NK-Life

ARABINOXYLAN & LIPOIC ACID

AN INNOVATIVE FORMULATION TO STRENGTHEN IMMUNE, ANTIRADICALIC, REGENERATING AND CONFISCATING CAPACITIES

Arabinoxylan

Arabinoxylan is a “treated” not-starchy polysaccharide vegetable food.

It has been proved to have beneficial effects on pathologies linked to life-style or to pathogenic agents, because it protects the body.

Arabinoxylans are present in Nature in Gramineae bran (Graminiae) and in a kind of rice bran (food fibres) (1,2).

Arabinoxylans are also called NSP (Not-Starchy Polysaccharides or Pectins), mainly contained in wheat (main component: rice Hemicellulose).

The following figure shows the configuration of a polymer composed of several Arabinoxylans.

Arabinoxylans are made of Alpha L-arabinofuranose residues linked as Beta branch-points (1-4) to a polymeric framework composed of D-xylopyranose chains.

Although the structural framework of Xylan is similar to the one present in Cellulose, its macromolecule does not reach the same degree of crystal-clearness and stiffness, as the presence of Arabinose reduces interaction between the chains.

When tracts of D-substituted polymeric Xylan are present, the chain becomes stiffer and loop-shaped (horseshoe-like) (2).

Beta-xylan loop-framework shows a hydrophobic cavity similar to cyclodextrins; this hydrophobic site has the capacity (like cyclodextrins) to complex other molecules.

These food fibres go through stomach and small intestine, without being completely digested, then they are partially broken down by intestinal bacteria and absorbed by large intestine.

In comparison with other fibres containing polysaccharides, which have a very high molecular weight so they are hardly absorbable and bring no therapeutic aid, Hemicellulose extracted from maize (Arabinoxylan), thanks to its low molecular weight, shows a marked cellular permeability which grants the therapeutic effect described afterwards.

Degradation and use of NSP

NSP, Not-Starchy Polysaccharides or Pectins, are degraded by specific enzymes in small intestine.

Their digestion mainly produces Xylose and Arabinose which are actively absorbed by intestinal mucous membrane.

These sugars scarcely contribute to energetic demand, for their inadequate metabolic use.

Enzymatic hydrolysis taking place in small intestine is not complete, and it can be ended in large intestine by microflora producing fat acids. Each cereal is characterized by a kind of soluble and insoluble NSP (3).

Nisshoku Arabinoxylan

Arabinoxylan is present in Nature in Gramineae bran, both soluble and insoluble in water. The second one is the main structure present in bran.

Nisshoku Arabinoxylan is made of the water-soluble part extracted from maize’s husk. Its oral and constant administration, thanks to its chemical-physical and biologic properties, grants a protective effect on human body, defending it against pathologies linked to life-style or caused by pathogenic agents (4,5).

The composition of hydrophilic preparation (Nisshoku Arabinoxylan) includes a polysaccharide extracted from maize, structured by D-xylose and bound to D-arabinose. The molecular weight of this disaccharide, according to the molecular mass, is 53kDa (4).

Micro test

Aerobic count < 3.000cfu/g

Choliforms: negative

Nutritional Value

(% of lipids, proteins, carbohydrates, vitamins, minerals, fibres)

Lipids                                      0.0%

Proteins                                   0.67%

Carbohydrates (fibres)             94.1% (77.6%)

Vitamins                                  ---

Minerals                                  1.13% (ashes)

Kcal                                        223.5

PHARMACOLOGICAL ASPECTS

Arabinoxylan

Arabinoxylan is essentially formed by two monosaccharides (Xylose and Arabinose); thanks to their low molecular weight and to the specific structural configuration they give to the molecule, they contribute only minimally to energetic needs, despite their intestinal permeability. These molecular structures go through stomach and small intestine without being completely digested, then they are partially broken down by intestinal bacteria and absorbed by large intestine. Intestinal microflora breaks down Arabinoxylan in large intestine and produces fat acids (4).

