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      The antiviral and antimicrobial activities of licorice, a widely-used Chinese herb

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      Author(s): , , , * , **
      Publication date (Electronic):
      Journal: Acta Pharmaceutica Sinica. B
      Publisher: Elsevier
      Keywords: CCEC, cerebral capillary vessel endothelial, CCL5, chemokine (C-C motif) ligand 5, CVA16, coxsackievirus A16, CVB3, coxsackievirus B3, CXCL10, chemokine, (C-X-C motif) ligand 10, DGC, dehydroglyasperin C, DHV, duck hepatitis virus, EV71, enterovirus 71, GA, 18β-glycyrrhetinic acid, GATS, glycyrrhizic acid trisodium salt, GL, glycyrrhizin, GLD, glabridin, HBV, hepatitis B virus, HCV, hepatitis C virus, HIV, human immunodeficiency virus, HMGB1, high-mobility-group box1, HRSV, human respiratory syncytial virus, HSV, herpes simplex virus, HSV1, herpes simplex virus type 1, IFN, interferon, IL-6, interleukin-6, LCA, licochalcone A, LCE, licochalcone E, ISL, isoliquiritigenin, LTG, liquiritigenin, MgIG, magnesium isoglycyrrhizinate, MRSA, methicillin-resistant Staphylococcus aureus, MSSA, methicillin-sensitive Staphylococcus aureus, PMN, polymorph nuclear, PrV, pseudorabies virus, TCM, traditional Chinese medicine, Licorice, Antiviral, Antimicrobial, Glycyrrhizin, Glycyrrhetinic acid, Chalcone

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          Abstract

          Licorice is a common herb which has been used in traditional Chinese medicine for centuries. More than 20 triterpenoids and nearly 300 flavonoids have been isolated from licorice. Recent studies have shown that these metabolites possess many pharmacological activities, such as antiviral, antimicrobial, anti-inflammatory, antitumor and other activities. This paper provides a summary of the antiviral and antimicrobial activities of licorice. The active components and the possible mechanisms for these activities are summarized in detail. This review will be helpful for the further studies of licorice for its potential therapeutic effects as an antiviral or an antimicrobial agent.

          Graphical abstract

          Licorice is a common herb which has been used in traditional Chinese medicine for centuries. This paper provides a summary of the antiviral and antimicrobial activities of licorice. The active components and the possible mechanisms for these activities are summarized in detail.

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          Glycyrrhizic acid and 18β-glycyrrhetinic acid modulate lipopolysaccharide-induced inflammatory response by suppression of NF-κB through PI3K p110δ and p110γ inhibitions.

          Wen-Sui Lo, Tzu-Cheg Kao, Chin-En Yen … (2011)
          The roots and rhizomes of licorice ( Glycyrrhia ) species have been used extensively as natural sweeteners and herbal medicines. The aim of this work was to determine the in vitro anti-inflammatory effects of glycyrrhizic acid (GA) and 18β-glycyrrhetinic acid (18βGA) from licorice in a lipopolysaccharide (LPS)-stimulated macrophage model. The results showed that treatment with 25-75 μM GA or 18βGA did not reduce RAW 264.7 cell viability but did significantly inhibit the production of LPS-induced nitric oxide (NO), prostaglandin E(2) (PGE(2)), and intracellular reactive oxygen species (ROS). Western blotting and reverse transcriptase polymerase chain reaction (RT-PCR) analyses revealed that GA and 18βGA significantly reduced the protein and mRNA levels of iNOS and COX-2 in LPS-induced macrophages. Both GA and 18βGA inhibited the activation of NF-κB and the activities of phosphoinositide-3-kinase (PI3K) p110δ and p110γ isoforms and then reduced the production of LPS-induced tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-1β in a dose-dependent manner. In conclusion, these results indicate that GA and 18βGA may provide an anti-inflammatory effect by attenuating the generation of excessive NO, PGE(2), and ROS and by suppressing the expression of pro-inflammatory genes through the inhibition of NF-κB and PI3K activity. Thus, the results suggest that GA and 18βGA might serve as potential agents for the treatment of inflammatory-mediated diseases.
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            Water extract of licorice had anti-viral activity against human respiratory syncytial virus in human respiratory tract cell lines

