Printer Friendly

Neutrophils--a potent source of immune enhancement.


Neutrophils, one of the three types of granulocytic white blood cells (leukocytes), are the hallmark of acute inflammation. (1) They serve as key components in the defense against infection and are the most abundant of white blood cells, accounting for ~60% of all leukocytes. They are primarily associated with acute bacterial inflammation, and their reaction time is immediate, typically within one hour of tissue injury. Neutrophils are phagocytes, capable of ingesting microorganisms or particles. Each phagocytic event results in the formation of a phagosome into which reactive oxygen species and hydrolytic enzymes are secreted. Due to the consumption of oxygen during this event, a "respiratory bust" ensues. This "respiratory bust" in turn activates the enzyme NADPH oxidase, resulting in the production of large amounts of superoxide. The superoxide anion is subsequently converted to hypochlorous acid (HOCl) via the enzyme myeloperoxidate, which is presumed to result in the elimination of the phagocytized bacteria. (2)

The other two classes of granular leukocytes are the eosinophils and basophils. Eosinophils are activated during allergic diseases, infections, or other medical conditions, and elevated levels are associated with an allergic response or parasitic infestation. They contain coarse, cytoplasmic granules of uniform size and make up 1-3% of the total circulating leukocytes. Basophils have a nuclei size similar to eosinophils, however, when activated, they degranulate and release cellular components, including histamine and proteoglycans, stored within the granules, along with proteolytic enzymes. (2) They represent approximately 0.01-0.3% of the circulating leukocytes.

Interestingly, neutrophil activity has also been correlated with coronary artery disease. Sarndahl, et al., reported a significant reduction in neutrophillic ROS production in patients with stable coronary artery disease, noting a 30% [+ or -]17 mean reduction, compared to matched controls. It was also noted that as a consequence of non-receptor mediated response, a significantly lower neutrophillic ROS production ensued (a reduction of 21% [+ or -]12). (3) A separate study also noted a reduced capacity in the ability to up-regulate CD11b cells as well as to produce [H.sub.2][O.sub.2], both functional aspects of neutrophil activation, compared to healthy controls. (4)

All leukocytes have a minimal life span, and thus a high turnover rate. As such, they are extremely vulnerable to mineral, vitamin, and antioxidant deficiencies. The complex interplay between multiple cell types and intercellular messengers makes nutritional status both subtle and far-reaching, particularly when it involves immune activation.

Minerals Associated with Neutrophil Activation Chronic low-grade type infections, associated with neutrophil influx, are characteristic of a number of disease processes, ranging from periodontal infections and asthma to cardiovascular disease, pulmonary complications, and rheumatoid arthritis. Certain minerals play important roles in supporting optimal immune function. Zinc, copper, calcium, and phosphorous are particularly important mineral participants in this role.

Zinc: As an essential cofactor for over 70 enzymes, zinc is a vital component in immunocompetence. It is particularly important for highly proliferating cells including those of the immune system. Overt signs of zinc deficiency are numerous and have been well documented. They include atrophy of the thymus, spleen, and lymph nodes; decreased or delayed hypersensitivity response and allograft rejection; lowered production of B- and T-lymphocytes; decreased natural killer cell activity; decreased phagocytosis; and dcreased thymic hormone activity. (5, 6) A deficiency in zinc results in a rapid and extensive effect on the immune system (7) including decreased function of monocytes and macrophages, decreased phagocytosis of the neutrophil granulocytes, and decreased cytotoxicity of natural killer cells. (8) Additionally, the number and activity of NK cells have shown to be dependent upon the level of serum zinc. (9) Zinc malabsorption is evidenced by poor wound healing as well as an increased susceptibility to infections. Short periods of zinc supplementation have shown to substantially improve immune defenses, particularly in children, the elderly, and individuals with certain diseases including chronic gastrointestinal disorders. (10)

Copper: Anemia and neutropenia are two known hematological manifestations of copper deficiency. The phagocytic capacity of the neutrophil is markedly modified in copper insufficiency. (11) Neurological manifestations of copper deficiency have also been observed, a typical presentation being myelopathy. (12) Deficiencies in copper, in conjunction with other vitamin and mineral deficiencies, have been correlated with a loss of thymic cellularity, which results in a diminished differentiation of T-lymphocytes. Subsequently, a maturational defect in T-lymphocytes ensues, observed by a decrease in both total T-cells (T3 and rosette-forming T-cells), and in T4 helper/inducer cells. In mice deficient in copper, iron, and zinc, cytotoxic T-lymphocyte (CTL) activity is impaired. In vitro studies have also reported a reduced number and function of T-cells with experimental deficiencies in copper, zinc, iron, vitamin E, and vitamin A. (13)

