Larch Arabinogalactan is a Novel Immune Modulator
PETER D'ADAMO, ND
Originally published in: J. Naturopath. Med 1996 (4);32-39
This paper discusses some of the applications and characteristics of naturally occurring arabinogalactans, with a special emphasis on those arabinogalactans derived from Western Larch. The unusual immunological properties of larch arabinogalactan (wood gum, wood sugar, larch gum, "Stractan", "ARA-6") suggest it may be used in numerous, exciting future applications. Evidence of this can be seen in the medicinal chemical, pharmaceutical, and bio-technical fields where current research and development has resulted in the creation of arabinogalactan-based products with unique characteristics. Larch arabinogalactan possesses minimal toxicity and is approved for food use. (55 references, 1 illustration)
Larch arabinogalactan is composed of galactose and arabinose units in a 6:1 ratio, with a trace of uronic acid. The molecular weights of the major fractions of arabinogalactan in larch are 16,000 and 100,000. Gel chromatography indicates arabinogalactan is a single species of 19 kDa, while light scattering gave a molecular weight of 40 kDa. Glycosyl linkage analysis of arabinogalactan is consistent with a highly branched structure comprising a backbone of 1,3-linked galactopyranose connected by 1,3-glycosidic linkages, comprised of 3,4,6-,3,6-, and 3,4- as well as 3-linked residues (23). [See figure 1]
EFFECT ON IMMUNOLOGIC SYSTEMS
Natural Killer cell (NK) and Macrophage activation The receptor specificity of arabinogalactan is not well characterized. Cultures of human peripheral blood mononuclear cells as well as cultures of preseparated peripheral non-adherent cells and monocytes showed enhancement of natural killer cytotoxicity against K562 tumor cells when pretreated with larch arabinogalactan for 48-72 h. Moreover, preseparated peripheral non-adherent cells and monocytes of individual donors could exhibit various responses to arabinogalactan when cultures derived from bleedings after intervals of several months were assayed. Arabinogalactan-mediated enhancement of NK cytotoxicity was not initiated directly but was found to be governed by the cytokine network. Generally, larch arabinogalactan pretreatment induced an increased release of interferon gamma (IFN gamma), tumor necrosis factor alpha, interleukin-1 beta (IL-1 beta) and IL-6 but only IFN gamma was involved in enhancement of NK cytotoxicity (1).
A similar response has been noted for arabinogalactans isolated from Echinacea purpurea (47) This polysaccharide induced macrophages to produce tumor necrosis factor (TNF-alpha), interleukin-1 (IL-1), and interferon-beta.
Acidic arabinogalactan, a highly purified polysaccharide from plant cell cultures of Echinacea purpurea, with a molecular weight of 75,000, was effective in activating macrophages to cytotoxicity against tumor cells and microorganisms (Leishmania enriettii). This arabinogalactan did not activate B cells and did not induce T cells to produce interleukin-2, interferon-beta 2, or interferon-gamma, but it did induce a slight increase in T-cell proliferation. When injected ip, arabinogalactan stimulated macrophages. Other known immunomodulatory plants with effects known to be derived from their polysaccharide fraction include Baptisia tinctoria, Angelica acutiloba, and Thuja occidentalis. Researchers have concluded that the antigenic regions of immunoreactive arabinogalactans from all the sources, (Echinacea, Baptisia, Thuja and Larix) show structural differences (19). Initial information obtained from comparative studies indicates that larch arabinogalactan presumably interacts with a receptor that showed specificity for a NK-cytotoxicity-enhancing oligo-saccharide from Viscum album, since the action of both components was not synergistic but rather competitive (1).
Low to middle MW (5,000_50,000) arabinogalactan polysaccharrides were found to have strong immunostimulating properties with simultaneous anti-inflamatory properties, and were especially suitable as radiation protecting agents in doses as low as 20-50mg orally (47). The anti-inflamatory effects were also shown to be effective in the treatment of numerous allergies (46).
Ukonan C, a phagocytosis-activating arabinogalactan isolated from the rhizome of Curcuma longa L., was found to have reticuloendothelial system-potentiating action. Oxidation caused a decrease in or disappearance of the immunological activities (21). Sanchinan-A, a reticuloendothelial system-activating arabinogalactan has also been isolated from sanchi-ginseng (roots of Panax notoginseng) (22).
