In vitro trypsin inhibitory activities of some plant and fruit extracts and chemical compounds
Year 2023,
, 282 - 292, 08.10.2023
Ebru İlhan Lale
,
İsmet Burcu Turkyilmaz
,
Refiye Yanardağ
Abstract
Trypsin, an enzyme from the serine protease class, is known to be involved in the degradation of proteins. Excessive activity of trypsin is strongly implicated in triggering many diseases, such as acute pancreatitis, inflammation, and tumour. Therefore, this enzyme's regular and balanced activity is necessary for normal physiological functions. Thus, there is a need to develop new trypsin inhibitors from natural sources and chemical compounds. In this study, the inhibitory effects of aqueous extracts prepared from 29 different plants and 10 different chemical compounds were investigated on the activity of trypsin due to its importance in the health sector. The present study's plant extracts and chemical compounds showed trypsin-inhibitory effects. The inhibitory activities of the extracts and chemical compounds increased in a dose-dependent manner. Several plant extracts and chemical compounds that showed high trypsin inhibitory activities may be appropriate for use as trypsin inhibitors to provide additional support to drug treatment in the health field.
Supporting Institution
Scientific Research Projects Coordination Unit of Istanbul University
References
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Clemente, M., Corigliano, M., Pariani, S., Sánchez-López, E., Sander, V., Ramos-Duarte, V. (2019). Plant serine protease inhibitors: Biotechnology application in agriculture and molecular farming. International Journal of Molecular Sciences, 20, 1345. https://doi.org/10.3390/ijms20061345
Dağsuyu, E., Yanardağ, R. (2021). In vitro urease and trypsin inhibitory activities of some sulfur compounds. Istanbul Journal of Pharmacy, 51, 85–91. https://dergipark.org.tr/en/download/article-file/1461510
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- Fan, F.Y., Huang, C.S., Tong, Y.L., Guo, H.W., Zhou, S.J., Ye, J.H., Gong, S.Y. (2021). Widely targeted metabolomics analysis of white peony teas with different storage time and association with sensory attributes. Food Chemistry, 362, 130257. https://doi.org/10.1016/j.foodchem.2021.130257
- Feng, Y., Lv, M., Lu, Y., Liu, K., Liu, L., He, Z., Wu, K., Wang, X., Zhang, B., Wu, X. (2018). Characterization of binding interactions between selected phenylpropanoid glycosides and trypsin. Food Chemistry, 243, 118–124. https://doi.org/10.1016/j.foodchem.2017.09.118
- Geisslitz, S., Weegels, P., Shewry, P., Zevallos, V., Masci, S., Sorrells, M., Gregorini, A., Colomba, M., Jonkers, D., Huang, X., de Giorgio, R., Caio, G.P., D’Amico, S., Larré, C., Brouns, F. (2022). Wheat amylase/trypsin inhibitors (ATIs): occurrence, function and health aspects. European Journal of Nutrition, 61, 2873-2880. https://doi.org/10.1007/s00394-022-02841-y
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- Haq, S.K., Atif, S.M., Khan, R.H. (2004). Protein proteinase inhibitor genes in combat against insects, pests, and pathogens: natural and engineered phytoprotection. Archives of Biochemistry and Biophysics, 431, 145–159. https://doi.org/10.1016/j.abb.2004.07.022
