ImmunityUP
Viruses mutate at a much faster pace than their hosts. This is particularly true for RNA viruses such as influenza viruses and corona-viruses. It poses as a seemingly indomitable challenge for drug and vaccine makers.
On the other hand, some, if not most, of the greatest medicines in human history came from nature --- aspirin, morphine, quinine, penicillin, metformin, artemisinin, the list goes on. Many of them are anti-infectives (which include anti-bacterials, antibiotics, anti-fungals, anti-protozoals, and anti-virals). Over the long history of traditional Chinese medicine (TCM), it has played a crucial role in helping the Chinese to overcome countless epidemics over the millennia, most notably during the 2002-2003 SARS epidemic. As a result, TCM was adopted from the very beginning of COVID-19 pandemic in China. National statistics showed that 91.5% of all patients used TCM.
In recent years, increasingly more scientific and clinical research data have substantiated the anti-viral power of a number of herbal products, often acting through distinct mechanisms of action, such as inducing interferons (key players of host anti-viral defense) and other enhancements of host immune function (see references below). Furthermore, biomedical researchers on COVID-19 in the past few months has yielded exciting new evidence that may explain the anti-viral power of herbal ingredients (see below).
Over the past 20 years, we have chosen concentrated extracts (standardized if available) of seven remarkable herbs to make one exceptional "cocktail", ImmunityUP, in order to synergistically boost host immune function in face of viral infection. Here's the list of reasons why it is extraordinary:
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ImmunityUP has been successfully used and continuously perfected over the last two decades in Boston area integrative healthcare clinics. It is made of concentrated/standardized extracts from seven herbs, each of which is chosen for its unique property and function, based on traditional medicine expertise and latest biomedical research. It is encapsulated and bottled for convenient usage.
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The selection and the carefully balanced proportion of these ingredients draw from the wisdom of traditional Chinese medicine, based on how they've been used in age-old formulae. Interestingly, according the latest version of "Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia" published by China's State Health Commission, herbs that we used have also been selected for recommended TCM formulae. Most importantly, we do NOT use herbs banned by the FDA, as some of those recommended formulae, such as Ma Huang and Xixin. Nor do we use possibly harmful herbs including Bing Lang, Kuan Dong Hua, and Ze Xie.
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Amazingly, in the past few months researchers have added evidence by showing that main compounds in our ingredients may:
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bind angiotensin-converting enzyme II (ACE2), in addtion to the ability to downregulate proinflammatory cytokines, inhibit the accumulation of intracellular reactive oxygen species (ROS), inhibit thrombin, inhibit the hyperproduction of airway exudates, and induce endogenous interferon (Licorice glycyrrhizin)[4].
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bind to the exact SARS-CoV-2 Spike protein interface for human ACE2 receptor binding (Orange peel hesperidin)[5].
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REFERENCES:
[4] Luo P, Liu D, Li J. Pharmacologic perspective: glycyrrhizin may be an efficacious therapeutic agent for COVID-19 [published online ahead of print, 2020 Apr 23]. Int J Antimicrob Agents. 2020;105995. doi:10.1016/j.ijantimicag.2020.105995
[5] Wu Canrong et al., Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computationalmethods, Acta Pharmaceutica Sinica B, https://doi.org/10.1016/j.apsb.2020.02.008
See below for research data around these herbs.
Licorice Extract (26% Glycyrrhizin)
The main compound glycyrrhizin (aka glycyrrhizic acid) extracted from licorice root has antiviral and antibacterial effects. Cinatl J et al. [6] compared the effects of glycyrrhizin, as compared to classic antiviral drugs ribavirin, 6-azauridine, pyrazofurin, mycophenolic acid, on SARS-CoV. The results show that glycyrrhizin is the most active in inhibiting replication of the SARS-associated coronavirus. Research from Hoever G et al. [7] also shows that glycyrrhizin and some of its derivatives have good anti-SARS-CoV effect. As we know, SARS-CoV-2 and SARS-CoV are similar and their encoded proteins are 95% - 100% homologous. In another study, glycyrrhizin is shown to promote T cell production of IFN-γ [8].
Recent studies have shown that SARS-CoV-2 and SARS-CoV use the same host receptor, ACE2 (angiotensin-converting enzyme 2), and glycyrrhizic acid can bind to ACE2 [9]. Another study shows that glycyrrhizic acid has an inhibitory effect on HIV propagation [10]. Moreover, licorice contains volatile oils, among which thymol and carvacrol have significant antiviral and bactericidal effects [11]. Not surprisingly, licorice is a key ingredient in these popular TCM formulae, Huoxiang Zhengqi （藿香正气），Jinhua Qinggan（金花清感），Lianhua Qingwen（连花清瘟），Shufeng Jiedu（疏风解毒）， as well as Gancao Ganjiang Tang（甘草干姜汤）.
REFERENCES:
[6] Cinatl J,Rabenau H,Morgenstern B,et al. Glycyrrhizin,an active component of liquorice roots,and replication of SARS-associated coronavirus[J]. Lancet, 2003,361(9374):2045-2046.
[7] Hoever G,Baltina L,Michaelis M,et al. Antiviral activity of glycyrrhizic acid derivatives against SARS-coronavirus[J]. J Med Chem,2005,48(4):1256-1259.