Saposhnikovan A, an acidic arabinogalactan polysaccharide isolated from the roots and rhizomes of Saposhnikovia divaricata, showed remarkable reticuloendothelial system-potentiating activity in a carbon clearance test (24).
Effects on complement
An anti-complementary polysaccharide, AR-arabinogalactan, was isolated from the roots of Angelica acutiloba Kitagawa (Japanese name = Yamato-Tohki), After incubation of serum with AR-arabinogalactan in the absence of Ca2+ ions, a cleavage of C3 in the serum was detected by immunoelectrophoresis as well as from the consumption of complement when rabbit erythrocytes were used in the assay system. A marked consumption of C4 was also observed to have occurred when serum was incubated with AR-arabinogalactan in the presence of Ca2+ ions. Collectively considered these results indicate that the mode of complement activation by AR-arabinogalactan is via both the alternative and the classical pathway (25,26).
AR-arabinogalactan is comprised of comprised one neutral and two acidic arabinogalactan units and one neutral arabinan unit). Neutral arabinogalactan showed the most potent anti-complementary activity, while both acidic arabinogalactans had simliar moderate activities, but arabinan had weak activity. Acidic arabinogalactan anti-complemenary activity is expressed mainly through the classical pathway, whereas neutral arabinogalactan had markedly increased activity through the alterative pathway (27).
Ukonan C, the reticuloendothelal actvating arabinogalactan from the rhizome of Curcuma longa L., was also found to have anti-complementary activities (21).
Arabinogalactans enhance the effectiveness of viral nucleotide analogs. Daily injections of a conjugate consisting of adenine arabinoside 5'-monophosphate (araAMP, vidarabine monophosphate) and arabinogalactan (7.9 residues araAMP per molecule arabinogalactan), at a dose of 3 mg of araAMP/kg, into woodchuck carriers of woodchuck hepatitis virus (WHV) decreased serum levels of WHV DNA. A dose of 3 mg/kg of unconjugated araAMP was ineffective, while a higher dose of araAMP (15 mg/kg, 14 days) produced a slight drop in WHV DNA. After cessation of dosing with the conjugate, serum viral DNA levels remained depressed for 42 days. In contrast, after cessation of dosing with araAMP alone, WHV DNA rapidly returned to original levels (28).
EFFECTS IN METASTATIC DISEASE
Blocking of organ-specific experimental metastasis
Metastatic disease most commonly spreads to the liver, in preference to other organ sites. This has been theorized to be the result of a reaction between the galactose-based glycocongates on the metastatic cells and a hepatic-specific lectin (e.g., the D-galactose-specific hepatic binding protein) found in liver parenchyma. Several studies have compellingly shown that arabinogalactan inhibits this reaction, thus acting as a "reverse lectin."
In one study, the effects of arabinogalactan was investigated in a syngeneic tumor-host system using a new tumor which primarily colonizes the liver upon intravenous injection. The study included systemic treatment with D-galactose and arabinogalactan as well as cell pretreatment with arabinogalactan and two other glycoconjugates. Treatment with arabinogalactan reduced the amount of liver metastases and prolonged the survival times of the animals in both studies. Host treatment was more effective than tumor cell pretreatment. This was shown to be an effect of arabinogalactan blockade of potential liver receptorsby covering of galactose-specific binding sites (29). Ths was also verified in a repeat study (30).
In a third study, the rapid clearance and uptake by the liver of tritiated alpha 1-acid (asialo)glycoprotein from the circulation of Balb/c mice was markedly delayed after preinjection of D-galactose or arabinogalactan. The preinjection (1 h) and regular application (for 3 days after tumor cell inoculation in Balb/c mice) of the receptor blocking agents D-galactose and arabinogalactan prevented the settling of sarcoma L-1 tumor in the liver completely. Other galactans, dextrans, and phosphate-buffered saline showed no effect. Therefore, when lectins were blocked with competitive-specific glycoconjugates, colonization was prevented (31).
Arabinogalactan completely prevented the settling of metastatic cells of sarcoma L-1 tumor in the liver of Balb/c mice and greatly reduced the colonization process of highly metastatic Esb lymphoma cells of the liver of DBA/2 mice. Therefore, when hepatic lectins were blocked with competitive glycoconjugates, tumor cell colonization of the liver could be prevented in two different model systems (32).
