Research Article
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Year 2021, Volume: 5 Issue: 4, 628 - 639, 15.12.2021
https://doi.org/10.31015/jaefs.2021.4.23

Abstract

References

  • Aoki-Kinoshita, K. F., & Kanehisa, M. (2007). Gene annotation and pathway mapping in KEGG. In Comparative genomics (pp. 71-91). Humana Press.
  • Athanasios, A., Charalampos, V., & Vasileios, T. (2017). Protein-protein interaction (PPI) network: recent advances in drug discovery. Current drug metabolism, 18(1), 5-10.
  • Fishilevich, S., Zimmerman, S., Kohn, A., Iny Stein, T., Olender, T., Kolker, E., ... & Lancet, D. (2016). Genic insights from integrated human proteomics in GeneCards. Database, 2016.
  • Gezici, S., & Sekeroglu, N. (2020). Novel SARS-CoV-2 and COVID-2019 outbreak: Current perspectives on plant-based antiviral agents and complementary therapy. Ind J Pharm Educ Res, 54(3s), 442-56.
  • Harel, A., Inger, A., Stelzer, G., Strichman-Almashanu, L., Dalah, I., Safran, M., & Lancet, D. (2009). GIFtS: annotation landscape analysis with GeneCards. BMC bioinformatics, 10(1), 1-11.
  • Hastings, J., Owen, G., Dekker, A., Ennis, M., Kale, N., Muthukrishnan, V., ... & Steinbeck, C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic acids research, 44(D1), D1214-D1219.
  • Hosseinzadeh, H., & Nassiri‐Asl, M. (2015). Pharmacological effects of Glycyrrhiza spp. and its bioactive constituents: update and review. Phytotherapy Research, 29(12), 1868-1886.
  • Hsu, Y. L., Wu, L. Y., Hou, M. F., Tsai, E. M., Lee, J. N., Liang, H. L., ... & Kuo, P. L. (2011). Glabridin, an isoflavan from licorice root, inhibits migration, invasion and angiogenesis of MDA‐MB‐231 human breast adenocarcinoma cells by inhibiting focal adhesion kinase/Rho signaling pathway. Molecular nutrition & food research, 55(2), 318-327.
  • Huang, X. F., Cheng, W. B., Jiang, Y., Liu, Q., Liu, X. H., Xu, W. F., & Huang, H. T. (2020). A network pharmacology-based strategy for predicting anti-inflammatory targets of ephedra in treating asthma. International immunopharmacology, 83, 106423.
  • Huang, H. L., Hsieh, M. J., Chien, M. H., Chen, H. Y., Yang, S. F., & Hsiao, P. C. (2014). Glabridin mediate caspases activation and induces apoptosis through JNK1/2 and p38 MAPK pathway in human promyelocytic leukemia cells. PLoS One, 9(6), e98943.
  • Kanehisa, M., Furumichi, M., Tanabe, M., Sato, Y., & Morishima, K. (2017). KEGG: new perspectives on genomes, pathways, diseases and drugs. Nucleic acids research, 45(D1), D353-D361.
  • Karthikkeyan, G., Pervaje, R., Subbannayya, Y., Patil, A. H., Modi, P. K., & Prasad, T. S. K. (2020). Plant omics: metabolomics and network pharmacology of liquorice, Indian Ayurvedic Medicine Yashtimadhu. OMICS: A Journal of Integrative Biology, 24(12), 743-755.
  • Lagunin A, Ivanov S, Rudik A, Filimonov D, Poroikov V. DIGEP-Pred: web service for in silico prediction of drug-induced gene expression profiles based on structural formula. Bioinformatics 2013; 29(16): 2062e3. https://doi.org/10.1093/bioinformatics/btt322.
  • Lee, H. S., Lee, I. H., Kang, K., Park, S. I., Kwon, T. W., & Lee, D. Y. (2020). An Investigation of the Molecular Mechanisms Underlying the Analgesic Effect of Jakyak-Gamcho Decoction: A Network Pharmacology Study. Evidence-Based Complementary and Alternative Medicine, 2020.
  • Lee, A. Y., Park, W., Kang, T. W., Cha, M. H., & Chun, J. M. (2018). Network pharmacology-based prediction of active compounds and molecular targets in Yijin-Tang acting on hyperlipidaemia and atherosclerosis. Journal of Ethnopharmacology, 221, 151-159.
