Screening of potential tropical fruits in protecting endothelial dysfunction in vitro

Keywords: endothelial cells; nitric oxide; functional food; nutraceuticals, cardiovascular diseases

Abstract

Background: High consumption of antioxidant-rich fruits and vegetables reduces the endothelial damage involved in cardiovascular disease pathogenesis.

Objective: To evaluate the phytochemical content, antioxidant and scavenging activities (FRAP, ORAC, OH, HOCl, H2O2, and O2), endothelial H2O2-cytoprotective effect, nitric oxide (NO) release activation potential, and endothelial wound healing properties of 10 tropical fruits, comprising pineapple, sugar apple, papaya fruit, longan, mangosteen, lychee, langsat, mango, rambutan, and guava.

Design: Experimental study. The experiments were conducted in vitro using endothelial cell line EA.hy926.

Results: The high performance liquid chromatography (HPLC) phytochemical analysis indicated the presence of gallic acid and quercetin in all fruits, along with the overall absence of ellagic acid. Chlorogenic acid was only detected in three fruits, that is, pineapple, ripe papaya, and guava. The antioxidant and scavenging activities of all fruits were concentration-dependent. Only the H2O2 scavenging activity exhibited broad positive associations with other ROS-scavenging activities. Sugar apple and unripe papaya induced a significant reduction in H2O2-induced cell death in endothelial cells while pineapple, sugar apple, longan, and langsat activated NO release.

Discussion: All the studied tropical fruits contained bioactive phytoantioxidants with wide ranges of antioxidant capacity and scavenging activities. The endothelial functional tests were relevant to the screening for fruits that may benefit cardiovascular health. Among the four fruits that promoted endothelial wound closure, only sugar apple and unripe papaya induced cell migration and vascular capillary-like tube formation.

Conclusion: Sugar apple and unripe papaya are potential functional fruits that can protect against oxidative cell death and enhance endothelial wound healing.

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References


  1. Incalza MA, D’Oria R, Natalicchio A, Perrini S, Laviola L, Giorgino F. Oxidative stress and reactive oxygen species in endothelial dysfunction associated with cardiovascular and metabolic diseases. Vascul Pharmacol 2018; 100: 1–19. doi: 10.1016/j.vph.2017.05.005

  2. Hirase T, Node K. Endothelial dysfunction as a cellular mechanism for vascular failure. Am J Physiol Heart Circ Physiol 2012; 302(3): H499–505. doi: 10.1152/ajpheart.00325.2011

  3. Daiber A, Chlopicki S. Revisiting pharmacology of oxidative stress and endothelial dysfunction in cardiovascular disease: evidence for redox-based therapies. Free Radic Biol Med 2020; 157: 15–37. doi: 10.1016/j.freeradbiomed.2020.02.026

  4. Lee J, Bae EH, Ma SK, Kim SW. Altered nitric oxide system in cardiovascular and renal diseases. Chonnam Med J 2016; 52(2): 81–90. doi: 10.4068/cmj.2016.52.2.81

  5. Yang Y, Yin D, Wang F, Hou Z, Fang Z. In situ eNOS/NO up-regulation-a simple and effective therapeutic strategy for diabetic skin ulcer. Sci Rep 2016; 6(1): 30326. doi: 10.1038/srep30326

  6. Szewczyk A, Jarmuszkiewicz W, Koziel A, Sobieraj I, Nobik W, Lukasiak A, et al. Mitochondrial mechanisms of endothelial dysfunction. Pharmacol Rep 2015; 67(4): 704–10. doi: 10.1016/j.pharep.2015.04.009

  7. Kim K, Vance TM, Chun OK. Greater total antioxidant capacity from diet and supplements is associated with a less atherogenic blood profile in U.S. adults. Nutrients 2016; 8(1): 15. doi: 10.3390/nu8010015

  8. Vrolijk MF, Opperhuizen A, Jansen EH, Godschalk RW, Van Schooten FJ, Bast A, et al. The shifting perception on antioxidants: the case of vitamin E and beta-carotene. Redox Biol 2015; 4(Apr): 272–8. doi: 10.1016/j.redox.2014.12.017

  9. Ye Y, Li J, Yuan Z. Effect of antioxidant vitamin supplementation on cardiovascular outcomes: a meta-analysis of randomized controlled trials. PLoS One 2013; 8(2): e56803. doi: 10.1371/journal.pone.0056803

  10. Alissa EM, Ferns GA. Dietary fruits and vegetables and cardiovascular diseases risk. Crit Rev Food Sci Nutr 2017; 57(9): 1950–62. doi: 10.1080/10408398.2015.1040487

  11. Aune D, Giovannucci E, Boffetta P, Fadnes LT, Keum N, Norat T, et al. Fruit and vegetable intake and the risk of cardiovascular disease, total cancer and all-cause mortality-a systematic review and dose-response meta-analysis of prospective studies. Int J Epidemiol 2017; 46(3): 1029–56. doi: 10.1093/ije/dyw319

