Source of Phytochemical : Glycyrrihza glabra.

Uses / Pharmacology :

Derived from Licorice root, mono-ammonium glycyrrhizinate is a unique product that has an extremely sweet taste. MAG can be used in many products, not only to sweeten, but also to enhance the natural product flavor while saving cost on expensive ingredients. It is used to flavor tobacco for expensive cigarettes.Uses include dairy products, confections, baked goods, and beverages where sweetness or flavor enhancement is desired. It is an excellent addition to sauces such as gravy, BBQ, soy, beverages, chocolate puddings, ice cream, candies, cough syrups or cough drops and even cosmetics. Ammonium Glycyrrhizinate is an excellent foaming agent that acts as a co-emulsifier. It is also excellent in recipes that require gelling or suspension properties for a consistent feeling in the mouth or a stable cloud effect in the product.Very small quantities are required to achieve the desired results, usually a few parts per million. However, varying amounts should be evaluated in your product for best taste.MAG is up to 50 times sweeter than sucrose — and can greatly enhance an already sweetened product as a result of synergies with both natural and synthetic sweeteners. In a study conducted at the Institute of Microbiology II, University of of Cagliari, Italy. investigators have reported that the ammonium salt of glycyrrhizic acid was found to be active against viruses, while not affecting cell activity and ability to replicate. It was also reported that glycyrrhizic acid inactivates herpes simplex particles irreversibly.Numerous reports on the efficacy of glycyrrhizin (GL) in treating HIV disease have come from Japan, where GL has been used for treating ulcers, chronic liver disease and other inflammatory illnesses for many years. GL in HIV treatment is biologically-sustainable, multifactorial intervention for a complex, multifactorial disease. Mono-ammonium glycyrrizinate, the active ingredient, is a sulfated polysaccharide plant lectin. GL has numerous properties and activities in vivo. GL inhibits PKC, the enzyme system which attaches substances to CD4 receptors on immune response white blood cells. This aids in restraining the damaging immune dysregulation, immune overactivation and autoimmune components increasingly acknowledged in PWHIV. The PKC system activates free radical-driven nuclear factor kappa B (NFkB), which in turn stimulates a major transcriptional pathway that activates many (not just HIV) virally-infected cells. GL inhibits this critical disease-progressing system both directly, by inhibiting PKC, and indirectly, by dramatically reducing inflammation and free radicals/oxidative stressors, since HIV disease creates immune- generated oxidative stressors that damage and unbalance many different cell systems. This severe oxidative stressor-generated auto-toxicity further impairs cellular immunity and reduces T4 counts through premature apoptosis (pre-programmed cell death). Like other sulfated polysaccarides, it is hypothesized that GL appears to act directly by either attaching to fat-coated microorganisms or parasites, or by blocking cell receptor sites in various cell populations thereby inhibiting the penetration, uncoating, or release of viral particles. However, the exact mechanisms are yet to be elucidated. This "interference" property affects many infective agents seen in HIV disease, acting directly or indirectly upon HIV-1, HIV-2, the herpesvirus family, the hepatitis virus family, Mycobacterium tuberculosis, Staphylococcus, Salmonella, Entamoeba, Histoplasmosis, Mycobacterium avium and several other classes of parasites. With HIV itself, GL directly does four things:

1) it inhibits viral replication in chronically infected monocytes, macrophages and other cell populations;

2) it interferes with cell-to-cell and

3) virus-to-cell binding; and

4) severely limits the clumping (syncitia) of HIV-infected leukocytes.

Using SNMC/IV (Stronger Neo-Minophagen C) intravenous glychrrhizin, nine hemophiliac HIV+ asymptomatic persons given doses from 200 to 800 mg per day had no serious side effects. CD4 counts increased by 90% or more in 8 of the 9, and CD4/CD8 ratios rose from 2 to 20 points in all persons (Mori, 1989). In tests comparing antiviral activities of the nucleoside analogs AZT and DHT with GL and other sulfer-containing polysaccharides, both types of substances prevented virus-to-cell infection. However, the polysaccharides and GL prevent cell-to-cell infection while the nucleoside analogs did not (Tochikura, 1989). In an in vivo study of antioxidant properties of GL, it was found that GL blocked the increase of free radical-mediated tumor necrosis factor (TNF), which is known to lead to latent viral activations through the NFkB pathway, as well as severe wasting in some PWAs (Mashiba, 1990). Long-term oral administration of GL (12 to 24 mo.) to ten HIV+ asymptomatic persons resulted in no indication of disease progression in measuring leukocyte markers. Among the ten untreated controls, two developed AIDS and expired; one developed lymphadenopathy (Ikegami, et al., 1989). This small study suggests that GL is an effective preventive of progression to AIDS. GL has potent anti-inflammatory and antioxidant properties. It functions to reduce inflamed tissue and to normalize cell membrane permeability. It has been shown to inhibit the release of histamine, excessive cortisol, reactive oxygen species, prooxidant prostaglandin E2, leukotriene C, anions and immune-related peroxides. Glycyrrhizin dramatically reduces cancer-promoting electrophillic (highly reactive) viral peptides and subsequent immune-generated free radicals. This blocks free radical depletion of critical and scarce intracellular glutathione. GL also blocks other histological disorders resulting from chronic disease states. Excessive releases of inflammatory cytokines, TNF and acid-labile interferon are blocked. Abnormal levels of inflammatory cytokines are central factors in PWHIV's maintenance of immune dysregulation and steady state viral replication, while promoting severe oxidative stressor-generated autotoxicity with cellular immune impairment and loss. GL also has potent immunomodulatory effects: increasing neutrophillic phagocytosis and natural killer (NK) activity, interferon-gamma (IF-gamma) as well as MHC Class I H(2) cell-surface antigens which upregulates viral recognition. It modulates adrenocortical hormone activity by inhibiting hormonal deactivation in the liver, and supports immune-stressed adrenal gland functions. GL displays its formidable detoxification properties by increasing tolerance to toxins by substantially raising the LD50 value (the median lethal dose for toxic survivability). GL has been the treatment of choice for severe allergic drug reactions in Japan. In patients on sulfa drugs and other antibiotic regimens showing poor response, combination therapy with GL has aided in resolution of infections, notably TB. It is a protector of many organs-lungs, adrenals, kidneys, alimentary organs, pancreas and liver through its strong antiviral, antioxidant and anti-inflammatory activity. SNMC/IV is prepared with 0.2% monoammonium glycyrrhizinate, 0.1% > cysteine, and 2.0% glycine. Cysteine aids in enhancing liver detoxification and reducing allergic effects. Glycine prevents GL's mild aldosterone-like effect of interfering with Na+ and K+ reabsorption regulation in the kidneys. Glyceron Tablets are prepared with 25 mg of monoammonium glycyrrhizinate, 25 mg of glycine, and 25 mg of methionine, which efficiently delivers cysteine to the liver.

