The effect of chayote leaves (Sechium edule)’s flavonoid fraction on the reduction of the serum uric acid levels through the inhibition of xanthine oxidase activity
DOI:
https://doi.org/10.5219/1667Keywords:
flavonoids, Sechium edule, xanthine oxidase, uric acidAbstract
Uric acid is the final product of purine metabolism and is categorized as hyperuricemia when it reaches >6.0 mg.dL-1 for women and >7.0 mg.dL-1 for men. The chayote leaves (Sechium edule) contain a high amount of flavonoid and might be used as an alternative to reduce hyperuricemia. The purpose of this study is to analyze the effect of chayote leaves (Sechium edule)’s flavonoid fraction on the level of uric acid and the activity of xanthine oxidase (XO) in Sprague Dawley Rats. The flavonoid fraction (FF) was obtained by extracting the chayote leaves, fractionating with n-hexane, hydrolyzing with HCl, and finally re-fractionating with ethyl acetate. Thirty male Sprague Dawley rats were induced for hyperuricemia by potassium oxonate and broth block for 21 days, and the interventions were given orally for 14 days. The rats were divided randomly into five groups: normal control (K-), hyperuricemia control (K+), hyperuricemia with FF dose 50 mg.200g-1 body weight (P1), hyperuricemia with FF dose 100 mg.200g-1 body weight (P2) and hyperuricemia with allopurinol 1.8 mg.200g-1 body weight. Xanthine oxidase activity was measured by CheKineTM Xanthine Oxidase Assay Kit, with simple colorimetry methods. The statistical analysis for XO activity was done using Kruskal-Wallis followed by Mann Whitney. The results showed that chayote leaves (Sechium edule)’s flavonoid fraction contains apigenin, apigenin o-glucoside, and luteolin. It also has antioxidant activity with 98.45% inhibition. There was a significant reduction in xanthine oxidase activity in groups treated with FF (p <0.005). The best dose of FF affecting XO activity was 100 mg.200g-1 body weight. The combination of FF and allopurinol can be more effective in decreasing uric acid levels by inhibiting XO activity.
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Abdulhafiz, F., Mohammed, A., Kayat, F., Bhaskar, M., Hamzah, Z., Podapati, S. K., Reddy, L. V. 2020. Xanthine oxidase inhibitory activity, chemical composition, antioxidant properties and GC-MS analysis of keladi candik (Alocasia longiloba Miq). Molecules, vol. 25, no. 11, p. 2658. https://doi.org/10.3390/molecules25112658 DOI: https://doi.org/10.3390/molecules25112658
Aladdin, N. A., Husain, K., Jalil, J., Sabandar, C. W., Jamal, J. A. 2020. Xanthine oxidase inhibitory activity of a new isocoumarin obtained from Marantodes pumilum var. pumila leaves. BMC Complementary Medicine and Therapies, vol. 20, no. 1, p. 1-12. https:/doi.org/10.1186/s12906-020-03119-8 DOI: https://doi.org/10.1186/s12906-020-03119-8
Bove, M., Cicero, A. F. G., Veronesi, M., Borghi, C. 2017. An evidence-based review on urate-lowering treatments: Implications for optimal treatment of chronic hyperuricemia. Vascular Health and Risk Management, vol. 13, p. 23-28. https://doi.org/10.2147/VHRM.S115080 DOI: https://doi.org/10.2147/VHRM.S115080