Calcium: Calcium mobilization plays a critical role in the activation of cytokine gene expression in helper T-cells, as it is an integral part of calcineurin, the calcium-dependent phosphatase, which is essential for the activation of cytokine gene expression in helper T-cells. Calcineurin activation is required for lytic granule exocytosis in cytotoxic T-lymphocytes. (14) Intracellular calcium signals ([Ca.sup.2+]) also play an essential role in the signaling of Interleukin-8 (IL-8), which is an important constituent in neutrophil activation. (15)

Phosphorous: Cellular phosphorous is closely linked to calcium, typically referenced as being between the ratio of 1:2 and 2:1, calcium to phosphorous. Phosphorous is an essential constituent of nucleic acids, ATP, and phospholipids. Studies have demonstrated an association of the phospholipid phosphatidylinositol with the activated neutrophil. (16) In animal studies the effect of dietary phosphorous on inflammation has also been demonstrated. As an example, in a study with pigs, the effect on cellular and humoral immune response was assessed when associated with an inflammatory challenge. A linear increase in the average daily gain (P<0.02) was associated with an increase in dietary phosphorous, which was correlated to enhanced cell-mediated immune response with a corresponding reduction in humoral response. (17)

Vitamins Associated with Neutrophil Activation

Vitamin A: Vitamin A provides immunosupport via its action on cellular immunity in response to challenges, as well as by means of its role in the support of mucosal cell surfaces. (18) It also aids in maintaining the integrity of lymphatic tissues and the level of antibodies, especially that of secretory IgA. Antibody production is effected by hypovitaminosis A, evidenced by a 55% reduction in NK cell activity (P[less than or equal to]0.05) in animals presented with an immune challenge. Vitamin A repletion restored function either partially or completely. Additionally, when spleen cells were assessed, the deficiency in vitamin A was correlated to significantly less Interferon production (P[less than or equal to]0.05), theoretically implicating a decreased immune response and an increased susceptibility to disease. (19) In pediatric patients with irritable bowel disease (IBD), low vitamin A status (<20 mcg/dL) was determined to be a common occurrence (16% of the population), which was correlated to the severity of the disease. (20) In adults with IBD, in addition to other deficiencies a 26% inadequacy in vitamin A was observed. (21) Deficiency, however, appears to be only partially alleviated by the consumption of dark green, leafy vegetables, (22) which has been correlated to a low bioavailability of vitamin A in fruits and vegetables. (23) Natural mixed carotenoids containing alpha and beta carotene, lutein, and zeaxanthin seem to be more readily absorbed and to be more effective antioxidants than synthetic (all trans) beta carotene. (24)

Vitamin C: Vitamin C is a potent water-soluble antioxidant and functions as an active electron donor and acceptor. (25) It dynamically participates in immune support as it acts as both an anti-inflammatory mediator and an immunomodulator. The neutrophil is a known concentrator of vitamin C, increasing its intracellular concentration as much as 10-fold upon activation. (26, 27) Neutrophils have also been designated as ascorbate recyclers, having the capability to enhance their intracellular vitamin C concentration as much as 30-fold in the presence of microorganisms, which was correlated to extracellular ascorbate concentration. (28) Ascorbic acid (2 g/day for 5 days) supplementation has been demonstrated to significantly increase the cellular ascorbic acid content of both granulocytes and platelets. (29) Conversely, with a deficiency in ascorbate, a defect in the clearance and apoptosis of macrophages has been observed, which was correlated to macrophage recognition inability, implicated as a "novel and important function for vitamin C in inflammatory cells." The mechanism ascribed was the upregulation of the hypoxia-inducible factor-1[alpha] (HIF-1[alpha]). (30) This mechanism has also been attributed to the depletion of ascorbate by nickel(II) and cobalt(II). (312)

