Nutr Res Pract.  2024 Feb;18(1):33-45. 10.4162/nrp.2024.18.1.33.

Effect of onion (Allium cepa L.) peel extract on natural killer cell and cytokines in a randomized, doubleblind, placebo-controlled trial

Affiliations
  • 1Department of Food and Nutrition, Hanyang University, Seoul 04763, Korea
  • 2National Institute of Agricultural Science, Wanju 55365, Korea

Abstract

BACKGROUND/OBJECTIVES
Onion, particularly onion peel, is a quercetin-rich food with, anti-inflammatory and immunomodulatory effects. However, the effect of onion peel extract (OPE) in humans is unclear. Thus, the present study aimed to investigate whether OPE improves natural killer (NK) cell activity and cytokine concentration in a randomized doubleblind placebo-controlled trial.
SUBJECTS/METHODS
Eighty participants aged 19–64 yrs old with a white blood cell count of 4,000–10,000 cells/µL, symptoms of upper respiratory infection at least once within the previous 12 mon, and perceived stress scale (PSS) over 14 were included. Participants were randomly assigned to take either 1,000 mg/day OPE or a placebo for 8 weeks.
RESULTS
Compliance were 87.4 ± 8.6% and 86.9 ± 79.0% in OPE and placebo groups. Compared to the placebo, OPE supplementation improved “Hoarseness” (P = 0.038) of the Wisconsin Upper Respiratory Symptom Survey (WURSS)-21 symptom, and stress scores (P = 0.001; 0.021) of PSS. Supplementation of OPE had no significant effect on NK cell activity and concentrations of cytokines such as interleukin (IL)-2, IL-6, IL-12, IL-1β, interferon-γ, and tumor necrosis factor-α. At baseline, the WURSS-21 symptom and PSS score (P = 0.024; 0.026) were higher in the OPE group than the placebo group. Among participants with higher than median WURSS-21 symptom score, OPE supplementation increased NK cell activity (P = 0.038). Supplementation of OPE had no significant effects on safety measurements and adverse events.
CONCLUSIONS
The present study suggested that OPE supplementation improves NK cell activity in participants with moderate upper respiratory symptoms without any significant adverse effects.

Keyword

Cytokine; natural killer cells; onion; perceived stress scale; respiratory symptom

Figure

  • Fig. 1 Schematic diagram of the study design.NK, natural killer; OPE, onion peel extract.

  • Fig. 2 NK cell activity according to the WURSS-21 symptom score between OPE and placebo for 8 weeks. P-values were determined by the independent t-test or χ2 test between OPE and placebo groups.NK, natural killer; OPE, onion peel extract; WURSS-21, Wisconsin Upper Respiratory Symptom Survey-21.


