Food Science and Industry (식품과학과 산업)

Korean Society of Food Science and Technology (한국식품과학회)
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COVID-19 pandemic and the immune regulatory function of foods

COVID-19 팬데믹과 식품의 면역조절 기능

  • Kim, Gun-Dong (Aging and Metabolism Research Group, Food Functionality Research Division, Korea Food Research Institute) ;
  • Lee, So-Young (Aging and Metabolism Research Group, Food Functionality Research Division, Korea Food Research Institute) ;
  • Shin, Hee Soon (Aging and Metabolism Research Group, Food Functionality Research Division, Korea Food Research Institute)
  • 김근동 (한국식품연구원 식품기능연구본부 노화대사연구단) ;
  • 이소영 (한국식품연구원 식품기능연구본부 노화대사연구단) ;
  • 신희순 (한국식품연구원 식품기능연구본부 노화대사연구단)
  • Received : 2022.08.04
  • Accepted : 2022.09.12
  • Published : 2022.09.30
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Abstract

Coronavirus, known as one of the causes of colds including mild upper respiratory tract disease in humans, has mutated into the infectious severe disease, COVID-19 through SARS and MERS. The mortality and symptoms of COVID-19 are related to the ability to regulate innate immunity, which acts as the first barrier against microorganisms and viruses. During the COVID-19 pandemic, the demand for food that helps to strengthen immunity is rapidly increasing. Functional foods promote general health and alleviate the risk of disease symptoms by activating multiple biological functions. A recent, there is an interest in discovering functional substances that can induce enhancement of immunity and prevent viral infection as well as relieve disease symptoms. Therefore, this article focus to understand the concept of immune response and highlights the recent status of functional foods and research trends that can help prevent and treat viral infections by inducing the enhancement of immune function.

Keywords

References

  1. Abouelela ME, Assaf HK, Abdelhamid RA, Elkhyat ES, Sayed AM, Oszako T, Belbahri L, El Zowalaty AE, Abdelkader MSA. Identification of potential SARS-CoV-2 main protease and spike protein inhibitors from the genus Aloe: An in silico study for drug development. Molecules. 26: (2021)
  2. Ahn H, Kang SG, Yoon SI, Kim PH, Kim D, Lee GS. Poly-gam- ma-glutamic acid from Bacillus subtilis upregulates pro-inflammatory cytokines while inhibiting NLRP3, NLRC4 and AIM2 inflammasome activation. Cell. Mol. Immunol. 15: 111-119 (2018) https://doi.org/10.1038/cmi.2016.13
  3. Bibi S, Hasan MM, Wang YB, Papadakos SP, Yu H. Cordycepin as a promising inhibitor of SARS-CoV-2 RNA dependent RNA polymerase (RdRp). Curr Med Chem. 29: 152-162 (2022) https://doi.org/10.2174/0929867328666210820114025
  4. Chelleng N, Puzari M, Chetia P, Tamuly C. Phenolic compounds of Zanthoxylum armatum DC as potential inhibitors of urease and SARS-CoV2 using molecular docking approach and with simulation study. Nat Prod Res. 1-5 (2022)
  5. Cheng D, Wan Z, Zhang X, Li J, Li H, Wang C. Dietary Chlorell vulgaris ameliorates altered immunomodulatory functions in cyclo- phosphamide-induced immunosuppressive mice. Nutrients. 9: 708 (2017) https://doi.org/10.3390/nu9070708
  6. Cheng LQ, Na JR, Bang MH, Kim MK, Yang DC. Conversion of major ginsenoside Rb1 to 20(S)-ginsenoside Rg3 by microbacterium sp. GS514. Phytochemistry. 69: 218-224 (2008) https://doi.org/10.1016/j.phytochem.2007.06.035