Vitamin E: Vitamin E acts as a potent oxygen free-radical scavenger and has shown to be protective against injury to the gut mucosal. (32, 33) It is also the major membrane and lipid antioxidant of the body. In healthy individuals, short-term vitamin E supplementation was shown to improve immune responsiveness, as evidenced by a decrease in lipid-peroxidation products, including PGE2. (34) Supplemental vitamin E has also been associated with a reduced incidence of respiratory tract infections in the elderly, (35) and has shown to significantly reduce both the incidence and number of common colds in the elderly. (36) Animals deficient in vitamin E were shown to have a 90-fold depletion in alpha-tocopherol, which was correlated to a significant decline in antioxidants, as well as to the accumulation of lipid peroxidation products, both of which were associated with a greater incidence of inflammation. (37)

Nucleotides and Immune Activation

RNA: Nucleotides, along with their metabolites, are important to many bodily processes and have documented efficiency in optimizing function. Nucleotides are considered essential for both cell-mediated immunity and T-lymphocyte function. (38,39) The need for dietary nucleotides is particularly evident in times where there is a high physiological demand such as rapid growth, metabolic stress, recovery from a major surgery or trauma, or with inadequate liver function. (40) An adequate supply of nucleotides in the form of purines and pyrimidines, which comprise RNA and DNA, allows for rapid cell proliferation and protein synthesis. In tissue culture studies coculturing nucleotides with specific antigens were demonstrated to have an influence on both immune cell growth and cytokine secretion. (41) Other studies have indicated that cellular immunity is significantly depressed when animals are maintained on a nucleotide-free diet. (42) When reversed, a nucleotide-supplemented diet was shown to upregulate Th1 immune response via the enhancement of IL-12 production with a noted corresponding suppression of antigen-specific IgE response. This was correlated to a significantly higher production of antigen-specific interferon-[gamma] by spleen cells. (43)

Botanicals Associated with Neutrophil Activation

Maitake mushroom (Grifola frondosa): Maitake, an edible mushroom, is a source of complex carbohydrates (glucans), polysaccharides, and minerals. A standardized beta-glucan polysaccharide (beta-1,6 glucan and beta 1,3 glucan) from Maitake, termed the D-fraction, has been extensively studied. In these studies administration has demonstrated immunomodulatory effects, including enhanced humoral immunity, and increased production in nitric oxide, interleukin (IL) 10, (44) and IL-12, which resulted in enhanced cytotoxicity of NK cells. (45) Others have noted an increased NK cell activity with Maitake intake. (46) In a separate study animals given a 20% Maitake-fortified diet were observed to have an altered lipid metabolism, which was attributed to both inhibition of lipid accumulation and deterrence of lipid elevation. (47) These observations correlated with previous studies, which also noted a beneficial effect of Maitake on lipid metabolism. (48, 49) Maitake has also shown favorable outcomes in animals studies of hypertension (47, 50) and diabetes mellitus. (51-53) In one animal study administration of Maitake, along with vancomycin, resulted in macrophage activation and a 2.7-fold increase in the production of IL-1[beta]. Enhanced bactericidal activity of splenic T-cells was also observed, denoting a 2.6-fold increase in activity with Maitake intake, as compared to non-treated cells. (54) Both observations indicate Maitake's potent action on immunocompetent cells.

Chrysanthemum morifolium: Although traditionally used as a beverage component, specifically in tea, the flower portion of Chrysanthemum has documented medicinal benefits. The flower contains flavonoids, amino acids, vitamins and trace elements, as well as caffe-oylquinic acids, (55) luteolin and apigenin, the latter two being ascribed as the primary bioactive components. (56) Evidence of the beneficial attributes of Chrysanthemum morifolium (Cm) was demonstrated in one in vitro study, in which cardioprotective effects were observed in isolated rat heart following ischemia/anoxia and reperfusion/reoxygenation. Cm was shown to have a protective effect on the ventricular myocytes by virtue of its attenuation of the reduction of left ventricular pressure and coronary flow caused by ischemia/reperfusion. (57) The Chinese literature documents Cm for prevention of sore throat and promoting fever reduction when drunk as a tea. (58) The Chinese Materia Medica also indicates its effectiveness against Staphlococcus aureus, B-hemolytic Streptococcus and Shigella sonnei. (59)

Loquat (Eriobotrya japonica): In an animal study administration of Eriobotrya japonica (Ej) was demonstrated to exert a significant hypoglycemic effect, as evidenced by a lowered blood glucose level in both normal and/or alloxan-diabetic mice. (60) Ej is known to contain triterpene acids, and in a separate study the inflammatory response of experimentally induced chronic bronchitis was investigated. Animals given Ej were noted to have a significantly decreased level of inflammatory cytokines, including TNF-alpha, IL-1, NF-kB, PGE2, and leukotriene B4 {LTB(4)} expression, as compared to the control group. The investigators concluded that Ej "inhibited NF-kB activation" and "led to down-regulation of TNF-alpha, IL-1, PGE2, and LTB(4) expression" in a dose-dependent manner, (61) thus demonstrating immunosupportive properties.

