Impact on cardioprotective effect of Psidium guajava leaves extract in streptozotocin-induced Wistar mice with molecular in silico analysis
Main Article Content
Keywords
Psidium guajava, lysosomal enzymes, mitochondrial enzymes, cardiac markers
Abstract
Cardiovascular disease (CVD) and its complications have been regarded as the leading cause of morbidity and mortality. The drugs available in the market are effective to treat CVD, but with many adverse reactions. Nowadays, herbal products are the attention of researchers because of their less adverse effects. In this study, the cardioprotective effects of ethanolic leaves extract of Psidium guajava Linn. (Guava) (P. guajava) were evaluated in streptozotocin (STZ)-treated animal models. Mice acquired for the study were divided into five groups, each consisting of six mice. The toxin-induced mice were treated with the ethanolic leaves extract of P. guajava (300 mg/kg body weight [b.w.]). The results were compared to the standard drug (glibenclamide)-treated mice (3 mg/kg b.w.). The following parameters were considered for further investigations: creatine kinase-muscle brain (CK-MB), creatine kinase (CK), troponin, lysosomal, and mitochondrial enzymes. Then the docking study was accomplished. The levels of cardiac marker enzymes and lysosomal enzymes increased significantly in the toxin-induced mice, while the level of mitochondrial enzyme decreased significantly. During treatment with the ethanolic leaves extract of P. guajava, the levels of all parameters were notably reversed to normal range (P < 0.05). Further, in docking analysis, the interaction of compounds, such as alpha-terpineol, cyclopentanecarboxamide, guaiol (a sesquiterpenoid alcohol), 1H-cyclopropanaphthalene, tetracyclotridecan-9-ol, dormin/abscisic acid, and epiglobulol, with the respective protein molecules, evidenced the cardioprotective effect of P. guajava leaves. Hence, it was concluded that the ethanolic leaves extract of P. guajava leaves have a cardioprotective effect.
References
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Daswani, P.G., Gholkar, M.S. and Birdi, T.J., 2017. Psidium guajava: A single plant for multiple health problems of rural Indian population. Pharmacognosy Reviews 11(22): 167. 10.4103/phrev.phrev_17_17
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Gutiérrez, R.M., Mitchell, S. and Solis, R.V., 2008. Psidium guajava: A review of its traditional uses, phytochemistry and pharmacology. Journal of Ethnopharmacology 117: 1–27. 10.1016/j.jep.2008.01.025
Hikmawanti N.P., Fatmawati S. and Asri A.W., 2021. The effect of ethanol concentrations as the extraction solvent on antioxidant activity of Katuk (Sauropus Androgynus (L.) Merr.) leaves extracts. In: IOP conference series: Earth and environmental science, Vol. 755, No. 1. IOP Publishing, Bristol, UK, p. 12060. 10.1088/1755-1315/755/1/012060
Hoffstein, S. and Weissmann, G., 1975. Mechanisms of lysosomal enzyme release from leukocytes. Arthiritis and Rheumatism 18(2): 153–165. 10.1002/art.1780180213
Karthikeyan, K., Sarala Bai, B.R. and Niranjali Devaraj, S., 2007. Cardioprotective effect of grape seed proanthocyanidins on isoproterenol-induced myocardial injury in rats. International Journal of Cardiology 115: 326–333. 10.1016/j.ijcard.2006.03.016
Kawai, Y. and Anno, K., 1971. Mucopolysaccharide-degrading enzymes from the liver of the squid, Ommastrephessloanipacificus I. Hyaluronidase. Biochimica et Biophysica Acta 242: 428–436. 10.1016/0005-2744(71)90234-8
King, J., 1965. In: Van, D. (ed.) Prac Clini Enzymology. Nostrand, London, Pp. 83–93.
Kumar, A., Khan, S.A., Parvez, A., Zaheer, M.S., Rabbani, M.U. and Zafar L., 2011. The prevalence of hyperhomocysteinemia and its correlation with conventional risk factors in young patients with myocardial infarction in a tertiary care centre of India. Biomedical Research 22: 225–229.