  12. Larsson SC, Virtamo J, Wolk A. Total and specific fruit and vegetable consumption and risk of stroke: a prospective study. Atherosclerosis 2013; 227(1): 147–52. doi: 10.1016/j.atherosclerosis.2012.12.022

  13. Khoo HE, Azlan A, Kong KW, Ismail A. Phytochemicals and medicinal properties of indigenous tropical fruits with potential for commercial development. Evid Based Complement Alternat Med 2016; 2016: 7591951. doi: 10.1155/2016/7591951

  14. Huang F, Liu H, Zhang R, Dong L, Liu L, Ma Y, et al. Physicochemical properties and prebiotic activities of polysaccharides from longan pulp based on different extraction techniques. Carbohydr Polym 2019; 206: 344–51. doi: 10.1016/j.carbpol.2018.11.012

  15. Shahrajabian MH, Sun W, Cheng Q. Modern pharmacological actions of Longan fruits and their usages in traditional herbal remedies. J Med Plants Stud 2019; 7(4): 179–85.

  16. Khan F, Ray S, Craigie AM, Kennedy G, Hill A, Barton KL, et al. Lowering of oxidative stress improves endothelial function in healthy subjects with habitually low intake of fruit and vegetables: a randomized controlled trial of antioxidant- and polyphenol-rich blackcurrant juice. Free Radic Biol Med 2014; 72(July): 232–7. doi: 10.1016/j.freeradbiomed.2014.04.006

  17. Li B, Li F, Wang L, Zhang D. Fruit and vegetables consumption and risk of hypertension: a meta-analysis. J Clin Hypertens 2016; 18(5): 468–76. doi: 10.1111/jch.12777

  18. Sarker U, Oba S. Nutrients, minerals, pigments, phytochemicals, and radical scavenging activity in Amaranthus blitum leafy vegetables. Sci Rep 2020; 10(1): 3868. doi: 10.1038/s41598-020-59848-w

  19. Pękal A, Pyrzynska K. Evaluation of aluminium complexation reaction for flavonoid content assay. Food Anal Methods 2014; 7(9): 1776–82. doi: 10.1007/s12161-014-9814-x

  20. Benzie IF, Strain JJ. The ferric reducing ability of plasma (FRAP) as a measure of ‘antioxidant power’: the FRAP assay. Anal Biochem 1996; 239(1): 70–6. doi: 10.1006/abio.1996.0292

  21. Jarisarapurin W, Sanrattana W, Chularojmontri L, Kunchana K, Wattanapitayakul SK. Antioxidant properties of unripe Carica papaya fruit extract and its protective effects against endothelial oxidative stress. Evid Based Complement Alternat Med 2019; 2019(Jun): 4912631. doi: 10.1155/2019/4912631

  22. Sarker U, Oba S. Antioxidant constituents of three selected red and green color Amaranthus leafy vegetable. Sci Rep 2019; 9(1): 18233. doi: 10.1038/s41598-019-52033-8

  23. Sawant L, Prabhakar B, Mahajan A, Pai N, Pandita N. Development and validation of HPLC method for quantification of phytoconstituents in Phyllanthus emblica. J Chem Pharm Res 2011; 3(7): 937–44.

  24. Kleinhenz DJ, Fan X, Rubin J, Hart CM. Detection of endothelial nitric oxide release with the 2,3-diaminonapthalene assay. Free Radic Biol Med 2003; 34(7): 856–61. doi: 10.1016/s0891-5849(02)01438-7

  25. Chularojmontri L, Suwatronnakorn M, Wattanapitayakul SK. Phyllanthus emblica L. enhances human umbilical vein endothelial wound healing and sprouting. Evid Based Complement Alternat Med 2013; 2013(Mar): 720728. doi: 10.1155/2013/720728

  26. Yan GN, Lv YF, Yang L, Yao XH, Cui YH, Guo DY. Glioma stem cells enhance endothelial cell migration and proliferation via the Hedgehog pathway. Oncol Lett 2013; 6(5): 1524–30. doi: 10.3892/ol.2013.1569

  27. Phowichit S, Kobayashi M, Fujinoya Y, Sato Y, Sanphanya K, Vajragupta O, et al. Antiangiogenic effects of VH02, a novel urea derivative: in vitro and in vivo studies. Molecules 2016; 21(9): 1258. doi: 10.3390/molecules21091258

  28. Ciumarnean L, Milaciu MV, Runcan O, Vesa SC, Rachisan AL, Negrean V, et al. The effects of flavonoids in cardiovascular diseases. Molecules 2020; 25(18): 4320. doi: 10.3390/molecules25184320