Dyer's-Woad (Isatis indigotica): Isatis has noted antibacterial actions, demonstrating effectiveness against strains of staphylococci, pneumococci, and meningococci. It is also considered an effective agent against viruses including influenza. Its actions are described as antipyretic and anti-inflammatory, and it demonstrates choleretic actions. (62)

Prickley Ash (Zanthoxylum americanum): In traditional Chinese medicine, Zanthoxylum is utilized to increase blood flow and to promote the circulation of qi. (62) Its actions are considered warming and stimulating, thus benefiting circulation. (63) The native Indians of North America have long utilized it for rheumatism and toothaches (odontalgic). (64) The bark is considered an irritant and demonstrates anti-rheumatic properties. (65) Both the roots and bark have been utilized as a tonic in debilitating conditions of the stomach and digestive organs. (66)

Thyme (Thymus vulgaris): Thyme's medicinal properties are associated with its actions as a bronchial antispasmodic, an antibacterial agent, and an expectorant. The chief components of thyme are thymol (20-55%) and carvacrol, along with other minor ingredients. (67) Carvacrol has demonstrated effectiveness as both an antimicrobial (68) and an antifungal agent. (69)

Mullein (Verbascum thapsus): Verbascum's use is correlated to its effectiveness as an expectorant, in stimulating the expulsion of phlegm, and in association with reducing mucus formation. Its classical use is in the management of tracheitis and bronchitis. (64) The leaves and flowers are claimed to be anodyne, antiinflammatory, antiseptic, antispasmodic, astringent, demulcent, diuretic, emollient, expectorant, and vulnerary. (66,70-76) Extracts contain various derivates, including arabinogalactans, iridoids (catalpol derivatives), saponins (verbasosaponin), flavonoids (kaempferol, luteolin, rutin, apigenin), and phenolic acids (caffeic acid, ferulic acid). In folk medicine Verbascum has been utilized in supporting wound healing, bronchial function, and immune responses, perhaps as a function of the antioxidant activity of the flavonoids and phenolic acids. (77)

Reed Herb (Phragmites communis): Common compounds isolated from Phragmites include tricine, luteolin, chrysoeriol, rutin, and isoquercitrin. (67) The root properties are noted as being beneficial in asthma, as an aid for nausea and vomiting (antiemetic), as an aid in reducing fevers, as a cough suppressant (antitussive), as a cleansing agent, as a diuretic, as a fever reducer (febrifuge), as an aid in the prevention of stone formation (lithontripic agent), as an aid in increasing the flow of saliva (sialogogue), as a stomach toner (stomachic), and as a sedative. (78-81) It is traditionally used for diarrhea, fevers, cough, vomiting, coughs with phlegm, urinary tract infections, and food poisoning, especially from sea foods. (81, 82)

Barberry (Berberis vulgaris): Berberis is a source of vitamin C and isoquinoline alkaloids including berberine, berbamine, and oxyacanthin. It is documented to have antipyretic and cholagogue effects, (67) and the root bark has been shown to aid in normalizing blood pressure. Other properties attributed to the bark include antiseptic, astringent, cholagogue, hepatic, purgative, stomachic and tonic qualities. (66, 73, 76, 83-86) Berberine has also shown effectiveness as anti-diarrheal agent. (87, 88)

Oregon Grape Root (Mahonia aquifolium): The chemical components of Mahonia aquifolium (Ma) consist of isoquinolin and isoquinoline derivates including berberine, berbamine, and oxyacanthine. (67) The traditional use of Ma by North American Indian tribes was for the treatment of appetite loss and debility. (64) Its uses have included treating gastritis, general digestive weakness, and catarrhal problems as well as stimulating kidney and gallbladder function. (64, 82) Its immunosupportive properties have been attributed to its synergistic antibacterial, anti-inflammatory, and bile-stimulating characteristics. (89) Earlier studies demonstrated that Ma exhibited a strong ability to quench the superoxide anion radical, contrary to a strong radical scavenging ability. Recently, Ma was demonstrated to have an inhibitory effect on lipoxygenase, indicating its potential role in modulating inflammatory processes. (90)