Reference

1. Chadorshabi S, Hallaj-Nezhadi S, Ghasempour Z. Red onion skin active ingredients, extraction and biological properties for functional food applications. Food Chem. 2022; 386:132737. PMID: 35509169.
2. Slimestad R, Fossen T, Vågen IM. Onions: a source of unique dietary flavonoids. J Agric Food Chem. 2007; 55:10067–10080. PMID: 17997520.
3. Rodríguez Galdón B, Rodríguez Rodríguez EM, Díaz Romero C. Flavonoids in onion cultivars (Allium cepa L.). J Food Sci. 2008; 73:C599–C605. PMID: 19019103.
4. Osojnik Črnivec IG, Skrt M, Šeremet D, Sterniša M, Farčnik D, Štrumbelj E, Poljanšek A, Cebin N, Pogačnik L, Smole Možina S, et al. Waste streams in onion production: bioactive compounds, quercetin and use of antimicrobial and antioxidative properties. Waste Manag. 2021; 126:476–486. PMID: 33838387.
5. Fuentes J, de Camargo AC, Atala E, Gotteland M, Olea-Azar C, Speisky H. Quercetin oxidation metabolite present in onion peel protects caco-2 cells against the oxidative stress, NF-kB activation, and loss of epithelial barrier function induced by NSAIDs. J Agric Food Chem. 2021; 69:2157–2167. PMID: 33591188.
6. Li Y, Yao J, Han C, Yang J, Chaudhry MT, Wang S, Liu H, Yin Y. Quercetin, inflammation and immunity. Nutrients. 2016; 8:167. PMID: 26999194.
7. Dehghani F, Sezavar Seyedi Jandaghi SH, Janani L, Sarebanhassanabadi M, Emamat H, Vafa M. Effects of quercetin supplementation on inflammatory factors and quality of life in post-myocardial infarction patients: a double blind, placebo-controlled, randomized clinical trial. Phytother Res. 2021; 35:2085–2098. PMID: 33216421.
8. Javadi F, Ahmadzadeh A, Eghtesadi S, Aryaeian N, Zabihiyeganeh M, Rahimi Foroushani A, Jazayeri S. The effect of quercetin on inflammatory factors and clinical symptoms in women with rheumatoid arthritis: a double-blind, randomized controlled trial. J Am Coll Nutr. 2017; 36:9–15. PMID: 27710596.
9. Vaez S, Parivr K, Amidi F, Rudbari NH, Moini A, Amini N. Quercetin and polycystic ovary syndrome; inflammation, hormonal parameters and pregnancy outcome: a randomized clinical trial. Am J Reprod Immunol. 2023; 89:e13644. PMID: 36317442.
10. Egert S, Bosy-Westphal A, Seiberl J, Kürbitz C, Settler U, Plachta-Danielzik S, Wagner AE, Frank J, Schrezenmeir J, Rimbach G, et al. Quercetin reduces systolic blood pressure and plasma oxidised low-density lipoprotein concentrations in overweight subjects with a high-cardiovascular disease risk phenotype: a double-blinded, placebo-controlled cross-over study. Br J Nutr. 2009; 102:1065–1074. PMID: 19402938.
11. Zahedi M, Ghiasvand R, Feizi A, Asgari G, Darvish L. Does quercetin improve cardiovascular risk factors and inflammatory biomarkers in women with type 2 diabetes: a double-blind randomized controlled clinical trial. Int J Prev Med. 2013; 4:777–785. PMID: 24049596.
12. Dower JI, Geleijnse JM, Gijsbers L, Schalkwijk C, Kromhout D, Hollman PC. Supplementation of the pure flavonoids epicatechin and quercetin affects some biomarkers of endothelial dysfunction and inflammation in (pre)hypertensive adults: a randomized double-blind, placebo-controlled, crossover trial. J Nutr. 2015; 145:1459–1463. PMID: 25972527.
13. Bobe G, Albert PS, Sansbury LB, Lanza E, Schatzkin A, Colburn NH, Cross AJ. Interleukin-6 as a potential indicator for prevention of high-risk adenoma recurrence by dietary flavonols in the polyp prevention trial. Cancer Prev Res (Phila). 2010; 3:764–775. PMID: 20484173.
14. Bae JH, Kim JY, Kim MJ, Chang SH, Park YS, Son CH, Park SJ, Chung JS, Lee EY, Kim SH, et al. Quercetin enhances susceptibility to NK cell-mediated lysis of tumor cells through induction of NKG2D ligands and suppression of HSP70. J Immunother. 2010; 33:391–401. PMID: 20386467.
15. Abdel-Latif M, Riad A, Soliman RA, Elkhouly AM, Nafae H, Gad MZ, Motaal AA, Youness RA. MALAT-1/p53/miR-155/miR-146a ceRNA circuit tuned by methoxylated quercitin glycoside alters immunogenic and oncogenic profiles of breast cancer. Mol Cell Biochem. 2022; 477:1281–1293. PMID: 35129780.
16. Steele TA, Brahmi Z. Phosphatidylinositol metabolism accompanies early activation events in tumor target cell-stimulated human natural killer cells. Cell Immunol. 1988; 112:402–413. PMID: 2833358.
17. Chiu HF, Shen YC, Huang TY, Venkatakrishnan K, Wang CK. Cardioprotective efficacy of red wine extract of onion in healthy hypercholesterolemic subjects. Phytother Res. 2016; 30:380–385. PMID: 26631904.