USES IN LABORATORY PRACTICE
Contamination of platelets
Contamination with plasma proteins could not be detected with use of unlabeled platelets that had been incubated with radiolabeled plasma proteins followed by washing with larch arabinogalactan ("Stractan"). The arabinogalactan washed platelets were assessed for function by using aggregometry. The response of arabinogalactan washed platelets to collagen and thrombin was identical to that of unwashed platelets. The morphology of the arabinogalactan-washed platelets indicated that degranulation had not occurred. With use of antibodies directed against the alpha granule membrane protein GMP-140 or fibrinogen, no evidence of secretion or plasma protein contamination was observed. The results indicate that this procedure is a convenient method for the separation of platelets from platelet-rich plasma, free of plasma proteins, which are suitable for bioassays, functional studies, and morphologic investigations (33).
As a carrier molecule for drug or diagnostic agents
Arabinogalactan has properties that make it suitable as a carrier for delivering diagnostic or therapeutic agents to hepatocytes via the asialoglycoprotein receptor (23). Arabinogalactan produced no adverse reactions in single intravenous dose (mouse, 5000 mg/kg) and repeat dose toxicity studies (rats, 500 mg/kg/day, 90 days) (23). The 9 kDa and 37 kDa fractions from larch arabinogalactan are apparently the best candidates for use in hepatocyte directed drug delivery (34). Larch arabinogalactan improves liver contrast enhancement, and has a significant effect on hepatic lesion detection as assessed by CNR (35).
EFFECTS ON VASCULAR PERMIABILITY
Several studies have shown larch arabingalactan to enhance vascular permiability (36). Intravenous injection of arabinogalactan together with pontamine sky-blue dye into mice increased vascular permeability and led to marked blueing of the ears. Arabinogalactan caused a rapidly progressing ear blueing (maximal coloration 20-30 min after injection). This response was suppressed by pretreating the animals with the histamine H1-antihistamines levocabastine and loratadine (37).
OCCURENCE IN MICROBIAL SYSTEMS
As a component of Mycobacteria
As previously mentioned, arabinogalactan is a structural component of the cell wall of most acid-fast bacteria, including M. Tuberculosis (3), M. Leprae (38) and M. smegmatis (39). The antitubercular drug ethambutol's mechanism of action is thought to be through the inhibition of arabinogalactan synthesis (40). During tuberculosis, exposure of monocytes to circulating factors, including arabinogalactan, may induce the suppressor activity observed in some anergic patients. In addition, TB plasma and arabinogalactan directly inhibited the phytohemagglutinin-stimulated responses of T lymphocytes. In a quantitative assay of monocyte attachment to plastic, both TB plasma and AG significantly increased monocyte adherence from basal levels, suggesting that arabinogalactans circulating alone or bound in immune complexes may account for the observed effects of TB plasma.
Similar in vivo exposure may contribute to the cell-mediated suppression of lymphocyte responses in tuberculosis (41), although it is highly unlikely that that larch arabinogalactan could produce the same effects, as particular arabinogalactan receptors are highly individualized (1,19), and much of the anergy-inducing activity of TB arabinogalactan is probably produced by its matrixing with peptidoglycan (41).
Until appropriate studies are performed, I would not recommend using arabinogalactans in an active tuberculosis patient. Nonetheless, it is intriguing to note the often observed lack of malignant disease in tubercular populations (52).
Larch arabinogalactan is also an excellent source of dietary fiber (48), and has been shown to increase the production of short-chain fatty acids (SCFA), principally butyrate. Butyrate has a particularly important role in the colon. It is the preferred substrate for energy generation by colonic epithelial cells (49) and it has also been shown that butyrate protects these cells against agents that lead to cellular differentiation (50).
In one study in vitro faecal incubation system was used to study the metabolism of complex carbohydrates by intestinal bacteria. Homogenates of human faeces were incubated anaerobically with added lactulose, pectin, arabinogalactan, and cellulose, both before and after subjects had been pre-fed each carbohydrate. Fermentation of added substrate was assessed by the production of short-chain fatty acids and suppression of net ammonia generation over 48 h of incubation.