The properties described above grant the following therapeutic result. Chemical-physical and biologic properties of Arabinoxylan have a protective effect on human body, defending it against pathologies linked to life-style or caused by pathogenic agents. When orally administered, according to the specific therapeutic program we are going to show later, it has highlighted some interesting properties. The following graphs show the scientifically proved immunological effects of hydrolized Arabinoxylan extracted from maize on guinea pigs (4).

• Increase of immune activity in viral pathologies through the activation of different cytokines, like Interleukin 2 (IL-2) and Gamma Interferon (INF-●) and the cancerous necrosis factor (TNF-●) (4).

• Increase of natural killers’ activity (NK leucocytes), of macrophages and lymphocytes T and B, with inhibition of cancerous cell production (4,5,6,7).

NK cells are important because they can function more or less independently, without any special instruction given by immunological system, to recognize and attack an unknown cell. So, they form the “first line” of the defence system against viruses or ill cells.

When meeting an anomalous cell, NK cell adheres to the cellular membrane of the atypical cell, injecting cytoplasmatic granules which rapidly dissolve the attacked cell (cytotossic activity).

• Reduction of skin symptoms in atopic eczema developed in guinea-pigs (4).

These results show numerous therapeutic potentialities of Arabinoxylan: it increases NK’s activity levels, stimulates the production of IL-2 and INF-● thus activating an anti-inflammatory activity. It has been proved that Arabinoxylan can reduce skin symptoms in atopic eczema (4).

Lipoic Acid

Not long ago, Lipoic Acid (LA), or Thioctic Acid, was considered as a vitamin. Natural sources of LA are potatoes, broccoli and spinaches. The main and major source is anyway red meat and some offal (particularly heart). Even if LA does not represent really an essential constituent, since our body is able to synthesize it, it can be found in reduced quantity in it. There are some problems of bioavailability of the LA contained in food, because it is present together with Lipolysine, and they create an overall larger molecule, more difficult to be absorbed. All these remarks promote the assumption of LA as an integrator. Alpha-lipoic Acid is a relatively small molecule formed by a chain of eight atoms of Carbon and two of Sulphur situated in the final part. In the reduced form, also known as Dihydrolipoic Acid (DHLA), the atoms of Sulphur are present as free thiols (-SH), while in the oxidized form (LA), thanks to the creation of a disulphide bind (-S-S), they originate a terminal ring structure (“dithiolane ring”) (8,9). Thanks to its particular molecular structure, Alpha-lipoic Acid can both face reactions of oxidation-reduction and function as electron- or acetylic group-bearer.

For this reason, Alpha-lipoic Acid acts as a cofactor for numerous enzymes taking part to the conversion process of glucose, of fat acids and other power sources in Adenosin-triphosphate (ATP), for instance Pyruvate Dehydrogenase, Alphachetoglutarate Dehydrogenase.

This process, taking place at mitochondrial cell level, includes that complex system of reactions known as “Krebs cycle”. Availability of LA at the cellular level, increases the “trafficability” of Krebs cycle and consequently the efficiency of the whole process, too.

LIPOIC ACID’S ACTIVITY

LA and DHLA’s various functions can be summed up in the following fig. 1 and 2.

Fig. 1

Fig. 2

Lipoic Acid, for its particular structure, is readily absorbed and transported through cellular membranes, where it can act both in watery cellular compartments (cytoplasm) and in the lipidic ones (cellular membrane).

• LA is a free radical confiscator (10, 11, 12, 13, 14).

• It has a regenerating effect on other antioxidants, giving its electron to oxidized forms (then no more active) of Glutathione (Disulphide Glutathione) Vitamin C (Dehydroascorbic Acid), regenerating them at a reduced Glutathione and Ascorbic Acid.

Vitamin C reduced form, in its turn, is able to reactivate the oxidized form of Vitamin E, reducing it to Tocopherol (Active Vitamin E).

