Exploring the Role of Licorice and Its Derivatives in Cell Signaling Pathway NF-B and MAPK

Overview

Journal J Nutr Metab

Publisher Wiley

Date 2024 Oct 31

PMID 39479405

Authors

Ieaman Fatima

Amna Sahar

Amna Tariq

Tabana Naz

Muhammad Usman

Affiliations

Soon will be listed here.

Abstract

Licorice is a therapeutic herb in traditional Chinese herbal medicine. Licorice is considered as an anti-inflammatory agent due to its suppression and inhibition of inflammatory pathways. Licorice has many bioactive compounds such as glycyrrhetinic acid, glycyrrhizin, liquiritigenin, and isoliquirtigenin which are principally accountable for its therapeutic benefits. These bioactive components reduce inflammation by preventing the activation of important inflammatory pathways including mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-B). As a result of this tumor necrosis factor-alpha (TNF-), interleukin-1 beta (IL-1) and interleukin-6 (IL-6) are among the proinflammatory cytokines whose production is inhibited. Components present in licorice inhibit the activation by suppressing the IB phosphorylation and degradation. Moreover, licorice compounds also attenuate the MAPK signaling cascades by inhibiting the MAPK kinase phosphorylation and downstream MAPKs such as extracellular signal-regulated kinase (ERK), p38 MAPK, and c-Jun N-terminal kinase (JNK). The present review focuses on the current understanding of licorice effect on the NF-B and MAPK inflammatory cell signaling pathways at molecular level. Furthermore, emerging evidence suggested that licorice-derived bioactive compounds may attenuate the molecular mechanism which is associated with inflammation, providing the additional insights into the therapeutic potential. Further studies explained the precise molecular mechanism at the cellular level underlying the licorice anti-inflammatory effect and potential application in managing inflammatory disorders. In conclusion, licorice has a complex mode of action and is a valuable natural anti-inflammatory. Its natural origin and effectiveness in clinical applications make it an intriguing topic for additional study. As licorice becomes more widely used in medicine, future research should focus on refining its formulations to optimize therapeutic advantages.

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References

Pastorino G, Cornara L, Soares S, Rodrigues F, Oliveira M . Liquorice (Glycyrrhiza glabra): A phytochemical and pharmacological review. Phytother Res. 2018; 32(12):2323-2339. PMC: 7167772. DOI: 10.1002/ptr.6178. View

Chen K, Yang R, Shen F, Zhu H . Advances in Pharmacological Activities and Mechanisms of Glycyrrhizic Acid. Curr Med Chem. 2019; 27(36):6219-6243. DOI: 10.2174/0929867325666191011115407. View

Kyriakis J, Avruch J . Mammalian MAPK signal transduction pathways activated by stress and inflammation: a 10-year update. Physiol Rev. 2012; 92(2):689-737. DOI: 10.1152/physrev.00028.2011. View

Wahab S, Annadurai S, Abullais S, Das G, Ahmad W, Ahmad M . (Licorice): A Comprehensive Review on Its Phytochemistry, Biological Activities, Clinical Evidence and Toxicology. Plants (Basel). 2021; 10(12). PMC: 8703329. DOI: 10.3390/plants10122751. View

Peti W, Page R . Molecular basis of MAP kinase regulation. Protein Sci. 2013; 22(12):1698-710. PMC: 3843625. DOI: 10.1002/pro.2374. View

Bhatia H, Apweiler M, Sun L, Baron J, Tirkey A, Fiebich B . Licochalcone A Inhibits Prostaglandin E by Targeting the MAPK Pathway in LPS Activated Primary Microglia. Molecules. 2023; 28(4). PMC: 9965579. DOI: 10.3390/molecules28041927. View

Richard S . Exploring the Pivotal Immunomodulatory and Anti-Inflammatory Potentials of Glycyrrhizic and Glycyrrhetinic Acids. Mediators Inflamm. 2021; 2021:6699560. PMC: 7808814. DOI: 10.1155/2021/6699560. View

Gao R, Zhang Y, Kang Y, Xu W, Jiang L, Guo T . Glycyrrhizin Inhibits PEDV Infection and Proinflammatory Cytokine Secretion via the HMGB1/TLR4-MAPK p38 Pathway. Int J Mol Sci. 2020; 21(8). PMC: 7215578. DOI: 10.3390/ijms21082961. View

Harrison J, Zyla T, Bardes E, Lew D . Stress-specific activation mechanisms for the "cell integrity" MAPK pathway. J Biol Chem. 2003; 279(4):2616-22. DOI: 10.1074/jbc.M306110200. View

10.

Kaminska B . MAPK signalling pathways as molecular targets for anti-inflammatory therapy--from molecular mechanisms to therapeutic benefits. Biochim Biophys Acta. 2005; 1754(1-2):253-62. DOI: 10.1016/j.bbapap.2005.08.017. View

11.

. Evaluation of certain food additives. World Health Organ Tech Rep Ser. 2017; (1000):1-162. View

12.

Cai M, Xu Y, Deng B, Chen J, Chen T, Zeng K . Radix Glycyrrhizae extract and licochalcone a exert an anti-inflammatory action by direct suppression of toll like receptor 4. J Ethnopharmacol. 2022; 302(Pt A):115869. DOI: 10.1016/j.jep.2022.115869. View

13.

Yao L, Sun T . Glycyrrhizin administration ameliorates Streptococcus aureus-induced acute lung injury. Int Immunopharmacol. 2019; 70:504-511. DOI: 10.1016/j.intimp.2019.02.046. View

14.

Kwon Y, Son D, Chung T, Lee Y . A Review of the Pharmacological Efficacy and Safety of Licorice Root from Corroborative Clinical Trial Findings. J Med Food. 2019; 23(1):12-20. DOI: 10.1089/jmf.2019.4459. View

15.

Sui Y, Zhao Z, Liu R, Cai B, Fan D . Adenosine monophosphate-activated protein kinase activation enhances embryonic neural stem cell apoptosis in a mouse model of amyotrophic lateral sclerosis. Neural Regen Res. 2014; 9(19):1770-8. PMC: 4238165. DOI: 10.4103/1673-5374.143421. View

16.

Khalil H, Nada A, Mahrous H, Hassan A, Rijo P, A Ibrahim I . Amelioration effect of 18β-Glycyrrhetinic acid on methylation inhibitors in hepatocarcinogenesis -induced by diethylnitrosamine. Front Immunol. 2024; 14:1206990. PMC: 10844948. DOI: 10.3389/fimmu.2023.1206990. View

17.

Chen L, Deng H, Cui H, Fang J, Zuo Z, Deng J . Inflammatory responses and inflammation-associated diseases in organs. Oncotarget. 2018; 9(6):7204-7218. PMC: 5805548. DOI: 10.18632/oncotarget.23208. View

18.

Smedegaard S, Svart M . Licorice induced pseudohyperaldosteronism, severe hypertension, and long QT. Endocrinol Diabetes Metab Case Rep. 2019; 2019. PMC: 6935715. DOI: 10.1530/EDM-19-0109. View

19.

Sun S, Chang J, Jin J . Regulation of nuclear factor-κB in autoimmunity. Trends Immunol. 2013; 34(6):282-9. PMC: 3664242. DOI: 10.1016/j.it.2013.01.004. View

20.

Gowda P, Patrick S, Joshi S, Kumawat R, Sen E . Glycyrrhizin prevents SARS-CoV-2 S1 and Orf3a induced high mobility group box 1 (HMGB1) release and inhibits viral replication. Cytokine. 2021; 142:155496. PMC: 7953444. DOI: 10.1016/j.cyto.2021.155496. View