Exploration in the Mechanism of Action of Licorice by Network Pharmacology.

Meimei Chen,Xinmei Lai,Yuxing Gao,Huijuan Gan,Jie Kang,Jingru Zhu,Fafu Yang

doi:10.3390/molecules24162959

Abstract

Licorice is a popular sweetener and a thirst quencher in many food products particularly in Europe and the Middle East and also one of the oldest and most frequently used herbs in traditional Chinese medicine. As a wide application of food additive, it is necessary to clarify bioactive chemical ingredients and the mechanism of action of licorice. In this study, a network pharmacology approach that integrated drug-likeness evaluation, structural similarity analysis, target identification, network analysis, and KEGG pathway analysis was established to elucidate the potential molecular mechanism of licorice. First, we collected and evaluated structural information of 282 compounds in licorice and found 181 compounds that met oral drug rules. Then, structural similarity analysis with known ligands of targets in the ChEMBL database (similarity threshold = 0.8) was applied to the initial target identification, which found 63 compounds in licorice had 86 multi-targets. Further, molecular docking was performed to study their binding modes and interactions, which screened out 49 targets. Finally, 17 enriched KEGG pathways (p < 0.01) of licorice were obtained, exhibiting a variety of biological activities. Overall, this study provided a feasible and accurate approach to explore the safe and effective application of licorice as a food additive and herb medicine.

Highlights

Licorice is a popular sweetener and a thirst quencher found in many soft drinks, food products, and snacks, in Europe and the Middle East
To the best of our knowledge, our study led to the first discovery that: migration inhibitory factor (MIF), ALOX5, ALOX15, NOS2, and ADORA3 are involved in the inflammatory response; CDK1, CDK6, DYRK1A, CCNB3, and CDK3 referred to cell cycle, cell division, and apotosis; AKR1B15, HSD11B2, and HSD17B2 are involved in steroid metabolism; MAOB and MAOA are related with neurotransmitters transformation; ALOX12B, ALOX15B, ALOX15, HSD17B2, and ABCB4 are involved in lipid metabolism; PTPN11 and NADPH oxidase 4 (NOX4) referred to glucose homeostasis, which were implicated by licorice
86 multi-targets were initially identified based on structural similarity measures with known ligands of targets in the ChEMBL database using the tanimoto coefficient calculation, which led to the discovery of 63 bioactive compounds in licorice

Summary

Introduction

Licorice is a popular sweetener and a thirst quencher found in many soft drinks, food products, and snacks, in Europe and the Middle East. The traditional concept that licorice is a healthy natural substance without side effects promotes its liberal consumption, which can occasionally be dangerous [1]. Licorice is honored as the reconciler in most Chinese herbal prescriptions, which is one of the oldest and most frequently prescribed herbs in traditional Chinese medicine [2]. The main constituent of licorice, glycyrrhizic acid, of which the sweetness is 200 to 250 times that of sucrose, widely used in various foods, and the sweetness retains for a long time [8]. Glycyrrhizic acid holds with bioactivity including neuroprotection, anti-inflammatory, and anti-allergic reactions [9,10]; Molecules 2019, 24, 2959; doi:10.3390/molecules24162959 www.mdpi.com/journal/molecules

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Results

Conclusion