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

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.

Anti-inflammatory agents as modulators of the inflammation in adipose tissue: A systematic review

“…Kwon et al [ 76 ] evaluated the mechanisms and effects of Coptidis rhizoma on obesity-induced inflammation. The results showed that the treatment reduced the percentage of M1 CD11c macrophages and increased the M2 CD206 macrophages.…”

“…In some studies, the authors reported that the browning of white adipose tissue occurred, which increased thermogenesis, energy expenditure, and weight reduction. Besides, reducing M1-type macrophages and increasing M2-type macrophages in fat and liver impact reduced insulin resistance and reduced inflammation, especially in adipose and liver tissue [ 50 , 51 , 52 , 56 – 59 , 64 – 66 , 69 , 70 , 72 , 75 , 76 , 83 ].…”

Nutraceuticals and the Network of Obesity Modulators

“…However, aberrant activation of NLRP3 inflammasome has been related to obesity. An extract from Coptidis rhizoma has been shown to have successful effects in obese rats affected by glomerulopathy [ 84 ]. Subsequent studies on Coptidis rhizome, used in oriental medicine, showed that its anti-inflammatory activity is linked to berberine derivatives [ 85 ].…”

Dissecting and Evaluating the Therapeutic Targets of Coptis Chinensis Franch in the Treatment of Urinary Tract Infections Induced by Escherichia coli

“…In China, Coptis chinensis Franch (CCF), especially the dried root of Coptis chinensis Makino, has been widely used in traditional medicine and food consumption for its functions of clearing heat and detoxification ( Meng et al, 2018 ; Wang et al, 2018 ). Currently, the compounds in CCF have been reported to exhibit a wide spectrum of pharmacological properties, including antibacterial ( Jamshaid et al, 2020 ; Gaba et al, 2021 ), anti-inflammatory ( Tarabasz and Kukula-Koch, 2020 ; Gaba et al, 2021 ), and immunoregulatory effects ( Wang et al, 2018 ; Kwon et al, 2021 ) among others. Besides, almost most of the articles have constantly given special emphasis on the alkaloids of CCF, especially palmatine, berberine, and berberrubine ( Meng et al, 2018 ; Wang et al, 2018 ; Jamshaid et al, 2020 ; Tarabasz and Kukula-Koch, 2020 ; Gaba et al, 2021 ; Kwon et al, 2021 ).…”

“…Currently, the compounds in CCF have been reported to exhibit a wide spectrum of pharmacological properties, including antibacterial ( Jamshaid et al, 2020 ; Gaba et al, 2021 ), anti-inflammatory ( Tarabasz and Kukula-Koch, 2020 ; Gaba et al, 2021 ), and immunoregulatory effects ( Wang et al, 2018 ; Kwon et al, 2021 ) among others. Besides, almost most of the articles have constantly given special emphasis on the alkaloids of CCF, especially palmatine, berberine, and berberrubine ( Meng et al, 2018 ; Wang et al, 2018 ; Jamshaid et al, 2020 ; Tarabasz and Kukula-Koch, 2020 ; Gaba et al, 2021 ; Kwon et al, 2021 ). Actually, CCF is tackled as a whole herb in traditional Chinese medicine (TCM) for thousands of years.…”