A randomized double blinded placebo controlled clinical trial for the evaluation of green coffee extract on immune health in healthy adults

10.1016/j.jtcme.2022.01.007

Jeyaparthasarathy Narayanaperumal；Avin D'souza；Amarnath Miriyala；Bhavna Sharma；Ganesh Gopal

Green coffee extract ； Immunity ； Inflammation ； Innate immune response ； Cell mediated immune response ； Humoral immune response

Journal of Traditional and Complementary Medicine

12卷5期（2022 / 09 / 01）

455 - 465

英文

Background: The immune system functions to protect the host from a broad array of infectious diseases. Here, we evaluated the in vitro immunomodulatory effects of green coffee extract (GCE), and conducted a double-blinded, randomized and placebo-controlled trial among apparently healthy individuals. Methods: We determined the levels and functions of inflammatory and immune markers viz., phospho-NF-κB p65 ser536, chemotaxis, phagocytosis, TH1/TH2 cytokines and IgG production. We also evaluated several immunological markers such as total leukocyte counts, differential leukocyte counts, NK cell activity, CD4/CD8 ratio, serum immunoglobulin, C-reactive protein (CRP) and pro-inflammatory cytokines (IL-6 and TNF-α). Results and conclusion: GCE significantly inhibited LPS-induced NF-κB p65 ser536 phosphorylation, MCP-1-induced chemotaxis and significantly enhanced phagocytosis and IgG production. In addition, GCE modulated PMA/PHA-induced TH1/TH2 cytokine production. Clinical investigations suggested that the expression of CD56 and CD16 was markedly augmented on NK cells following GCE treatment. GCE significantly enhanced IgA production before and after influenza vaccination. Similarly, IL-6, TNF-α and CRP levels were significantly inhibited by GCE. Together, GCE confers several salubrious immunomodulatory effects at different levels attributing to optimal functioning of immune responses in the host. Taxonomy: Cell biology, Clinical study, Clinical Trial.