Leslie, V.A., Alarjani, K.M., Arunkumar, M., Balamuralikrishnan, B., 2021. Bacteriocin producing microbes with bactericidal activity against multidrug resistant pathogens. Journal of Infection and Public Health 14: 1802–1809. 10.1016/j.jiph.2021.09.029
Lutterodt, G.D., 1992. Inhibition of microlax induced experimental diarrhoea with narcotics like extracts of Psidium guajavain rats. Journal of Ethnopharmacology 37(2): 151–157. 10.1016/0378-8741(92)90073-Z
Manikandan, R. and Vijaya Anand, A., 2015. Evaluation of antioxidant activity of Psidium guajava Linn. in streptozotocin-induced diabetic rats. Free Radicals and Antioxidants 6(1): 72–76. 10.5530/fra.2016.1.9
Manikandan, R., Vijaya Anand, A. and Durai Muthumani, G., 2013. Phytochemical and in vitro anti-diabetic activity of methanolic extract of Psidium guajava leaves. International Journal of Current Microbiology and Applied Sciences 2(2): 15–19.
Manikandan, R., Vijaya Anand, A., Sampathkumar, P. and Manoharan, N., 2018. Protective effect of Psidium guajava leaf ethanolic extract against streptozotocin induced diabetes and lipidosis in rats. Indian Journal of Animal Research 52(8): 1198–1205. 10.18805/ijar.B-3337
Manikandan, R., Vijay Anand, A., Sampathkumar, P. and Pushp, 2016. Phytochemical and in vitro antidiabetic activity of Psidium guajava leaves. Pharmacognosy Journal 2016,8,4,392-394. 10.5530/pj.2016.4.13
Mehler, A.H., Kornberg, A., Grisolia, S. and Ochoa, S., 1948. The enzymatic mechanism of oxidation-reductions between malate or isocitrate or pyruvate. Journal of Biological Chemistry 174: 961–977. 10.1016/S0021-9258(18)57306-3
Moore, J.C. and Morris, J.E., 1982. A simple automated colorimetric method for determination of N-acetyl β-D glucosaminidase. Annals of Clinical Biochemistry 19: 157–159. 10.1177/000456328201900305
O’Brien, P.J., Smith, D.E., Knechtel, T.J., Marchak, M.A., Pruimboom-Bress, I., Bress, D.J., et al. 2006. Cardiac troponin I is a sensitive, specific biomarker of cardiac injury in laboratory animals. Laboratory Animals 40(2): 153–171. 10.1258/002367706776319042
Okinada, S., Kumagai, H. and Ebashi, S.H., 1961. Serum creatine phosphokinase. Activity in progressive muscular dystrophy and neuromuscular diseases. Archives of Neurology 4: 520–525. 10.1001/archneur.1961.00450110050006
Panche A.N., Diwan A.D. and Chandra S.R., 2016. Flavonoids: an overview. Journal of Nutritional Science 5: e47. 10.1017/jns.2016.41.
Pearl, W., Cascarano, J. and Zweifach, B.W., 1963. Micro determination of cytochromeoxidase in rat tissues by the oxidation on N-phenyl-p-phenylene diamine or ascorbic acid. Journal of Histochemistry and Cytochemistry 11: 102–104. 10.1177/11.1.102
Reed, L.J. and Mukherjee, R.B., 1969. Α-ketoglutarate dehydrogenase complex from Escherichia coli. Methods Enzymology 13: 55-51. 10.1016/0076-6879(69)13016-5
Sapolsky, A.I., Altman, R.D. and Howell, D.S., 1973. Cathepsin-D activity in normal and osteoarthritic human cartilage. Federation Proceedings 32: 1489–1493.
Seager, M.J., Singal, P.K., Orchard, R., Pierce, G.N. and Dhalla, N.S., 1984. Cardiac cell damage: a primary myocardial disease in streptozotocin-induced chronic diabetes. British Journal of Experimental Pathology 65(5): 613–623.