- Hegyi, E., Sahin-Tóth, M. (2017). Genetic risk in chronic pancreatitis: The trypsin-dependent pathway. Digestive Diseases and Sciences, 62, 1692–1701. https://doi.org/10.1007/s10620-017-4601-3
- Hovhannisyan, N., Harutyunyan, Sh., Hovhannisyan, A., Hambardzumyan, A., Chitchyan, M., Melkumyan, M., Oganezova, G., Avetisyan, N. (2009). The novel inhibitors of serine proteases. Amino Acids, 37, 531–536. https://doi.org/10.1007/s00726-009-0257-4
- Kan, L., Capuano, E., Fogliano, V., Verkerk, R., Mes, J.J., Tomassen, M.M.M., Oliviero, T. (2021). Inhibition of α-glucosidases by tea polyphenols in rat intestinal extract and Caco-2 cells grown on transwell. Food Chemistry, 361, 130047. https://doi.org/10.1016/j.foodchem.2021.130047
- Li, Q., Wei, Q., Yuan, E., Yang, J., Ning, Z. (2014). Interaction between four flavonoids and trypsin: effect on the characteristics of trypsin and antioxidant activity of flavonoids. International Journal of Food Science & Technology, 49, 1063–1069. https://doi.org/10.1111/ijfs.12401
- Mancek-Keber, M. (2014). Inflammation-mediating proteases: Structure, function in (patho) physiology and inhibition. Protein and Peptide Letters, 21, 1209–1229. https://doi.org/10.2174/0929866521666140819123932
- Mashayekhi-Sardoo, H., Razavi, B.M., Ekhtiari, M., Kheradmand, N., Imenshahidi, M. (2020). Gastroprotective effects of both aqueous and ethanolic extracts of Lemon verbena leaves against indomethacin-induced gastric ulcer in rats. Iranian Journal of Basic Medical Sciences, 23, 1639–1646. https://doi.org/10.22038/ijbms.2020.44341.10377
- Navaei-Bonab, R., Kazzazi, M., Saber, M., Vatanparast, M. (2018). Differential inhibition of Helicoverpa armigera (Lep.: Noctuidae) gut digestive trypsin by extracted and purified inhibitor of datura metel (Solanales: Solanaceae). Journal of Economic Entomology, 111, 178–186. https://doi.org/10.1093/jee/tox209
- Park, K.C., Dharmasivam, M., Richardson, D.R. (2020). The role of extracellular proteases in tumor progression and the development of innovative metal ion chelators that inhibit their activity. International Journal of Molecular Sciences, 21, 6805. https://doi.org/10.3390/ijms21186805
- Regulski, M., Regulska, K., Stanisz, B., Murias, M., Gieremek, P., Wzgarda, A., Niznik, B. (2015). Chemistry and pharmacology of angiotensin-converting enzyme inhibitors. Current Pharmaceutical Design, 21, 1764–1775. https://doi.org/10.2174/1381612820666141112160013
- Ribeiro, J.K.C., Cunha, D.D.S., Fook, J.M.S.LL., Sales, M.P. (2010). New properties of the soybean trypsin inhibitor: Inhibition of human neutrophil elastase and its effect on acute pulmonary injury. European Journal of Pharmacology, 644, 238–244. https://doi.org/10.1016/j.ejphar.2010.06.067
- Saberi, A., Abbasloo, E., Sepehri, G., Yazdanpanah, M., Mirkamandari, E., Sheibani, V., Safi, Z. (2016). The Effects of methanolic extract of Melissa officinalis on experimental gastric ulcers in rats. Iranian Red Crescent Medical Journal, 18, e24271. https://doi.org/10.5812/ircmj.24271
- Sacan, O., Yildiz Turhan, E. (2014). Lipoxygenase inhibitory activities of some plant extracts and chemical compounds. European Journal of Biology, 73, 47–52.