            Chia Feng Yeh, Kuo Chih Wang, Lien Chai Chiang … (2013)
            Ethnopharmacological relevance Licorice (Glycyrrhiza uralensis Fisch., Leguminosae) has been used in herbal medicine and food supplement worldwide for centuries. Licorice is a common ingredient of several prescriptions of traditional Chinese medicine which have been proved to inhibit infection of human respiratory syncytial virus (HRSV). There are two preparations of licorice, Radix Glycyrrhizae and Radix Glycyrrhizae Preparata. However, it is unknown whether licorice or which preparation of licorice is effective against HRSV, nor is its active constituent. Aim of the study We tested the hypothesis that Radix Glycyrrhizae can effectively decrease HRSV-induced plaque formation in respiratory mucosal cell lines. We also tried to find out the active constituent. Materials and methods Anti-HRSV activities of hot water extracts of preparations of licorice, glycyrrhizin and 18β-glycyrrhetinic acid (18β-GA), the active constituents of licorice, were examined by plaque reduction assay in both human upper (HEp-2) and low (A549) respiratory tract cell lines. Abilities of crude licorice to inhibit viral replication and to stimulate IFN-β were evaluated by reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Results Radix Glycyrrhizae and Radix Glycyrrhizae Preparata dose-dependently inhibited HRSV-induced plaque formation in both HEp-2 and A549 cell lines (p<0.0001). The effect of Radix Glycyrrhizae was better than that of Radix Glycyrrhizae Preparata on HEp-2 cells. However, there was no difference of their anti-HRSV effects on A549 cells. Besides, glycyrrhizin was ineffective at all. Nevertheless, 18β-GA showed a potent anti-HRSV activity. Radix Glycyrrhizae was more effective when given before viral inoculation (p<0.0001) which may be due to its inhibition of viral attachment on (p<0.0001) and penetration (p<0.0001) into the host cells. The anti-HRSV activity of Radix Glycyrrhizae was further confirmed by RT-PCR and qRT-PCR. 300 μg/ml Radix Glycyrrhizae markedly decreased the viral amounts within the cells and in the suspension. Radix Glycyrrhizae might further stimulate mucosal cells to secrete IFN-β to counteract viral infection. Conclusions Both Radix Glycyrrhizae and Radix Glycyrrhizae Preparata are effective against HRSV infection on airway epithelial cells. Radix Glycyrrhizae inhibited HRSV mainly by preventing viral attachment, internalization, and by stimulating IFN secretion. 18β-GA may be one of its active constituents.
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              Anti-inflammatory/Anti-oxidative stress activities and differential regulation of Nrf2-mediated genes by non-polar fractions of tea Chrysanthemum zawadskii and licorice Glycyrrhiza uralensis.

              Ah-Ng Kong, S Loh, Constance Lay Lay Saw … (2011)
              Accumulating evidence from epidemiological studies indicates that chronic inflammation and oxidative stress play critical roles in neoplastic development. The aim of this study was to investigate the anti-inflammatory, anti-oxidative stress activities, and differential regulation of Nrf2-mediated genes by tea Chrysanthemum zawadskii (CZ) and licorice Glycyrrhiza uralensis (LE) extracts. The anti-inflammatory and anti-oxidative stress activities of hexane/ethanol extracts of CZ and LE were investigated using in vitro and in vivo approaches, including quantitative real-time PCR (qPCR) and microarray. Additionally, the role of the transcriptional factor Nrf2 (nuclear erythroid-related factor 2) signaling pathways was examined. Our results show that CZ and LE extracts exhibited potent anti-inflammatory activities by suppressing the mRNA and protein expression levels of pro-inflammatory biomarkers IL-1β, IL-6, COX-2 and iNOS in LPS-stimulated murine RAW 264.7 macrophage cells. CZ and LE also significantly suppressed the NO production of LPS-stimulated RAW 264.7 cells. Additionally, CZ and LE suppressed the NF-κB luciferase activity in human HT-29 colon cancer cells. Both extracts also showed strong Nrf2-mediated antioxidant/Phase II detoxifying enzymes induction. CZ and LE induced NQO1, Nrf2, and UGT and antioxidant response element (ARE)-luciferase activity in human hepatoma HepG2 C8 cells. Using Nrf2 knockout [Nrf2 (-/-)] and Nrf2 wild-type (+/+) mice, LE and CZ showed Nrf2-dependent transactivation of Nrf2-mediated antioxidant and phase II detoxifying genes. In summary, CZ and LE possess strong inhibitory effects against NF-κB-mediated inflammatory as well as strong activation of the Nrf2-ARE-anti-oxidative stress signaling pathways, which would contribute to their overall health promoting pharmacological effects against diseases including cancer.
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                Author and article information