Regulation of the neutrophil is critical for immunocompetence. A dynamic balance in neutrophillic sequestration exists, that being between the bone marrow and hepatic sequestration, (91) implicating a complex system of neutrophillic regulation. Supporting neutrophillic activation and regulation with an appropriate nutritional regimen affords a healthy immune system, particularly important in the elderly and those with compromised immune systems. Thus, support of neutrophil activation in these patients, as well as in those with cardiovascular diseases, affords reduced illness and a healthy immune system. The mentioned components serve to provide both general immune support and the support of immune response.


1) McWilliam A, et al. "Rapid dendritic cell recruitment is a hallmark of the acute inflammatory response at mucosal surfaces." J Exp Me; 179(4): 1331-1336.


3) Sarndahl E, Bergstrom I, et al. "Neutrophil activation status in stable coronary artery disease." PLoS ONE, 2007; 2(10: e1056 doi:10.1371/journal.pone.0001056.

4) Paulsson J, Dadfar E, et al. "Activation of peripheral and in vivo transmigrated neutrophils in patients with stable coronary artery disease." Atherosclerosis, 2007; 192(2):328-34. Epub Sep 11, 2006.

5) Mathur NK, et al. "AIDS, zinc deficiency & thymic hormone failure." JAMA, 1988; 259:839-840.

6) Fraker PJ and King LE. Reprogramming of the immune system during zinc deficiency. Annu Rev Nutr. 2004;24:277-98.

7) Fraker PJ, King LE, et al. "The dynamic link between the integrity of the immune system and zinc status." J Nutr, 2000; 130(5S Suppl):1399S-406S.

8) Ibs KH and Rink L. "Zinc-altered immune function." J Nutr; 133:1452S-1456S.

9) Ravaglia G, Forti P, et al. "Effect of micronutrient status on natural killer cell immune function in healthy free-living subjects aged >/=90 y." Am J Clin Nutr, 2000; 71(2):590-8.

10) Fraker PJ, King LE, et al. "The dynamic link between the integrity of the immune system and zinc status." J Nutr, 2000; 130(5S Suppl):1399S-406S.

11) Olivares M and Uauy R. "Copper as an essential nutrient." Am J Clin Nutr, 1996; 63(5):791S-6S.

12) Kumar N. "Copper deficiency myelopathy (human swayback)." Mayo Clin Proc, 2006; 81(10): 1371-84.

13) McMurray DN. "Cell-mediated immunity in nutritional deficiency." Prog Food Nutr Sci, 1984; 8(3-4):193-228.

14) Grybko MJ, Bartnik JP, et al. "Calcineurin activation is only one calcium-dependent step in cytotoxic T-lymphocyte granule exocytosis." J Biol Chem, 2007; 282(25):18009-17. Epub May 2, 2007.

15) Schorr W, Swandulla D, and Zeilhofer HU. "Mechanisms of IL-8-induced Ca2+ signaling in human neutrophil granulocytes." Eur J Immunol, 1999; 29(3):897-904.

16) Traynor-Kaplan AE, Thompson BL, et al. "Transient increase in phosphatidylinositol 3,4-bisphosphate and phosphatidylinositol trisphosphate during activation of human neutrophils." Biol Chem, 1989; 264(26): 15668-15673.

17) Kegley EB, Spears JW, and Auman SK. "Dietary phosphorus and an inflammatory challenge affect performance and immune function of weanling pigs." J Anim Sci, 2001; 79(2):413-9.

18) Bates CJ. "Vitamin A." Lancet, 1995; 345:31-34.

19) Bowman TA, Goonewardenen IM, et al. "Vitamin A deficiency decreases natural killer cell activity and interferon production in rats." J Nutr, 1990; 120(10):1264-73.

20) Bousvaros A, Zurakowski D, et al. "Vitamins A and E serum levels in children and young adults with inflammatory bowel disease: effect of disease activity." J Pediatr Gastroenterol Nutr, 1998; 26(2):129-35.