1. Ahmed, GM,El-Ghamery, HE,Samy, MF(2013).Effect of green and degree of roasted Arabic coffee on hyperlipidemia and antioxidant status in diabetic rats.Adv J Food Sci Technol,5,619-626.
2. Albers, R,Antoine, JM,Bourdet-Sicard, R(2005).Markers to measure immune-modulation in human nutrition intervention studies.Br J Nutr,94,452-481.
3. Ali, N,Rashid, S,Nafees, S(2017).Protective effect of Chlorogenic acid against methotrexate induced oxidative stress, inflammation and apoptosis in rat liver: an experimental approach.Chem Biol Interact,272,80-91.
4. Baxter, D(2007).Active and passive immunity, vaccine types, excipients and licensing.Occup Med.,57,552-556.
5. Beutler, BA(2009).TLRs and innate immunity.Blood,113,1399-1407.
6. Bhaskaram, P(2001).Immunobiology of mild micronutrient deficiencies.Br J Nutr.,85(Suppl 2),S75-S80.
7. Bonilla, FA,Oettgen, HC(2010).Adaptive immunity.J Allergy Clin Immunol,125(Suppl 2),S33-S40.
8. Boring, L,Gosling, J,Cleary, M,Charo, IF(1998).Decreased lesion formation in CCR2-/-mice reveals a role for chemokines in the initiation of atherogenesis.Nature,394,894-897.
9. Bradt, BM,Kolb, WP,Cooper, NR(1998).Complement-dependent proinflammatory properties of the Alzheimer's disease beta-peptide.J Exp Med,188,431-438.
10. Butcher, SK,Chahal, H,Nayak, L(2001).Senescence in innate immune responses: reduced neutrophil phagocytic capacity and CD16 expression in elderly humans.J Leukoc Biol,70,881-886.
11. Caro-Gómez, E,Sierra, JA,Escobar, JS(2019).Green coffee extract improves car- diometabolic parameters and modulates gut microbiota in high-fat-diet-fed ApoE-/- mice.Nutrients,11(3),497.
12. Chaplin, DD(2003).The immune system. Overview of the immune response.J Allergy Clin Immunol,111,S442-S459.
13. Chen, J,Xie, H,Chen, D(2018).Chlorogenic acid improves intestinal development via suppressing mucosa inflammation and cell apoptosis in weaned pigs.ACS Omega,3(2),2211-2219.
14. Chen, L,Deng, H,Cui, H(2018).Inflammatory responses and inflammation-associated diseases in organs.Oncotarget,9(6),7204-7218.
15. Chiang, LC,Ng, LT,Chiang, W,Chang, MY,Lin, CC(2003).Immunomodulatory activities of flavonoids, monoterponoids, triterpenoids, iridoid glycosides and phenolic compounds of Plantago species.Planta Med,69(7),600-604.
16. Cho, AS,Jeon, SM,Kim, MJ(2010).Chlorogenic acid exhibits anti-obesity property and improves lipid metabolism in high-fat diet-induced-obese mice.Food Chem Toxicol,48,937-943.
17. Combs, CK,Karlo, JC,Kao, SC,Landreth, GE(2001).Beta-amyloid stimulation of microglia and monocytes results in TNFalpha-dependent expression of inducible nitric oxide synthase and neuronal apoptosis.J Neurosci,21,1179-1188.
18. Cooper, MA,Fehniger, TA,Caligiuri, MA(2001).The biology of human natural killer-cell subsets.Trends Immunol,22,633-640.
19. Coxon, A,Cullere, X,Knight, S(2001).Fc gamma RIII mediates neutrophil recruitment to immune complexes: a mechanism for neutrophil accumulation in immune-mediated inflammation.Immunity,14,693-704.
20. Crimeen-Irwin, B,Scalzo, K,Gloster, S,Mottram, PL,Plebanski, M(2005).Failure of immune homeostasis - the consequences of under and over reactivity.Curr Drug Targets - Immune, Endocr Metab Disord,5(4),413-422.
21. Croen, KD(1993).Evidence for antiviral effect of nitric oxide. Inhibition of herpes simplex virus type 1 replication.J Clin Invest,91,2446-2452.
22. Cummings, JH,Antoine, JM,Azpiroz, F(2004).PASSCLAIM-dgut health and immunity.Eur J Clin Nutr,43(suppl 2),118-173.
23. Dao, L,Friedman, M(1992).Chlorogenic acid content of fresh and processed potatoes determined by ultraviolet spectrophotometry.J Agric Food Chem,40,2152-2156.
24. Goldszmid, RS,Caspar, P,Rivollier, A(2012).NK cell-derived interferon-gamma orchestrates cellular dynamics and the differentiation of monocytes into dendritic cells at the site of infection.Immunity,36,1047-1059.
25. Grigore, A.(2017).Plant Phenolic Compounds as Immunomodulatory Agents.Phenolic Compounds - Biological Activity