  29. Vetrani C, Costabile G, Vitale M, Giacco R. (Poly)phenols and cardiovascular diseases: looking in to move forward. J Funct Foods 2020; 71: 104013. doi: 10.1016/j.jff.2020.104013

  30. Kanaan GN, Harper ME. Cellular redox dysfunction in the development of cardiovascular diseases. Biochim Biophys Acta Gen Subj 2017; 1861(11 Pt A): 2822–9. doi: 10.1016/j.bbagen.2017.07.027

  31. Schlesier K, Harwat M, Bohm V, Bitsch R. Assessment of antioxidant activity by using different in vitro methods. Free Radic Res 2002; 36(2): 177–87. doi: 10.1080/10715760290006411

  32. Ou B, Huang D, Hampsch-Woodill M, Flanagan JA, Deemer EK. Analysis of antioxidant activities of common vegetables employing oxygen radical absorbance capacity (ORAC) and ferric reducing antioxidant power (FRAP) assays: a comparative study. J Agric Food Chem 2002; 50(11): 3122–8. doi: 10.1021/jf0116606

  33. Payne AC, Mazzer A, Clarkson GJ, Taylor G. Antioxidant assays – consistent findings from FRAP and ORAC reveal a negative impact of organic cultivation on antioxidant potential in spinach but not watercress or rocket leaves. Food Sci Nutr 2013; 1(6): 439–44. doi: 10.1002/fsn3.71

  34. Karimi-Khouzani O, Heidarian E, Amini SA. Anti-inflammatory and ameliorative effects of gallic acid on fluoxetine-induced oxidative stress and liver damage in rats. Pharmacol Rep 2017; 69(4): 830–5. doi: 10.1016/j.pharep.2017.03.011

  35. Mittal AK, Kumar S, Banerjee UC. Quercetin and gallic acid mediated synthesis of bimetallic (silver and selenium) nanoparticles and their antitumor and antimicrobial potential. J Colloid Interface Sci 2014; 431(Oct): 194–9. doi: 10.1016/j.jcis.2014.06.030

  36. Mohammadi-Sartang M, Mazloom Z, Sherafatmanesh S, Ghorbani M, Firoozi D. Effects of supplementation with quercetin on plasma C-reactive protein concentrations: a systematic review and meta-analysis of randomized controlled trials. Eur J Clin Nutr 2017; 71(9): 1033–9. doi: 10.1038/ejcn.2017.55

  37. Tamtaji OR, Milajerdi A, Dadgostar E, Kolahdooz F, Chamani M, Amirani E, et al. The effects of quercetin supplementation on blood pressures and endothelial function among patients with metabolic syndrome and related disorders: a systematic review and meta-analysis of randomized controlled trials. Curr Pharm Des 2019; 25(12): 1372–84. doi: 10.2174/1381612825666190513095352

  38. Sahebkar A. Effects of quercetin supplementation on lipid profile: a systematic review and meta-analysis of randomized controlled trials. Crit Rev Food Sci Nutr 2017; 57(4): 666–76. doi: 10.1080/10408398.2014.948609

  39. Patel RV, Mistry BM, Shinde SK, Syed R, Singh V, Shin HS. Therapeutic potential of quercetin as a cardiovascular agent. Eur J Med Chem 2018; 155: 889–904. doi: 10.1016/j.ejmech.2018.06.053

  40. Deng Q, Li XX, Fang Y, Chen X, Xue J. Therapeutic potential of quercetin as an antiatherosclerotic agent in atherosclerotic cardiovascular disease: a review. Evid Based Complement Alternat Med 2020; 2020: 5926381. doi: 10.1155/2020/5926381

  41. Tian R, Jin Z, Zhou L, Zeng XP, Lu N. Quercetin attenuated myeloperoxidase-dependent HOCl generation and endothelial dysfunction in diabetic vasculature. J Agric Food Chem 2021; 69(1): 404–13. doi: 10.1021/acs.jafc.0c06335

  42. Luo M, Tian R, Lu N. Quercetin inhibited endothelial dysfunction and atherosclerosis in apolipoprotein e-deficient mice: critical roles for NADPH oxidase and heme oxygenase-1. J Agric Food Chem 2020; 68(39): 10875–83. doi: 10.1021/acs.jafc.0c03907

  43. Badhani B, Sharma N, Kakkar R. Gallic acid: a versatile antioxidant with promising therapeutic and industrial applications. RSC Advances 2015; 5(35): 27540–57. doi: 10.1039/c5ra01911g

  44. Choubey S, Varughese LR, Kumar V, Beniwal V. Medicinal importance of gallic acid and its ester derivatives: a patent review. Pharm Pat Anal 2015; 4(4): 305–15. doi: 10.4155/ppa.15.14