- Satoh, H., Amagase, K., Takeuchi, K. (2014). Mucosal protective agents prevent exacerbation of NSAID-induced small intestinal lesions caused by antisecretory drugs in rats. Journal of Pharmacology and Experimental Therapeutics, 348, 227–235. https://doi.org/10.1124/jpet.113.208991
- Srikanth, S., Chen, Z. (2016). Plant protease inhibitors in therapeutics-focus on cancer therapy. Frontiers in Pharmacology, 7, 470. https://doi.org/10.3389/fphar.2016.00470
- Sultana, M.S., Millwood, R.J., Mazarei, M., Stewart, C.N. (2022). Proteinase inhibitors in legume herbivore defense: From natural to genetically engineered protectants. Plant Cell Reports, 41, 293–305. https://doi.org/10.1007/s00299-021-02800-7
- Tarantino, A., Difonzo, G., Lopriore, G., Disciglio, G., Paradiso, V.M., Gambacorta, G., Caponio, F. (2020). Bioactive compounds and quality evaluation of ‘Wonderful’ pomegranate fruit and juice as affected by deficit irrigation. Journal of the Science of Food and Agriculture, 100, 5539–5545. https://doi.org/10.1002/jsfa.10606
- Topaloglu, D., Turkyilmaz, I.B., Yanardag, R. (2022). Gastroprotective effect of vitamin U in D-galactosamine-induced hepatotoxicity. Journal of Biochemical and Molecular Toxicology, 36, e23124. https://doi.org/10.1002/jbt.23124
- Turkyilmaz, I.B., Coskun, Z.M., Bolkent, S., Yanardag, R. (2019). The effects of antioxidant combination on indomethacin-induced gastric mucosal injury in rats. Cellular and Molecular Biology, 65, 76-83. https://doi.org/10.14715/cmb/2019.65.3.11
- Uçan, F., Ağçam, E., Akyildiz, A. (2016). Bioactive compounds and quality parameters of natural cloudy lemon juices. Journal of Food Science and Technology, 53, 1465–1474. https://doi.org/10.1007/s13197-015-2155-y
- Viskupicova, J., Danihelova, M., Majekova, M., Liptaj, T., Sturdik, E. (2012). Polyphenol fatty acid esters as serine protease inhibitors: a quantum-chemical QSAR analysis. Journal of Enzyme Inhibition and Medicinal Chemistry, 27, 800–809. https://doi.org/10.3109/14756366.2010.616860
- Yi, C., Wu, W., Zheng, D., Peng, G., Huang, H., Shen, Z., Teng, X. (2020). Targeted inhibition of endothelial calpain delays wound healing by reducing inflammation and angiogenesis. Cell Death & Disease, 11, 533. https://doi.org/10.1038/s41419-020-02737-x
- Zhan, X., Wan, J., Zhang, G., Song, L., Gui, F., Zhang, Y., Li, Y., Guo, J., Dawra, R.K., Saluja, A. K., Haddock, A.N., Zhang, L., Bi, Y., Ji, B. (2019). Elevated intracellular trypsin exacerbates acute pancreatitis and chronic pancreatitis in mice. American Journal of Physiology-Gastrointestinal and Liver Physiology, 316, G816–G825. https://doi.org/10.1152/ajpgi.00004.2019
- Zhang, J., Yang, X., Li, Y. (2021). Key active sites of proteases and protease inhibitors: A review. Chinese Journal of Biotechnology, 37, 561–579.