18. Mirabeau TY, Samson ES. Effect of Allium cepa and Allium sativum on some immunological cells in rats. Afr J Tradit Complement Altern Med. 2012; 9:374–379. PMID: 23983369.
19. Akrami R, Gharaei A, Mansour MR, Galeshi A. Effects of dietary onion (Allium cepa) powder on growth, innate immune response and hemato-biochemical parameters of beluga (Huso huso Linnaeus, 1754) juvenile. Fish Shellfish Immunol. 2015; 45:828–834. PMID: 26067169.
20. Marefati N, Eftekhar N, Kaveh M, Boskabadi J, Beheshti F, Boskabady MH. The effect of Allium cepa extract on lung oxidant, antioxidant, and immunological biomarkers in ovalbumin-sensitized rats. Med Princ Pract. 2018; 27:122–128. PMID: 29471299.
21. Lisanti A, Formica V, Ianni F, Albertini B, Marinozzi M, Sardella R, Natalini B. Antioxidant activity of phenolic extracts from different cultivars of Italian onion (Allium cepa) and relative human immune cell proliferative induction. Pharm Biol. 2016; 54:799–806. PMID: 26452395.
22. Jakaria M, Azam S, Cho DY, Haque ME, Kim IS, Choi DK. The methanol extract of Allium cepa L. protects inflammatory markers in LPS-induced BV-2 microglial cells and upregulates the antiapoptotic gene and antioxidant enzymes in N27-A cells. Antioxidants. 2019; 8:348. PMID: 31480531.
23. Kim JS, Lee EB, Choi JH, Jung J, Jeong UY, Bae UJ, Jang HH, Park SY, Cha YS, Lee SH. Antioxidant and immune stimulating effects of Allium cepa skin in the RAW 264.7 cells and in the C57BL/6 mouse immunosuppressed by cyclophosphamide. Antioxidants. 2023; 12:892. PMID: 37107267.
24. Jung JY, Lim Y, Moon MS, Kim JY, Kwon O. Onion peel extracts ameliorate hyperglycemia and insulin resistance in high fat diet/streptozotocin-induced diabetic rats. Nutr Metab (Lond). 2011; 8:18. PMID: 21439094.
25. Emamat H, Foroughi F, Eini-Zinab H, Hekmatdoost A. The effects of onion consumption on prevention of nonalcoholic fatty liver disease. Indian J Clin Biochem. 2018; 33:75–80. PMID: 29371773.
26. Elberry AA, Mufti S, Al-Maghrabi J, Abdel Sattar E, Ghareib SA, Mosli HA, Gabr SA. Immunomodulatory effect of red onion (Allium cepa Linn) scale extract on experimentally induced atypical prostatic hyperplasia in Wistar rats. Mediators Inflamm. 2014; 2014:640746. PMID: 24829522.
27. Kim OY, Lee SM, Do H, Moon J, Lee KH, Cha YJ, Shin MJ. Influence of quercetin-rich onion peel extracts on adipokine expression in the visceral adipose tissue of rats. Phytother Res. 2012; 26:432–437. PMID: 21833991.
28. Seo MY, Kim KR, Lee JJ, Ryu G, Lee SH, Hong SD, Dhong HJ, Baek CH, Chung SK, Kim HY. Therapeutic effect of topical administration of red onion extract in a murine model of allergic rhinitis. Sci Rep. 2019; 9:2883. PMID: 30814581.
29. Kang BK, Kim KB, Ahn NK, Choi YU, Kim M, Bark SW, Pak WM, Kim BR, Park JH, Bae NY, et al. Anti-inflammatory effect of onion (Allium cepa) peel hot water extract in vitro and in vivo . KSBB Journal. 2015; 30:148–154.
30. Kim KA, Yim JE. The Effect of onion peel extract on inflammatory mediators in Korean overweight and obese women. Clin Nutr Res. 2016; 5:261–269. PMID: 27812515.
31. Brüll V, Burak C, Stoffel-Wagner B, Wolffram S, Nickenig G, Müller C, Langguth P, Alteheld B, Fimmers R, Stehle P, et al. No effects of quercetin from onion skin extract on serum leptin and adiponectin concentrations in overweight-to-obese patients with (pre-)hypertension: a randomized double-blinded, placebo-controlled crossover trial. Eur J Nutr. 2017; 56:2265–2275. PMID: 27423432.
32. Lim JU, Lee JH, Kim JS, Hwang YI, Kim TH, Lim SY, Yoo KH, Jung KS, Kim YK, Rhee CK. Comparison of World Health Organization and Asia-Pacific body mass index classifications in COPD patients. Int J Chron Obstruct Pulmon Dis. 2017; 12:2465–2475. PMID: 28860741.
33. Cederbrant K. Natural killer cell assay. Vohr HW, editor. Encyclopedic Reference of Immunotoxicology. Berlin, Heidelberg: Springer Berlin Heidelberg;2005. p. 469–472.
34. Barrett B, Brown R, Mundt M, Safdar N, Dye L, Maberry R, Alt J. The Wisconsin Upper Respiratory Symptom Survey is responsive, reliable, and valid. J Clin Epidemiol. 2005; 58:609–617. PMID: 15878475.
35. Cohen S, Kamarck T, Mermelstein R. A global measure of perceived stress. J Health Soc Behav. 1983; 24:385–396. PMID: 6668417.
36. Nikiphorou E, Radner H, Chatzidionysiou K, Desthieux C, Zabalan C, van Eijk-Hustings Y, Dixon WG, Hyrich KL, Askling J, Gossec L. Patient global assessment in measuring disease activity in rheumatoid arthritis: a review of the literature. Arthritis Res Ther. 2016; 18:251. PMID: 27793211.