Sinha, A.K., 1972. Colorimetric assay of catalase. Analytical Biochemistry 47: 389–394. 10.1016/0003-2697(72)90132-7
Sivakumar, V. and Dhana Rajan, M.S., 2011. Standardization & characterization of Tinospora cordifolia (Willd.) Miers ex Hook. F. & Thoms. Plant stem extract in different solvent fractions. Asian Journal of Biochemical and Pharmaceutical Research (AJBPR) 1(4): 105–112.
Slater, E.C. and Bonner, W.D., 1952. The effect of fluoride on succinic oxidase system. Biochemical Journal 52: 185–196. 10.1042/bj0520185
Subashini, R. and Sumathi, P., 2012. Cardioprotective effect of Nelumbo nucifera on mitochondrial lipid peroxide enzymes and electrolytes against isoproterenol-induced cardiotoxicity in Wistar rats. Asian Pacific Journal of Tropical Disease 2(2): S588–S591. 10.1016/S2222-1808(12)60227-8
Sudharsan, P.T., Mythili, Y., Selvakumar, E. and Varalakshmi P., 2006. Lupeol and its ester exhibit protective role against cyclophosphamide-induced cardiac mitochondrial toxicity. Journal of Cardiovascular Pharmacology 47(2): 205–210. 10.1097/01.fjc.0000200658.89629.ba
Sultana, B., Anwar, F. and Ashraf, M., 2009. Effect of extraction solvent/technique on the antioxidant activity of selected medicinal plant extracts. Molecules 14(6): 2167–2180. 10.3390/molecules14062167
Tsoo, E., King, R. and Howard, L., 1967. Preparations and properties of soluble NADH dehydrogenases from cardiac muscle. Methods in Enzymology 275–294. 10.1016/0076-6879(67)10055-4
Vijayakumar, K., Rengarajan, R.L., Radhakrishnan, R. and Anand, A.V., 2018. Hypolipidemic effect of Psidium guajava leaf extract against hepatotoxicity in rats. Pharmacognosy Magazine 14(53): 4–8. 10.4103/pm.pm_167_17
Vijayakumar K., Arumugam V.A., Ramasamy M., Natesan M., Palanisamy S., Thajuddin NB., et al. 2020. Hepatoprotective effects of Psidium guajava on mitochondrial enzymes and inflammatory markers in carbon tetrachloride-induced hepatotoxicity. Drug Development and Industrial Pharmacy 46(12): 2041–2050. 10.1080/03639045.2020.1843474
Vishal, D. Joshi, Akash, P. Dahake and Ashok, P. Suthar., 2010. Adverse effects associated with the use of antihypertensive drugs: an overview. International Journal of PharmTech Research 1 & 2: 10–13.
Xie, F., Wang, H., Cao, Q., Chen, Q. and Lin, F. 2022. The effects of Oldenlandia diffusa water extract on glucose metabolism and inflammation level in rats with streptozotocin-induced gestational diabetes mellitus. Quality Assurance and Safety of Crops & Foods 14(1): 24–30. 10.15586/qas.v14i1.970
Zakaria, M. and Mohd, M.S., 1994. Traditional Malay medicinal plants. Penerbit Fasar Bakti Suden Berhard, Selangor, Malaysia, pp. 129–132.
Arafa M.H., Mohammad N.S., Atteia H.H. and Abd-Elaziz H.R., 2014. Protective effect of resveratrol against doxorubicin-induced cardiotoxicity and fibrosis in male experimental rats. Journal of Physiology and Biochemistry 70: 701–711. 10.1007/s13105-014-0339-y
Bell, J.L. and Baron, D.N., 1960. A colorimetric method for determination of isocitrate dehydrogenase. Clinica Chimica Acta 5: 740–747. 10.1016/0009-8981(60)90017-6
Burtis, C.A. and Ashwood, E.R., 1996. Tietz fundamentals of clinical chemistry, 4th edition. W.B. Saunders, London, 881 p.