21) Vagianos K, Bector S, et al. "Nutrition assessment of patients with inflammatory bowel disease." J Parenter Enteral Nutr, 2007; 31(4):311-9.

22) De Pee S, West CE, et al. "Lack of improvement in vitamin A status with increased consumption of dark-green leafy vegetables." Lancet, 1995; 346(8967):75-81.

23) Khan NC, West CE, et al. "The contribution of plant foods to the vitamin A supply of lactating women in Vietnam: A randomized controlled trial." Am J Clin Nutr, 2007; 85(4):1112-20.

24) Gaziano JM, et al. "Discrimination in absorption or transport of beta carotene isomers after oral supplementation with either all trans or 9-cis beta carotene." Am J Clin Nutr, 1995; 61:1248-1252.

25) Padayatty SJ, Katz A, et al. "Vitamin C as an antioxidant: Evaluation of its role in disease prevention." J Am Coll Nutr, 2003; 22(1):18-35.

26) Washko P, Rotrosen D, and Levine M. "Ascorbic acid transport and accumulation in human neutrophils." J Biol Chem, 1989; 264:18996-19002.

27) Jacob RA, Pianalto FS, and Agee RE. "Cellular ascorbate depletion in healthy men." J Nutr, 1992; 122(5):1111-8.

28) Wang Y, Russo TA, et al. "Ascorbate recycling in human neutrophils: Induction by bacteria." Proc Natl Acad Sci USA, 1997; 94(25):13816-9.

29) Evans RM, Currie L, and Campbell A. "The distribution of ascorbic acid between various cellular components of blood in normal individuals, and its relation to the plasma concentration." Br J Nutr, 1982; 47:473-482.

30) Vissers MC and Wilkie RP. "Ascorbate deficiency results in impaired neutrophil apoptosis and clearance and is associated with up-regulation of hypoxia-inducible factor 1alpha." J Leukoc Biol, 2007; 81(5): 1236-44. Epub Jan 30, 2007.

31) Salnikow K, Donald SP, et al. "Depletion of intracellular ascorbate by the carcinogenic metals nickel and cobalt results in the induction of hypoxic stress." J Biol Chem, 2004; 279(39):40337-44. Epub July 22, 2004.

32) Fesharaki M, Nasimi A, et al. "Reactive oxygen metabolites and anti-oxidative defenses in aspirin-induced gastric damage in rats: Gastroprotection by vitamin E." Pathophysiology, 2006; 13(4):237-43. Epub Sep 11, 2006.

33) Sugimoto N, Yoshida N, et al. "Influence of vitamin E on gastric mucosal injury induced by Helicobacter pylori infection." Biofactors, 2006; 28(1):9-19.

34) Meydani SN, Barklund MP, et al. "Vitamin E supplementation enhances cell-mediated immunity in healthy elderly subjects." Am J Clin Nutr, 1990; 52(3):557-63.

35) Meydani SN, Leka LS, et al. "Vitamin E and respiratory tract infections in elderly nursing home residents." JAMA, 2004; 292(7):828-36.

36) Meydani SN, Han SN, and Hamer DH. "Vitamin E and respiratory infection in the elderly." Ann NY Acad Sci, 2004; 1031:214-22.

37) Shvedova AA, Kisin ER, et al. "Vitamin E deficiency enhances pulmonary inflammatory response and oxidative stress induced by single-walled carbon nanotubes in C57BL/6 mice." Toxicol Appl Pharmacol, 2007; 221(3):339-48.

38) Van Buren CT, Kulkarni AD, et al. "The influence of dietary nucleotides on cell-mediated immunity." Transplantation, 1983; 40:694-7.

39) Rudolf FB, Kulkarni AD, et al. "Role of RNA as a dietary source of pyrimidines and purines in immune function." Nutrition, 1990; 6:45-52.

40) Jyonouchi H. "Nucleotide Actions on Humoral Immune Responses." J Nutr, 1994; 124:138S-143S.

41) Holen E, Bjorge OA, and Jonsson R. "Dietary nucleotides and human immune cells. II. Modulation of PBMC growth and cytokine secretion." Nutrition, 2006; 22(1):90-6.

42) Rudolph FB, Kulkarni AD, et al. "Role of RNA as a dietary source of pyrimidines and purines in immune function." Nutrition, 1990; 6(1):45-52; discussion 59-62. Review.