26. Hu, KJ,Qu, FJ,Wang, ZL(2004).Experimental study on the induction of a-tinterferon of human leucocyte in vitro by chlorogenic acid.J Harbin Eng Univ,38,120-122.
27. Ignatowicz, E,Balana, B,Vulimiri, SV,Szaefer, H,Baer-Dubowska, W(2003).The effect of plant Phenolics on the formaiton of 7, 12-dimethylbenz[a] an-thracene-DNA adducts and TPA- stimulated polymorphonuclear neutrophifls chemiluminescence in vitro.Toxicology,189(3),199-209.
28. Indik, ZK,Park, JG,Hunter, S,Schreiber, AD.(1995).The molecular dissection of Fc gamma receptor mediated phagocytosis.Blood,86,4389-4399.
29. Ivory, K(2017).Selenium supplementation has beneficial and detrimental effects on immunity to influenza vaccine in older adults.Clin Nutr,36(2),407-415.
30. Ji, L,Jiang, P,Lu, B,Sheng, Y,Wang, X,Wang, Z(2013).Chlorogenic acid, a dietary polyphenol, protects acetaminophen-induced liver injury and its mechanism.J Nutr Biochem,24,1911-1919.
31. Kang, E-J(2013).The effect of probiotics on prevention of common cold: a meta-analysis of randomized controlled trial studies.Kor J Fam Med.,34(1),2-10.
32. Karin, M,Ben-Neriah, Y(2000).Phosphorylation meets ubiquitination: the control of NF-[kappa] B activity.Annu Rev Immunol,18,621-663.
33. Kasai, H,Fukada, S,Yamaizumi, Z,Sugie, S,Mori, H(2000).Action of chlorogenic acid in vegetables and fruits as an inhibitor of 8-hydroxy-deoxyguanseine formation in vitro and in a rat carcinogenesis mode1.Food Chem Toxicol,38(5),467-471.
34. Kim, JY,Jung, KS,Lee, KJ(2004).The coffee diterpene kahweol suppress the inducible nitric oxide synthase expression in macrophages.Cancer Lett,213,147-154.
35. Kim, JY,Kim, DH,Jeong, HG(2006).Inhibitory effect of the coffee diterpene kahweol on carrageenan-induced inflammation in rats.Biofactors,26,17-28.
36. Kim, SH,Park, SY,Park, YL,Myung, DS,Rew, JS,Joo, YE(2017).Chlorogenic acid suppresses lipopolysaccharide-induced nitric oxide and interleukin-1ß expression by inhibiting JAK2/STAT3 activation in RAW264.7 cells.Mol Med Rep,16,9224-9232.
37. Kumagai, Y,Akira, S(2010).Identification and functions of pattern-recognition receptors.J Allergy Clin Immunol,125,985-992.
38. Lee, SW,Kwon, OE,Chung, MY(2002).Screening of monocyte chemoattractant protein-1-induced chemotaxis inhibitors from medicinal herbs.Korean J Pharmacogn,33,352-358.
39. Li, Y,Shi, W,Li, Y,Zhou, Y,Hu, X,Song, C(2008).Neuroprotective effects of chlorogenic acid against apoptosis of PC12 cells induced by methylmercury.Environ Toxicol Pharmacol,26,13-21.
40. Liang, N,Kitts, DD(2015).Role of chlorogenic acids in controlling oxidative and inflammatory stress conditions.Nutrients,8(1),16.
41. Liu, F,Xia, Y,Parker, AS(2012).Verma. IMIKK biology.Immunol Rev,246(1),239-253.
42. Ludwig, IA,Mena, P,Calani, L(2014).Variations in caffeine and chlorogenic acid contents of coffees: what are we drinking?.Food Funct,5,1718-1726.
43. Ma, Y,Gao, M,Liu, D(2015).Chlorogenic acid improves high fat diet-induced hepatic steatosis and insulin resistance in mice.Pharm Res,32,1200-1209.
44. Marshall, JS,Warrington, R,Watson, W,Kim, HL(2018).An introduction to immunology and immunopathology.Allergy Asthma Clin Immunol,14,49.
45. Martín-Fontecha, A,Thomsen, LL,Brett, S(2004).Induced recruitment of NK cells to lymph nodes provides IFN-gamma for T(H)1 priming.Nat Immunol,5,1260-1265.
46. McCarty, MF,DiNicolantonio, JJ(2020).Nutraceuticals have potential for boosting the type 1 interferon response to RNA viruses including influenza and coronavirus.Prog Cardiovasc Dis
47. McGeer, PL,McGeer, EG,Yasojima, K(2000).Alzheimer's disease and neuro-inflammation.J Neural Transm Suppl,59,53-57.
48. Moser, B,Willimann, K(2004).Chemokines: role in inflammation and immune surveillance.Ann Rheum Dis.,63(Suppl 2),ii84-ii89.
49. Mousa, HA(2017).Prevention and treatment of influenza, influenza-like illness, and common cold by herbal, complementary, and natural therapies.J Evid Based Compl Altern Med,22(1),166-174.