  7. Cheng S-C, Quintin J, Cramer RA, Shepardson KM, Saeed S, Kumar V, Giamarellos-Bourboulis EJ, Martens JH, Rao NA, Aghajanirefah A, Manjeri GR, Li Y, Ifrim DC, Arts RJ, van der Veer BM, Deen PM, Logie C, O'Neill LA, Willems P, van de Veerdonk FL, van der Meer JW, Ng A, Joosten LA, Wijmenga C, Stunnenberg HG, Xavier RJ, Netea MG. mTOR- and HIF- 1alpha-mediated aerobic glycolysis as metabolic basis for trained immunity. Science. 345: 1250684 (2014) https://doi.org/10.1126/science.1250684
  8. Cho H-S, Yoon J-J, Lee Y-T. The effect of Phellinus linteus on leukocytes chemotaxis in mouse transplanted with sarcoma-180 tumor cells. Journal of Korean Association of Cancer Prevention. 4: 187-195 (1999)
  9. Cho JM, Chae J, Jeong SR, Moon MJ, Shin DY, Lee JH. Immune activation of Bio-Germanium in a randomized, double-blind, placebo-controlled clinical trial with 130 human subjects: Therapeutic opportunities from new insights. PLoS One. 15: e0240358 (2020) https://doi.org/10.1371/journal.pone.0240358
  10. Cho JM, Yoo D, Lee JY, Oh MS, Ha KC, Baek HI, Lee SM, Lee JH, Yoo HJ. Supplementation with a natural source of amino acids, Sil-Q1 (silk peptide), enhances natural killer cell activity: A redesigned clinical trial with a reduced supplementation dose and minimized seasonal effects in a larger population. Nutrients. 13: 2930 (2021) https://doi.org/10.3390/nu13092930
  11. Coronaviridae Study Group of the International Committee on Taxonomy of V. The species severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Nat. Microbiol. 5: 536-544 (2020) https://doi.org/10.1038/s41564-020-0695-z
  12. Costela-Ruiz VJ, Illescas-Montes R, Puerta-Puerta JM, Ruiz C, Melguizo-Rodriguez L. SARS-CoV-2 infection: The role of cytokines in COVID-19 disease. Cytokine Growth Factor Rev. 54: 62-75 (2020) https://doi.org/10.1016/j.cytogfr.2020.06.001
  13. Deniau AL, Mosset P, Pedrono F, Mitre R, Le Bot D, Legrand AB. Multiple beneficial health effects of natural alkylglycerols from shark liver oil. Mar. Drugs. 8: 2175-2184 (2010) https://doi.org/10.3390/md8072175
  14. Fritz JH, Le Bourhis L, Sellge G, Magalhaes JG, Fsihi H, Kufer TA, Collins C, Viala J, Ferrero RL, Girardin SE, Philpott DJ. NOD1-mediated innate immune recognition of peptidoglycan contributes to the onset of adaptive immunity. Immunity. 26: 445-459 (2007) https://doi.org/10.1016/j.immuni.2007.03.009
  15. Garg S, Anand A, Lamba Y, Roy A. Molecular docking analysis of selected phytochemicals against SARS-CoV-2 M(pro) receptor. Vegetos. 33: 766-781 (2020) https://doi.org/10.1007/s42535-020-00162-1
  16. Gizawy HA, Boshra SA, Mostafa A, Mahmoud SH, Ismail MI, Alsfouk AA, Taher AT, Al-Karmalawy AA. Pimenta dioica (L.) Merr. bioactive constituents exert anti-SARS-CoV-2 and anti-inflammatory activities: Molecular docking and dynamics, in vitro, and in vivo studies. Molecules. 26: (2021)
  17. Heo J-Y, Shin H-J, Oh D-H, Cho S-K, Yang C-J, Kong I-K, Lee S-S, Choi K-S, Choi S-H, Kim S-C, Choi H-Y, Bae I. Quality properties of appenzeller cheese added with Chlorella. KOREAN J. FOOD SQ. ANI. RESOUR. 26: 525-531 (2006)
  18. Hicks EG, Kandel SE, Lampe JN. Identification of Aloe-derived natural products as prospective lead scaffolds for SARS-CoV-2 main protease (M(pro)) inhibitors. Bioorg Med Chem Lett. 66: 128732 (2022) https://doi.org/10.1016/j.bmcl.2022.128732
  19. Hikino H, Oshima Y, SuzukI Y, Konno C. Isolation and hypoglycemic activity of panaxan F, G and H, glycan of Panax ginseng root. Shoyakugaku Zasshi. 39: 331-333 (1985)