Casagrande, A. C. M., Wamser, M. N., De Lima, D. D., Da Cruz, J. G. P., Wyse, A. T. S., Dal Magro, D. D. 2013. In vitro stimulation of oxidative stress by hypoxanthine in blood of rats: Prevention by vitamins e plus C and allopurinol. Nucleosides, Nucleotides and Nucleic Acids, vol. 32, no. 1, p. 42-57. https://doi.org/10.1080/15257770.2012.760043 DOI: https://doi.org/10.1080/15257770.2012.760043
Dalbeth, N., Merriman, T., Stamp, L. 2016. Gout. The Lancet, vol. 388, no. 10055, p. 2039-2052. https://doi.org/10.1016/S0140-6736(16)00346-9 DOI: https://doi.org/10.1016/S0140-6736(16)00346-9
Dolati, K., Rakhshandeh, H., Golestani, M., Forouzanfar, F., Sadeghnia, R., Sadeghnia, H. 2018. Inhibitory effects of apium graveolens on xanthine oxidase activity and serum Uric acid levels in hyperuricemic mice. Preventive Nutrition and Food Science, vol. 23, no. 2, p. 127-133. http://doi.org/10.3746/pnf.2018.23.2.127 DOI: https://doi.org/10.3746/pnf.2018.23.2.127
Hamada, T., Ichida, K., Hosoyamada, M., Mizuta, E., Yanagihara, K., Sonoyama, K., Sugihara, S., Igawa, O., Hosoya, T., Ohtahara, A., Shigamasa, C., Yamamoto, Y., Ninomiya, H., Hisatome, I. 2008. Uricosuric action of losartan via the inhibition of urate transporter 1 (URAT 1) in hypertensive patients. American Journal of Hypertension, vol. 21, no. 10, p. 1157-1162. https://doi.org/10.1038/ajh.2008.245 DOI: https://doi.org/10.1038/ajh.2008.245
Harwoko, H., Warsinah, W. 2020. Phytochemical analysis and evaluation of purified extract of Tinospora crispa stem for in vivo antihyperuricemic. Journal of Reports in Pharmaceutical Sciences, vol. 9, no. 1, p. 46-51. https://doi.org/10.4103/jrptps.JRPTPS_45_19 DOI: https://doi.org/10.4103/jrptps.JRPTPS_45_19
Hu, Q. H., Zhang, X., Wang, X., Jiao, R. Q., Kong, L. D. 2012. Quercetin regulates organic ion transporter and uromodulin expression and improves renal function in hyperuricemic mice. European Journal of Nutrition, vol. 51, no. 5, p. 593-606. https://doi.org/10.1007/s00394-011-0243-y DOI: https://doi.org/10.1007/s00394-011-0243-y
Huang, J., Wang, S., Zhu, M., Chen, J., Zhu, X. 2011. Effects of genistein, apigenin, quercetin, rutin and astilbin on serum uric acid levels and xanthine oxidase activities in normal and hyperuricemic mice. Food and Chemical Toxicology, vol. 49, no. 9, p. 1943-1947. https://doi.org/10.1016/j.fct.2011.04.029 DOI: https://doi.org/10.1016/j.fct.2011.04.029
Jiang, L. L., Gong, X., Ji, M. Y., Wang, C. C., Wang, J. H., Li, M. H. 2020. Bioactive compounds from plant-based functional foods: A promising choice for the prevention and management of hyperuricemia. Foods, vol. 9, no. 8, p. 973. https://doi.org/10.3390/foods9080973 DOI: https://doi.org/10.3390/foods9080973
Kuo, C. F., Grainge, M. J., Zhang, W., Doherty, M. 2015. Global epidemiology of gout: Prevalence, incidence and risk factors. Nature Reviews Rheumatology, vol. 11, no. 11, p. 649-662. https://doi.org/10.1038/nrrheum.2015.91 DOI: https://doi.org/10.1038/nrrheum.2015.91
Kushiyama, A., Nakatsu, Y., Matsunaga, Y., Yamamotoya, T., Mori, K., Ueda, K., Inoue, Y., Sakoda, H., Fujishiro, M., Ono, H., Asano, T. 2016. Role of uric acid metabolism-related inflammation in the pathogenesis of metabolic syndrome components such as atherosclerosis and nonalcoholic steatohepatitis. Mediators of Inflammation, vol. 2016, p. 1-15. https://doi.org/10.1155/2016/8603164 DOI: https://doi.org/10.1155/2016/8603164