This process has a cyclic character: after giving an electron, Dihydrolipoic Acid (DHLA) comes back to the oxidized form of Lipoic Acid (LA). Since Lipoic Acid in its oxidized form has some antioxidant properties too, regenerative cycle can go on in favour of the cell. DHLA and LA form a “redox couple”, which is able to “capture” a high number of species relating to oxygen, besides other free radicals like Hydroxyl, Nitric Oxide, Peroxynitrite, Hydrogen Peroxide and Hypochlorite. LA, but not DHLA, is able to capture the dangerous singlet Oxygen; DHLA, but not LA, is able to catch the radicals Superoxide and Peroxyl-reactive Oxygen (15,16,17).

Lipoic Acid has a protective function against damages due to perfusion (circulation-ictus) and to oxidative stress like diabetes, polyneuropathies and diabetic nephropathies (18).

• Agent reducing insulin resistance

Lipoic Acid has the property to reduce insulin resistance (that is, pancreas goes on producing insulin, even without a food stimulus, for instance during long-lasting stressing situations), insulin that cannot be used peripherally, a phenomenon which is well-known for diabetes incoming and the so-called X SYNDROME (a disease always connected to insulin resistance, with hyperinsulinemia, overweight, hypertension, cataract, hypertriglyceridemia and hypercholesteremia).

Lipoic Acid intervenes in this situation, interacting with sulfidrilic groups of cellular insulin-receptors, granting a greater sensibility for this hormone that, consequently, will allow a better income of Glucose and Nutrients inside the cell, above all the muscular one, reducing glycemia. Probably this action is possible thanks to the neutralization of free radicals which damage and occupy cellular insulin receptors.

Another way to increase consumption of Glucose is through the stimulation of GLUT 1 and GLUT 4 carriers, which carry this sugar into blood inside cells, using independent ways from those of insulin itself.

• Agent reducing protein glycation

In case of high glycemia, many molecules of Glucose are available, which can react (condensation reaction) with muscular proteins, collagen, myelin, skin, nerves, connective tissue, compromising their integrity and causing an accelerated ageing and a series of pathologies recognizable in diabetic complications, with the consequent production of radical-like compounds, the so-called AGEs (Advanced Glycation End-products).

Protein glycation is a form of catabolism, as it is able to damage all tissular proteins. LA consumption reduces glycemia, and the consequent risk of this glycation and of organic harm.

• Detoxifying agent

Lipoic Acid protects liver against damages caused by mushrooms poisoning, like White Amanita and Galeriana and any other form of poisoning, besides chemiotherapy and/or radiotherapy. In all these cases, the beneficial action of Alpha-lipoic Acid is not only directed to the neutralization of toxins, but above all to the stimulation of liver’s cell reactivity. This is directly visible in the gradual normalisation of some enzymes, for instance SGPT.

LA has the same action on drugs that strain and damage liver hindering its various functions.

• Metabolism-accelerator agent

LA makes a larger quantity of Acetyl-CoA (deriving from Pyruvate) available to enter the Krebs Cycle, increasing  the production of ATP and supplying more energy to the body.

• Agent facilitating the passage from anaerobic to aerobic glycolysis, increasing the use of fat acids to produce energy and reducing the production of Lactic Acid and toxins.

• Agent improving nervous functionality

Alpha-lipoic Acid is excellent for nervous functionality, too, as it protects nerves, acting at various levels. Firstly, it limits damages caused by free radicals, preserving nerves from a dangerous degeneration. Secondly, it improves the speed of nervous communication and its functionality. Besides, Alpha-lipoic Acid has a normalizing action on nervous sensibility, consequently reducing both pain and sensorial torpidity. In the specific case of sciatica, for instance, Alpha-lipoic Acid administration seems to increase the quantity of some neurotropic substances like Y Neuropeptide in the sciatic nerve. This could substantially improve nervous functionality and reduce pain.