  • Leung, Y. K. (2001). Expression of UDP-glucuronosyltransferases (UGTs) in rat liver cells induced by an aqueous extract of licorice root. The Chinese University of Hong Kong (Hong Kong).
  • Li, C. X., Li, T. H., Zhu, M., Lai, J., & Wu, Z. P. (2021). Pharmacological properties of glabridin (a flavonoid extracted from licorice): A comprehensive review. Journal of Functional Foods, 85, 104638.
  • Liu, Y., Wang, Y., Song, X., Dong, L., Wang, W., & Wu, H. (2019). P38 mitogen-activated protein kinase inhibition attenuates mechanical stress induced lung injury via up-regulating AQP5 expression in rats. Biotechnology & Biotechnological Equipment, 33(1), 472-480.
  • Ng, H. H., Shen, M., Samuel, C. S., Schlossmann, J., & Bennett, R. G. (2019). Relaxin and extracellular matrix remodeling: Mechanisms and signaling pathways. Molecular and cellular endocrinology, 487, 59-65.
  • Sekeroglu, N., & Gezici, S. (2020) Koronavirüs Pandemisi ve Türkiye’nin Bazı Şifalı Bitkileri. Anadolu Kliniği Tıp Bilimleri Dergisi, 25 (Özel Sayı 1), 163-182. https://doi:10.21673/anadoluklin.724210.
  • Shahabi, P., Siest, G., Meyer, U. A., & Visvikis-Siest, S. (2014). Human cytochrome P450 epoxygenases: variability in expression and role in inflammation-related disorders. Pharmacology & therapeutics, 144(2), 134-161.
  • Simmler, C., Pauli, G. F., & Chen, S. N. (2013). Phytochemistry and biological properties of glabridin. Fitoterapia, 90, 160-184.
  • Su Wei Poh, M., Voon Chen Yong, P., Viseswaran, N., & Chia, Y. Y. (2015). Estrogenicity of glabridin in Ishikawa cells. PLoS One, 10(3), e0121382.
  • Su Wei Poh, M., Voon Chen Yong, P., Viseswaran, N., & Chia, Y. Y. (2015). Estrogenicity of glabridin in Ishikawa cells. PLoS One, 10(3), e0121382.
  • Tsai, Y. M., Yang, C. J., Hsu, Y. L., Wu, L. Y., Tsai, Y. C., Hung, J. Y., ... & Kuo, P. L. (2011). Glabridin inhibits migration, invasion, and angiogenesis of human non–small cell lung cancer A549 cells by inhibiting the FAK/Rho signaling pathway. Integrative cancer therapies, 10(4), 341-349.
  • Tsai, Y. M., Yang, C. J., Hsu, Y. L., Wu, L. Y., Tsai, Y. C., Hung, J. Y., ... & Kuo, P. L. (2011). Glabridin inhibits migration, invasion, and angiogenesis of human non–small cell lung cancer A549 cells by inhibiting the FAK/Rho signaling pathway. Integrative cancer therapies, 10(4), 341-349.
  • Vaillancourt, K., LeBel, G., Pellerin, G., Ben Lagha, A., & Grenier, D. (2021). Effects of the Licorice Isoflavans Licoricidin and Glabridin on the Growth, Adherence Properties, and Acid Production of Streptococcus mutans, and Assessment of Their Biocompatibility. Antibiotics, 10(2), 163.
  • Wang, Z., Luo, S., Wan, Z., Chen, C., Zhang, X., Li, B., ... & Huang, Z. (2016). Glabridin arrests cell cycle and inhibits proliferation of hepatocellular carcinoma by suppressing braf/MEK signaling pathway. Tumor Biology, 37(5), 5837-5846.
  • Wu, J., Vallenius, T., Ovaska, K., Westermarck, J., Mäkelä, T. P., & Hautaniemi, S. (2009). Integrated network analysis platform for protein-protein interactions. Nature methods, 6(1), 75-77.
  • Zhang, L. P., & Li, J. G. (2016). Glabridin reduces lipopolysaccharide-induced lung injury in rats by inhibiting p38 mitogen activated protein kinase/extracellular regulated protein kinases signaling pathway. Zhonghua yi xue za zhi, 96(48), 3893-3897.
  • Zhu, K., Li, K., Wang, H., Kang, L., Dang, C., & Zhang, Y. (2019). Discovery of glabridin as potent inhibitor of epidermal growth factor receptor in SK-BR-3 cell. Pharmacology, 104(3-4), 113-125.