  20. Huang CT, Hung CY, Hseih YC, Chang CS, Velu AB, He YC, Huang YL, Chen TA, Chen TC, Lin CY, Lin YC, Shih SR, Dutta A. Effect of aloin on viral neuraminidase and hemagglutinin-specific T cell immunity in acute influenza. Phytomedicine. 64: 152904 (2019) https://doi.org/10.1016/j.phymed.2019.152904
  21. Hyun SH, Ahn HY, Kim HJ, Kim SW, So SH, In G, Park CK, Han CK. Immuno-enhancement effects of Korean red ginseng in healthy adults: a randomized, double-blind, placebo-controlled trial. J. Ginseng. Res. 45: 191-198 (2021) https://doi.org/10.1016/j.jgr.2020.08.003
  22. Ichinohe T, Ainai A, Nakamura T, Akiyama Y, Maeyama J, Odagiri T, Tashiro M, Takahashi H, Sawa H, Tamura S, Chiba J, Kurata T, Sata T, Hasegawa H. Induction of cross-protective immunity against influenza A virus H5N1 by an intranasal vaccine with extracts of mushroom mycelia. J. Med. Virol. 82: 128-137 (2010) https://doi.org/10.1002/jmv.21670
  23. Jang S-H, Oh MS, Baek HI, Ha KC, Lee JY, Jang YS. Silk peptide treatment potentiates natural killer cell activity in vitro and induces natural killer cell maturation and activation in mouse splenocytes. Pharm. Biol. 57: 369-379 (2019) https://doi.org/10.1080/13880209.2019.1617749
  24. Joo SS, Won TJ, Lee YJ, Kim MJ, Park S-Y, Lee SH, Hwang KW, Lee DI. Effect of geranti Bio-Ge yeast, a dried yeast containing biogermanium, on the production of antibodies by B cells Immune Network. 6: 86-92 (2006) https://doi.org/10.4110/in.2006.6.2.86
  25. Jung S-J, Jung ES, Choi EK, Sin HS, Ha KC, Chae SW. Immunomodulatory effects of a mycelium extract of Cordyceps (Paecilomyces hepiali; CBG-CS-2): a randomized and double-blind clinical trial. BMC Complement Altern. Med. 19: 77 (2019) https://doi.org/10.1186/s12906-019-2483-y
  26. Kang HJ, Baik HW, Kim SJ, Lee SG, Ahn HY, Park JS, Park SJ, Jang EJ, Park SW, Choi JY, Sung JH, Lee SM. Cordyceps militaris enhances cell-mediated immunity in healthy Korean men. J. Med. Food. 18: 1164-1172 (2015) https://doi.org/10.1089/jmf.2014.3350
  27. Kawai T, Akira S. Toll-like receptors and their crosstalk with other innate receptors in infection and immunity. Immunity. 34: 637-650 (2011) https://doi.org/10.1016/j.immuni.2011.05.006
  28. Kenarova B, Neychev H, Hadjiivanova C, Petkov VD. Immunomodulating activity of ginsenoside Rg1 from Panax ginseng. Jpn. J. Pharmacol. 54: 447-454 (1990) https://doi.org/10.1254/jjp.54.447
  29. Kim EH, Lee BW, Ryu B, Cho HM, Kim SM, Jang SG, Casel MAB, Rollon R, Yoo JS, Poo H, Oh WK, Choi YK. Inhibition of a broad range of SARS-CoV-2 variants by antiviral phytochemicals in hACE2 mice. Antiviral Res. 204: 105371 (2022) https://doi.org/10.1016/j.antiviral.2022.105371
  30. Kim G-Y, Lee JY, Lee JO, Ryu CH, Choi BT, Jeong YK, Lee KW, Jeong SC, Choi YH. Partial characterization and immunostimulatory effect of a novel polysaccharide-protein complex extracted from Phellinus linteus. Biosci. Biotechnol. Biochem. 70: 1218-1226 (2006) https://doi.org/10.1271/bbb.70.1218
  31. Kim G-Y, Park SK, Lee MK, Lee SH, Oh YH, Kwak JY, Yoon S, Lee JD, Park YM. Proteoglycan isolated from Phellinus linteus activates murine B lymphocytes via protein kinase C and protein tyrosine kinase. Int. Immunopharmacol. 3: 1281-1292 (2003) https://doi.org/10.1016/S1567-5769(03)00115-2
  32. Kim HM, Han SB, Oh GT, Kim YH, Hong DH, Hong ND, Yoo ID. Stimulation of humoral and cell mediated immunity by polysaccharide from mushroom Phellinus linteus. Int. J. Immunopharmacol. 18: 295-303 (1996) https://doi.org/10.1016/0192-0561(96)00028-8
  33. Kim KH, Lee YS, Jung IS, Park SY, Chung HY, Lee IR, Yun YS. Acidic polysaccharide from Panax ginseng, ginsan, induces Th1 cell and macrophage cytokines and generates LAK cells in synergy with rIL-2. Planta. Med. 64: 110-115 (1998) https://doi.org/10.1055/s-2006-957385
  34. Kim YS, Park KM, Shin HJ, Song KS, Nam KY, Park JD. Anticancer activities of red ginseng acidic polysaccharide by activation of macrophages and natural killer cells. YAKHAK HOEJI. 46: 113-119 (2002)
  35. Konno C, Hikino H. Isolation and Hypoglycemic Activity of Panaxans M, N, O and P, Glycans of Panax ginseng Roots. International Journal of Crude Drug Research. 25: 53-56 (1987) https://doi.org/10.3109/13880208709060912
  36. Konno C, Murakami M, Oshima Y, Hikino H. Isolation and hypoglycemic activity of panaxans Q, R, S, T and U, glycans of Panax ginseng roots. J Ethnopharmacol. 14: 69-74 (1985) https://doi.org/10.1016/0378-8741(85)90030-3
  37. Konno C, Sugiyama K, Kano M, Takahashi M, Hikino H. Isolation and hypoglycaemic activity of panaxans A, B, C, D and E, glycans of Panax ginseng roots. Planta Med. 50: 434-436 (1984) https://doi.org/10.1055/s-2007-969757
  38. Kwak JH, Baek SH, Woo Y, Han JK, Kim BG, Kim OY, Lee JH. Beneficial immunostimulatory effect of short-term Chlorella supplementation: enhancement of natural killer cell activity and early inflammatory response (randomized, double-blinded, placebocontrolled trial). Nutr. J. 11: 53 (2012) https://doi.org/10.1186/1475-2891-11-53
  39. Kwak Y-S. Immunomodulatory activity of Korean ginseng (Panax ginseng C.A. Meyer). Food Science and Industry. 45: 23-38 (2012)
  40. Kwak Y-S, Baeg I-H. Review on the current research of red ginseng acidic polysaccharide for its immunostimulating activity. The Korean Ginseng research and industry. 4: 20-35 (2010)
  41. Lee BE, Ryu SY, Kim EH, Kim YH, Kwak KA, Song HY. Immunostimulating effect of Mycelium extract of Phellinus linteus. Kor. J. Pharmacogn. 43: 157-162 (2012)
  42. Lee JK, Lee MK, Yun YP, Kim Y, Kim JS, Kim YS, Kim K, Han SS, Lee CK. Acemannan purified from Aloe vera induces phenotypic and functional maturation of immature dendritic cells. Int. Immunopharmacol. 1: 1275-1284 (2001) https://doi.org/10.1016/S1567-5769(01)00052-2
  43. Lee JS, Hwang HS, Ko EJ, Lee YN, Kwon YM, Kim MC, Kang SM. Immunomodulatory activity of red ginseng against influenza A virus infection. Nutrients. 6: 517-529 (2014a) https://doi.org/10.3390/nu6020517
  44. Lee JS, Kwon DS, Lee KR, Park JM, Ha SJ, Hong EK. Mechanism of macrophage activation induced by polysaccharide from Cordyceps militaris culture broth. Carbohydr. Polym. 120: 29-37 (2015) https://doi.org/10.1016/j.carbpol.2014.11.059
  45. Lee SI, Heo HJ, Row KH. Physical property and extraction of squalene and alkoxyglycerol from shark liver oil. Korean Chem. Eng. Res. 49: 617-622 (2011) https://doi.org/10.9713/kcer.2011.49.5.617
  46. Lee SW, Park HJ, Park SH, Kim N, Hong S. Immunomodulatory effect of poly-gamma-glutamic acid derived from Bacillus subtilis on natural killer dendritic cells. Biochem. Biophys. Res. Commun. 443: 413-421 (2014b) https://doi.org/10.1016/j.bbrc.2013.11.097
  47. Lee W, Lee SH, Ahn DG, Cho H, Sung MH, Han SH, Oh JW. The antiviral activity of poly-gamma-glutamic acid, a polypeptide secreted by Bacillus sp., through induction of CD14-dependent type I interferon responses. Biomaterials. 34: 9700-9708 (2013) https://doi.org/10.1016/j.biomaterials.2013.08.067
  48. Lee Y, Kim J, An J, Lee H, Kong H, Song Y, Shin E, Do SG, Lee CK, Kim K. Aloe QDM complex enhances specific cytotoxic T lymphocyte killing in vivo in metabolic disease mice. Biosci. Biotechnol. Biochem. 81: 595-603 (2017) https://doi.org/10.1080/09168451.2016.1258986
  49. Lewkowicz P, Banasik M, Glowacka E, Lewkowicz N, Tchorzewski H. Effect of high doses of shark liver oil supplementation on T cell polarization and peripheral blood polymorphonuclear cell function. Pol. Merkur. Lekarski. 18: 686-692 (2005)
  50. Liu S, Liu F, Wang T, Liu J, Hu C, Sun L, Wang G. Polysaccharides Extracted From Panax Ginseng C.A. Mey Enhance Complement Component 4 Biosynthesis in Human Hepatocytes. Front Pharmacol. 12: 734394 (2021) https://doi.org/10.3389/fphar.2021.734394
  51. Liu X, Zhang Z, Liu J, Wang Y, Zhou Q, Wang S, Wang X. Ginsenoside Rg3 improves cyclophosphamide-induced immunocompetence in Balb/c mice. Int. Immunopharmacol. 72: 98-111 (2019) https://doi.org/10.1016/j.intimp.2019.04.003
  52. McKenzie ANJ, Spits H, Eberl G. Innate lymphoid cells in inflammation and immunity. Immunity. 41: 366-374 (2014) https://doi.org/10.1016/j.immuni.2014.09.006
  53. Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ, Hlh Across Speciality Collaboration UK. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 395: 1033-1034 (2020) https://doi.org/10.1016/S0140-6736(20)30628-0
  54. Meng J, Meng Y, Liang Z, Du L, Zhang Z, Hu X, Shan F. Phenotypic and functional analysis of the modification of murine bone marrow dendritic cells (BMDCs) induced by neutral ginseng poly-saccharides (NGP). Hum. Vaccin. Immunother. 9: 233-241 (2013) https://doi.org/10.4161/hv.22612
  55. Mogensen TH. Pathogen recognition and inflammatory signaling in innate immune defenses. Clin. Microbiol. Rev. 22: 240-273, Table of Contents (2009) https://doi.org/10.1128/CMR.00046-08
  56. Moon J, Jung Y, Moon S, Hwang J, Kim S, Kim MS, Yoon JH, Kim K, Park Y, Cho JY, Kweon DH. Production and characterization of lentivirus vector-based SARS-CoV-2 pseudoviruses with dual reporters: Evaluation of anti-SARS-CoV-2 viral effect of Korean red ginseng. J Ginseng Res. (2022)
  57. Mpiana PT, Ngbolua KT, Tshibangu DST, Kilembe JT, Gbolo BZ, Mwanangombo DT, Inkoto CL, Lengbiye EM, Mbadiko CM, Matondo A, Bongo GN, Tshilanda DD. Identification of potential inhibitors of SARS-CoV-2 main protease from Aloe vera com- pounds: A molecular docking study. Chem Phys Lett. 754: 137751 (2020) https://doi.org/10.1016/j.cplett.2020.137751
  58. Natoli G, Ostuni R. Adaptation and memory in immune responses. Nat. Immunol. 20: 783-792 (2019) https://doi.org/10.1038/s41590-019-0399-9
  59. Netea MG, Joosten LA, Latz E, Mills KH, Natoli G, Stunnenberg HG, O'Neill LA, Xavier RJ. Trained immunity: A program of innate immune memory in health and disease. Science. 352: aaf1098 (2016) https://doi.org/10.1126/science.aaf1098
  60. NutritionBusinessJournal. NBJ's global supplement & nutrition industry report (2017)
  61. NutritionBusinessJournal. Global supplement business report (2019)
  62. Oshima Y, Konno C, Hikino H. Isolation and hypoglycemic activity of panaxans I, J, K and L, glycans of Panax ginseng roots. J Ethnopharmacol. 14: 255-259 (1985) https://doi.org/10.1016/0378-8741(85)90091-1
  63. Palmieri B, Pennelli A, Di Cerbo A. Jurassic surgery and immunity enhancement by alkyglycerols of shark liver oil. Lipids Health Dis. 13: 178 (2014) https://doi.org/10.1186/1476-511X-13-178
  64. Park H-R, Jo SK, Jung U, Yee ST. Restoration of the immune functions in aged mice by supplementation with a new herbal composition, HemoHIM. Phytother. Res. 22: 36-42 (2008) https://doi.org/10.1002/ptr.2255
  65. Park H-R, Jo SK, Jung U, Yee ST, Kim SH. Protective effects of HemoHIM on immune and hematopoietic systems against gammairradiation. Phytother. Res. 28: 245-251 (2014) https://doi.org/10.1002/ptr.4982
  66. Park JD. Recent studies on the chemical constituents of Korean ginseng (Panax ginseng C. A. Meyer). Journal of Ginseng Research. 20: 389-415 (1996)
  67. Park S-K, Kim GY, Lim JY, Kwak JY, Bae YS, Lee JD, Oh YH, Ahn SC, Park YM. Acidic polysaccharides isolated from Phellinus linteus induce phenotypic and functional maturation of murine dendritic cells. Biochem. Biophys. Res. Commun. 312: 449-458 (2003) https://doi.org/10.1016/j.bbrc.2003.10.136
  68. Parkin J, Cohen B. An overview of the immune system. Lancet. 357: 1777-1789 (2001) https://doi.org/10.1016/S0140-6736(00)04904-7
  69. Qian L, Zhang M, Wu S, Zhong Y, Van Tol E, Cai W. Alkylglycerols modulate the proliferation and differentiation of non-specific agonist and specific antigen-stimulated splenic lymphocytes. PLoS One. 9: e96207 (2014) https://doi.org/10.1371/journal.pone.0096207
  70. Rabaan AA, Bakhrebah MA, Mutair AA, Alhumaid S, Al-Jishi JM, AlSihati J, Albayat H, Alsheheri A, Aljeldah M, Garout M, Alfouzan WA, Alhashem YN, AlBahrani S, Alshamrani SA, Alotaibi S, AlRamadhan AA, Albasha HN, Hajissa K, Temsah MH. Systematic review on pathophysiological complications in severe COVID-19 among the non-vaccinated and vaccinated population. Vaccines (Basel). 10: 985 (2022) https://doi.org/10.3390/vaccines10070985
  71. Rabie AM. Potent inhibitory activities of the adenosine analogue Cordycepin on SARS-CoV-2 replication. ACS Omega. 7: 2960-2969 (2022) https://doi.org/10.1021/acsomega.1c05998
  72. Rashmi S, Kulshreshtha DK. Bioactive polysaccharides from plants. Phytochemistry. 28: 2877-2883 (1989) https://doi.org/10.1016/0031-9422(89)80245-6
  73. Reynolds T, Dweck AC. Aloe vera leaf gel: a review update. J. Ethnopharmacol. 68: 3-37 (1999) https://doi.org/10.1016/S0378-8741(99)00085-9
  74. Sadgrove NJ, Simmonds MSJ. Pharmacodynamics of Aloe vera and acemannan in therapeutic applications for skin, digestion, and immunomodulation. Phytother. Res. 35: 6572-6584 (2021) https://doi.org/10.1002/ptr.7242
  75. Seo SH. Ginseng protects ACE2-transgenic mice from SARS-CoV-2 infection. Front Biosci (Landmark Ed). 27: 180 (2022) https://doi.org/10.31083/j.fbl2706180
  76. Shaw ML. The next wave of influenza drugs. ACS Infect. Dis. 3: 691-694 (2017) https://doi.org/10.1021/acsinfecdis.7b00142
  77. Shin M, Park M, Youn M, Lee Y, Nam M, Park I, Jeong Y. Effects of silk protein hydrolysates on blood glucose and serum lipid in db/db diabetic mice. J. Korean Soc. Food Sci. Nutr. 35: 1343-1348 (2006) https://doi.org/10.3746/jkfn.2006.35.10.1343
  78. Shin MS, Hwang SH, Yoon TJ, Kim SH, Shin KS. Polysaccharides from ginseng leaves inhibit tumor metastasis via macrophage and NK cell activation. Int. J. Biol. Macromol. 103: 1327-1333 (2017) https://doi.org/10.1016/j.ijbiomac.2017.05.055
  79. Singhal T. A review of coronavirus disease-2019 (COVID-19). Indian J. Pediatr. 87: 281-286 (2020) https://doi.org/10.1007/s12098-020-03263-6
  80. Tomoda M, Matsumoto K, Shimizu N, Gonda R, Ohara N. Characterization of a neutral and an acidic polysaccharide having immunological activities from the root of Paeonia lactiflora. Biol. Pharm. Bull. 16: 1207-1210 (1993a) https://doi.org/10.1248/bpb.16.1207
  81. Tomoda M, Shimada K, Konno C, Sugiyama K, Hikino H. Partial structure of panaxan A, a hypoglycaemic glycan of Panax ginseng roots. Planta Med. 50: 436-438 (1984) https://doi.org/10.1055/s-2007-969758
  82. Tomoda M, Takeda K, Shimizu N, Gonda R, Ohara N, Takada K, Hirabayashi K. Characterization of two acidic polysaccharides having immunological activities from the root of Panax ginseng. Biol. Pharm. Bull. 16: 22-25 (1993b) https://doi.org/10.1248/bpb.16.22
  83. Verma AK. Cordycepin: a bioactive metabolite of Cordyceps militaris and polyadenylation inhibitor with therapeutic potential against COVID-19. J Biomol Struct Dyn. 40: 3745-3752 (2022) https://doi.org/10.1080/07391102.2020.1850352
  84. Vivier E, Malissen B. Innate and adaptive immunity: specificities and signaling hierarchies revisited. Nat. Immunol. 6: 17-21 (2005) https://doi.org/10.1038/ni1153
  85. Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, Shi Z, Hu Z, Zhong W, Xiao G. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 30: 269-271 (2020) https://doi.org/10.1038/s41422-020-0282-0
  86. Wang WX, Zhang YR, Luo SY, Zhang YS, Zhang Y, Tang C. Chlorogenic acid, a natural product as potential inhibitor of COVID-19: virtual screening experiment based on network pharmacology and molecular docking. Nat Prod Res. 36: 2580-2584 (2022) https://doi.org/10.1080/14786419.2021.1904923
  87. Yesudhas D, Srivastava A, Gromiha MM. COVID-19 outbreak: history, mechanism, transmission, structural studies and therapeutics. Infection. 49: 199-213 (2021) https://doi.org/10.1007/s15010-020-01516-2
  88. Yu JW, Wang L, Bao LD. Exploring the active compounds of traditional Mongolian medicine in intervention of novel coronavirus (COVID-19) based on molecular docking method. J Funct Foods. 71: 104016 (2020) https://doi.org/10.1016/j.jff.2020.104016
  89. Zheng S, Zheng H, Zhang R, Piao X, Hu J, Zhu Y, Wang Y. Immunomodulatory effect of ginsenoside Rb2 against cyclophosphamide-induced immunosuppression in mice. Front. Pharmacol. 13: 927087 (2022) https://doi.org/10.3389/fphar.2022.927087
  90. Zhu SJ, Pan J, Zhao B, Liang J, Ze-Yu W, Yang JJ. Comparisons on enhancing the immunity of fresh and dry Cordyceps militaris in vivo and in vitro. J. Ethnopharmacol. 149: 713-719 (2013) https://doi.org/10.1016/j.jep.2013.07.037
  91. Zhuang X, Zhang D, Qin W, Deng J, Shan H, Tao L, Li Y. A comparison on the preparation of hot water extracts from Chlorella pyrenoidosa (CPEs) and radical scavenging and macrophage activation effects of CPEs. Food Funct. 5: 3252-3260 (2014) https://doi.org/10.1039/C4FO00214H
  92. 국민건강보험공단. 건강보험정책연구원 2019년도 건강보험제도 국민인식조사 ('19.12) (2019)
  93. 식품안전나라. 건강기능식품 기능별정보. Available from: https://www.foodsafetykorea.go.kr/portal/board/board.do?menu_grp=MENU_NEW01&menu_no=2660. Accessed Jul. 27. 2022.
  94. 식품의약품안전처. 2020년도 식품 등의 생산실적 (2021)
  95. 식품의약품안전처. 건강기능식품의 기준 및 규격 고시전문 (식약처 고시 제 2022-25호, 2022.3.31) (2022)
  96. 오픈서베이. 건강관리 트렌드 리포트 2020 (2020)