Research Paper Volume 9, Issue 10 pp 2069—2082
Natural product celastrol suppressed macrophage M1 polarization against inflammation in diet-induced obese mice via regulating Nrf2/HO-1, MAP kinase and NF-κB pathways
- 1 School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong
- 2 Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong
Received: July 4, 2017 Accepted: October 6, 2017 Published: October 16, 2017
https://doi.org/10.18632/aging.101302How to Cite
Abstract
Macrophage polarization is implicated in the inflammation in obesity. The aim of the present study was to examine the anti-inflammatory activities of botanical triterpene celastrol against diet-induced obesity. We treated diet-induced obese C57BL/6N male mice with celastrol (5, 7.5 mg/kg/d) for 3 weeks, and investigated macrophage M1/M2 polarization in adipose and hepatic tissues. Celastrol reduced fat accumulation and ameliorated glucose tolerance and insulin sensitivity. Celastrol down-regulated the mRNA levels of macrophage M1 biomarkers (e.g., IL-6, IL-1β, TNF-α, iNOS) in cell culture and in mice. The underlying mechanisms were investigated in murine macrophage RAW264.7 cells. Our results demonstrated that celastrol might control macrophage polarization through modulating the cross-talk between the following three mechanisms: 1) suppressing LPS-induced activation of MAP kinases (e.g., ERK1/2, p38, JNK) in a concentration dependent manner; 2) attenuating LPS-induced nuclear translocation of NF-κB p65 subunit in a time dependent manner; 3) activating Nrf2 and subsequently inducing HO-1 expression. HO-1 inhibitor SnPP diminished the inhibitory effects of celastrol on the activation of NF-κB pathway and the pro-inflammatory M1 macrophage polarization. Taken together, celastrol exhibited anti-obesity effects via suppressing pro-inflammatory M1 macrophage polarization. Thus, our results provide new evidence for the potential of celastrol in the treatment of obesity.