Bioinformatics analyses on molecular pathways and pharmacological properties of Glabridin

Year 2021, Volume: 5 Issue: 4, 628 - 639, 15.12.2021
https://doi.org/10.31015/jaefs.2021.4.23

Abstract

Glabridin, a bioactive compound that originally isolated from the roots of licorice (Glycyrrhiza glabra L., Fam. Fabaceae), has a wide range of pharmacological properties for instance anti-inflammatory, anti-cancer, anti-microbial, anti-viral, anti-osteoporosis, anti-diabetic, anti-atherogenic, neuroprotective, estrogenic, and skin-whitening. Even though, biological activities and pharmacological properties of glabridin have already been determined, molecular signaling pathways, gene targets, and pharmacological properties based on bioinformatics analyses have not been fully elucidated. Thus, in the presented research, network-based bioinformatics approaches were applied to demonstrate targets of glabridin in human genomes and proteomes. The glabridin was input into the ChEBI database, and the targets of its were predicted using DIGEP-Pred, and then, top interacting genes were identified by GeneCards database. Afterward, STRING and KEGG enrichment database were used to construct a protein-protein interaction (PPI) network and molecular targeting pathway network, respectively. A total of 14 genes coding proteins such as UGT1A1, MAPK1, CYP2B6, MMP9, CHKA, CYP3A4, EGFR, PON1, SLC6A4, SRC, EPHX2, TYR, PTK2, and PPIG effected by glabridin were determined by gene set enrichment analysis. Furthermore, multiple pathways including endocrine resistance, bladder cancer, ErbB signaling pathway, VEGF signaling pathway, chemical carcinogenesis, proteoglycans in cancer, relaxin signaling pathway, and estrogen signaling pathway were also identified to be regulated by glabridin. This research showed that glabridin exhibits highly active pharmacological activity as an anti-infective agent, chemopreventive agent, membrane permeability inhibitor, melanin inhibitor, and apoptosis agonist. Taken together, this study is network-based scientific research that will be very useful in elucidating the biological, molecular and pharmacological properties of glabridin for clinical applications in detail.