Arabinogalactan increased the yield of SCFA and acetate in all samples at all times and butyrate concentrations exceeded propionate in all samples. Faecal homogenates incubated with cellulose showed no greater SCFA production than controls. Pectin and arabinogalactan also decreased ammonia generation, but the reductions were not significant unless subjects were pre-fed these materials; cellulose had no effect on ammonia generation (42,43). Larch arabinogalactans are easily digested by human colonic Bacteroides growing in continuous culture, yielding butyrate (44).
Arabinogalactans are useful for therapeutic treatment of infections caused by pathogenic microorganisms, particularly intestinal bacteria, such as Gram-negative types. Treatment with arabinogalactan is particularly applicable to bacterias of the Enterobacteriaceae type such as Escherichia coli bacteria, particularly those strains manifesting K88+ fimbrae. Arabinogalactans were shown to have dramatic effects on bacterial adherence (45).
Blood group activity
Some arabinogalactans appear to have blood group H activity, although this may be species specific (51).
SAFETY AND TOXICITY
Preliminary acute toxicity tests performed on albino rats have indicated that larch arabinogalactan is significantly less toxic than methyl cellulose (48). Other studies have shown that laboratory diets comprising of up to 50% larch arabinogalactan had no apparent ill-effects on animal subjects after 6 months (47).
Larch arabinogalactan is FDA approved for use in food applications as per 121.1174 and 121.1219 (Code of Federal Regulations, Title 21, 1974)and may be safely used as anemulsifier, stabilizer, binder, or bodying agent in essential oils, nonnutritive sweeteners, flavor bases,non-standard dressings, and pudding mixes. The use of Larch arabinogalactan has also been formally approved by the Canadian Governor-in-Council (Canada Gazette, Part II, Vol. 105, January 27, 1971).
It is possible that the multiplicity of biologic actions in those medicinal plants known to contain polysaccharides result from a series of "ranges" in which certain size polysaccharides produce either immune augmentation or inhibition?
In general, it may be said that "low" molecular weight polysaccharides (5,000-15,000) tend to produce more of an anti-inflamatory, anti-complementary, anti-allergy effect (25,46); whereas "high" molecular weight polysaccharides (75,000-125,000) produce more reticuloendothelial stimulation (21,24) and monocyte-enhanced natural killer cytotoxicity (1). The "mid" weight polysaccharides (15,000-50,000) seem to act in an altogether different way, enhancing carbon and other types of toxin clearance by macrophages (24). The molecular weights of the major fractions of larch arabinogalactan are 16,000 (low/mid) and 100,000 (high) which perhaps explain its peculiarly diverse actions.
Use in conjunction with other agents
In general, oxidative agents inhibit the activity of most polysaccharides (21) whilst reduction can notably enhance them (53), typically by "reducing" side chains into more antigenic forms. Thus, concurrent administration of arabinogalactans with anti-oxidants such as ascorbate may enhance their efficacy. The use of halide donors, such as potassium iodide, in conjunction with arabinogalactan and ascorbate can produce quite prodigious increases in cellular myeloperoxidase activity, as measured by a candicidal index (54). Myeloperoxidase levels are typically depressed in chronic candidasis and increased in breast cancer (55).
The reticuloendothelial-activating effects of arabinogalactan would certainly dovetail well in such a therapeutic scenario. Larch arabinogalactan has been studied for use in experimental models of metastatic disease spread to the liver, including its use in conjunction with modified citrus pectin. Both polysaccharides work in essentially the same way, that is, by inhibiting the attachment of metastatic cells to liver parenchyma by competive binding to a liver lectin, the hepatic galactose receptor.
Use in pediatric otitis media
Prophylactic use of larch arabinogalactan can decrease the frequency and severity of pediatic otitis media (54), especially in circumstances where the predominant organisms are gram negative rods (46). This may be the result of phagocytosis enhancement, improvement in opsonization, competitive binding of bacteral fimbrae, or all three.
Use in HIV
Although shown to produce only slight increases in CD4 cells, treatment of HIV disease with larch arabinogalactan can result in significant improvement in succeptibility of HIV related opportunistic infections (54). This may result from activation or enhancement of macrophage/monocyte/NK cell activity, typically the role of CD4 cells.
Use as a delivery adjunct
Because of its effects on vascularity and rate of hepatic uptake, concurrent administration of larch arabinogalactan with other therapeutic agents can be considered rational. This may apply to anti-hepatitis agents in addition to hepatoprotective drugs. The immunoaugmentive effects, anti-radiation effects and drug facilitative effects of larch arabinogalactan indicate promise as a concurrent therapy in patients undergoing conventional cancer treatment.
