in macrophages through inhibiting NFκB, MAPK and STAT3 activation and blocking metabolic reprogramming

Bibliographic Details
Title: Norbergenin prevents LPS-induced inflammatory responses in macrophages through inhibiting NFκB, MAPK and STAT3 activation and blocking metabolic reprogramming
Authors: Wan Li, Zhengnan Cai, Florian Schindler, Sheyda Bahiraii, Martin Brenner, Elke H. Heiss, Wolfram Weckwerth
Source: Frontiers in Immunology, Vol 14 (2023)
Publisher Information: Frontiers Media S.A., 2023.
Publication Year: 2023
Collection: LCC:Immunologic diseases. Allergy
Subject Terms: norbergenin, anti-inflammation, proteomics, metabolomics, macrophages, NFκB signaling pathway, Immunologic diseases. Allergy, RC581-607
More Details: Inflammation is thought to be a key cause of many chronic diseases and cancer. However, current therapeutic agents to control inflammation have limited long-term use potential due to various side-effects. This study aimed to examine the preventive effects of norbergenin, a constituent of traditional anti-inflammatory recipes, on LPS-induced proinflammatory signaling in macrophages and elucidate the underlying mechanisms by integrative metabolomics and shotgun label-free quantitative proteomics platforms. Using high-resolution mass spectrometry, we identified and quantified nearly 3000 proteins across all samples in each dataset. To interpret these datasets, we exploited the differentially expressed proteins and conducted statistical analyses. Accordingly, we found that LPS-induced production of NO, IL1β, TNFα, IL6 and iNOS in macrophages was alleviated by norbergenin via suppressed activation of TLR2 mediated NFκB, MAPKs and STAT3 signaling pathways. In addition, norbergenin was capable of overcoming LPS-triggered metabolic reprogramming in macrophages and restrained the facilitated glycolysis, promoted OXPHOS, and restored the aberrant metabolites within the TCA cycle. This is linked to its modulation of metabolic enzymes to support its anti-inflammatory activity. Thus, our results uncover that norbergenin regulates inflammatory signaling cascades and metabolic reprogramming in LPS stimulated macrophages to exert its anti-inflammatory potential.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 1664-3224
Relation: https://www.frontiersin.org/articles/10.3389/fimmu.2023.1117638/full; https://doaj.org/toc/1664-3224
DOI: 10.3389/fimmu.2023.1117638
Access URL: https://doaj.org/article/1bce8259c0d547f6a3eb107e1aab0f94
Accession Number: edsdoj.1bce8259c0d547f6a3eb107e1aab0f94
Database: Directory of Open Access Journals
More Details
ISSN:16643224
DOI:10.3389/fimmu.2023.1117638
Published in:Frontiers in Immunology
Language:English