References

  • Aoki-Kinoshita, K. F., & Kanehisa, M. (2007). Gene annotation and pathway mapping in KEGG. In Comparative genomics (pp. 71-91). Humana Press.
  • Athanasios, A., Charalampos, V., & Vasileios, T. (2017). Protein-protein interaction (PPI) network: recent advances in drug discovery. Current drug metabolism, 18(1), 5-10.
  • Fishilevich, S., Zimmerman, S., Kohn, A., Iny Stein, T., Olender, T., Kolker, E., ... & Lancet, D. (2016). Genic insights from integrated human proteomics in GeneCards. Database, 2016.
  • Gezici, S., & Sekeroglu, N. (2020). Novel SARS-CoV-2 and COVID-2019 outbreak: Current perspectives on plant-based antiviral agents and complementary therapy. Ind J Pharm Educ Res, 54(3s), 442-56.
  • Harel, A., Inger, A., Stelzer, G., Strichman-Almashanu, L., Dalah, I., Safran, M., & Lancet, D. (2009). GIFtS: annotation landscape analysis with GeneCards. BMC bioinformatics, 10(1), 1-11.
  • Hastings, J., Owen, G., Dekker, A., Ennis, M., Kale, N., Muthukrishnan, V., ... & Steinbeck, C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic acids research, 44(D1), D1214-D1219.
  • Hosseinzadeh, H., & Nassiri‐Asl, M. (2015). Pharmacological effects of Glycyrrhiza spp. and its bioactive constituents: update and review. Phytotherapy Research, 29(12), 1868-1886.
  • Hsu, Y. L., Wu, L. Y., Hou, M. F., Tsai, E. M., Lee, J. N., Liang, H. L., ... & Kuo, P. L. (2011). Glabridin, an isoflavan from licorice root, inhibits migration, invasion and angiogenesis of MDA‐MB‐231 human breast adenocarcinoma cells by inhibiting focal adhesion kinase/Rho signaling pathway. Molecular nutrition & food research, 55(2), 318-327.
  • Huang, X. F., Cheng, W. B., Jiang, Y., Liu, Q., Liu, X. H., Xu, W. F., & Huang, H. T. (2020). A network pharmacology-based strategy for predicting anti-inflammatory targets of ephedra in treating asthma. International immunopharmacology, 83, 106423.
  • Huang, H. L., Hsieh, M. J., Chien, M. H., Chen, H. Y., Yang, S. F., & Hsiao, P. C. (2014). Glabridin mediate caspases activation and induces apoptosis through JNK1/2 and p38 MAPK pathway in human promyelocytic leukemia cells. PLoS One, 9(6), e98943.
  • Kanehisa, M., Furumichi, M., Tanabe, M., Sato, Y., & Morishima, K. (2017). KEGG: new perspectives on genomes, pathways, diseases and drugs. Nucleic acids research, 45(D1), D353-D361.
  • Karthikkeyan, G., Pervaje, R., Subbannayya, Y., Patil, A. H., Modi, P. K., & Prasad, T. S. K. (2020). Plant omics: metabolomics and network pharmacology of liquorice, Indian Ayurvedic Medicine Yashtimadhu. OMICS: A Journal of Integrative Biology, 24(12), 743-755.
  • Lagunin A, Ivanov S, Rudik A, Filimonov D, Poroikov V. DIGEP-Pred: web service for in silico prediction of drug-induced gene expression profiles based on structural formula. Bioinformatics 2013; 29(16): 2062e3. https://doi.org/10.1093/bioinformatics/btt322.
  • Lee, H. S., Lee, I. H., Kang, K., Park, S. I., Kwon, T. W., & Lee, D. Y. (2020). An Investigation of the Molecular Mechanisms Underlying the Analgesic Effect of Jakyak-Gamcho Decoction: A Network Pharmacology Study. Evidence-Based Complementary and Alternative Medicine, 2020.
  • Lee, A. Y., Park, W., Kang, T. W., Cha, M. H., & Chun, J. M. (2018). Network pharmacology-based prediction of active compounds and molecular targets in Yijin-Tang acting on hyperlipidaemia and atherosclerosis. Journal of Ethnopharmacology, 221, 151-159.
  • Leung, Y. K. (2001). Expression of UDP-glucuronosyltransferases (UGTs) in rat liver cells induced by an aqueous extract of licorice root. The Chinese University of Hong Kong (Hong Kong).
  • Li, C. X., Li, T. H., Zhu, M., Lai, J., & Wu, Z. P. (2021). Pharmacological properties of glabridin (a flavonoid extracted from licorice): A comprehensive review. Journal of Functional Foods, 85, 104638.