Use as a fiber supplement
Because of its ability to increase colonic butyrate and decrease colonic amonia concentrations, arabinogalactan may be a preferable form of fiber therapy, as the major commercial source, methyl cellulose does not do this to any significant degree (in addition to having a lower LD50!)
Copyright 1996 Peter D'Adamo. All rights reserved. Unauthorized reproduction without the express consent of the author is prohibited.
1. Hauer J Anderer FA. Mechanism of stimulation of human natural killer cytotoxicity by arabinogalactan from Larix occidentalis. Cancer Immunol Immunother (1993) 36(4):237-44
2. Roitt I. Essential Immunology. Balckwell Scientific Publications, 6th Edition
3. McNeil M Wallner SJ Hunter SW Brennan PJ. Demonstration that the galactosyl and arabinosyl residues in the cell wall arabinogalactan of Mycobacterium leprae and Mycobacterium tuberculosis are furanoid. Carbohydr Res (1987 Sep 1) 166(2):299-308
4. Rohringer R Chong J Gillespie R Harder DE Gold-conjugated arabinogalactan-protein and other lectins as ultrastructural probes for the wheat/stem rust complex. Histochemistry (1989) 91(5):383-93
5. Pennell RI Knox JP Scofield GN Selvendran RR Roberts K. A family of abundant plasma membrane-associated glycoproteins related to the arabinogalactan proteins is unique to flowering plants. J Cell Biol (1989 May) 108(5):1967-77
6. Kikuchi S Ohinata A Tsumuraya Y Hashimoto Y Kaneko Y Matsushima H. Production and characterization of antibodies to the beta-(1_>6)- galactotetraosyl group and their interaction with arabinogalactan proteins. Planta (1993) 190(4):525-35
7. Susheelamma NS Rao MV. Isolation and characterization of arabinogalactan from black gram (Phaseolus mungo). J Agric Food Chem (1978 Nov-Dec) 26 (6):1434-7
8. Chen CG Pu ZY Moritz RL Simpson RJ Bacic A Clarke AE Mau SL. Molecular cloning of a gene encoding an arabinogalactan-protein from pear (Pyrus communis) cell suspension culture. Proc Natl Acad Sci U S A (1994 Oct 25) 91(22):10305-9
9. Schindler T Bergfeld R Schopfer P. Arabinogalactan proteins in maize coleoptiles: developmental relationship to cell death during xylem differentiation but not to extension growth. Plant J (1995 Jan) 7(1):25-36
10. Baldo BA Neukom H Stone BA Uhlenbruck G. Reaction of some invertebrate and plant agglutinins and a mouse myeloma anti-galactin protein with an arabinogalactan from wheat. Aust J Biol Sci (1978) 31(2):149-160 1978
11. Fincher GB Sawyer WH Stone BA. Chemical and physical properties of an arabinogalactan-peptide from wheat endosperm. Biochem J (1974 Jun) 139 (3):535-45
12. Waters EJ Pellerin P Brillouet JM. A wine arabinogalactan-protein that reduces heat-induced wine protein haze. Biosci Biotechnol Biochem (1994 Jan) 58(1):43-8
13. Saulnier L Brillouet JM Moutounet M Herve du Penhoat C Michon V. New investigations of the structure of grape arabinogalactan-protein. Carbohydr Res (1992 Feb 7) 224:219-35
14. Schibeci A Pnjak A Fincher GB. Biosynthesis of arabinogalactan-protein in Lolium multiflorum (Italian ryegrass) endosperm cells. Subcellular distribution of galactosyltransferases. Biochem J (1984 Mar 1) 218(2):633-6
15. Pogson BJ Davies C. Characterization of a cDNA encoding the protein moiety of a putative arabinogalactan protein from Lycopersicon esculentum. Plant Mol Biol (1995 May) 28(2):347-52
16. Kind LS Nilsson B. The biological activity of a ragweed arabinogalactan. I. Galactose specificity of in vitro and in vivo effects. Immunology (1967 Nov) 13(5):477-82
17. Sakai S, et al Polysaccharides and preparations thereof. US Patent #3418311, Dec 245 1968. US Patent Office