1)      Ordaz-Ortiz JJ, Devaux MF, Saulnier L. Classification of wheat varieties based on structural features of arabinoxylans as revealed by endoxylanase treatment of flour and grain. J Agric Food Chem. 2005; 53(21):8349-56

2)      Robert P, Marquis M, Barron C, Guillon F, Saulnier L. FT-IR investigation of cell wall polysaccharides from cereal grains. Arabinoxylan infrared assignment. J Agric Food Chem. 2005; 53(18):7014-8

3)      Hopkins MJ, Englyst HN, Macfarlane S, Furrie E, Macfarlane GT, McBain AJ. Degradation of cross-linked and non-cross-linked arabinoxylans by the intestinal microbiota in children. Appl Environ Microbiol. 2003; 69(11):6354-60

4)      Ogawa K, Takeuchi M, Nakamura N. Immunological effects of partially hydrolyzed arabinoxylan from corn husk in mice. Biosci Biotechnol Biochem. 2005 Jan;69(1):19-25.

5)      Ghoneum M, Matsuura M. Augmentation of macrophage phagocytosis by modified arabinoxylan rice bran (MGN-3/biobran. Int J Immunopathol Pharmacol. 2004; 17(3):283-92.

6)      Ghoneum M, Gollapudi S. Cancer Lett. Modified arabinoxylan rice bran (MGN-3/Biobran) sensitizes human T cell leukaemia cells to death receptor (CD95)-induced apoptosis. 2003; 201(1):41-9.

7)      McDermott C, Richards SC, Thomas PW, Montgomery J, Lewith G. A placebo-controlled, double-blind, randomized controlled trial of a natural killer cell stimulant (BioBran MGN-3) in chronic fatigue syndrome. QJM. 2006; 99(7):461-8. Epub 2006

8)      Dupre S, Spoto G, Matrese RM et al. Biosynthesis of -lipoic acid in the rat: incorporation of S- and C-labeled precursors. Arch Biochem Biophys  1980; 202: 361-365

9)      Handelman GJ, Han D, Tritscheler H, Packer L– α-Lipoic acid reduction by mammalian cells to the dithiol form and release into the culture medium. Biochem Pharmacol.  1994; 47: 1725-1730

10)  Scholich H, Murphy ME, Sies H. – Antioxidant activity of dihydrolipoate against microsomal lipid peroxidation and its dependance on a-tocopherol. Biochem Biophys Acta  1989; 1001: 256-262

11)  Suzuki YJ, Tsuchiya M, Packer L. – Thioctic acid and dihydrolipoic acid are novel antioxidants which interact with reactive oxygen species. Free Rad Res Comms  1991; 15: 255-263

12)  Scott BC, Arouma OI, Evans PJ et al. – Lipoic and dihydrolipoic acid as antioxidants: a critical evaluation. Free Rad Res Comms  1994; 20: 119-133

13)  Packer L, Witt EH, Tritscheler HJ. – Alpha-lipoic as a biological antioxidant. Free Rad Biol Med  1995, 19: 227-250

14)  Passwater RA. – Lipoic acid: the metabolic antioxidant. New Canaan, CT, Keats Publishing Inc., p. 1-47 (1995).

15)  Kagan V, Serbinova E, Packer L. Antioxidant effects of ubiquinones in microsomes and mitochondria are mediated by tocopherol recycling. Biochem Biophys Res Comm  1990; 169: 851-857

16)  Xu DP, Wells WW. – a-Lipoic acid dependent regeneration of ascorbic acid from dehydroascorbic acid in rat liver mitochondria. J Bionerg Biomembr  199628: 77-85

17)  Podda M, Tritschaler HK, Ulrich H, Packer L. – Alpha-lipoic acid supplementation prevents symptoms of vitamin E deficiency. Biochem Biophys Res Comm  1994; 204: 98-104

18)  Smith AR, Shenvi SV, Widlansky M et al. Lipoic acid as a potential therapy for chronic diseases associated with oxidative stress. Curr Med Chem.  2004. 11: 1135-1146

  italian version

I prodotti descritti non sostituiscono le terapie mediche, ma ne rappresentano un utile complemento alimentare che favorisce il ripristino delle condizioni fisiologiche dell'organismo.

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