  45. Hsu WC, Chang SP, Lin LC, Li CL, Richardson CD, Lin CC, et al. Limonium sinense and gallic acid suppress hepatitis C virus infection by blocking early viral entry. Antiviral Res 2015; 118(Jun): 139–47. doi: 10.1016/j.antiviral.2015.04.003

  46. Kianbakht S, Khalighi-Sigaroodi F, Dabaghian FH. Improved glycemic control in patients with advanced type 2 diabetes mellitus taking Urtica dioica leaf extract: a randomized double-blind placebo-controlled clinical trial. Clin Lab 2013; 59(9–10): 1071–6. doi: 10.7754/clin.lab.2012.121019

  47. Jin L, Piao ZH, Sun S, Liu B, Kim GR, Seok YM, et al. Gallic acid reduces blood pressure and attenuates oxidative stress and cardiac hypertrophy in spontaneously hypertensive rats. Sci Rep 2017; 7(1): 15607. doi: 10.1038/s41598-017-15925-1

  48. Akbari G. Molecular mechanisms underlying gallic acid effects against cardiovascular diseases: an update review. Avicenna J Phytomed 2020; 10(1): 11–23.

  49. Shanmuganathan S, Angayarkanni N. Chebulagic acid chebulinic acid and gallic acid, the active principles of triphala, inhibit TNFalpha induced pro-angiogenic and pro-inflammatory activities in retinal capillary endothelial cells by inhibiting p38, ERK and NFkB phosphorylation. Vascul Pharmacol 2018; 108: 23–35. doi: 10.1016/j.vph.2018.04.005

  50. Hakkou Z, Maciuk A, Leblais V, Bouanani NE, Mekhfi H, Bnouham M, et al. Antihypertensive and vasodilator effects of methanolic extract of Inula viscosa: biological evaluation and POM analysis of cynarin, chlorogenic acid as potential hypertensive. Biomed Pharmacother 2017; 93(Sep): 62–9. doi: 10.1016/j.biopha.2017.06.015

  51. Tajik N, Tajik M, Mack I, Enck P. The potential effects of chlorogenic acid, the main phenolic components in coffee, on health: a comprehensive review of the literature. Eur J Nutr 2017; 56(7): 2215–44. doi: 10.1007/s00394-017-1379-1

  52. Jorjong S, Butkhup L, Samappito S. Phytochemicals and antioxidant capacities of Mao-Luang (Antidesma bunius L.) cultivars from Northeastern Thailand. Food Chem 2015; 181: 248–55. doi: 10.1016/j.foodchem.2015.02.093

  53. Udomkasemsab A, Ngamlerst C, Adisakwattana P, Aroonnual A, Tungtrongchitr R, Prangthip P. Maoberry (Antidesma bunius) ameliorates oxidative stress and inflammation in cardiac tissues of rats fed a high-fat diet. BMC Complement Altern Med 2018; 18(1): 344. doi: 10.1186/s12906-018-2400-9

  54. Ademosun AO, Oboh G. Effect of pineapple, orange and watermelon juices on phosphodiesterase, monoamine oxidase and angiotensin-I converting enzyme activities in rat heart and brain homogenates. Orient Pharm Exp Med 2017; 17(3): 269–76. doi: 10.1007/s13596-017-0279-5

  55. Prado SBR, Beukema M, Jermendi E, Schols HA, de Vos P, Fabi JP. Pectin interaction with immune receptors is modulated by ripening process in papayas. Sci Rep 2020; 10(1): 1690. doi: 10.1038/s41598-020-58311-0

  56. Palafox-Carlos H, Yahia EM, González-Aguilar GA. Identification and quantification of major phenolic compounds from mango (Mangifera indica, cv. Ataulfo) fruit by HPLC–DAD–MS/MS-ESI and their individual contribution to the antioxidant activity during ripening. Food Chem 2012; 135(1): 105–11. doi: 10.1016/j.foodchem.2012.04.103

  57. Wang C, Mao C, Lou Y, Xu J, Wang Q, Zhang Z, et al. Monotropein promotes angiogenesis and inhibits oxidative stress-induced autophagy in endothelial progenitor cells to accelerate wound healing. J Cell Mol Med 2018; 22(3): 1583–600. doi: 10.1111/jcmm.13434

  58. Poljsak B, Suput D, Milisav I. Achieving the balance between ROS and antioxidants: when to use the synthetic antioxidants. Oxid Med Cell Longev 2013; 2013(Apr): 956792. doi: 10.1155/2013/956792

Published
2021-09-01
How to Cite
Wattanapitayakul S. K., Kunchana K., Jarisarapurin W., & Chularojmontri L. (2021). Screening of potential tropical fruits in protecting endothelial dysfunction <em>in vitro</em&gt;. Food & Nutrition Research, 65. https://doi.org/10.29219/fnr.v65.7807
Section
Original Articles