18. Svensson, S et al. Arabinogalactans, their preparation and compositions using same. European Patent Application Pub # 0138784 A2. European Patent Office. Filing Date: 8/20/84
19. Egert D Beuscher N. Studies on antigen specifity of immunoreactive arabinogalactan proteins extracted from Baptisia tinctoria and Echinacea purpurea. Planta Med (1992 Apr) 58(2):163-5
20. Kiyohara H Cyong JC Yamada H. Relationship between structure and activity of an anti-complementary arabinogalactan from the roots of Angelica acutiloba Kitagawa. Carbohydr Res (1989 Oct 31) 193:193-200
21. Gonda R Tomoda M Ohara N Takada K. Arabinogalactan core structure and immunological activities of ukonan C, an acidic polysaccharide from the rhizome of Curcuma longa. Biol Pharm Bull (1993 Mar) 16(3):235-8
22. Odonmazig P Ebringerova A Machova E Alfoldi J. Structural and molecular properties of the arabinogalactan isolated from Mongolian larchwood (Larix dahurica L.). Carbohydr Res (1994 Jan 15) 252:317-24
23. Groman EV Enriquez PM Jung C Josephson L. Arabinogalactan for hepatic drug delivery. Bioconjug Chem (1994 Nov-Dec) 5(6):547-56
24. Shimizu N Tomoda M Gonda R Kanari M Takanashi N Takahashi N. The major pectic arabinogalactan having activity on the reticuloendothelial system from the roots and rhizomes of Saposhnikovia divaricata. Chem Pharm Bull (Tokyo) (1989 May) 37(5):1329-32
25. Yamada H Kiyohara H Cyong JC Otsuka Y. Studies on polysaccharides from Angelica acutiloba_IV. Characterization of an anti-complementary arabinogalactan from the roots of Angelica acutiloba Kitagawa. Mol Immunol (1985 Mar) 22(3):295-304
26. Kiyohara H Yamada H Cyong JC Otsuka Y. Studies on polysaccharides from Angelica acutiloba. V. Molecular aggregation and anti-complementary activity of arabinogalactan from Angelica acutiloba. J Pharmacobiodyn (1986 Apr) 9(4):339-46
27. Yamada H Kiyohara H Cyong JC Otsuka Y. Structural characterisation of an anti-complementary arabinogalactan from the roots of Angelica acutiloba Kitagawa. Carbohydr Res (1987 Feb 1) 159(2):275-91
28. Enriquez PM Jung C Josephson L Tennant BC. Conjugation of adenine arabinoside 5'-monophosphate to arabinogalactan: synthesis, characterization, and antiviral activity. Bioconjug Chem (1995 Mar-Apr) 6(2):195-202
29. Hagmar B Ryd W Skomedal H. Arabinogalactan blockade of experimental metastases to liver by murine hepatoma. Invasion Metastasis (1991) 11(6):348-55
30. Uhlenbruck G Beuth J Oette K Roszkowski W Ko HL Pulverer G. Prevention of experimental liver metastases by arabinogalactan. Naturwissenschaften (1986 Oct) 73(10):626-7 (4b2)
31. Beuth J Ko HL Oette K Pulverer G Roszkowski K Uhlenbruck G. Inhibition of liver metastasis in mice by blocking hepatocyte lectins with arabinogalactan infusions and D-galactose. J Cancer Res Clin Oncol (1987) 113(1):51-5
32. Beuth J Ko HL Schirrmacher V Uhlenbruck G Pulverer G. Inhibition of liver tumor cell colonization in two animal tumor models by lectin blocking with D-galactose or arabinogalactan. Clin Exp Metastasis (1988 Mar-Apr) 6(2):115-20
33. Hill RJ Stenberg PE Sullam PM Levin J. Use of arabinogalactan to obtain washed murine platelets free of contaminating plasma proteins and appropriate for studies of function, morphology, and thrombopoiesis. J Lab Clin Med (1988 Jan) 111(1):73-83
34. Prescott JH Enriquez P Jung C Menz E Groman E. Larch arabinogalactan for hepatic drug delivery: isolation and characterization of a 9 kDa arabinogalactan fragment. Carbohydr Res (1995 Nov 30) 278(1):113-28
35. Wisner ER Amparo EG Vera DR Brock JM Barlow TW Griffey SM Drake C Katzberg RW Arabinogalactan-coated superparamagnetic iron oxide: effect of particle size in liver MRI. J Comput Assist Tomogr (1995 Mar-Apr) 19(2):211-5
