Liquiritigenin inhibits hepatic fibrogenesis and TGF-β1/Smad with Hippo/YAP signal

Lee, Eun Hye; Park, Kwang-Il; Kim, Kwang S.; Lee, Ju Hee; Jang, Eun Jeong; Ku, Sae Kwang; Kim, Sang Chan; Suk, Ho Young; Park, Ji Young; Baek, Su Youn; Kim, Young Woo

doi:10.1016/j.phymed.2018.12.003

Cited by 46 publications

(32 citation statements)

References 39 publications

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“…Liquiritigenin has potent pharmacologic activity, including inhibitory effects on fibrogenesis and inflammation in the liver ( Huang et al, 2019 ; Lee et al, 2019 ). We predicted the following proteins to be the putative targets of liquiritigenin in the heat-clearing and detoxifying effects of licorice: AKT1, cyclin-dependent kinase 6, heat-shock protein (HSP)90AA1, HSPA2, Janus kinase, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit γ, casein kinase 2α1, CCAAT enhancer-binding protein β, β-actin, estrogen receptor 1, nuclear receptor coactivator (NCOA)1, and NCOA2.…”

Section: Resultsmentioning

confidence: 99%

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

Chen

et al. 2021

Front. Pharmacol.

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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.

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Section: Resultsmentioning

confidence: 99%

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

Chen

et al. 2021

Front. Pharmacol.

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“…Liang et al reported that expression of MMP2 and MMP9 proteins were upregulated in carbon tetrachloride-induced liver injury, while treatment with MOL2 significantly reduced the expression levels of MMP2 and MMP9 proteins [55]. MOL7 and MOL14 were found to decrease MMP2 [56,57]. MOL7, MOL10, MOL17 and MOL9 were reported to down-regulate MMP9 [58][59][60].…”

Section: Discussionmentioning

confidence: 99%

“…As for HIF1A, there were seven compounds were reported to suppress the expression of HIF1A, including MOL5, MOL6, MOL9, MOL10, MOL13, MOL14, and MOL15 [67][68][69][70][71][72][73]. Lee et al found that MOL7 significantly inhibited liver fibrosis through blocking the transforming growth factor-β1-induced the transcript levels of SER-PINE1 and matrix MMP2 [56]. MOL10 can also exert SERPINE1 inhibitory activity [74].…”

Section: Discussionmentioning

confidence: 99%

Insights into the molecular mechanisms of Huangqi decoction on liver fibrosis via computational systems pharmacology approaches

Wang

et al. 2021

Chin Med

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Background The traditional Chinese medicine Huangqi decoction (HQD) consists of Radix Astragali and Radix Glycyrrhizae in a ratio of 6: 1, which has been used for the treatment of liver fibrosis. In this study, we tried to elucidate its action of mechanism (MoA) via a combination of metabolomics data, network pharmacology and molecular docking methods. Methods Firstly, we collected prototype components and metabolic products after administration of HQD from a publication. With known and predicted targets, compound-target interactions were obtained. Then, the global compound-liver fibrosis target bipartite network and the HQD-liver fibrosis protein–protein interaction network were constructed, separately. KEGG pathway analysis was applied to further understand the mechanisms related to the target proteins of HQD. Additionally, molecular docking simulation was performed to determine the binding efficiency of compounds with targets. Finally, considering the concentrations of prototype compounds and metabolites of HQD, the critical compound-liver fibrosis target bipartite network was constructed. Results 68 compounds including 17 prototype components and 51 metabolic products were collected. 540 compound-target interactions were obtained between the 68 compounds and 95 targets. Combining network analysis, molecular docking and concentration of compounds, our final results demonstrated that eight compounds (three prototype compounds and five metabolites) and eight targets (CDK1, MMP9, PPARD, PPARG, PTGS2, SERPINE1, TP53, and HIF1A) might contribute to the effects of HQD on liver fibrosis. These interactions would maintain the balance of ECM, reduce liver damage, inhibit hepatocyte apoptosis, and alleviate liver inflammation through five signaling pathways including p53, PPAR, HIF-1, IL-17, and TNF signaling pathway. Conclusions This study provides a new way to understand the MoA of HQD on liver fibrosis by considering the concentrations of components and metabolites, which might be a model for investigation of MoA of other Chinese herbs.

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“…Luteolin-7-O-glucoside, another flavonoid constituent of KYQG, exhibits antioxidative activity through the regulation of the HO-1 signaling cascade in RAW 264.7 cells ( Song and Park, 2014 ). Liquiritigenin has been reported to exert anti-inflammatory, antioxidant, antidiabetic, and antitumor activities ( Lee et al., 2018 ). Liquiritin could protect against UVB−induced skin injury by inhibiting TLR4/MyD88/NF−κB mitogen−activated protein kinases and caspase pathways, which lead to alleviating the inflammatory response, oxidative stress, and apoptosis in mice and cells ( Li X.-Q.…”

Section: Discussionmentioning

confidence: 99%

Pharmacodynamic and Metabolomics Studies on the Effect of Kouyanqing Granule in the Treatment of Phenol-Induced Oral Ulcer Worsened by Sleep Deprivation

Chen

Yao²,

Sui

et al. 2020

Front. Pharmacol.

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Liquiritigenin inhibits hepatic fibrogenesis and TGF-β1/Smad with Hippo/YAP signal

Cited by 46 publications

References 39 publications

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

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

Insights into the molecular mechanisms of Huangqi decoction on liver fibrosis via computational systems pharmacology approaches

Pharmacodynamic and Metabolomics Studies on the Effect of Kouyanqing Granule in the Treatment of Phenol-Induced Oral Ulcer Worsened by Sleep Deprivation

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