Year 2023,
, 282 - 292, 08.10.2023
Ebru İlhan Lale
,
İsmet Burcu Turkyilmaz
,
Refiye Yanardağ
References
- Abd el-Rady, N.M., Dahpy, M.A., Ahmed, A., Elgamal, D.A., Hadiya, S., Ahmed, M.A.M., Sayed, Z.E.A.A., Abdeltawab, D., Abdelmohsen, A.S., Farrag, A.A.M., Ashmawy, A.M., Khairallah, M.K., Galal, H.M. (2021). Interplay of biochemical, genetic, and immunohistochemical factors in the etio-pathogenesis of gastric ulcer in rats: A comparative study of the effect of pomegranate loaded nanoparticles versus pomegranate peel extract. Frontiers in Physiology, 12 (649462). https://doi.org/10.3389/fphys.2021.649462
- Abdellatif, F., Boudjella, H., Zitouni, A., Hassani, A. (2014). Chemical composition and antimicrobial activity of the essential oil from leaves of Algerian Melissa officinalis L. EXCLI Journal, 13, 772–781. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4464394/pdf/EXCLI-13-772.pdf
- Bateman, K.S., James, M.N.G. (2011). Plant protein proteinase inhibitors: structure and mechanism of inhibition. Current Protein & Peptide Science, 12, 340–347. https://doi.org/10.2174/138920311796391124
- Cid-Gallegos, M.S., Corzo-Ríos, L.J., Jiménez-Martínez, C., Sánchez-Chino, X.M. (2022). Protease inhibitors from plants as therapeutic agents - A review. Plant Foods for Human Nutrition, 77, 20–29. https://doi.org/10.1007/s11130-022-00949-4
- Cheshomi, H., Bahrami, A.R., Rafatpanah, H., Matin, M.M. (2022). The effects of ellagic acid and other pomegranate (Punica granatum L.) derivatives on human gastric cancer AGS cells. Human and Experimental Toxicology, 41, 1-16. https://doi.org/10.1177/09603271211064534
Clemente, M., Corigliano, M., Pariani, S., Sánchez-López, E., Sander, V., Ramos-Duarte, V. (2019). Plant serine protease inhibitors: Biotechnology application in agriculture and molecular farming. International Journal of Molecular Sciences, 20, 1345. https://doi.org/10.3390/ijms20061345
Dağsuyu, E., Yanardağ, R. (2021). In vitro urease and trypsin inhibitory activities of some sulfur compounds. Istanbul Journal of Pharmacy, 51, 85–91. https://dergipark.org.tr/en/download/article-file/1461510
- de Oliveira Braga, L.E., da Silva, G.G., de Oliveira Sousa, I.M., de Oliveira, E.C.S., Jorge, M.P., Monteiro, K.M., Sedano, T.C., Foglio, M.A., Ruiz, A.L.T.G. (2022). Gastrointestinal effects of Mentha aquatica L. essential oil. Inflammopharmacology, 30, 2127-2137. https://doi.org/10.1007/s10787-022-00989-x
- Elsässer, B., Goettig, P. (2021). Mechanisms of proteolytic enzymes and their inhibition in QM/MM studies. International Journal of Molecular Sciences, 22, 3232. https://doi.org/10.3390/ijms22063232
- Fan, F.Y., Huang, C.S., Tong, Y.L., Guo, H.W., Zhou, S.J., Ye, J.H., Gong, S.Y. (2021). Widely targeted metabolomics analysis of white peony teas with different storage time and association with sensory attributes. Food Chemistry, 362, 130257. https://doi.org/10.1016/j.foodchem.2021.130257
- Feng, Y., Lv, M., Lu, Y., Liu, K., Liu, L., He, Z., Wu, K., Wang, X., Zhang, B., Wu, X. (2018). Characterization of binding interactions between selected phenylpropanoid glycosides and trypsin. Food Chemistry, 243, 118–124. https://doi.org/10.1016/j.foodchem.2017.09.118
- Geisslitz, S., Weegels, P., Shewry, P., Zevallos, V., Masci, S., Sorrells, M., Gregorini, A., Colomba, M., Jonkers, D., Huang, X., de Giorgio, R., Caio, G.P., D’Amico, S., Larré, C., Brouns, F. (2022). Wheat amylase/trypsin inhibitors (ATIs): occurrence, function and health aspects. European Journal of Nutrition, 61, 2873-2880. https://doi.org/10.1007/s00394-022-02841-y
- Ghosh, K.S., Debnath, J., Pathak, T., Dasgupta, S. (2008). Using proton nuclear magnetic resonance to study the mode of ribonuclease A inhibition by competitive and noncompetitive inhibitors. Bioorganic & Medicinal Chemistry Letters, 18, 5503–5506. https://doi.org/10.1016/j.bmcl.2008.09.014
