Abstract
Licorice (Glycyrrhiza spp.) is used widely in traditional Chinese medicine (TCM) due to its numerous pharmacologic effects. However, the mechanisms of action of the chemical constituents of licorice and their structure–function relationships are not fully understood. To address these points, we analyzed the chemical compounds in licorice listed in the TCM Systems Pharmacology database and TCM Integrated database. Target proteins of the compounds were predicted using Integrative Pharmacology-based Research Platform of TCM v2.0. Information on the pharmacologic effects of licorice was obtained from the 2020 Chinese Pharmacopoeia, and disease-related genes that have been linked to these effects were identified from the Encyclopedia of TCM database. Pathway analyses using the Kyoto Encyclopedia of Genes and Genomes database were carried out for target proteins, and pharmacologic networks were constructed based on drug target–disease-related gene and protein–protein interactions. A total of 451 compounds were analyzed, of which 211 were from the medicinal parts of the licorice plant. The 241 putative targets of 106 bioactive compounds in licorice comprised 52 flavonoids, 47 triterpenoids, and seven coumarins. Four distinct pharmacologic effects of licorice were defined: 61 major hubs were the putative targets of 23 compounds in heat-clearing and detoxifying effects; 68 were targets of six compounds in spleen-invigorating and qi-replenishing effects; 28 were targets of six compounds in phlegm-expulsion and cough-suppressant effects; 25 compounds were targets of six compounds in spasm-relieving and analgesic effects. The major bioactive compounds of licorice were identified by ultra-high-performance liquid chromatography–quadrupole time-of-flight–tandem mass spectrometry. The anti-inflammatory properties of liquiritin apioside, liquiritigenin, glycyrrhizic acid and isoliquiritin apioside were demonstrated by enzyme-linked immunosorbent assay (ELISA) and Western blot analysis. Liquiritin apioside, liquiritigenin, isoliquiritin, isoliquiritin apioside, kaempferol, and kumatakenin were the main active flavonoids, and 18α- and 18β-glycyrrhetinic acid were the main active triterpenoids of licorice. The former were associated with heat-clearing and detoxifying effects, whereas the latter were implicated in the other three pharmacologic effects. Thus, the compounds in licorice have distinct pharmacologic effects according to their chemical structure. These results provide a reference for investigating the potential of licorice in treatment of various diseases.
Highlights
Licorice is a food and dietary supplement that has been used widely in traditional Chinese medicine (TCM) for ∼4,000 years
A total of 451 compounds were screened from Traditional Chinese Medicine Systems Pharmacology (TCMSP) and Traditional Chinese Medicines Integrated database (TCMID) (Supplementary Table S2)
We found that 26 compounds were duplicated in TCMID and, there were 298 chemical compounds; 127 were common to both TCMSP and TCMID
Summary
Licorice (referred toin Chinese as “GanCao”) is a food and dietary supplement that has been used widely in traditional Chinese medicine (TCM) for ∼4,000 years. Network pharmacology is used widely to investigate the molecular mechanisms underlying the pharmacologic effects of TCM formulations (Li H. et al, 2014; Xiong et al, 2018; Piao et al, 2019); appropriate TCM prescriptions for the treatment of specific diseases (Li et al, 2007; Li X. et al, 2014; Shi et al, 2014; Ke et al, 2016; Fang et al, 2017a, 2017b; Hu and Sun, 2017; Dai et al, 2018; Shi et al, 2019); bioactive components of medicines (Lv et al, 2014; Zhang Y.-F. et al, 2019; Ma et al, 2019; Song et al, 2019; Guo et al, 2020). We analyzed the mechanisms of action underlying the pharmacologic effects of licorice
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
