Mechanisms and Effect of Coptidis Rhizoma on Obesity-Induced Inflammation: In Silico and In Vivo Approaches.

Oh-Jun Kwon,Ji-Won Noh,Byung-Cheol Lee

doi:10.3390/ijms22158075

Oh-Jun Kwon, Ji-Won Noh + Show 1 more

Open Access

https://doi.org/10.3390/ijms22158075

Copy DOI

Abstract

Obesity is characterized as a chronic, low-grade inflammation state accompanied by the infiltration of immune cells into adipose tissue and higher levels of inflammatory cytokines and chemokines. This study aimed to investigate the mechanisms and effects of Coptidis Rhizoma (CR) on obesity and its associated inflammation. First, we applied a network pharmacology strategy to search the target genes and pathways regulated by CR in obesity. Next, we performed in vivo experiments to confirm the antiobesity and anti-inflammatory effects of CR. Mice were assigned to five groups: normal chow (NC), control (high-fat diet (HFD)), HFD + CR 200 mg/kg, HFD + CR 400 mg/kg, and HFD + metformin 200 mg/kg. After 16 weeks of the experimental period, CR administration significantly reduced the weight of the body, epididymal fat, and liver; it also decreased insulin resistance, as well as the area under the curve of glucose in the oral glucose tolerance test and triglyceride in the oral fat tolerance test. We observed a decrease in adipose tissue macrophages (ATMs) and inflammatory M1 ATMs, as well as an increase in anti-inflammatory M2 ATMs. Gene expression levels of inflammatory cytokines and chemokines, including tumor necrosis factor-α, F4/80, and C-C motif chemokine (CCL)-2, CCL4, and CCL5, were suppressed in adipose tissue in the CR groups than levels in the control group. Additionally, histological analyses suggested decreased fat accumulation in the epididymal fat pad and liver in the CR groups than that in the control group. Taken together, these results suggest that CR has a therapeutic effect on obesity-induced inflammation, and it functions through the inhibition of macrophage-mediated inflammation in adipose tissue.

Highlights

The pandemic of obesity is a substantial public health crisis and has caused a dramatic rise in metabolic diseases
The mechanism linking inflammation and metabolic syndromes remains unclear [2], but previous studies have suggested that the infiltration and activation of immune cells, including dendritic cells, lymphocytes, monocytes, and macrophages, in adipose tissue contributes to the proinflammatory state and pathogenesis of insulin resistance [3]
The findings indicate that the oral administration of Coptidis Rhizoma (CR) suppressed macrophage infiltration and inflammatory gene expression in adipose tissue, which led to the identification of multiple ameliorated metabolic markers

Summary

Introduction

The pandemic of obesity is a substantial public health crisis and has caused a dramatic rise in metabolic diseases. The mechanism linking inflammation and metabolic syndromes remains unclear [2], but previous studies have suggested that the infiltration and activation of immune cells, including dendritic cells, lymphocytes, monocytes, and macrophages, in adipose tissue contributes to the proinflammatory state and pathogenesis of insulin resistance [3]. CR has been found to ameliorate insulin resistance, glucose metabolism, and obesity in multiple experimental studies [5,6,7]. Most previous studies have focused on the actions of specific alkaloids of CR such as berberine, even though CR is prescribed as a whole herb in oriental medicine. The goal of this study is to screen potential mechanisms of CR itself on obesity and investigate its effect by evaluating phenotypic changes, ATM populations, and the gene expression of inflammatory markers. This study is an integrated in silico and in vivo study to determine the effects of CR on obesity-induced inflammation and its related target genes and pathways

Objectives

Methods

Results

Conclusion