- Gräwe, A., Ranglack, J., Weber, W., Stein, V. (2020). Engineering artificial signaling functions with proteases. Current Opinion in Biotechnology, 63, 1–7. https://doi.org/10.1016/j.copbio.2019.09.017
- Greene, C.M., McElvaney, N.G. (2009). Proteases and antiproteases in chronic neutrophilic lung disease - relevance to drug discovery. British Journal of Pharmacology, 158, 1048–1058. https://doi.org/10.1111/j.1476-5381.2009.00448.x
- Haq, S.K., Atif, S.M., Khan, R.H. (2004). Protein proteinase inhibitor genes in combat against insects, pests, and pathogens: natural and engineered phytoprotection. Archives of Biochemistry and Biophysics, 431, 145–159. https://doi.org/10.1016/j.abb.2004.07.022
- Hegyi, E., Sahin-Tóth, M. (2017). Genetic risk in chronic pancreatitis: The trypsin-dependent pathway. Digestive Diseases and Sciences, 62, 1692–1701. https://doi.org/10.1007/s10620-017-4601-3
- Hovhannisyan, N., Harutyunyan, Sh., Hovhannisyan, A., Hambardzumyan, A., Chitchyan, M., Melkumyan, M., Oganezova, G., Avetisyan, N. (2009). The novel inhibitors of serine proteases. Amino Acids, 37, 531–536. https://doi.org/10.1007/s00726-009-0257-4
- Kan, L., Capuano, E., Fogliano, V., Verkerk, R., Mes, J.J., Tomassen, M.M.M., Oliviero, T. (2021). Inhibition of α-glucosidases by tea polyphenols in rat intestinal extract and Caco-2 cells grown on transwell. Food Chemistry, 361, 130047. https://doi.org/10.1016/j.foodchem.2021.130047
- Li, Q., Wei, Q., Yuan, E., Yang, J., Ning, Z. (2014). Interaction between four flavonoids and trypsin: effect on the characteristics of trypsin and antioxidant activity of flavonoids. International Journal of Food Science & Technology, 49, 1063–1069. https://doi.org/10.1111/ijfs.12401
- Mancek-Keber, M. (2014). Inflammation-mediating proteases: Structure, function in (patho) physiology and inhibition. Protein and Peptide Letters, 21, 1209–1229. https://doi.org/10.2174/0929866521666140819123932
- Mashayekhi-Sardoo, H., Razavi, B.M., Ekhtiari, M., Kheradmand, N., Imenshahidi, M. (2020). Gastroprotective effects of both aqueous and ethanolic extracts of Lemon verbena leaves against indomethacin-induced gastric ulcer in rats. Iranian Journal of Basic Medical Sciences, 23, 1639–1646. https://doi.org/10.22038/ijbms.2020.44341.10377
- Navaei-Bonab, R., Kazzazi, M., Saber, M., Vatanparast, M. (2018). Differential inhibition of Helicoverpa armigera (Lep.: Noctuidae) gut digestive trypsin by extracted and purified inhibitor of datura metel (Solanales: Solanaceae). Journal of Economic Entomology, 111, 178–186. https://doi.org/10.1093/jee/tox209
- Park, K.C., Dharmasivam, M., Richardson, D.R. (2020). The role of extracellular proteases in tumor progression and the development of innovative metal ion chelators that inhibit their activity. International Journal of Molecular Sciences, 21, 6805. https://doi.org/10.3390/ijms21186805
- Regulski, M., Regulska, K., Stanisz, B., Murias, M., Gieremek, P., Wzgarda, A., Niznik, B. (2015). Chemistry and pharmacology of angiotensin-converting enzyme inhibitors. Current Pharmaceutical Design, 21, 1764–1775. https://doi.org/10.2174/1381612820666141112160013
- Ribeiro, J.K.C., Cunha, D.D.S., Fook, J.M.S.LL., Sales, M.P. (2010). New properties of the soybean trypsin inhibitor: Inhibition of human neutrophil elastase and its effect on acute pulmonary injury. European Journal of Pharmacology, 644, 238–244. https://doi.org/10.1016/j.ejphar.2010.06.067
- Saberi, A., Abbasloo, E., Sepehri, G., Yazdanpanah, M., Mirkamandari, E., Sheibani, V., Safi, Z. (2016). The Effects of methanolic extract of Melissa officinalis on experimental gastric ulcers in rats. Iranian Red Crescent Medical Journal, 18, e24271. https://doi.org/10.5812/ircmj.24271
- Sacan, O., Yildiz Turhan, E. (2014). Lipoxygenase inhibitory activities of some plant extracts and chemical compounds. European Journal of Biology, 73, 47–52.
