Regulation of appetite-related neuropeptides by Panax ginseng: A novel approach for obesity treatment

Abstract

Obesity is a primary factor provoking various chronic disorders, including cardiovascular disease, diabetes, and cancer, and causes the death of 2.8 million individuals each year. Diet, physical activity, medications, and surgery are the main therapies for overweightness and obesity. During weight loss therapy, a decrease in energy stores activates appetite signaling pathways under the regulation of neuropeptides, including anorexigenic [corticotropin-releasing hormone, proopiomelanocortin (POMC), cholecystokinin (CCK), and cocaine- and amphetamine-regulated transcript] and orexigenic [agouti-related protein (AgRP), neuropeptide Y (NPY), and melanin-concentrating hormone] neuropeptides, which increase food intake and lead to failure in attaining weight loss goals. Ginseng and ginsenosides reverse these signaling pathways by suppressing orexigenic neuropeptides (NPY and AgRP) and provoking anorexigenic neuropeptides (CCK and POMC), which prevent the increase in food intake. Moreover, the results of network pharmacology analysis have revealed that constituents of ginseng radix, including campesterol, beta-elemene, ginsenoside Rb1, biotin, and pantothenic acid, are highly correlated with neuropeptide genes that regulate energy balance and food intake, including ADIPOQ, NAMPT, UBL5, NUCB2, LEP, CCK, GAST, IGF1, RLN1, PENK, PDYN, and POMC. Based on previous studies and network pharmacology analysis data, ginseng and its compounds may be a potent source for obesity treatment by regulating neuropeptides associated with appetite.

Keywords: Appetite; Food intake; Ginsenosides; Network pharmacology analysis; Neuropeptide; Obesity; Panax ginseng.

Graphical abstract

Fig. 1

Structures of ginsenosides.

Fig. 2

Structures of non-ginsenosides.

Fig. 3

Description of compounds analyzed in this study. (A) Selection criteria for the compounds evaluated in this study. (B) Distribution of the number of targets of compounds.

Fig. 4

Etiology of obesity.

Fig. 5

Proximity between neuropeptide family genes and targets of compounds. Relative distances higher than −0.5 are masked.

Fig. 6

Interactome neighborhood showing associations between the neuropeptide gene families including the (A) adipose neuropeptide gene family, (B) CCK and gastrin gene family, (C) insulin family, and (D) opioid gene family and compounds in ginseng radix. Nodes and edges indicate proteins and their interactions, respectively. Colors filled in nodes indicate whether the protein belongs to the neuropeptides, compound targets, or proteins that connect signaling between neuropeptides and compound targets. Colors filled in borders of nodes indicate the compound that targets the protein.