Network Pharmacology-Based Strategy for Elucidating the Molecular Basis Forthe Pharmacologic Effects of Licorice (Glycyrrhiza spp.)

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.

Liquiritin alleviates alpha‐naphthylisothiocyanate‐induced intrahepatic cholestasis through the Sirt1/FXR/Nrf2 pathway

“…Since GA has been reported to have a strong protective function in ANIT‐induced cholestasis (Wu et al, 2018), how about the other main active ingredient in licorice? Liquiritin (LQ) is an important monomer active component in flavonoids of licorice (Chen et al, 2021). However, the study on the effect and mechanism of LQ on cholestatic liver injury is rare.…”

In Silico Analysis of Selected Glycyrrhiza glabra (Licorice) Constituents: Exploring Their Modulatory Effects on Human Superoxide Dismutase, Human Phosphodiesterase-9 and Human Dipeptidyl Peptidase-4

“…Several studies have reported the various phyto-constituents from Glycyrrhiza species, especially G. glabra , comprise more than 20 tri-terpenoids and approximately 300 flavonoids [ 8 , 4 ]. Moreover, the roots of G. glabra (Licorice) have been reported to possess a high content of glycyrrhizin (tri-terpene saponin) [ 9 ].…”

Integration of UPLC–QE–MS/MS and network pharmacology to investigate the active components and action mechanisms of tea cake extract for treating cough

“…Network pharmacology meets the holistic view of TCM theory, and is an effective strategy to elucidate the potential active compounds and action mechanisms of TCM (Zhu et al, 2019). Chen et al employed network pharmacology to elucidate the chemical basis and molecular mechanisms for the pharmacological effects of licorice, and carried out experimental verification (Chen, Li, Hu, et al, 2021). Zhen et al predicted two important compounds (columbianadin and osthole) and two key targets (PTGS1 and PTGS2) by integrating UPLC–MS/MS and network pharmacology (Wang et al, 2022).…”