50. Mubarak, A,Bondonno, CP,Liu, AH(2012).Acute effects of chlorogenic acid on nitric oxide status, endothelial function, and blood pressure in healthy volunteers: a randomized trial.J Agric Food Chem,60,9130-9136.
51. Murphy, KM,Travers, P,Walport, M(2007).Janeway's Immunobiology.New York:Garland Science.
52. Nabi(ed.)(2013).Building Blocks of the Cell.San Rafael, CA:Morgan & Claypool Life Sciences.
53. Naveed, M,Hejazi, V,Abbas, M(2017).Chlorogenic acid (CGA): a pharmacological review and call for further research.Biomed Pharmacother,97,67-74.
54. Onakpoya, IJ,Spencer, EA,Thompso, MJ,Heneghan, CJ(2015).The effect of chlorogenic acid on blood pressure: a systematic review and meta-analysis of randomized clinical trials.J Hum Hypertens,29,77-81.
55. Ong, KW,Hsu, A,Tan, BK(2013).Anti-diabetic and anti-lipidemic effects of chlorogenic acid are mediated by ampk activation.Biochem Pharmacol,85,1341-1351.
56. Pahl, HL(1999).Activators and target genes of Rel/NF-kappaB transcription factors.Oncogene,18(49),6853-6866.
57. Paur, I,Balstad, TR,Blomhoff, R(2010).Degree of roasting is the main determinant of the effects of coffee on NF-kB and EpRE.Free Radic Biol Med,48,1218-1227.
58. Reyna-Margarita, HR,Irais, CM,Mario-Alberto, RG,Agustina, RM,Luis-Benjamín, SG,David, PE(2019).Plant phenolics and lectins as vaccine adjuvants.Curr Pharmaceut Biotechnol,20(15),1236-1243.
59. Romagnani, S(1999).Th1/Th2 cells.Inflamm Bowel Dis,5(4),285-294.
60. Shang, F,Li, X,Jiang, X(2016).Coffee consumption and risk of the metabolic syndrome: a meta-analysis.Diabetes Metab,42,80-87.
61. Shen, MY,Liu, YJ,Don, MJ(2011).Combined phytochemistry and chemotaxis assays for identification and mechanistic analysis of anti-inflammatory phytochemicals in Fallopia japonica.PLoS One.,6(11),e27480.
62. Sproston, NR,Ashworth, JJ(2018).Role of C-reactive protein at sites of inflammation and infection.Front Immunol,9,754.
63. Szliszka, E,Krol, W(2011).The role of dietary polyphenols in tumor necrosis factor-related apoptosis inducing ligand (TRAIL)-induced apoptosis for cancer chemoprevention.Eur J Cancer Prev,20(1),63-69.
64. Tajik, N,Tajik, M,Mack, I,Enck, P(2017).The potential effects of chlorogenic acid, the main phenolic componentsin coffee, on health: a comprehensive review of the literature.Eur J Nutr.,56,2215-2244.
65. Takeuchi, O,Akira, S(2010).Pattern recognition receptors and inflammation.Cell,140,805-820.
66. Tanaka, Y,Furuta, A,Asano, K,Kobayashi, H(2020).Modulation of Th1/Th2 cytokine balance by quercetin in vitro.Medicines,7(8),46.
67. Tauchi, Y,Yamada, A,Kawakita, T(1993).Enhancement of immunoglobulin A production in Peyer’ s patches by oral administration of a traditional Chinese medicine, xiao-chai-hutang (Shosaiko-to).Immunopharmacol Immunotoxicol,15,251-272.
68. Twigg, HL(2005).Humoral immune defence (antibodies): recent advances.Proc Am Thorac Soc.,2,417-421.
69. Udani, JK.(2013).Immunomodulatory effects of ResistAid™: a randomized, double-blind, placebo-controlled, multidose study.J Am Coll Nutr,32(5),331-338.
70. Upadhyay, R,Mohan, Rao, LJ(2013).An outlook on chlorogenic acids-occurrence, chemistry, technology, and biological activities.Crit Rev Food Sci Nutr,53,968-984.
71. Vesely, MD,Kershaw, MH,Schreiber, RD,Smyth, MJ(2011).Natural innate and adaptive immunity to cancer.Annu Rev Immunol,29,235-271.
72. Vidarsson, G,Dekkers, G,Rispens, T(2014).IgG subclasses and allotypes: from structure to effector functions.Front Immunol,5,520.
73. Vinson, JA,Hao, Y,Su, X,Zubik, L(1998).Phenol antioxidant quantity and quality in foods:vegetables.J Agric Food Chem,46(9),3630-3634.
74. Vivier, E,Tomasello, E,Baratin, M(2008).Functions of natural killer cells.Nat Immunol,9,503-510.
75. Warrington, R,Watson, W,Kim, HL,Antonetti, FR(2011).introduction to immunology and immunopathology.All Asth Clin Immun,7(Suppl 1),S1.
76. Yeap, SK,Omar, AR,Ho, WY,Beh, BK,Ali, AM,Alitheen, NB(2013).Rhaphidophora korthalsii modulates peripheral blood natural killer cell proliferation, cytokine secretion and cytotoxicity.BMC Compl Alternative Med,13,145.