  • Liu, Y., Wang, Y., Song, X., Dong, L., Wang, W., & Wu, H. (2019). P38 mitogen-activated protein kinase inhibition attenuates mechanical stress induced lung injury via up-regulating AQP5 expression in rats. Biotechnology & Biotechnological Equipment, 33(1), 472-480.
  • Ng, H. H., Shen, M., Samuel, C. S., Schlossmann, J., & Bennett, R. G. (2019). Relaxin and extracellular matrix remodeling: Mechanisms and signaling pathways. Molecular and cellular endocrinology, 487, 59-65.
  • Sekeroglu, N., & Gezici, S. (2020) Koronavirüs Pandemisi ve Türkiye’nin Bazı Şifalı Bitkileri. Anadolu Kliniği Tıp Bilimleri Dergisi, 25 (Özel Sayı 1), 163-182. https://doi:10.21673/anadoluklin.724210.
  • Shahabi, P., Siest, G., Meyer, U. A., & Visvikis-Siest, S. (2014). Human cytochrome P450 epoxygenases: variability in expression and role in inflammation-related disorders. Pharmacology & therapeutics, 144(2), 134-161.
  • Simmler, C., Pauli, G. F., & Chen, S. N. (2013). Phytochemistry and biological properties of glabridin. Fitoterapia, 90, 160-184.
  • Su Wei Poh, M., Voon Chen Yong, P., Viseswaran, N., & Chia, Y. Y. (2015). Estrogenicity of glabridin in Ishikawa cells. PLoS One, 10(3), e0121382.
  • Su Wei Poh, M., Voon Chen Yong, P., Viseswaran, N., & Chia, Y. Y. (2015). Estrogenicity of glabridin in Ishikawa cells. PLoS One, 10(3), e0121382.
  • Tsai, Y. M., Yang, C. J., Hsu, Y. L., Wu, L. Y., Tsai, Y. C., Hung, J. Y., ... & Kuo, P. L. (2011). Glabridin inhibits migration, invasion, and angiogenesis of human non–small cell lung cancer A549 cells by inhibiting the FAK/Rho signaling pathway. Integrative cancer therapies, 10(4), 341-349.
  • Tsai, Y. M., Yang, C. J., Hsu, Y. L., Wu, L. Y., Tsai, Y. C., Hung, J. Y., ... & Kuo, P. L. (2011). Glabridin inhibits migration, invasion, and angiogenesis of human non–small cell lung cancer A549 cells by inhibiting the FAK/Rho signaling pathway. Integrative cancer therapies, 10(4), 341-349.
  • Vaillancourt, K., LeBel, G., Pellerin, G., Ben Lagha, A., & Grenier, D. (2021). Effects of the Licorice Isoflavans Licoricidin and Glabridin on the Growth, Adherence Properties, and Acid Production of Streptococcus mutans, and Assessment of Their Biocompatibility. Antibiotics, 10(2), 163.
  • Wang, Z., Luo, S., Wan, Z., Chen, C., Zhang, X., Li, B., ... & Huang, Z. (2016). Glabridin arrests cell cycle and inhibits proliferation of hepatocellular carcinoma by suppressing braf/MEK signaling pathway. Tumor Biology, 37(5), 5837-5846.
  • Wu, J., Vallenius, T., Ovaska, K., Westermarck, J., Mäkelä, T. P., & Hautaniemi, S. (2009). Integrated network analysis platform for protein-protein interactions. Nature methods, 6(1), 75-77.
  • Zhang, L. P., & Li, J. G. (2016). Glabridin reduces lipopolysaccharide-induced lung injury in rats by inhibiting p38 mitogen activated protein kinase/extracellular regulated protein kinases signaling pathway. Zhonghua yi xue za zhi, 96(48), 3893-3897.
  • Zhu, K., Li, K., Wang, H., Kang, L., Dang, C., & Zhang, Y. (2019). Discovery of glabridin as potent inhibitor of epidermal growth factor receptor in SK-BR-3 cell. Pharmacology, 104(3-4), 113-125.
There are 31 citations in total.

Details

Primary Language English
Subjects Food Engineering
Journal Section Research Articles
Authors

Sevgi Gezici 0000-0002-4856-0221

Nazım Şekeroğlu 0000-0002-0630-0106

Publication Date December 15, 2021
Submission Date August 20, 2021
Acceptance Date November 28, 2021
Published in Issue Year 2021 Volume: 5 Issue: 4

Cite

APA Gezici, S., & Şekeroğlu, N. (2021). Bioinformatics analyses on molecular pathways and pharmacological properties of Glabridin. International Journal of Agriculture Environment and Food Sciences, 5(4), 628-639. https://doi.org/10.31015/jaefs.2021.4.23


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