Lin, C. M., Chen, C. S., Che, T. S., Liang, Y. C. 2002. Molecular modeling of flavonoids that inhibits xanthine oxidase. Biochemical and Biophysical Research Communication, vol. 294, p. 167-172. http://doi.org/10.1016/S0006-291X(02)00442-4 DOI: https://doi.org/10.1016/S0006-291X(02)00442-4
Lin, Y., Liu, P. G., Liang, W. Q., Hu, Y. J., Xu, P., Zhou, J., Pu, J. B., Zhang, H. J. 2018. Luteolin-4′-O-glucoside and its aglycone, two major flavones of Gnaphalium affine D. Don, resist hyperuricemia and acute gouty arthritis activity in animal models. Phytomedicine, vol. 41, p. 54-61. https://doi.org/10.1016/j.phymed.2018.02.002 DOI: https://doi.org/10.1016/j.phymed.2018.02.002
Ling, X., Bochu, W. 2014. A review of phytotherapy of gout: Perspective of new pharmacological treatments. Pharmazie, vol. 69, no. 4, p. 243-256. https://doi.org/10.1691/ph.2014.3642
Loizzo, M. R., Bonesi, M., Menichini, F., Tenuta, M. C., Leporini, M., Tundis, R. 2016. Antioxidant and carbohydrate-hydrolysing enzymes potential of Sechium edule (Jacq.) Swartz (Cucurbitaceae) Peel, leaves and Pulp fresh and processed. Plant Foods for Human Nutrition, vol. 71, no. 4, p. 381-387. https://doi.org/10.1007/s11130-016-0571-4 DOI: https://doi.org/10.1007/s11130-016-0571-4
Ma, Z., Wang, Y., Xu, C., Ai, F., Huang, L., Wang, J., Peng, J., Zhou, Y., Yin, M., Zhang, S., Yang, X. 2019. Obesity-related genetic variants and hyperuricemia risk in Chinese men. Frontiers in Endocrinology, vol. 10, 18 p. https://doi.org/10.3389/fendo.2019.00230 DOI: https://doi.org/10.3389/fendo.2019.00230
Managa, M. G., Akinola, S. A., Remize, F., Garcia, C., Sivakumar, D. 2021. Physicochemical Parameters and Bioaccessibility of Lactic Acid Bacteria Fermented Chayote Leaf (Sechium edule) and Pineapple (Ananas comosus) Smoothies. Front Nutr., vol. 8, p. 649189. https://doi.org/10.3389%2Ffnut.2021.649189 DOI: https://doi.org/10.3389/fnut.2021.649189
Mohos, V., Fliszár-Nyúl, E., Poór, M. 2020. Inhibition of xanthine oxidase-catalyzed xanthine and 6-mercaptopurine oxidation by flavonoid aglycones and some of their conjugates. International Journal of Molecular Sciences, vol. 21, no. 9, p. 3256. https://doi.org/10.3390/ijms21093256 DOI: https://doi.org/10.3390/ijms21093256
Nurshad, A., Perveen, R., Shahnaz, R., Shakil, M., Sadaqur, R., Shiful, I., Tangigul, H., Abu Hasan, S., Rahanuma, R. K., Noyan, H. M., Farjan, I., Nayan, C. M., Shaikh, M. N., Shamim, A., Mustafizur, R. 2018. Prevalence of hyperuricemia and the relationship between serum uric acid and obesity : A study on Bangladeshi adults. Plos One, vol. 13, no. 11, p. e0206850. https://doi.org/10.1371/journal.pone.0206850 DOI: https://doi.org/10.1371/journal.pone.0206850
Pauff, J. M., Hille, R. 2009. Inhibition studies of bovine xanthine oxidase by luteolin, silibhinin, quercetin and curcumin. J Nut Food, vol. 72, no. 4, p. 725-731. https://doi.org/10.1021/np8007123 DOI: https://doi.org/10.1021/np8007123