43) Nagafuchi S, Hachimura S, et al. "Dietary nucleotides can up-regulate antigen-specific Thl immune responses and suppress antigen-specific IgE responses in mice." Int Arch Allergy Immunol, 2000; 122(1):33-41.

44) Kodama N, Murata Y, and Nanba H. "Administration of a polysaccharide from Grifola frondosa stimulates immune function of normal mice." J Med Food, 2004; 7(2):141-5.

45) Kodama N, Asakawa A, et al. "Enhancement of cytotoxicity of NK cells by D-Fraction, a polysaccharide from Grifola frondosa." Oncol Rep, 2005; 13(3):497-502.

46) Kodama N, Komuta K, and Nanba H. "Effect of Maitake (Grifola frondosa) D-Fraction on the activation of NK cells in cancer patients." J Med Food, 2003; 6(4):371-7.

47) Talpur NA, Echard BW, et al. "Antihypertensive and metabolic effects of whole Maitake mushroom powder and its fractions in two rat strains." Mol Cell Biochem, 2002; 237(1-2):129-36.

48) Kubo K and Nanba H. "The effect of maitake mushrooms on liver and serum lipids."Altern Ther Health Med, 1996; 2(5):62-66.

49) Kubo K and Nanba H. "anti-hyperliposis effect of maitake fruit body (Grifola frondosa). I". Biol Pharm Bull, 1997; 20(7):781-5.

50) Talpur NA, Echard BW, et al. "Antihypertensive and metabolic effects of whole Maitake mushroom powder and its fractions in two rat strains." Mol Cell Biochem, 2002; 237(1-2):129-36.

51) Kubo K, Aoki H, and Nanba H. "Anti-diabetic activity present in the fruit body of Grifola frondosa (Maitake)." Biol Phar Bull; 17(8):1106-1110.

52) Hong L, Xun M, and Wutong W. "Anti-diabetic effect of an alpha-glucan from fruit body of maitake (Grifola frondosa) on KK-Ay mice." J Pharm Pharmacol, 2007; 59(4):575-82.

53) Konno, S, Tortorelis DG, et al. "A possible hypoglycaemic effct of maitake mushroom on Type 2 diabetic patients." Diabet Med; 18(12):1010.

54) Kodama N, Yamada M, and Nanba H. "Addition of Maitake D-fraction reduces the effective dosage of vancomycin for the treatment of Listeria-infected mice." Jpn J Pharmacol, 2001; 87(4):327-32.

55) Lai JP, Lim YH, et al. "Identification and characterization of major flavonoids and caffeoylquinic acids in three Compositae plants by LC/DAD-APCI/MS." J Chromatogr B Analyt Technol Biomed Life Sci, 2007; 848(2):215-25. Epub Nov 2, 2006.

56) Chen T, Li LP, et al. "Absorption and excretion of luteolin and apigenin in rats after oral administration of Chrysanthemum morifolium extract." J Agric Food Chem, 2007: 55(2):273-7.

57) Jiang H, Xia Q, et al. "Chrysanthemum morifolium attenuated the reduction of contraction of isolated rat heart and cardiomyocytes induced by ischemia/reperfusion." Pharmazie, 2004; 59(7):565-7.


59) Bensky D and Gamble A. Chinese Herbal Medicine Materia Medica. Eastland Press, Incorporated., 1993; 44.

60) Li WL, Wu JL, et al. "Pharmacological studies on anti-hyperglycemic effect of folium eriobotryae." Am J Chin Med, 2007; 35(4):705-11.

61) Huang Y, Li J, et al. "Effect of triterpene acids of eriobotrya japonica (Thunb.) Lindl. Leaf on inflammatory cytokine and mediator induction from alveolar macrophages of chronic bronchitic rats." Inflamm Res, 2007; 56(2):76-82.

62) Huang KC. The Pharmacology of Chinese Herbs. Second edition. CRC Press LLC, 1999.


64) Chevallier A. The Encyclopedia of Medicinal Plants. Dorling Kindersley, London, 1996. ISBN 9-780751-303148.

65) Weiner MA. Earth Medicine. Earth Food. Ballantine Books, 1980. ISBN 0-449-90589-6.

66) Grieve M. A Modern Herbal. Dover Publications, 1984. ISBN 0-14-046-440-9.