                Contributors
                Ying Liu
                Chunsheng Liu
                Journal
                Journal ID (nlm-ta): Acta Pharm Sin B
                Journal ID (iso-abbrev): Acta Pharm Sin B
                Title: Acta Pharmaceutica Sinica. B
                Publisher: Elsevier
                ISSN (Print): 2211-3835
                ISSN (Electronic): 2211-3843
                Publication date PMC-release: 17 June 2015
                Publication date (Print): July 2015
                Publication date (Electronic): 17 June 2015
                Volume: 5
                Issue: 4
                Pages: 310-315
                Affiliations
                [0005]School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China
                Author notes
                [* ]Corresponding author. Tel.: +86 10 84738646; fax: +86 10 84738611. liuyliwd@ 123456sina.com
                [** ]Corresponding author. Tel.: +86 10 84738624. maxliucs@ 123456263.net
                Article
                Publisher ID: S2211-3835(15)00079-9
                DOI: 10.1016/j.apsb.2015.05.005
                PMC ID: 4629407
                PubMed ID: 26579460
                SO-VID: e1038106-eb99-4c76-a58a-1056bc6a2ece
                Copyright © © 2015 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.
                License:

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                Date received : 3 December 2014
                Date revision received : 2 February 2015
                Date accepted : 5 February 2015
                Categories
                Subject: Review

                Keywords: ccec, cerebral capillary vessel endothelial,ccl5, chemokine (c-c motif) ligand 5,cva16, coxsackievirus a16,cvb3, coxsackievirus b3,cxcl10, chemokine, (c-x-c motif) ligand 10,dgc, dehydroglyasperin c,dhv, duck hepatitis virus,ev71, enterovirus 71,ga, 18β-glycyrrhetinic acid,gats, glycyrrhizic acid trisodium salt,gl, glycyrrhizin,gld, glabridin,hbv, hepatitis b virus,hcv, hepatitis c virus,hiv, human immunodeficiency virus,hmgb1, high-mobility-group box1,hrsv, human respiratory syncytial virus,hsv, herpes simplex virus,hsv1, herpes simplex virus type 1,ifn, interferon,il-6, interleukin-6,lca, licochalcone a,lce, licochalcone e,isl, isoliquiritigenin,ltg, liquiritigenin,mgig, magnesium isoglycyrrhizinate,mrsa, methicillin-resistant staphylococcus aureus,mssa, methicillin-sensitive staphylococcus aureus,pmn, polymorph nuclear,prv, pseudorabies virus,tcm, traditional chinese medicine,licorice,antiviral,antimicrobial,glycyrrhizin,glycyrrhetinic acid,chalcone
                Data availability:
                Keywords: ccec, cerebral capillary vessel endothelial, ccl5, chemokine (c-c motif) ligand 5, cva16, coxsackievirus a16, cvb3, coxsackievirus b3, cxcl10, chemokine, (c-x-c motif) ligand 10, dgc, dehydroglyasperin c, dhv, duck hepatitis virus, ev71, enterovirus 71, ga, 18β-glycyrrhetinic acid, gats, glycyrrhizic acid trisodium salt, gl, glycyrrhizin, gld, glabridin, hbv, hepatitis b virus, hcv, hepatitis c virus, hiv, human immunodeficiency virus, hmgb1, high-mobility-group box1, hrsv, human respiratory syncytial virus, hsv, herpes simplex virus, hsv1, herpes simplex virus type 1, ifn, interferon, il-6, interleukin-6, lca, licochalcone a, lce, licochalcone e, isl, isoliquiritigenin, ltg, liquiritigenin, mgig, magnesium isoglycyrrhizinate, mrsa, methicillin-resistant staphylococcus aureus, mssa, methicillin-sensitive staphylococcus aureus, pmn, polymorph nuclear, prv, pseudorabies virus, tcm, traditional chinese medicine, licorice, antiviral, antimicrobial, glycyrrhizin, glycyrrhetinic acid, chalcone

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