Buynes, J.W. and Thorpe, S.R., 2000. Glyoxidation and lipoxidation in atherogenesis. Free Radical Biology and Medicine 28: 1708–1716. 10.1016/S0891-5849(00)00228-8
Canceras, A., Figeroa, L., Taracena, A.M. and Samayoa, B.E., 1993. Plant used in Guatemala for the treatment of respiratory disease II. Evaluation of activity of 16 plants against Gram-positive bacteria. Journal of Ethnopharmacology 39(1): 77–82. 10.1016/0378-8741(93)90053-8
Daswani, P.G., Gholkar, M.S. and Birdi, T.J., 2017. Psidium guajava: A single plant for multiple health problems of rural Indian population. Pharmacognosy Reviews 11(22): 167. 10.4103/phrev.phrev_17_17
Decker RS, Wildenthal K., 1980. Lysosomal alterations in hypoxic and reoxygenated hearts. I. Ultrastructural and cytochemical changes. The American journal of pathology. 1980 Feb 98(2):425.
Frustaci, A., Kajastura, J., Chimenti, C., Jakonick, I., Leri, A., Maseri, A., et al. 2000. Myocardial cell death in human diabetes. Circulation Research 87: 1123–1132. 10.1161/01.RES.87.12.1123
Gessler, M.C., Nkunyak, M.H.H., Mwasumbi, L.B., Heinrich, M. and Tanner, M., 1994. Screening Tanzanian plants for antimalarial activity. Acta Tropica 56(1): 65–77. 10.1016/0001-706X(94)90041-8
Gutiérrez, R.M., Mitchell, S. and Solis, R.V., 2008. Psidium guajava: A review of its traditional uses, phytochemistry and pharmacology. Journal of Ethnopharmacology 117: 1–27. 10.1016/j.jep.2008.01.025
Hikmawanti N.P., Fatmawati S. and Asri A.W., 2021. The effect of ethanol concentrations as the extraction solvent on antioxidant activity of Katuk (Sauropus Androgynus (L.) Merr.) leaves extracts. In: IOP conference series: Earth and environmental science, Vol. 755, No. 1. IOP Publishing, Bristol, UK, p. 12060. 10.1088/1755-1315/755/1/012060
Hoffstein, S. and Weissmann, G., 1975. Mechanisms of lysosomal enzyme release from leukocytes. Arthiritis and Rheumatism 18(2): 153–165. 10.1002/art.1780180213
Karthikeyan, K., Sarala Bai, B.R. and Niranjali Devaraj, S., 2007. Cardioprotective effect of grape seed proanthocyanidins on isoproterenol-induced myocardial injury in rats. International Journal of Cardiology 115: 326–333. 10.1016/j.ijcard.2006.03.016
Kawai, Y. and Anno, K., 1971. Mucopolysaccharide-degrading enzymes from the liver of the squid, Ommastrephessloanipacificus I. Hyaluronidase. Biochimica et Biophysica Acta 242: 428–436. 10.1016/0005-2744(71)90234-8
King, J., 1965. In: Van, D. (ed.) Prac Clini Enzymology. Nostrand, London, Pp. 83–93.
Kumar, A., Khan, S.A., Parvez, A., Zaheer, M.S., Rabbani, M.U. and Zafar L., 2011. The prevalence of hyperhomocysteinemia and its correlation with conventional risk factors in young patients with myocardial infarction in a tertiary care centre of India. Biomedical Research 22: 225–229.
