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

Authors

  • Diah Pitaloka Putri Universitas Diponegoro, Faculty of Medicine, Department of Nutrition, Tembalang Semarang Indonesia, 50275 https://orcid.org/0000-0002-4053-6200
  • Aulia Putri Wahyuningtyas Universitas Diponegoro, Faculty of Medicine, Department of Nutrition, Tembalang Semarang Indonesia, 50275 https://orcid.org/0000-0002-1389-7772
  • Ahmad Ni'matullah Al-Baarri Universitas Diponegoro, Faculty of Animal and Agricultural Sciences, Department of Food Technology, Tembalang Semarang Indonesia 50275 https://orcid.org/0000-0002-1459-7069
  • Nani Maharani Universitas Diponegoro, Faculty of Medicine, Department of Pharmacology and Therapeutics, Tembalang Semarang Indonesia 50275 https://orcid.org/0000-0001-5984-6439

DOI:

https://doi.org/10.5219/1667

Keywords:

flavonoids, Sechium edule, xanthine oxidase, uric acid

Abstract

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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References

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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.

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)

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

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

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

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

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

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

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

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

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

Published

2021-10-28

How to Cite

Putri, D. P., Wahyuningtyas, A. P., Al-Baarri, A. N., & Maharani, N. (2021). 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 . Potravinarstvo Slovak Journal of Food Sciences, 15, 1049–1055. https://doi.org/10.5219/1667