37. World Health Organization. Global physical activity questionnaire (GPAQ) [Internet]. Geneva: World Health Organization;2021. cited 2023 August 10. Available from: https://www.who.int/publications/m/item/global-physical-activity-questionnaire.
38. Lee YJ, Paik DJ, Kwon DY, Yang HJ, Park Y. Agrobacterium sp.-derived β-1,3-glucan enhances natural killer cell activity in healthy adults: a randomized, double-blind, placebo-controlled, parallel-group study. Nutr Res Pract. 2017; 11:43–50. PMID: 28194264.
39. Abbey EL, Rankin JW. Effect of quercetin supplementation on repeated-sprint performance, xanthine oxidase activity, and inflammation. Int J Sport Nutr Exerc Metab. 2011; 21:91–96. PMID: 21558570.
40. Konrad M, Nieman DC, Henson DA, Kennerly KM, Jin F, Wallner-Liebmann SJ. The acute effect of ingesting a quercetin-based supplement on exercise-induced inflammation and immune changes in runners. Int J Sport Nutr Exerc Metab. 2011; 21:338–346. PMID: 21813917.
41. Nieman DC, Henson DA, Gross SJ, Jenkins DP, Davis JM, Murphy EA, Carmichael MD, Dumke CL, Utter AC, McAnulty SR, et al. Quercetin reduces illness but not immune perturbations after intensive exercise. Med Sci Sports Exerc. 2007; 39:1561–1569. PMID: 17805089.
42. McAnulty SR, McAnulty LS, Nieman DC, Quindry JC, Hosick PA, Hudson MH, Still L, Henson DA, Milne GL, Morrow JD, et al. Chronic quercetin ingestion and exercise-induced oxidative damage and inflammation. Appl Physiol Nutr Metab. 2008; 33:254–262. PMID: 18347680.
43. Nieman DC, Henson DA, Maxwell KR, Williams AS, McAnulty SR, Jin F, Shanely RA, Lines TC. Effects of quercetin and EGCG on mitochondrial biogenesis and immunity. Med Sci Sports Exerc. 2009; 41:1467–1475. PMID: 19516153.
44. Nieman DC, Henson DA, Davis JM, Angela Murphy E, Jenkins DP, Gross SJ, Carmichael MD, Quindry JC, Dumke CL, Utter AC, et al. Quercetin’s influence on exercise-induced changes in plasma cytokines and muscle and leukocyte cytokine mRNA. J Appl Physiol. 2007; 103:1728–1735. PMID: 17717114.
45. Panagiotakos DB, Pitsavos C, Chrysohoou C, Kavouras S, Stefanadis C. ATTICA Study. The associations between leisure-time physical activity and inflammatory and coagulation markers related to cardiovascular disease: the ATTICA Study. Prev Med. 2005; 40:432–437. PMID: 15530595.
46. World Health Organization. Physical activity [Internet]. Geneva: World Health Organization;2022. cited 2023 August 10. Available from: https://www.who.int/news-room/fact-sheets/detail/physical-activity.
47. Heinz SA, Henson DA, Nieman DC, Austin MD, Jin F. A 12-week supplementation with quercetin does not affect natural killer cell activity, granulocyte oxidative burst activity or granulocyte phagocytosis in female human subjects. Br J Nutr. 2010; 104:849–857. PMID: 20500927.
48. Dorresteijn PM, Muller D, Xie Y, Zhang Z, Barrett BP. Validation of the Nasal Mucus Index, a novel measurement of acute respiratory infection severity. Am J Rhinol Allergy. 2016; 30:324–328. PMID: 27657897.
49. Rai KR, Shrestha P, Yang B, Chen Y, Liu S, Maarouf M, Chen JL. Acute infection of viral pathogens and their innate immune escape. Front Microbiol. 2021; 12:672026. PMID: 34239508.
50. Boots AW, Drent M, de Boer VC, Bast A, Haenen GR. Quercetin reduces markers of oxidative stress and inflammation in sarcoidosis. Clin Nutr. 2011; 30:506–512. PMID: 21324570.
51. Grudzien M, Rapak A. Effect of natural compounds on NK cell activation. J Immunol Res. 2018; 2018:4868417. PMID: 30671486.
52. Freud AG, Mundy-Bosse BL, Yu J, Caligiuri MA. The broad spectrum of human natural killer cell diversity. Immunity. 2017; 47:820–833. PMID: 29166586.
53. Oliveira TT, Campos KM, Cerqueira-Lima AT, Cana Brasil Carneiro T, da Silva Velozo E, Ribeiro Melo IC, Figueiredo EA, de Jesus Oliveira E, de Vasconcelos DF, Pontes-de-Carvalho LC, et al. Potential therapeutic effect of Allium cepa L. and quercetin in a murine model of Blomia tropicalis induced asthma. Daru. 2015; 23:18. PMID: 25890178.
54. Rivera L, Morón R, Sánchez M, Zarzuelo A, Galisteo M. Quercetin ameliorates metabolic syndrome and improves the inflammatory status in obese Zucker rats. Obesity (Silver Spring). 2008; 16:2081–2087. PMID: 18551111.
Full Text Links
  • NRP
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr