ViraX Professional Formulation

Purpose of Product • Support the immune system • Support the body’s antiviral processes • Promote Th1 activity Use of product ViraX is a unique blend of botanicals and compounds designed to help nutritionally support antiviral activity and overall immune function. The ingredients in ViraX may help support the body’s antiviral processes as well as may help support T-helper 1 activity.

90 capsules and proliferation of neutrophils and natural killer cells, and proliferation and phagocytosis of macrophages30, as well Ingredients as increasing the cytokines IL-1, IL-6, IL-10, TNFa, and interferon30,31,32. Astragalus (Astragalus membranaceus) has been used for centuries in Traditional Chinese Medicine (TCM) for Licorice (glycyrrhiza galabra) is largely native to the its antioxidant, anti-inflammatory, and immunomodulatory Mediterranean region and contains a number of active supporting activities. Astralagus may also possess some constituents including triterpene saponins (i.e. glycyrrhizin), hepatoprotective and hypotensive properties. As an antiviral flavonoids, isoflavones and polysaccharides. Certain agent, astragalus has demonstrated the ability to reduce compounds in licorice appear to have antiviral properties, viral load and replication, or improve immunological function and have demonstrated to inhibit growth and cytopathology in HSV, HBV, CMV, and viral myocarditis.1-6 Numerous of numerous RNA and DNA viruses such as hepatitis A33,34, mechanisms for its antiviral effects have been suggested B35,36, and C37,38, coronavirus (SARS) 39, herpes40 and varicella including increased interferon production and potentiation7-9, zoster41, HIV42,43, CMV44, Epstein-Barr45, influenza46, entero increase NK cell activity10,11, activate macrophages12,13, and coxackie virus47, and others48. There are numerous increase the number or activity of T helper cells14-17, increase proposed mechanisms for the antiviral activities of licorice, lymphokine-activated killer cell activity18, and modulate and while it appears to be virus-dependent, they include cytokines towards a stronger Th1 profile19-23. immunomodulation, inhibition of virus replication, reduction of cell membrane fluidity and binding to cell, activate T Echinacea species is a perennial group of native lymphocyte proliferation, and induction of interferon 48,49. American wildflowers, indigenous to areas east of the Rocky Mountains, and is from the daisy family (Asteracea/ Maitake (Grifola frondosa) is the Japanese name for Compositae). It has a long history as an “immunostimulant” an edible mushroom used for culinary and medicinal due to the many effects it appears to have on the immune purposes, the latter largely due to its polysaccharides, system. As an antiviral agent, Echinacea has been shown perhaps most notably, the beta-glucans. Antiviral effects to be effective against herpes24,25 and infIuenza26, 27 as well of maitake may be due to multiple mechanisms including as other viruses28. Echinacea may possess mild direct direct effects, such as inhibition of viral enzymes, as well antiviral activates, by blocking cellular virus receptors26 and as indirect effects, which include immunomodulatory inhibiting hyaluronidases29, but the majority of its antiviral effects50. Such mechanisms include increased production effects appear to be indirect, by way of increasing activation of TNFa by macrophages51,52,53, increased lymphocyte

*These statements have not been evaluated by the Food and Drug Administration.This www.biogenetix.com product is not intended to diagnose, treat, cure, or prevent any disease. 54, 55, activity activation of the alternative complement pathway ViraX Supplement Facts 56,57, increasing phagocytosis and NK cell activity enhanced Serving size: 1 Capsule 58, neutrophil and monocyte function as well as increase Amount Per Serving %DV interferon-gamma, IL-12 and IL-18, while suppressing IL-4 Calories 2 and B cell activation59,60,61. Total Fat 0 Total Carbohydrate 0.5g ** Lemon Balm (Melissa officinalis) is a perennial herb Dietary Fiber 0.5g ** from the mint (Lamiacea) family, and is native to the Sugars 0g Mediterranean and southern Europe. Constituents of lemon Astragalus Extract 170mg ** balm include rosmarinic acid, caffeic acids, chlorogenic Echinacea Purpurea Extract 85mg ** acids, tannins, flavonoids, and sesquiterpenes. Compounds Licorice Extract 65mg ** from lemon balm have demonstrated activity against HIV- Ginseng Root Extract (PANAX) 25mg ** 162, herpes simplex63, as well as Newcastle disease virus, Maitake Mushroom Fruit Body 85mg ** vaccinia virus, and Semliki Forest virus64. Lemon balm Lemon Balm Extract (leaf) 85mg ** also appears to have immunomodulating effects of both the Quercetin 85mg ** cellular and humoral components of the immune system 65. † Daily Values are based on a 2,000 calorie diet. **Daily Value (DV) not established. Lemon balm’s antiviral effects are attributed to tannins66,67 Other ingredients: Gelatin Capsule (Gelatin, Purified Water), Magnesium Stearate, Silica. and polyphenols68,69,70 DOES NOT CONTAIN: Sugar, wheat, casein, gluten, soy, milk, egg, preservatives, yeast, artificial flavorings, colorings, peanuts, corn, tree nuts or fish. Quercitin is a flavonoid found in many foods including onions, berries, apples, and the Brassica family of Directions: Take 1 capsule 3 times per day, or as directed by your healthcare professional. vegetables. Quercetin is well known for its antioxidant Storage: Store in a cool, dry place away from direct sunlight. Product from unopened and anti-inflammatory properties, but has also shown to containers that have been stored under recommended conditions (55-85° F / 13-29°C) may be used for up to 24 months. have antiviral and immunomodulating abilities as well. Quercetin has been shown to be effective in reducing Warning: Consult your healthcare professional before use if pregnant, nursing, taking medications, or for any use by minors. Do not use if safety seal is broken or missing. infectivity or replication against rhinovirus71, poliovirus72,73, Keep out of reach of children. influenza74, respiratory syncytial virus75, herpes simplex and adenoviruses76, H1N177, hepatitis C78,79, and offers possible prophylaxis against Ebola infections80. Quercetin has also been shown to influence cytokine production. Specifically, quercetin appears to influence (suppress) interferon-gamma, IL-2, IL-4, IL-12 and TNF-alpha81,82,83,84,85. The preceding information has not been evaluated by the FDA, and was compiled from the scientific literature. The Ginseng (Panax ginseng) has a long history, and is well information should not be construed as a product claim to known for its adaptogenic activities and as a general tonic. diagnose, treat, reverse, cure, or prevent any particular It also has a number of immunomodulatory activities, disease, or provide any specific effect. Biogenetix, LLC. including antiviral properties. Ginseng has been shown asserts its products are solely intended to support the to be effective against multiple viruses, via numerous human body in its attempt to maintain health and balance. mechanisms, including respiratory syncytial virus86,87,88, Biogenetix, LLC’s. products are not intended to replace or rhinovirus89, influenza90,91,92,93, HIV94,95,96,97,98, herpes virus99,100, delay prescription medication. For nutritional use only. hepatitis virus101,102, and others103,104. The immunomodulatory effects of ginseng include increasing NK cell activity and antibody production105,106,107, as well as stimulating macrophages and lymphocytes108,109,110.

*These statements have not been evaluated by the Food and Drug Administration.This www.biogenetix.com product is not intended to diagnose, treat, cure, or prevent any disease. References

1. Liu, Zhao Lan, Zhi Jun Liu, Jian Ping Liu, Min Yang, and Joey 12. Jin, R., L. L. Wan, T. Mitsuishi, K. Kodama, and S. Kurashige. Kwong. 2010. “Herbal Medicines for Viral Myocarditis.” The 1994. “[Immunomodulative effects of Chinese herbs in mice treated Cochrane Database of Systematic Reviews, no. 7 (July): with anti-tumor agent cyclophosphamide].” Yakugaku Zasshi: CD003711. doi:10.1002/14651858.CD003711.pub3. Journal of the Pharmaceutical Society of Japan 114 (7): 533–38. 2. Kobayashi, H., N. Mizuno, H. Teramae, H. Kutsuna, S. Ueoku, 13. Zhang, Li-feng, Wei-dong Cheng, Man-man Gui, Xue-yan Li, and J. Onoyama, K. Yamanaka, N. Fujita, and M. Ishii. 2004. “Diet Dong-feng Wei. 2012. “[Comparative study of Radix Hedyseri and Japanese Herbal Medicine for Recalcitrant Atopic Dermatitis: as sulstitute for Radix Astragali of yupingfeng oral liquid on Efficacy and Safety.” Drugs Under Experimental and Clinical cellular immunity in immunosuppressed mice].” Zhong Yao Cai Research 30 (5–6): 197–202. = Zhongyaocai = Journal of Chinese Medicinal Materials 35 (2): 3. Wang, Shuguang, Jiyang Li, Hai Huang, Wen Gao, Changlong 269–73. Zhuang, Bo Li, Pei Zhou, and Deyun Kong. 2009. “Anti-Hepatitis B 14. Brush, Julie, Elissa Mendenhall, Alena Guggenheim, Tracy Chan, Virus Activities of Astragaloside IV Isolated from Radix Astragali.” Erin Connelly, Amala Soumyanath, Randal Buresh, Richard Barrett, Biological & Pharmaceutical Bulletin 32 (1): 132–35. and Heather Zwickey. 2006. “The Effect of Echinacea Purpurea, 4. McCulloch, Michael, Michael Broffman, Jin Gao, and John M. Astragalus Membranaceus and Glycyrrhiza Glabra on CD69 Colford. 2002. “Chinese Herbal Medicine and Interferon in the Expression and Immune Cell Activation in Humans.” Phytotherapy Treatment of Chronic Hepatitis B: A Meta-Analysis of Randomized, Research: PTR 20 (8): 687–95. doi:10.1002/ptr.1938. Controlled Trials.” American Journal of Public Health 92 (10): 15. Liu, Qing-yang, Yong-ming Yao, Shu-wen Zhang, and Zhi-yong 1619–28. Sheng. 2011. “Astragalus Polysaccharides Regulate T Cell- 5. Liu, Wen-jun, Bin Liu, Qu-lian Guo, Ying-chun Zhang, Ya-Jie Yuan, Mediated Immunity via CD11c(high)CD45RB(low) DCs in Vitro.” Xiao-dong Fu, Zheng-hua Deng, and Jiang Lin. 2004. “[Influence Journal of Ethnopharmacology 136 (3): 457–64. doi:10.1016/j. of ganciclovir and astragalus membranaceus on proliferation of jep.2010.06.041. hematopoietic progenitor cells of cord blood after cytomegalovirus 16. Wang, Run-tian, Bao-en Shan, and Qiao-xia Li. 2002. infection in vitro].” Zhonghua Er Ke Za Zhi = Chinese Journal of “[Extracorporeal experimental study on immuno-modulatory activity Pediatrics 42 (7): 490–94. of Astragalus memhranaceus extract].” Zhongguo Zhong Xi Yi Jie 6. Ma, Kun, Li-hua Sun, and Qing-hua Wang. 2003. “[Clinical study on He Za Zhi Zhongguo Zhongxiyi Jiehe Zazhi = Chinese Journal of treatment of 405 cases of irregular menstruation by tiaojing zhixue Integrated Traditional and Western Medicine 22 (6): 453–56. granules].” Zhongguo Zhong Yao Za Zhi = Zhongguo Zhongyao 17. Zhao, K. S., C. Mancini, and G. Doria. 1990. “Enhancement of the Zazhi = China Journal of Chinese Materia Medica 28 (1): 78–80. Immune Response in Mice by Astragalus Membranaceus Extracts.” 7. Kajimura, K., Y. Takagi, N. Ueba, K. Yamasaki, Y. Sakagami, H. Immunopharmacology 20 (3): 225–33. Yokoyama, and K. Yoneda. 1996. “Protective Effect of Astragali 18. Chu, D. T., J. Lepe-Zuniga, W. L. Wong, R. LaPushin, and G. M. Radix by Oral Administration against Japanese Encephalitis Virus Mavligit. 1988. “Fractionated Extract of Astragalus Membranaceus, Infection in Mice.” Biological & Pharmaceutical Bulletin 19 (9): a Chinese Medicinal Herb, Potentiates LAK Cell Cytotoxicity 1166–69. Generated by a Low Dose of Recombinant Interleukin-2.” Journal of 8. Qun, L., Q. Luo, Z. Y. Zhang, Y. C. Chen, J. B. Zhang, H. Dong, Clinical & Laboratory Immunology 26 (4): 183–87. and D. H. Lin. 1999. “Effects of Astragalus on IL-2/IL-2R System in 19. Denzler, Karen L., Robert Waters, Bertram L. Jacobs, Yvan Patients with Maintained Hemodialysis.” Clinical Nephrology 52 (5): Rochon, and Jeffrey O. Langland. 2010. “Regulation of 333–34. Inflammatory Gene Expression in PBMCs by Immunostimulatory 9. Wang, Gang, Chun-tao Liu, Zeng-li Wang, Cun-liang Yan, Feng- Botanicals.” PloS One 5 (9): e12561. doi:10.1371/journal. ming Luo, Lei Wang, and Ting-qian Li. 2006. “Effects of Astragalus pone.0012561. Membranaceus in Promoting T-Helper Cell Type 1 Polarization and 20. Mao, Su-ping, Kai-ling Cheng, and Yun-fen Zhou. 2004. Interferon-Gamma Production by up-Regulating T-Bet Expression “[Modulatory effect of Astragalus membranaceus on Th1/Th2 in Patients with Asthma.” Chinese Journal of Integrative Medicine cytokine in patients with herpes simplex keratitis].” Zhongguo 12 (4): 262–67. Zhong Xi Yi Jie He Za Zhi Zhongguo Zhongxiyi Jiehe Zazhi = 10. Zhao, X. Z. 1992. “[Effects of Astragalus membranaceus and Chinese Journal of Integrated Traditional and Western Medicine 24 Tripterygium hypoglancum on natural killer cell activity of peripheral (2): 121–23. blood mononuclear in systemic lupus erythematosus].” Zhongguo 21. Wei, Haiming, Rui Sun, Wei Xiao, Jinbo Feng, Chunyan Zhen, Zhong Xi Yi Jie He Za Zhi Zhongguo Zhongxiyi Jiehe Zazhi = Xiaoqun Xu, and Zhigang Tian. 2003. “Traditional Chinese Chinese Journal of Integrated Traditional and Western Medicine 12 Medicine Astragalus Reverses Predominance of Th2 Cytokines (11): 669–71, 645. and Their up-Stream Transcript Factors in Lung Cancer Patients.” 11. Jing, J.P.; Lin, W.F. 1983. “Preliminary study on effects of Oncology Reports 10 (5): 1507–12. mechanism of human umbilical cord blood derived interferon-a and 22. Wang, Juan, Qiu-Ye Zhang, and Yong-Xing Chen. 2009. “[Effects of Astragalus membranaceus on neutral killer toxicity.” Chin. J. of Astragalus membranaceus on cytokine secretion of peripheral Microbiol. Immunol., 3, 293–296. dendritic cells in children with Henoch-Schonlein purpura in the

*These statements have not been evaluated by the Food and Drug Administration.This www.biogenetix.com product is not intended to diagnose, treat, cure, or prevent any disease. acute phase].” Zhongguo Zhong Xi Yi Jie He Za Zhi Zhongguo A. Jouan, and R. Deloince. 1994. “Studies on Mechanism of Action Zhongxiyi Jiehe Zazhi = Chinese Journal of Integrated Traditional of Glycyrrhizin against Hepatitis A Virus Replication in Vitro.” and Western Medicine 29 (9): 794–97. Antiviral Research 23 (1): 63–76. 23. Zhao, K. W., and H. Y. Kong. 1993. “[Effect of Astragalan on 35. Sato, H., W. Goto, J. Yamamura, M. Kurokawa, S. Kageyama, T. secretion of tumor necrosis factors in human peripheral blood Takahara, A. Watanabe, and K. Shiraki. 1996. “Therapeutic Basis mononuclear cells].” Zhongguo Zhong Xi Yi Jie He Za Zhi of Glycyrrhizin on Chronic Hepatitis B.” Antiviral Research 30 (2–3): Zhongguo Zhongxiyi Jiehe Zazhi = Chinese Journal of Integrated 171–77. Traditional and Western Medicine 13 (5): 263–65, 259. 36. Takahara, T., A. Watanabe, and K. Shiraki. 1994. “Effects of 24. Binns, S. E., J. Hudson, S. Merali, and J. T. Arnason. 2002. Glycyrrhizin on Hepatitis B Surface Antigen: A Biochemical and “Antiviral Activity of Characterized Extracts from Echinacea Spp. Morphological Study.” Journal of Hepatology 21 (4): 601–9. (Heliantheae: Asteraceae) against Herpes Simplex Virus (HSV-I).” 37. Rossum, T. G. van, A. G. Vulto, W. C. Hop, J. T. Brouwer, H. G. Planta Medica 68 (9): 780–83. doi:10.1055/s-2002-34397. Niesters, and S. W. Schalm. 1999. “Intravenous Glycyrrhizin for the 25. Thompson, K. D. 1998. “Antiviral Activity of Viracea against Treatment of Chronic Hepatitis C: A Double-Blind, Randomized, Acyclovir Susceptible and Acyclovir Resistant Strains of Herpes Placebo-Controlled Phase I/II Trial.” Journal of Gastroenterology Simplex Virus.” Antiviral Research 39 (1): 55–61. and Hepatology 14 (11): 1093–99. 26. Pleschka, Stephan, Michael Stein, Roland Schoop, and James 38. Ashfaq, Usman A., Muhammad S. Masoud, Zafar Nawaz, and B. Hudson. 2009. “Anti-Viral Properties and Mode of Action Sheikh Riazuddin. 2011. “Glycyrrhizin as Antiviral Agent against of Standardized Echinacea Purpurea Extract against Highly Hepatitis C Virus.” Journal of Translational Medicine 9 (July): 112. Pathogenic Avian Influenza Virus (H5N1, H7N7) and Swine- doi:10.1186/1479-5876-9-112. Origin H1N1 (S-OIV).” Virology Journal 6 (November): 197. 39. 39. Cinatl, J., B. Morgenstern, G. Bauer, P. Chandra, H. Rabenau, doi:10.1186/1743-422X-6-197. and H. W. Doerr. 2003. “Glycyrrhizin, an Active Component of 27. Fusco, Dahlene, Xinyan Liu, Caroline Savage, Ying Taur, Liquorice Roots, and Replication of SARS-Associated Coronavirus.” Weilie Xiao, Edward Kennelly, Jianda Yuan, Barrie Cassileth, Lancet (London, England) 361 (9374): 2045–46. Mirella Salvatore, and Genovefa A. Papanicolaou. 2010. 40. Sabouri Ghannad, Masoud, Avid Mohammadi, Sohayla Safiallahy, “Echinacea Purpurea Aerial Extract Alters Course of Influenza Javad Faradmal, Mona Azizi, and Zohreh Ahmadvand. 2014. “The Infection in Mice.” Vaccine 28 (23): 3956–62. doi:10.1016/j. Effect of Aqueous Extract of Glycyrrhiza Glabra on Herpes Simplex vaccine.2010.03.047. Virus 1.” Jundishapur Journal of Microbiology 7 (7): e11616. 28. Sharma, Manju, Shawn A. Anderson, Roland Schoop, and James doi:10.5812/jjm.11616. B. Hudson. 2009. “Induction of Multiple pro-Inflammatory Cytokines 41. Baba, M., and S. Shigeta. 1987. “Antiviral Activity of Glycyrrhizin by Respiratory Viruses and Reversal by Standardized Echinacea, a against Varicella-Zoster Virus in Vitro.” Antiviral Research 7 (2): Potent Antiviral Herbal Extract.” Antiviral Research 83 (2): 165–70. 99–107. doi:10.1016/j.antiviral.2009.04.009. 42. Harada, Shinji. 2005. “The Broad Anti-Viral Agent Glycyrrhizin 29. Rousseau, Bernard, Ichiro Tateya, Xinhong Lim, Alejandro Directly Modulates the Fluidity of Plasma Membrane and HIV- Munoz-del-Rio, and Diane M. Bless. 2006. “Investigation of Anti- 1 Envelope.” The Biochemical Journal 392 (Pt 1): 191–99. Hyaluronidase Treatment on Vocal Fold Wound Healing.” Journal doi:10.1042/BJ20051069. of Voice: Official Journal of the Voice Foundation 20 (3): 443–51. 43. Hattori, T., S. Ikematsu, A. Koito, S. Matsushita, Y. Maeda, M. doi:10.1016/j.jvoice.2005.06.002. Hada, M. Fujimaki, and K. Takatsuki. 1989. “Preliminary Evidence 30. Barnes, Joanne, Linda A. Anderson, Simon Gibbons, and J. David for Inhibitory Effect of Glycyrrhizin on HIV Replication in Patients Phillipson. 2005. “Echinacea Species (Echinacea Angustifolia with AIDS.” Antiviral Research 11 (5–6): 255–61. (DC.) Hell., Echinacea Pallida (Nutt.) Nutt.,Echinacea Purpurea (L.) 44. Numazaki, K., M. Umetsu, and S. Chiba. 1994. “Effect of Moench): A Review of Their Chemistry, Pharmacology and Clinical Glycyrrhizin in Children with Liver Dysfunction Associated with Properties.” The Journal of Pharmacy and Pharmacology 57 (8): Cytomegalovirus Infection.” The Tohoku Journal of Experimental 929–54. doi:10.1211/0022357056127. Medicine 172 (2): 147–53. 31. Barrett, B. 2003. “Medicinal Properties of Echinacea: A 45. Lin, Jung Chung. 2003. “Mechanism of Action of Glycyrrhizic Acid Critical Review.” Phytomedicine: International Journal in Inhibition of Epstein-Barr Virus Replication in Vitro.” Antiviral of Phytotherapy and Phytopharmacology 10 (1): 66–86. Research 59 (1): 41–47. doi:10.1078/094471103321648692. 46. Utsunomiya, T., M. Kobayashi, R. B. Pollard, and F. Suzuki. 1997. 32. Burger, R. A., A. R. Torres, R. P. Warren, V. D. Caldwell, and B. G. “Glycyrrhizin, an Active Component of Licorice Roots, Reduces Hughes. 1997. “Echinacea-Induced Cytokine Production by Human Morbidity and Mortality of Mice Infected with Lethal Doses of Macrophages.” International Journal of Immunopharmacology 19 Influenza Virus.” Antimicrobial Agents and Chemotherapy 41 (3): (7): 371–79. 551–56. 33. Crance, J. M., E. Biziagos, J. Passagot, H. van Cuyck-Gandré, and 47. Wang, Jingjing, Xiaoqing Chen, Wei Wang, Yating Zhang, Ziying R. Deloince. 1990. “Inhibition of Hepatitis A Virus Replication in Yang, Yu Jin, Hui Ming Ge, Erguang Li, and Guang Yang. 2013. Vitro by Antiviral Compounds.” Journal of Medical Virology 31 (2): “Glycyrrhizic Acid as the Antiviral Component of Glycyrrhiza 155–60. Uralensis Fisch. against Coxsackievirus A16 and Enterovirus 71 of 34. 34. Crance, J. M., F. Lévêque, E. Biziagos, H. van Cuyck-Gandré,

*These statements have not been evaluated by the Food and Drug Administration.This www.biogenetix.com product is not intended to diagnose, treat, cure, or prevent any disease. Hand Foot and Mouth Disease.” Journal of Ethnopharmacology 147 of Maitake (Grifola Frondosa) D-Fraction on the Control of the T (1): 114–21. doi:10.1016/j.jep.2013.02.017. Lymph Node Th-1/Th-2 Proportion.” Biological & Pharmaceutical 48. Wang, Liqiang, Rui Yang, Bochuan Yuan, Ying Liu, and Chunsheng Bulletin 25 (4): 536–40. Liu. 2015. “The Antiviral and Antimicrobial Activities of Licorice, a 61. Spelman, Kevin, Jj Burns, Douglas Nichols, Nasha Winters, Widely-Used Chinese Herb.” Acta Pharmaceutica Sinica B 5 (4): Steve Ottersberg, and Mark Tenborg. 2006. “Modulation of 310–15. doi:10.1016/j.apsb.2015.05.005. Cytokine Expression by Traditional Medicines: A Review of Herbal 49. Wang, Liqiang, Rui Yang, Bochuan Yuan, Ying Liu, and Chunsheng Immunomodulators.” Alternative Medicine Review: A Journal of Liu. 2015. “The Antiviral and Antimicrobial Activities of Licorice, a Clinical Therapeutic 11 (2): 128–50. Widely-Used Chinese Herb.” Acta Pharmaceutica Sinica B 5 (4): 62. Geuenich, Silvia, Christine Goffinet, Stephanie Venzke, Silke 310–15. doi:10.1016/j.apsb.2015.05.005. Nolkemper, Ingo Baumann, Peter Plinkert, Jürgen Reichling, 50. Lindequist, Ulrike, Timo H. J. Niedermeyer, and Wolf-Dieter Jülich. and Oliver T Keppler. 2008. “Aqueous Extracts from Peppermint, 2005. “The Pharmacological Potential of Mushrooms.” Evidence- Sage and Lemon Balm Leaves Display Potent Anti-HIV-1 Activity Based Complementary and Alternative Medicine 2 (3): 285–99. by Increasing the Virion Density.” Retrovirology 5 (March): 27. doi:10.1093/ecam/neh107. doi:10.1186/1742-4690-5-27. 51. Adachi, Y., M. Okazaki, N. Ohno, and T. Yadomae. 1994. 63. Cohen, R. A., L. S. Kucera, and E. C. Herrmann. 1964. “Enhancement of Cytokine Production by Macrophages Stimulated “ANTIVIRAL ACTIVITY OF MELISSA OFFICINALIS (LEMON with (1-->3)-Beta-D-Glucan, Grifolan (GRN), Isolated from Grifola BALM) EXTRACT.” Proceedings of the Society for Experimental Frondosa.” Biological & Pharmaceutical Bulletin 17 (12): 1554–60. Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.) 117 (November): 431–34. 52. Ishibashi, K., N. N. Miura, Y. Adachi, N. Ohno, and T. Yadomae. 2001. “Relationship between Solubility of Grifolan, a Fungal 64. Dimitrova, Z., B. Dimov, N. Manolova, S. Pancheva, D. Ilieva, 1,3-Beta-D-Glucan, and Production of Tumor Necrosis Factor and S. Shishkov. 1993. “Antiherpes Effect of Melissa Officinalis L. by Macrophages in Vitro.” Bioscience, Biotechnology, and Extracts.” Acta Microbiologica Bulgarica 29: 65–72. Biochemistry 65 (9): 1993–2000. doi:10.1271/bbb.65.1993. 65. Drozd, Janina, and Elzbieta Anuszewska. 2003. “The Effect of the 53. Okazaki, M., Y. Adachi, N. Ohno, and T. Yadomae. 1995. Melissa Officinalis Extract on Immune Response in Mice.” Acta “Structure-Activity Relationship of (1-->3)-Beta-D-Glucans in the Poloniae Pharmaceutica 60 (6): 467–70. Induction of Cytokine Production from Macrophages, in Vitro.” 66. Buzzini, Pietro, Panagiotis Arapitsas, Marta Goretti, Eva Branda, Biological & Pharmaceutical Bulletin 18 (10): 1320–27. Benedetta Turchetti, Patrizia Pinelli, F. Ieri, and Annalisa Romani. 54. Kurashige, S., Y. Akuzawa, and F. Endo. 1997. “Effects 2008. “Antimicrobial and Antiviral Activity of Hydrolysable Tannins.” of Lentinus Edodes, Grifola Frondosa and Pleurotus Mini Reviews in Medicinal Chemistry 8 (12): 1179–87. Ostreatus Administration on Cancer Outbreak, and 67. Ueda, Kyoko, Ryoko Kawabata, Takashi Irie, Yoshiaki Nakai, Activities of Macrophages and Lymphocytes in Mice Yukinobu Tohya, and Takemasa Sakaguchi. 2013. “Inactivation Treated with a Carcinogen, N-Butyl-N-Butanolnitrosoamine.” of Pathogenic Viruses by Plant-Derived Tannins: Strong Effects Immunopharmacology and Immunotoxicology 19 (2): 175–83. of Extracts from Persimmon (Diospyros Kaki) on a Broad Range doi:10.3109/08923979709007657. of Viruses.” PLOS ONE 8 (1): e55343. doi:10.1371/journal. 55. Suzuki, I., K. Hashimoto, S. Oikawa, K. Sato, M. Osawa, and T. pone.0055343. Yadomae. 1989. “Antitumor and Immunomodulating Activities of 68. Catel-Ferreira, Manuella, Hédia Tnani, Claire Hellio, Pascal a Beta-Glucan Obtained from Liquid-Cultured Grifola Frondosa.” Cosette, and Laurent Lebrun. 2015. “Antiviral Effects of Chemical & Pharmaceutical Bulletin 37 (2): 410–13. Polyphenols: Development of Bio-Based Cleaning Wipes and 56. Kodama, Noriko, Kiyoshi Komuta, and Hiroaki Nanba. 2003. “Effect Filters.” Journal of Virological Methods 212 (February): 1–7. of Maitake (Grifola Frondosa) D-Fraction on the Activation of NK doi:10.1016/j.jviromet.2014.10.008. Cells in Cancer Patients.” Journal of Medicinal Food 6 (4): 371–77. 69. Sekizawa, Haruhito, Kazufumi Ikuta, Katsumi Mizuta, Seiichi doi:10.1089/109662003772519949. Takechi, and Tatsuo Suzutani. 2013. “Relationship between 57. Wu, Ming-Jiuan, Tso-Lin Cheng, Su-Yun Cheng, Tzi-Wei Lian, Lisu Polyphenol Content and Anti-Influenza Viral Effects of Berries.” Wang, and Shu-Yuan Chiou. 2006. “Immunomodulatory Properties Journal of the Science of Food and Agriculture 93 (9): 2239–41. of Grifola Frondosa in Submerged Culture.” Journal of Agricultural doi:10.1002/jsfa.6031. and Food Chemistry 54 (8): 2906–14. doi:10.1021/jf052893q. 70. Jassim, S. a. A., and M. A. Naji. 2003. “Novel Antiviral Agents: A 58. Kodama, Noriko, Kiyoshi Komuta, and Hiroaki Nanba. 2003. “Effect Medicinal Plant Perspective.” Journal of Applied Microbiology 95 of Maitake (Grifola Frondosa) D-Fraction on the Activation of NK (3): 412–27. Cells in Cancer Patients.” Journal of Medicinal Food 6 (4): 371–77. 71. Ganesan, Shyamala, Andrea N. Faris, Adam T. Comstock, doi:10.1089/109662003772519949. Qiong Wang, Suparna Nanua, Marc B. Hershenson, and Uma S. 59. Wu, Ming-Jiuan, Tso-Lin Cheng, Su-Yun Cheng, Tzi-Wei Lian, Lisu Sajjan. 2012. “Quercetin Inhibits Rhinovirus Replication in Vitro Wang, and Shu-Yuan Chiou. 2006. “Immunomodulatory Properties and in Vivo.” Antiviral Research 94 (3): 258–71. doi:10.1016/j. of Grifola Frondosa in Submerged Culture.” Journal of Agricultural antiviral.2012.03.005. and Food Chemistry 54 (8): 2906–14. doi:10.1021/jf052893q. 72. Castrillo, J L, and L Carrasco. 1987. “Action of 3-Methylquercetin 60. Inoue, Atsuyuki, Noriko Kodama, and Hiroaki Nanba. 2002. “Effect on Poliovirus RNA Replication.” Journal of Virology 61 (10): 3319–21.

*These statements have not been evaluated by the Food and Drug Administration.This www.biogenetix.com product is not intended to diagnose, treat, cure, or prevent any disease. 73. Neznanov, Nickolay, Anna Kondratova, Konstantin M. Chumakov, intimp.2008.10.021. Lubov Neznanova, Roman Kondratov, Amiya K. Banerjee, and 84. Yu, Eun Sun, Hyun Jung Min, Su Yeon An, Hee Yeon Won, Jeong Andrei V. Gudkov. 2008. “Quercetinase Pirin Makes Poliovirus Ho Hong, and Eun Sook Hwang. 2008. “Regulatory Mechanisms Replication Resistant to Flavonoid Quercetin.” DNA and Cell of IL-2 and IFNgamma Suppression by Quercetin in T Helper Biology 27 (4): 191–98. doi:10.1089/dna.2007.0682. Cells.” Biochemical Pharmacology 76 (1): 70–78. doi:10.1016/j. 74. Kim, Yunjeong, Sanjeev Narayanan, and Kyeong-Ok Chang. bcp.2008.03.020. 2010. “Inhibition of Influenza Virus Replication by Plant-Derived 85. Alice Grigore (2017). Plant Phenolic Compounds as Isoquercetin.” Antiviral Research 88 (2): 227–35. doi:10.1016/j. Immunomodulatory Agents, Phenolic Compounds - Biological antiviral.2010.08.016. Activity, Prof. Marcos Soto-Hernández (Ed.), InTech, DOI: 75. Kaul, T. N., E. Middleton, and P. L. Ogra. 1985. “Antiviral Effect of 10.5772/66112. Flavonoids on Human Viruses.” Journal of Medical Virology 15 (1): 86. Lee, Jong Seok, Min Kyoung Cho, Hye Suk Hwang, Eun-Ju 71–79. Ko, Yu-Na Lee, Young-Man Kwon, Min-Chul Kim, et al. 2014. 76. Chiang, L. C., W. Chiang, M. C. Liu, and C. C. Lin. 2003. “In Vitro “Ginseng Diminishes Lung Disease in Mice Immunized with Antiviral Activities of Caesalpinia Pulcherrima and Its Related Formalin-Inactivated Respiratory Syncytial Virus after Challenge Flavonoids.” The Journal of Antimicrobial Chemotherapy 52 (2): by Modulating Host Immune Responses.” Journal of Interferon & 194–98. doi:10.1093/jac/dkg291. Cytokine Research: The Official Journal of the International Society 77. Wan, Qiaofeng, Hao Wang, Yuan Lin, Ligang Gu, Mei Han, Zhiwei for Interferon and Cytokine Research 34 (11): 902–14. doi:10.1089/ Yang, Yanli Zhang, Rui Ma, Li Wang, and Zhisheng Wang. 2013. jir.2013.0093. “Effects of Quercetin on CDK4 mRNA and Protein Expression in 87. LEE, JONG SEOK, EUN-JU KO, HYE SUK HWANG, YU-NA LEE, A549 Cells Infected by H1N1.” Biomedical Reports 1 (5): 766–70. YOUNG-MAN KWON, MIN-CHUL KIM, and SANG-MOO KANG. doi:10.3892/br.2013.141. 2014. “Antiviral Activity of Ginseng Extract against Respiratory 78. Gonzalez, Oscar, Vanessa Fontanes, Santanu Raychaudhuri, Syncytial Virus Infection.” International Journal of Molecular Rachel Loo, Joseph Loo, Vaithilingaraja Arumugaswami, Ren Medicine 34 (1): 183–90. doi:10.3892/ijmm.2014.1750. Sun, Asim Dasgupta, and Samuel W. French. 2009. “The Heat 88. Lee, Jong Seok, Yu-Na Lee, Young-Tae Lee, Hye Suk Hwang, Shock Protein Inhibitor Quercetin Attenuates Hepatitis C Virus Ki-Hye Kim, Eun-Ju Ko, Min-Chul Kim, and Sang-Moo Kang. Production.” Hepatology (Baltimore, Md.) 50 (6). doi:10.1002/ 2015. “Ginseng Protects Against Respiratory Syncytial Virus by hep.23232. Modulating Multiple Immune Cells and Inhibiting Viral Replication.” 79. Khachatoorian, Ronik, Vaithilingaraja Arumugaswami, Santanu Nutrients 7 (2): 1021–36. doi:10.3390/nu7021021. Raychaudhuri, George K. Yeh, Eden M. Maloney, Julie Wang, 89. Song, Jae-Hyoung, Hwa-Jung Choi, Hyuk-Hwan Song, Eun-Hye Asim Dasgupta, and Samuel W. French. 2012. “Divergent Antiviral Hong, Bo-Ra Lee, Sei-Ryang Oh, Kwangman Choi, et al. 2014. Effects of Bioflavonoids on the Hepatitis C Virus Life Cycle.” “Antiviral Activity of Ginsenosides against Coxsackievirus B3, Virology 433 (2): 346–55. doi:10.1016/j.virol.2012.08.029. Enterovirus 71, and Human Rhinovirus 3.” Journal of Ginseng 80. Qiu, Xiangguo, Andrea Kroeker, Shihua He, Robert Kozak, Research 38 (3): 173–79. doi:10.1016/j.jgr.2014.04.003. Jonathan Audet, Majambu Mbikay, and Michel Chrétien. 2016. 90. Lee, Jong Seok, Hye Suk Hwang, Eun-Ju Ko, Yu-Na Lee, “Prophylactic Efficacy of Quercetin 3-β-O-D-Glucoside against Young-Man Kwon, Min-Chul Kim, and Sang-Moo Kang. 2014. Ebola Virus Infection.” Antimicrobial Agents and Chemotherapy 60 “Immunomodulatory Activity of Red Ginseng against Influenza A (9): 5182–88. doi:10.1128/AAC.00307-16. Virus Infection.” Nutrients 6 (2): 517–29. doi:10.3390/nu6020517. 81. Nair, Madhavan P., Supriya Mahajan, Jessica L. Reynolds, 91. Park, Eun Hye, Jung Yum, Keun Bon Ku, Heui Man Kim, Young Ravikumar Aalinkeel, Harikrishnan Nair, Stanley A. Schwartz, and Myong Kang, Jeong Cheol Kim, Ji An Kim, Yoo Kyung Kang, Chithan Kandaswami. 2006. “The Flavonoid Quercetin Inhibits and Sang Heui Seo. 2014. “Red Ginseng-Containing Diet Helps Proinflammatory Cytokine (Tumor Necrosis Factor Alpha) Gene to Protect Mice and Ferrets from the Lethal Infection by Highly Expression in Normal Peripheral Blood Mononuclear Cells via Pathogenic H5N1 Influenza Virus.” Journal of Ginseng Research 38 Modulation of the NF-Kappa Beta System.” Clinical and Vaccine (1): 40–46. doi:10.1016/j.jgr.2013.11.012. Immunology: CVI 13 (3): 319–28. doi:10.1128/CVI.13.3.319- 92. Yoo, Dae-Goon, Min-Chul Kim, Min-Kyung Park, Kyoung-Mi Park, 328.2006. Fu-Shi Quan, Jae-Min Song, Jae Joon Wee, et al. 2012. “Protective 82. Nair, Madhavan P. N., Chithan Kandaswami, Supriya Mahajan, Effect of Ginseng Polysaccharides on Influenza Viral Infection.” Kailash C. Chadha, Ram Chawda, Harikrishnan Nair, Niranjan PloS One 7 (3): e33678. doi:10.1371/journal.pone.0033678. Kumar, Raji E. Nair, and Stanley A. Schwartz. 2002. “The 93. Yoo, Dae-Goon, Min-Chul Kim, Min-Kyung Park, Jae-Min Song, Fu- Flavonoid, Quercetin, Differentially Regulates Th-1 (IFNgamma) Shi Quan, Kyoung-Mi Park, Young-Keol Cho, and Sang-Moo Kang. and Th-2 (IL4) Cytokine Gene Expression by Normal Peripheral 2012. “Protective Effect of Korean Red Ginseng Extract on the Blood Mononuclear Cells.” Biochimica Et Biophysica Acta 1593 (1): Infections by H1N1 and H3N2 Influenza Viruses in Mice.” Journal of 29–36. Medicinal Food 15 (10): 855–62. doi:10.1089/jmf.2012.0017. 83. Park, Hee-ju, Chang-Min Lee, In Duk Jung, Jun Sik Lee, Young-il 94. Cho, Y. K., H. Sung, H. J. Lee, C. H. Joo, and G. J. Cho. 2001. Jeong, Jeong Hyun Chang, Sung-Hak Chun, et al. 2009. “Quercetin “Long-Term Intake of Korean Red Ginseng in HIV-1-Infected Regulates Th1/Th2 Balance in a Murine Model of Asthma.” Patients: Development of Resistance Mutation to Zidovudine Is International Immunopharmacology 9 (3): 261–67. doi:10.1016/j. Delayed.” International Immunopharmacology 1 (7): 1295–1305.

*These statements have not been evaluated by the Food and Drug Administration.This www.biogenetix.com product is not intended to diagnose, treat, cure, or prevent any disease. 95. Cho, Young Keol, Heungsup Sung, Sun Hee Ahn, In Gyu Bae, 106. Kim, J. Y., D. R. Germolec, and M. I. Luster. 1990. “Panax Jun Hee Woo, Young Ho Won, Dae Ghon Kim, and Moon Won Ginseng as a Potential Immunomodulator: Studies in Mice.” Kang. 2002. “Frequency of Mutations Conferring Resistance Immunopharmacology and Immunotoxicology 12 (2): 257–76. to Nucleoside Reverse Transcriptase Inhibitors in Human doi:10.3109/08923979009019672. Immunodeficiency Virus Type 1-Infected Patients in Korea.” Journal 107. See, D. M., N. Broumand, L. Sahl, and J. G. Tilles. 1997. “In Vitro of Clinical Microbiology 40 (4): 1319–25. Effects of Echinacea and Ginseng on Natural Killer and Antibody- 96. Cho, Young-Keol, You-Sun Jung, Heungsup Sung, Mi-Kyung Sim, Dependent Cell Cytotoxicity in Healthy Subjects and Chronic and Yoo-Kyum Kim. 2009. “High Frequency of Gross Deletions in Fatigue Syndrome or Acquired Immunodeficiency Syndrome 5’ LTR/Gag and Nef Genes in Patients Infected with CRF02_AG of Patients.” Immunopharmacology 35 (3): 229–35. HIV Type 1 Who Survived for over 20 Years: An Association with 108. Jang, Hyo Il, and Heung Mook Shin. 2010. “Wild Panax Ginseng Korean Red Ginseng.” AIDS Research and Human Retroviruses 25 (Panax Ginseng C.A. Meyer) Protects against Methotrexate- (5): 535–41. doi:10.1089/aid.2008.0301. Induced Cell Regression by Enhancing the Immune Response 97. Sung, Heungsup, You-Sun Jung, and Young-Keol Cho. 2009. in RAW 264.7 Macrophages.” The American Journal of Chinese “Beneficial Effects of a Combination of Korean Red Ginseng and Medicine 38 (5): 949–60. doi:10.1142/S0192415X10008378. Highly Active Antiretroviral Therapy in Human Immunodeficiency 109. Liu, J., S. Wang, H. Liu, L. Yang, and G. Nan. 1995. “Stimulatory Virus Type 1-Infected Patients.” Clinical and Vaccine Immunology: Effect of Saponin from Panax Ginseng on Immune Function CVI 16 (8): 1127–31. doi:10.1128/CVI.00013-09. of Lymphocytes in the Elderly.” Mechanisms of Ageing and 98. Sung, Heungsup, Sang-Moo Kang, Moo-Song Lee, Tai Gyu Kim, Development 83 (1): 43–53. and Young-Keol Cho. 2005. “Korean Red Ginseng Slows Depletion 110. Mizuno, M., J. Yamada, H. Terai, N. Kozukue, Y. S. Lee, and H. of CD4 T Cells in Human Immunodeficiency Virus Type 1-Infected Tsuchida. 1994. “Differences in Immunomodulating Effects between Patients.” Clinical and Diagnostic Laboratory Immunology 12 (4): Wild and Cultured Panax Ginseng.” Biochemical and Biophysical 497–501. doi:10.1128/CDLI.12.4.497-501.2005. Research Communications 200 (3): 1672–78. doi:10.1006/ 99. Cho, Ara, Yoon Seok Roh, Erdenebileg Uyangaa, Surim Park, bbrc.1994.1644. Jong Won Kim, Kyu Hee Lim, Jungkee Kwon, Seong Kug Eo, Chae Woong Lim, and Bumseok Kim. 2013. “Protective Effects of Red Ginseng Extract against Vaginal Herpes Simplex Virus Infection.” Journal of Ginseng Research 37 (2): 210–18. doi:10.5142/ jgr.2013.37.210. 100. Liang, Yuan-Yuan, Bin Wang, Dong-Meng Qian, Ling Li, Zhi-Hao Wang, Ming Hu, and Xu-Xia Song. 2012. “Inhibitory Effects of Ginsenoside Rb1 on Apoptosis Caused by HSV-1 in Human Glioma Cells.” Virologica Sinica 27 (1): 19–25. doi:10.1007/s12250-012- 3220-6. 101. Kang, Li-Jung, Yeo-Jin Choi, and Seong-Gene Lee. 2013. “Stimulation of TRAF6/TAK1 Degradation and Inhibition of JNK/ AP-1 Signalling by Ginsenoside Rg3 Attenuates Hepatitis B Virus Replication.” The International Journal of Biochemistry & Cell Biology 45 (11): 2612–21. doi:10.1016/j.biocel.2013.08.016. 102. Lee, Min Hwa, Bog-Hieu Lee, Sanghyun Lee, and Changsun Choi. 2013. “Reduction of Hepatitis A Virus on FRhK-4 Cells Treated with Korean Red Ginseng Extract and Ginsenosides.” Journal of Food Science 78 (9): M1412-1415. doi:10.1111/1750-3841.12205. 103. Lee, Ji-Hye, Jin Sun Shim, Jung Sun Lee, Mi-Kyung Kim, Mi- Sook Chung, and Kyung Hyun Kim. 2006. “Pectin-like Acidic Polysaccharide from Panax Ginseng with Selective Antiadhesive Activity against Pathogenic Bacteria.” Carbohydrate Research 341 (9): 1154–63. doi:10.1016/j.carres.2006.03.032. 104. Wang, Xiaoyan, Yafeng Wang, Zhe Ren, Chuiwen Qian, Yicheng Li, Qingduan Wang, Yan Zhang, et al. 2012. “Protective Effects of 20(s)-Protopanaxtriol on Viral Myocarditis Infected by Coxsackievirus B3.” Pathobiology: Journal of Immunopathology, Molecular and Cellular Biology 79 (6): 285–89. doi:10.1159/000331229. 105. Jie, Y. H., S. Cammisuli, and M. Baggiolini. 1984. “Immunomodulatory Effects of Panax Ginseng C.A. Meyer in the Mouse.” Agents and Actions 15 (3–4): 386–91.

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