Presa, M., Pérez-Ruiz, F., Oyagüez, I. 2019. Second-line treatment with lesinurad and allopurinol versus febuxostat for management of hyperuricemia: a cost-effectiveness analysis for Spanish patients. Clinical Rheumatology, vol. 38, no. 12, p. 3521-3528. https://doi.org/10.1007/s10067-019-04739-3 DOI: https://doi.org/10.1007/s10067-019-04739-3
Raja, S., Kumar, A., Aahooja, R. D., Thakuria, U., Ochani, S., Shaukat, F. 2019. Frequency of hyperuricemia and its risk factors in the adult population. Cureus, vol. 6, no. 11, p. e4198 https://doi.org/10.7759/cureus.4198 DOI: https://doi.org/10.7759/cureus.4198
Rosado-Pérez, J., Aguiñiga-Sánchez, I., Santiago-Osorio, E., Mendoza-Núñez, V. 2019. Effect of Sechium edule var. nigrum spinosum (Chayote) on Oxidative stress and pro-inflammatory markers in older adults with metabolic syndrome: an exploratory study. Antioxidants, vol. 8, no. 5, p. 146. https://doi.org/10.3390/antiox8050146 DOI: https://doi.org/10.3390/antiox8050146
Sahnoun, M., Saibi, W. 2018. Apigenin isolated from A . americana encodes Human and Aspergillus oryzae S2 a -amylase inhibitions : credible approach for antifungal and antidiabetic therapies. Journal Food Science Technology. https://doi.org/10.1007/s13197-018-3065-6 DOI: https://doi.org/10.1007/s13197-018-3065-6
Sangeetha, K., Umamaheswari, K. S., Reddy, M., Kalkura, S. N. 2016. Flavonoids Therapeutic potential of natural pharmacological agents. International Journal of Pharmaceutical Sciences and Research, vol. 7, no. 10, p. 3924. https://doi.org/10.13040/IJPSR.0975-8232.7(10).3924-30 DOI: https://doi.org/10.13040/IJPSR.0975-8232.7(10).3924-30
Serrano, J. L., Figueiredo, J., Almeida, P., Silvestre, S. 2020. From Xanthine Oxidase Inhibition to in vivo hypouricemic effect: an integrated overview of in vitro and in vivo studies with focus on natural molecules and analogues. Evidence-Based Complementary and Alternative Medicine, vol. 2020, p. 9-11. https://doi.org/10.1155/2020/9531725 DOI: https://doi.org/10.1155/2020/9531725
Shah, P., Shah, G. 2015. Uricosuric activity of Tinospora cordifolia. Bangladesh Journal of Pharmacology, vol. 10, no. 4, p. 884-890. https://doi.org/10.3329/bjp.v10i4.25160 DOI: https://doi.org/10.3329/bjp.v10i4.25160
Shi, Y., Williamson, G. 2016. Quercetin lowers plasma uric acid in pre-hyperuricaemic males: A randomised, double-blinded, placebo-controlled, cross-over trial. British Journal of Nutrition, vol. 115, no. 5, p. 800-806. https://doi.org/10.1017/S0007114515005310 DOI: https://doi.org/10.1017/S0007114515005310
Siciliano, T., De Tommasi, N., Morelli, I., Braca, A. 2004. Study of flavonoids of Sechium edule (Jacq) Swartz (Cucurbitaceae) different edible organs by liquid chromatography photodiode array mass spectrometry. Journal of Agricultural and Food Chemistry, vol. 52, no. 21, p. 6510-6515. https://doi.org/10.1021/jf040214q. DOI: https://doi.org/10.1021/jf040214q
Sinata, N. 2019. Aktivitas etil asetat Artocarpus altilis (Parkinson Ex F.A.Zorn) fosberg terhadap kadar asam urat mencit putih jantan hiperurisemia (Ethyl acetate activity of Artocarpus altilis (parkinson ex f.a.zorn) fosberg on uric acid levels of hyperuricemic male rats). Jurnal Ilmiah Farmasi Farmasyifa (Scientific Journal of Farmasyifa Pharmacy), vol. 2, no. 2, p. 93-100. https://doi.org/10.29313/jiff.v2i2.4795 (In Indonesia) DOI: https://doi.org/10.29313/jiff.v2i2.4795