- Satoh, H., Amagase, K., Takeuchi, K. (2014). Mucosal protective agents prevent exacerbation of NSAID-induced small intestinal lesions caused by antisecretory drugs in rats. Journal of Pharmacology and Experimental Therapeutics, 348, 227–235. https://doi.org/10.1124/jpet.113.208991
- Srikanth, S., Chen, Z. (2016). Plant protease inhibitors in therapeutics-focus on cancer therapy. Frontiers in Pharmacology, 7, 470. https://doi.org/10.3389/fphar.2016.00470
- Sultana, M.S., Millwood, R.J., Mazarei, M., Stewart, C.N. (2022). Proteinase inhibitors in legume herbivore defense: From natural to genetically engineered protectants. Plant Cell Reports, 41, 293–305. https://doi.org/10.1007/s00299-021-02800-7
- Tarantino, A., Difonzo, G., Lopriore, G., Disciglio, G., Paradiso, V.M., Gambacorta, G., Caponio, F. (2020). Bioactive compounds and quality evaluation of ‘Wonderful’ pomegranate fruit and juice as affected by deficit irrigation. Journal of the Science of Food and Agriculture, 100, 5539–5545. https://doi.org/10.1002/jsfa.10606
- Topaloglu, D., Turkyilmaz, I.B., Yanardag, R. (2022). Gastroprotective effect of vitamin U in D-galactosamine-induced hepatotoxicity. Journal of Biochemical and Molecular Toxicology, 36, e23124. https://doi.org/10.1002/jbt.23124
- Turkyilmaz, I.B., Coskun, Z.M., Bolkent, S., Yanardag, R. (2019). The effects of antioxidant combination on indomethacin-induced gastric mucosal injury in rats. Cellular and Molecular Biology, 65, 76-83. https://doi.org/10.14715/cmb/2019.65.3.11
- Uçan, F., Ağçam, E., Akyildiz, A. (2016). Bioactive compounds and quality parameters of natural cloudy lemon juices. Journal of Food Science and Technology, 53, 1465–1474. https://doi.org/10.1007/s13197-015-2155-y
- Viskupicova, J., Danihelova, M., Majekova, M., Liptaj, T., Sturdik, E. (2012). Polyphenol fatty acid esters as serine protease inhibitors: a quantum-chemical QSAR analysis. Journal of Enzyme Inhibition and Medicinal Chemistry, 27, 800–809. https://doi.org/10.3109/14756366.2010.616860
- Yi, C., Wu, W., Zheng, D., Peng, G., Huang, H., Shen, Z., Teng, X. (2020). Targeted inhibition of endothelial calpain delays wound healing by reducing inflammation and angiogenesis. Cell Death & Disease, 11, 533. https://doi.org/10.1038/s41419-020-02737-x
- Zhan, X., Wan, J., Zhang, G., Song, L., Gui, F., Zhang, Y., Li, Y., Guo, J., Dawra, R.K., Saluja, A. K., Haddock, A.N., Zhang, L., Bi, Y., Ji, B. (2019). Elevated intracellular trypsin exacerbates acute pancreatitis and chronic pancreatitis in mice. American Journal of Physiology-Gastrointestinal and Liver Physiology, 316, G816–G825. https://doi.org/10.1152/ajpgi.00004.2019
- Zhang, J., Yang, X., Li, Y. (2021). Key active sites of proteases and protease inhibitors: A review. Chinese Journal of Biotechnology, 37, 561–579.