36. Kind LS Macedo-Sobrinho B Ako D. Enhanced vascular permeability induced in mice by larch arabinogalactan. Immunology (1970 Nov) 19(5):799-807
37. van Wauwe JP Goossens JG. Arabinogalactan- and dextran-induced ear inflammation in mice: differential inhibition by H1-antihistamines, 5-HT-serotonin antagonists and lipoxygenase blockers. Agents Actions (1989 Aug) 28(1-2):78-82
38. Roy A Agarwal A Ralhan R. Anti-arabinogalactan IgM/IgG ratio: a screening index for leprosy patients. Indian J Lepr (1990 Oct-Dec) 62(4):435-42
39. Gruber PR Gray GR. Isolation and analysis by the reductive-cleavage method of linkage positions and ring forms in the Mycobacterium smegmatis cell-wall arabinogalactan. Carbohydrate Res 1990 (Aug) 203(1):79-90
40. Takayama K Kilburn JO. Inhibition of synthesis of arabinogalactan by ethambutol in Mycobacterium smegmatis. Antimicrob Agents Chemother (1989 Sep) 33(9):1493-9
41. Kleinhenz ME Ellner JJ Spagnolo PJ Daniel TM. Suppression of lymphocyte responses by tuberculous plasma and mycobacterial arabinogalactan. Monocyte dependence and indomethacin reversibility. J Clin Invest (1981 Jul) 68(1):153-62
42. Vince AJ McNeil NI Wager JD Wrong OM. The effect of lactulose, pectin, arabinogalactan and cellulose on the production of organic acids and metabolism of ammonia by intestinal bacteria in a faecal incubation system. Br J Nutr (1990 Jan) 63(1):17-26
43. Englyst HN, Hay S, Macfarlane GT. Polysaccharide breakdown by mixed populations of human faecal bacteria. FEMS Microbiology Ecology (1987) 95: 163-71
44. Salyers AA Arthur R Kuritza A. Digestion of larch arabinogalactan by a strain of human colonic. Bacteroides growing in continuous culture. J Agric Food Chem (1981 May-Jun) 29(3):475-80 (10)
45. Svensson, S et al. Arabinogalactans, their preparation and compositions using same. European Patent Application Pub # 0138784 A2. European Patent Office. Filing Date: 8/20/84
46. Reith FJ. Pharmaceuticals containing lactic acid derivatives and Echinacea. Bundesrepublik Deutsches Patentamt 27 21 014 11/16/78
47. Wagner H. Low molecular weight polysaccharides from composite plants containing arabinogalactan, arabinoglucan and arabinoxylan. Bundesrepublik Deutsches Patentamt DE 3042491 7/15/82
48. Adams MF and Ettling BV. Industrial Gums, 2nd Edition: 1973, Academic Press
49. Roediger WEW. Utilization of nutrients by isolated epithelial cells of the rat colon. Gastroenterology 19892; 83; 424-29
50. Tsao D Shi Z Wong A and Kim YS. Effect of sodium butyrate on carcinoembryonic antigen production by human colonic adenocacinoma cells in culture. Cancer Res 1983; 43: 1217-1222
51. Yamamoto S Sakai I Iseki S. Purification, composition and immunochemical properties of arbinogalactan-protein H complex from Euonymus sieboldiana seeds. Immunol. Commun. 1981; 10(3): 215-36
52. Conversation with Stanley Blank, Bastyr College, 1982
53. Conversation with Hiroaki Nanba, Greenwich CT, 1994
54. D'Adamo P. Unpublished results.
55. D'Adamo P. A simple, inexpensive test to assess neutrophiil activity via a myeloperidase-mediated candicidal index. J. Naturopath Med 1990 (1) 68-71
We've combined four of our best-selling type O products into a hard to beat combination that saves you nearly 20% over purchasing these products separately.
Click to learn more
The statements made on our websites have not been evaluated by the FDA (U.S. Food & Drug Administration).
Our products and services are not intended to diagnose, cure or prevent any disease. If a condition persists, please contact your physician.
Copyright © 2015-2019, Hoop-A-Joop, LLC, Inc. All Rights Reserved. Log In