Song, S. H., Park, D. H., Bae, M. S., Choi, C. Y., Shim, J. H., Yoon, G., Cho, Y. C., Oh, D. S., Yoon, I. S., Cho, S. S. 2018. Ethanol extract of cudrania tricuspidata leaf ameliorates hyperuricemia in Mice via inhibition of hepatic and serum xanthine oxidase activity. Evidence-Based Complementary and Alternative Medicine, vol. 2018, p. 1-9. https://doi.org/10.1155/2018/8037925 DOI: https://doi.org/10.1155/2018/8037925
Spanou, C., Veskoukis, A., Kerasioti, T., Kontou, M., Angelis, A., Aligiannis, N., Skaltsounis, A., Kouretas, D. 2012. Flavonoid glycosides isolated from unique legume plant extracts as novel inhibitors of xanthine oxidase. PLoS ONE, vol. 7, no. 3, p. e32214. https://doi.org/10.1371/journal.pone.0032214 DOI: https://doi.org/10.1371/journal.pone.0032214
Stamp, L. K., O’Donnell, J. L., Zhang, M., James, J., Frampton, C., Barclay, M. L., Chapman, P. T. 2011. Using allopurinol above the dose based on creatinine clearance is effective and safe in patients with chronic gout, including those with renal impairment. Arthritis and Rheumatism, vol. 63, no. 2, p. 412-421. https://doi.org/10.1002/art.30119 DOI: https://doi.org/10.1002/art.30119
Van Hoorn, D. E. C., Nijveldt, R. J., Van Leeuwen, P. A. M., Hofman, Z., M’Rabet, L., De Bont, D. B. A., Van Norren, K. 2002. Accurate prediction of xanthine oxidase inhibition based on the structure of flavonoids. European Journal of Pharmacology, vol. 451, no. 2, p. 111-118. https://doi.org/10.1016/S0014-2999(02)02192-1 DOI: https://doi.org/10.1016/S0014-2999(02)02192-1
Vieira, E. F., Pinho, O., Ferreira, I. M. P. L. V. O., Delerue-Matos, C. 2019. Chayote (Sechium edule): A review of nutritional composition, bioactivities and potential applications. Food Chemistry, vol. 275, p. 557-568. https://doi.org/10.1016/j.foodchem.2018.09.146 DOI: https://doi.org/10.1016/j.foodchem.2018.09.146
Xiao, J. 2017. Dietary flavonoid aglycones and their glycosides : Which show better biological significance ? Critical Reviews in Food Science and Nutrition, vol. 57, no. 9, p. 1874-1905. https://doi.org/10.1080/10408398.2015.1032400 DOI: https://doi.org/10.1080/10408398.2015.1032400
Yang, H., Gao, L., Niu, Y., Zhou, Y., Jiang, J., Kong, X., Liu, X., Li, L. 2015. Mangiferin inhibits renal urate reabsorption by modulating urate transporters in experimental hyperuricemia. Biological and Pharmaceutical Bulletin, vol. 38, no. 10, p. 1591-1598. https://doi.org/10.1248/bpb.b15-00402 DOI: https://doi.org/10.1248/bpb.b15-00402
Yunita, Y., Santoso, A., Subandi, S. 2021. Xanthine oxidase inhibitory activity and identification of flavonoid in ethanol extract of sugar apple fruit (Annona squamosa L.). AIP Conference Proceedings, vol. 2353, p. 030068. https://doi.org/10.1063/5.0052695 DOI: https://doi.org/10.1063/5.0052695
Zeng, Y. C., Li, S., Liu, C., Gong, T., Sun, X., Fu, Y., Zhang, Z. R. 2017. Soluplus micelles for improving the oral bioavailability of scopoletin and their hypouricemic effect in vivo. Acta Pharmacologica Sinica, vol. 38, no. 3, p. 424-433. https://doi.org/10.1038/aps.2016.126 DOI: https://doi.org/10.1038/aps.2016.126
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