[8] Utsunomiya T,Kobayashi M,Pollard RB,et al. Glycyrrhizin, an active component of licorice roots, reduces morbidity and mortality of mice infected with lethal doses of influenza virus[J]. Antimicrob Agents Chemother,1997,41(3):551-556.
[9] Chen HS,Du QH. Potential natural compounds for preventing 2019-nCoV infection [J/OL]. Preprints,2020,1-13.
[10] Sasaki H,Takei M,Kobayashi M,et al. Effect of glycyrrhizin, an active component of licorice roots, on HIV replication in cultures of peripheral blood mono-nuclear cells from HIV-seropositive patients [J ]. Pathobiology,2002,70(4):229-236.
[11] Farag MA,Wessjohann LA. Volatiles profiling in medicinal licorice roots using steam distillation and solid-phase microextraction (SPME )coupled to chemometrics[J ]. J Food Sci,2012,77 (11): 1179-1184.
Astragalus Extract
Astragalus membranaceus is a well studied herb, and the polysaccharides and saponins contained in astragalus are the main components for its immune-promoting function [60]. One of the functions of the probiotic lactobacillus is to induce the production of IFN-β, and the extract of astragalus membranaceus can facilitate this process and enhance the effect of IFN -β[61]. A study on asthma patients show that astragalus significantly increases IFN-β and also has anti-inflammatory effects [62].
Cytokines IL-4 and IL-10 are important for immune defense against avian influenza virus infection; and astragalus extract can inhibit avian influenza virus H9N2 AIV, significantly increasing the levels of IL-2, IL-4 and IL-10 [63]. It is important to note that astragalus extract modulates immune function without inducing inflammation [64].
REFERENCES
[60] Denzler K,Moore K,Harrington H,et al. Characterization of the physiological response following in vivo administration of astragalus membranaceus[J]. Evid-Based Compl Alt,2016 :6861078.
[61] Frokiaer H,Henningsen L,Metzdorff SB,et al. Astragalus root and elderberry fruit extracts enhance the IFN-γ stimulatory effects of Lactobacillus acidophilus in murine-derived dendritic cells [J]. PLoS One,2012,7(10):e47878.
[62] Nalbantsoy A,Nesil T,Yilmaz-Dilsiz O,et al. Evaluation of the immunomodulatory properties in mice and in vitro anti-inflammatory activity of cycloartane type saponins from Astragalus species [J]. J Ethnopharmcol,2012,139(2):574-581.
[63] Kallon S,Li XR,Ji J,et al. Astragalus polysaccharide enhances immunity and inhibits H9N2 avian influenza virus in vitro and in vivo [J]. J Anim Sci Biotechnol,2013,4(4):325-335.
[64] Boroujerdnia MG,Azemi ME,Hemmati AA,et al. Immunomodulatory effects of astragalus gypsicolus hydroalcoholic extract in ovalbumin-induced allergic mice model[J]. Iran J Allergy Asthma Immunol,2011,10(4):281-288.
Orange Peel Extract
Citrus fruits such as oranges have a wide range of health benefits, including anti-bacterial, anti-fungal, anti-oxidant and anti-proliferative functions. Certain bio-active compounds they contain present as excellent drug candidates for fighting a number of diseases.[1]
Of particular interest is a flavanoid enriched in the orange peel, hesperidin. It is found to be the only compound that could target the binding interface between the SARS-CoV-2 Spike protein and human ACE2 receptor in a large scale analysis of therapeutic targets for SARS-CoV-2 by screening the ZINC drug database of 2924 known drugs plus a comprehensive library of 1066 natural compounds. [ 2]
REFERENCES
[1] Juan Manuel J. Favela-Hernández,1 Omar González-Santiago,2 Mónica A. Ramírez-Cabrera,2 Patricia C. Esquivel-Ferriño,2 and María del Rayo Camacho-Corona2,*, Chemistry and Pharmacology of Citrus sinensis, Molecules. 2016 Feb; 21(2): 247.
[2]CanrongWua1YangLiub1YueyingYangb1PengZhangbWuZhongcYaliWangbQiqiWangbYangXubMingxueLibXingzhouLicMengzhuZhengaLixiaChenbHuaLiab,Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods, Acta Pharmaceutica Sinica B, Available online 27 February 2020
Coptis Extract
Berberine is a key ingredient of coptis, which is also known as goldthread and has a long history of use in ethnic medicines. In recent years it has been a focus area in herbal medicine research and has the potential to become one of the most important herbal supplements in the world.
A large body of research data has shown its effects on promoting overall wellness in many areas. A recent review by Dr. Di Pierro (see reference below) summarizes that berberine’s influence on the gut microbiome accounts for much of its health benefit, which includes promoting weight loss, lowering blood lipids and blood pressure, and improving blood sugar control. We have chosen berberine not only because of it's been a key herb for thousands of years, but also because it’s become an important part of the answer to improving health via modulating the microbiota.
REFERENCES
Impact of berberine on human gut bacteria. Di Pierro F. Nutrafoods (2018) 17:5-8.
Berberine Modulates Gut Microbiota and Reduces Insulin Resistance via the TLR4 Signaling Pathway. Liu D, Zhang Y, Liu Y, Hou L, Li S, Tian H, Zhao T. Exp Clin Endocrinol Diabetes. 2018 Sep;126(8):513-520. doi: 10.1055/s-0043-125066. Epub 2018 Jan 24.
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