References:1. Ikegami, N. et al.: Clinical Evaluation of Glycyrrhizin on HIV-Infected Asymptomatic Hemophiliac Patients in Japan. Abstract submitted; V International Conference on AIDS Montreal. 1989. 2. Mashiba, H., et al.: Augments Antiproliferative Effect of Tumor Necrosis Factor (TNF, Lymphotoxin, and Glycyrrhizin in Combined Use with Diethyldicarbamate on MethA Tumor Cells In Vitro. Japan Journal of Experimental Medicine. 60(2):67-71. 1990. 3. Mori, K., et al.: Effects of Glycyrrhizin (SNMC/IV: Stronger Neo- Minophagen C) in Hemophilia Patients with HIV Infection. Tohoku Journal of Experimental Medicine. 158:25-35, 1989. .4. Tochikura, T.S., et al.: Antiviral Agents with Activity Against Human Retroviruses. Journal of Acquired Immune Deficiency Syndrome. 2:441- 447, 1989. Additional References ACT UP/NY, Treatment Alternatives Working Group: Glycyrrhizin. Published by ACT UP, 1991 5. Akamatsu, H., et al.: Mechanisms of Anti-Inflammatory Action of Glycyrrhizin: Effect of Neutrophil Functions Including Reactive Oxygen Species Generation. Planta Medica 57(2):119-121, 1991. 6. Endo, Y.: The Immunotherapy for AIDS with Glychrrhizin and/or Neurotropin. PO-B28-2141 IX International Conference on AIDS, Berlin. 1993. from Faculty of Applied Medical Sciences, Akita University, Japan. 7.Hattori, T., et al.: Preliminary Evidence for Inhibitory Effects of Glycyrrhizin on HIV Replication in Patients with AIDS. Antiviral Research. 11:255-262, 1989. 8. Hirabayashi, K., et al.: Antiviral Activities of Glycyrrhizin and its Modified Compounds Against Human Immunodeficiency Virus Type I (HIV-1) and Herpes Simplex Virus Type I (HSV-1) In Vitro. Chemical and Pharmaceutical Bulletin. 39(1):112-115. 1991. 9. Ikegami, N., et al.: Prophylactic Effect of Long-Term Oral Administration of Glychrrhizin on AIDS Development of Asymptomatic Patients. PO-825-0596 IX International Conference on AIDS, Berlin. 1993. from Clinical Research Institute, Osaka, Japan10. Ito, M., et al,: Inhibitory Effect of Glycyrhhizin on the In Vitro Infectivity and Cytopathic Activity of the Human Immunodeficiency Virus [HIV(HTLV-III/LAV)]. Antiviral Research 7:127-137, 1987. 11. ibid: Mechanism of Inhibitory Effect of Glycyrrhizin on Replication of Human Immunodeficiency Virus(HIV). Antiviral Research. 10:289-298, 1988. 12. James, J.S.: Licorice, Glycyrrhizin, and AIDS/ARC. AIDS Treatment News. San Francisco 17:1-6, 11/7/1987.13. Nakashima, H., et al.: A New Anti-Human Immunodeficiency Virus Substance, Glycyrrhizin Sulfate; Endowment of Glycyrrhizin with Reverse Transcriptase-Inhibitory Activity by Chemical Modification. Japanese Journal of Cancer Research (Gann). 78:767-771, 1987. 14. Plyasunova, O.A. et al.: Inhibition of HIV Production in Cell Cultures by Glycyrrhizic Acid Abstract PuA 6125, VIII International Conference on AIDS. Amsterdam. 1992. 15. Pokorovsky, A., et al: The Antiviral Activity of Beta-Glycyrrihizic Acid and its Derivatives Unpublished manuscript, 1992. 16. Pokorovsky, A.: Inhibiting viral activation and replication in chronically infected monocyte/macrophage cell lines. Personal Communication 1992. 17. Smith, Denny,: Glycyrrhizin: Research Still promising, Still Limited. AIDS Treatment News San Francisco; 103:2-3, 5/18/1990. 18. ibid.: Glycyrrhizin Correction and Update. AIDS Treatment News. San Francisco; 115:4, 11/23/1990.