Guggulsterone protects against lipopolysaccharide-induced inflammation and lethal endotoxemia via heme oxygenase-1.

Int Immunopharmacol

Hanbang Cardio-Renal Syndrome Research Center, Wonkwang University, Iksan, 54538 Jeonbuk, South Korea; Department of Herbology, School of Korean Medicine, Wonkwang University, Iksan, 54538 Jeonbuk, South Korea. Electronic address:

Published: November 2023

Guggulsterone (GS) is a phytosterol used to treat inflammatory diseases. Although many studies have examined the anti-inflammatory activities of GS, the detailed mechanisms of GS in lipopolysaccharide (LPS)-induced inflammation and endotoxemia have not yet been examined. Therefore, we investigated the anti-inflammatory effects of GS on LPS-induced inflammation. In murine peritoneal macrophages, the anti-inflammatory activity of GS was primarily mediated by heme oxygenase-1 (HO-1) induction. HO-1 induction by GS was mediated by GSH depletion and reactive oxygen species (ROS) production. The ROS generated by GS caused the phosphorylation of GSK3β (ser9/21) and p38, leading to the translocation of nuclear factor erythroid-related factor 2 (Nrf2), which ultimately induced HO-1. In addition, GS pretreatment significantly inhibited inducible nitric oxide synthase (iNOS), iNOS-derived NO, and COX-2 protein and mRNA expression, and production of COX-derived prostaglandin PGE2, interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α). In a mouse model of endotoxemia, GS treatment prolonged survival and inhibited the expression of inflammatory mediators, including IL-1β, IL-6, and TNF-α. GS treatment also inhibited LPS-induced liver injury. These results suggest that GS-induced HO-1 could exert anti-inflammatory effects via ROS-dependent GSK (ser21/9)-p38 phosphorylation and nuclear translocation of Nrf2.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.intimp.2023.111073DOI Listing

Publication Analysis

Top Keywords

heme oxygenase-1
8
lps-induced inflammation
8
anti-inflammatory effects
8
ho-1 induction
8
il-1β il-6
8
guggulsterone protects
4
protects lipopolysaccharide-induced
4
lipopolysaccharide-induced inflammation
4
inflammation lethal
4
lethal endotoxemia
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!