Leslie, V.A., Alarjani, K.M., Arunkumar, M., Balamuralikrishnan, B., 2021. Bacteriocin producing microbes with bactericidal activity against multidrug resistant pathogens. Journal of Infection and Public Health 14: 1802–1809. 10.1016/j.jiph.2021.09.029
Lutterodt, G.D., 1992. Inhibition of microlax induced experimental diarrhoea with narcotics like extracts of Psidium guajavain rats. Journal of Ethnopharmacology 37(2): 151–157. 10.1016/0378-8741(92)90073-Z
Manikandan, R. and Vijaya Anand, A., 2015. Evaluation of antioxidant activity of Psidium guajava Linn. in streptozotocin-induced diabetic rats. Free Radicals and Antioxidants 6(1): 72–76. 10.5530/fra.2016.1.9
Manikandan, R., Vijaya Anand, A. and Durai Muthumani, G., 2013. Phytochemical and in vitro anti-diabetic activity of methanolic extract of Psidium guajava leaves. International Journal of Current Microbiology and Applied Sciences 2(2): 15–19.
Manikandan, R., Vijaya Anand, A., Sampathkumar, P. and Manoharan, N., 2018. Protective effect of Psidium guajava leaf ethanolic extract against streptozotocin induced diabetes and lipidosis in rats. Indian Journal of Animal Research 52(8): 1198–1205. 10.18805/ijar.B-3337
Manikandan, R., Vijay Anand, A., Sampathkumar, P. and Pushp, 2016. Phytochemical and in vitro antidiabetic activity of Psidium guajava leaves. Pharmacognosy Journal 2016,8,4,392-394. 10.5530/pj.2016.4.13
Mehler, A.H., Kornberg, A., Grisolia, S. and Ochoa, S., 1948. The enzymatic mechanism of oxidation-reductions between malate or isocitrate or pyruvate. Journal of Biological Chemistry 174: 961–977. 10.1016/S0021-9258(18)57306-3
Moore, J.C. and Morris, J.E., 1982. A simple automated colorimetric method for determination of N-acetyl β-D glucosaminidase. Annals of Clinical Biochemistry 19: 157–159. 10.1177/000456328201900305
O’Brien, P.J., Smith, D.E., Knechtel, T.J., Marchak, M.A., Pruimboom-Bress, I., Bress, D.J., et al. 2006. Cardiac troponin I is a sensitive, specific biomarker of cardiac injury in laboratory animals. Laboratory Animals 40(2): 153–171. 10.1258/002367706776319042
Okinada, S., Kumagai, H. and Ebashi, S.H., 1961. Serum creatine phosphokinase. Activity in progressive muscular dystrophy and neuromuscular diseases. Archives of Neurology 4: 520–525. 10.1001/archneur.1961.00450110050006
Panche A.N., Diwan A.D. and Chandra S.R., 2016. Flavonoids: an overview. Journal of Nutritional Science 5: e47. 10.1017/jns.2016.41.
Pearl, W., Cascarano, J. and Zweifach, B.W., 1963. Micro determination of cytochromeoxidase in rat tissues by the oxidation on N-phenyl-p-phenylene diamine or ascorbic acid. Journal of Histochemistry and Cytochemistry 11: 102–104. 10.1177/11.1.102
Reed, L.J. and Mukherjee, R.B., 1969. Α-ketoglutarate dehydrogenase complex from Escherichia coli. Methods Enzymology 13: 55-51. 10.1016/0076-6879(69)13016-5
Sapolsky, A.I., Altman, R.D. and Howell, D.S., 1973. Cathepsin-D activity in normal and osteoarthritic human cartilage. Federation Proceedings 32: 1489–1493.
Seager, M.J., Singal, P.K., Orchard, R., Pierce, G.N. and Dhalla, N.S., 1984. Cardiac cell damage: a primary myocardial disease in streptozotocin-induced chronic diabetes. British Journal of Experimental Pathology 65(5): 613–623.
Sinha, A.K., 1972. Colorimetric assay of catalase. Analytical Biochemistry 47: 389–394. 10.1016/0003-2697(72)90132-7
Sivakumar, V. and Dhana Rajan, M.S., 2011. Standardization & characterization of Tinospora cordifolia (Willd.) Miers ex Hook. F. & Thoms. Plant stem extract in different solvent fractions. Asian Journal of Biochemical and Pharmaceutical Research (AJBPR) 1(4): 105–112.