67) Gruenwald J, Brendler T, and Jaenicke C. PDR for Herbal Medicines. Medical Economics Co., Inc., 2000.

68) Kisko G and Roller S. "Carvacrol and p-cymene inactivate Escherichia coli 0157:H7 in apple juice." BMC Microbiology, 2005; 5:36.

69) Chami N, Chami F, et al. "Antifungal treatment with carvacrol and eugenol of oral candidiasis in immunosuppressed rats." Braz J Infect Dis, 2004; 8(3):217-226.

70) Chiej R. Encyclopaedia of Medicinal Plants. MacDonald, 1984. ISBN 0-356-10541-5.

71) Triska. Dr. Hamlyn Encyclopaedia of Plants. Hamlyn, 1975. ISBN 0-600-33545-3

72) Lust J. The Herb Book. Bantam Books, 1983. ISBN 0-553-23827-2.

73) Uphof JC. Dictionary of Economic Plants. Weinheim, 1959.

74) De Bray L. The Wild Garden. Mayflower Books, New York, 1978.

75) Mills SY. The Dictionary of Modern Herbalism. Thorsons, Wellingborough, 1985.

76) Foster S and Duke JA. A Field Guide to Medicinal Plants: Eastern and Central North America. Houghton Mifflin Co., 1990. ISBN 0395467225.

77) Herbal Drugs and Phyto-Pharmaceuticals. Bisset NG, editor. CRC Press, Boca Raton, 1994.

78) Fogarty, JE. Barefoot Doctors Manual (Official Paramedical Manual). Anon, 1980.

79) Him-Che, Y. Handbook of Chinese Herbs and Formulas. Institute of Chinese Medicine, Los Angeles, 1985.

80) Duke JA and Ayensu ES. Medicinal Plants of China. Reference Publications, Inc., 1985. ISBN 0-917256-20-4.

81) Bown D. Encyclopaedia of Herbs and their Uses. Dorling Kindersley, London, 1995. ISBN 0-7513-020-31.

82) Moerman D. Native American Ethnobotany. Timber Press, Oregon, 1998. ISBN 0-88192-453-9.

83) Chiej R. Encyclopaedia of Medicinal Plants. MacDonald, 1984. ISBN 0-356-10541-5.

84) Launert. E. Edible and Medicinal Plants. Hamlyn, 1981. ISBN 0-600-37216-2.

85) Lust J. The Herb Book. Bantam Books, 1983. ISBN 0-553-23827-2.

86) Mills SY. The Dictionary of Modern Herbalism. Thorsons. Wellingborough, 1985.

87) Rabbani GH. "Mechanism and treatment of diarrhoea due to Vibrio cholerae and Escherichia coli: Roles of drugs and prostaglandins." Dan Med Bull, 1996;43(2):173-85. Review.

88) Rabbani GH, Butler T, et al. "Randomized controlled trial of berberine sulfate therapy for diarrhea due to enterotoxigenic Escherichia coli and Vibrio cholerae." J Infect Dis, 1987; 155(5):979-84.

89) Dattner AM. "From medical herbalism to phytotherapy in dermatology: Back to the future." Dermatol Ther, 2003; 16(2):106-13.

90) Rachova L, Oblozinsky M, et al. "Free radical scavenging activity and lipoxygenase inhibition of Mahonia aquifolium extract and isoquinoline alkaloids." J Inflamm (Lond), 2007;4(1):15 [Epub ahead of print].

91) Suratt BT, Young SK, et al. "Neutrophil maturation and activation determine anatomic site of clearance from circulation." Am J Physiol Lung Cell Mol Physiol, 2001; 281:L913-L921.

by Rachel Olivier, MS, ND, PhD
COPYRIGHT 2007 Original Internist, Inc.
No portion of this article can be reproduced without the express written permission from the copyright holder.
Copyright 2007 Gale, Cengage Learning. All rights reserved.

Article Details
Printer friendly Cite/link Email Feedback
Author:Olivier, Rachel
Publication:Original Internist
Geographic Code:1USA
Date:Dec 1, 2007
Previous Article:The dangers of magnesium deficiency in endurance athletes.
Next Article:The importance of leptin in managing patients with dysglycemia & metabolic syndrome.

Terms of use | Privacy policy | Copyright © 2019 Farlex, Inc. | Feedback | For webmasters