A System-Level Mechanism of Anmyungambi Decoction for Obesity: A Network Pharmacological Approach

Abstract

Obesity is a low-grade systemic inflammatory disease involving adipocytokines. As though Anmyungambi decoction (AMGB) showed significant improvement on obesity in a clinical trial, the molecular mechanism of AMGB in obesity remains unknown. Therefore, we explored the potential mechanisms of action of AMGB on obesity through network pharmacological approaches. We revealed that targets of AMGB are significantly associated with obesity-related and adipocyte-elevated genes. Evodiamine, berberine, genipin, palmitic acid, genistein, and quercetin were shown to regulate adipocytokine signaling pathway proteins which mainly involved tumor necrosis factor receptor 1, leptin receptor. In terms of the regulatory pathway of lipolysis in adipocytes, norephedrine, pseudoephedrine, quercetin, and limonin were shown to affect adrenergic receptor-beta, protein kinase A, etc. We also found that AMGB has the potentials to enhance the insulin signaling pathway thereby preventing type II diabetes mellitus. Additionally, AMGB was discovered to be able to control not only insulin-related proteins but also inflammatory mediators and apoptotic regulators and caspases, hence reducing hepatocyte injury in nonalcoholic fatty liver disease. Our findings help develop a better understanding of how AMGB controls obesity.

Keywords: adipocytokine; anmyungambi decoction; insulin signaling pathway; lipolysis; non-alcoholic fatty liver disease; obesity; traditional Asian medicine; type II diabetes mellitus.

Figure 1

Adipocytokine signaling pathway and targets of AMGB, visualized by KEGG mapper. Boxes represent proteins that compose the adipocytokine signaling pathway. The pink-colored boxes represent targets of compounds of AMGB which are significantly associated with the adipocytokine signaling pathway.

Figure 2

Association between herbs in AMGB and pathways related to lipolysis. (A) Cluster heatmap of combined scores of herbs. (B) Herb–compound network of AMGB, focusing on the association between compounds and pathways. (C) Pathway for regulation of lipolysis in adipocytes and predicted targets of AMGB, visualized by KEGG mapper. Boxes represent proteins that compose the pathway. The pink-colored boxes represent predicted targets of AMGB. All the details are the same as in Figure 1.

Figure 3

Association between herbs in AMGB and pathways related with complications resulting from obesity. (A) Cluster heatmap of combined scores of herbs. (B) Herb–compound network of AMGB, focusing on the association between compounds and pathways. (C) Pathway of non-alcoholic fatty liver disease and predicted targets of AMGB, visualized by KEGG mapper. Boxes represent proteins that compose the pathway. The pink-colored boxes represent predicted targets of AMGB. All the details are the same as in Figure 2.