Slater, E.C. and Bonner, W.D., 1952. The effect of fluoride on succinic oxidase system. Biochemical Journal 52: 185–196. 10.1042/bj0520185
Subashini, R. and Sumathi, P., 2012. Cardioprotective effect of Nelumbo nucifera on mitochondrial lipid peroxide enzymes and electrolytes against isoproterenol-induced cardiotoxicity in Wistar rats. Asian Pacific Journal of Tropical Disease 2(2): S588–S591. 10.1016/S2222-1808(12)60227-8
Sudharsan, P.T., Mythili, Y., Selvakumar, E. and Varalakshmi P., 2006. Lupeol and its ester exhibit protective role against cyclophosphamide-induced cardiac mitochondrial toxicity. Journal of Cardiovascular Pharmacology 47(2): 205–210. 10.1097/01.fjc.0000200658.89629.ba
Sultana, B., Anwar, F. and Ashraf, M., 2009. Effect of extraction solvent/technique on the antioxidant activity of selected medicinal plant extracts. Molecules 14(6): 2167–2180. 10.3390/molecules14062167
Tsoo, E., King, R. and Howard, L., 1967. Preparations and properties of soluble NADH dehydrogenases from cardiac muscle. Methods in Enzymology 275–294. 10.1016/0076-6879(67)10055-4
Vijayakumar, K., Rengarajan, R.L., Radhakrishnan, R. and Anand, A.V., 2018. Hypolipidemic effect of Psidium guajava leaf extract against hepatotoxicity in rats. Pharmacognosy Magazine 14(53): 4–8. 10.4103/pm.pm_167_17
Vijayakumar K., Arumugam V.A., Ramasamy M., Natesan M., Palanisamy S., Thajuddin NB., et al. 2020. Hepatoprotective effects of Psidium guajava on mitochondrial enzymes and inflammatory markers in carbon tetrachloride-induced hepatotoxicity. Drug Development and Industrial Pharmacy 46(12): 2041–2050. 10.1080/03639045.2020.1843474
Vishal, D. Joshi, Akash, P. Dahake and Ashok, P. Suthar., 2010. Adverse effects associated with the use of antihypertensive drugs: an overview. International Journal of PharmTech Research 1 & 2: 10–13.
Xie, F., Wang, H., Cao, Q., Chen, Q. and Lin, F. 2022. The effects of Oldenlandia diffusa water extract on glucose metabolism and inflammation level in rats with streptozotocin-induced gestational diabetes mellitus. Quality Assurance and Safety of Crops & Foods 14(1): 24–30. 10.15586/qas.v14i1.970
Zakaria, M. and Mohd, M.S., 1994. Traditional Malay medicinal plants. Penerbit Fasar Bakti Suden Berhard, Selangor, Malaysia, pp. 129–132.
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Apr 27, 2023
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Manikandan, R., Balamuralikrishnan, B., Boro, A., Karthika, P., Arun, M., Velayuthaprabhu, S., Malaisamy, A., Lakshminarayanan Rengarajan, R., & Vijaya Anand, A. (2023). Impact on cardioprotective effect of Psidium guajava leaves extract in streptozotocin-induced Wistar mice with molecular in silico analysis. Quality Assurance and Safety of Crops & Foods, 15(2), 209-221. https://doi.org/10.15586/qas.v15i2.1261
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Research Article
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How to Cite
Manikandan, R., Balamuralikrishnan, B., Boro, A., Karthika, P., Arun, M., Velayuthaprabhu, S., Malaisamy, A., Lakshminarayanan Rengarajan, R., & Vijaya Anand, A. (2023). Impact on cardioprotective effect of Psidium guajava leaves extract in streptozotocin-induced Wistar mice with molecular in silico analysis. Quality Assurance and Safety of Crops & Foods, 15(2), 209-221. https://doi.org/10.15586/qas.v15i2.1261