Journal of Information and Computational Science ISSN: 1548-7741
Functional Oligosaccharides: Physico-chemical Properties, Synthesis, Structures and Biological Applications
Dr. Pushpraj Singh Assistant Professor, Department of Chemistry, Govt. Girls Degree College, Chhibramau, Kannauj-209721, U.P., India Email: [email protected]
ABSTRACT
Oligosaccharides are the most biologically diverse and important carbohydrate among biological systems. Oligosaccharides of various origin like fruits, vegetables, milk, blood, bacteria, algae, fungi and higher plants have been used extensively both as food ingredients and pharmacological supplements. The non-digestible oligosaccharides have been implicated as dietary fibre, sweetener, weight controlling agent and humectant in confectioneries, bakeries and breweries. Functional oligosaccharides have been found effective in gastrointestinal normal flora proliferation and pathogen suppression, dental caries prevention, enhancement of immunity, facilitation of mineral absorption, source of anti-oxidant, antibiotic alternative, regulators of blood glucose in diabetics and serum lipids in hyperlipidemics. The enormous biological activities of oligosaccharides such as immunostimulant, anti-tumour, anti-cancer, anti-inflammatory, anti-complementary, anti-viral, anti-microbial, hypoglycemic activity, lipid lowering and regulation of mineral absorption are well reported in medicinal literature. Apart from the pharmacological applications, oligosaccharides have found use in drug delivery, cosmetics, animal and fishery feed, agriculture, etc. Keeping in view the importance of the functional oligosaccharides, we present an overview of their natural sources, types, structures, physiological properties. Conventional as well as novel synthesis, purification and analysis methods are summarized. Recent promising developments in this area are presented to facilitate their further exploitation.
Keywords: Biological activity, Oligosaccharides, Prebiotics, Probiotics, Microbiota.
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1. INTRODUCTION With the advent of recent researches and modernization in medical sciences, everyday invention of new diseases has been accomplished. Since biologists at the one hand invent more and more diseases, its complementary hand is approaching the invention of newer medicines for fighting with the diseases. Chemists and biologists together are trying to find out new target compounds as therapeutic agents, for which they are haunting the synthetic as well as natural sources. Isolation of biologically active compounds from natural sources is not a new approach but it hundreds year old and is still continuing. Based on the data of invented therapeutic agents it was postulated that the compounds either composed of glycans or containing carbohydrate moiety in them become more successful as a drug1,2. With the emphasis on carbohydrate based drug discovery a new stream termed as glycobiology has come out in which chemists and biologists together emphasized on the benefits of sugar based molecules and they invented number of glycosides, glyconjugates and oligosaccharides which are either under the process of investigation for future drugs or been marketed as medicine. Increasing health consciousness of modern consumers has enhanced the demand of specific types of dietary carbohydrates. The health promoting effects of non-digestible carbohydrates such as dietary fibers, oligosaccharides and resistant starch have been well documented3,4. Among the non-digestible carbohydrates, functional oligosaccharides are gaining outstanding popularity owing to their physiological benefits to the consumers. Oligosaccharides (OS) have been commercialised since the 1980s as low-calorie bulking agents. More recently, they have garnered much interest in food and pharmaceutical sector owing to overwhelming consumer preference for healthier food. The functional food concept was first introduced in Japan. In 1991, several oligosaccharides were classified as "FOods for Specified Health Use" (FOSHU) in Japan. Recent research findings across the globe, have led to the inclusion of non- digestible oligosaccharides (NDOs) under functional food. Currently, there exists a $27 billion US market for functional foods and experts forecast its 8.5-20% growth. The global market for functional foods was valued at $73.5 billion US in 2005, whereas by 2013, it is expected to reach a value of $90.5 billion US. Growing consumer health awareness is the primary driving force behind the boom of the functional food market. The largest markets for functional foods and supplements are the United States, Europe and Japan, accounting for 33.6, 28.2 and 20.9% of sales in 2003, respectively. In Canada, the Natural Health Product Regulations (2004), assess the evolution of functional food market, which hampers growth of this sector. China, India and Latin America are emerging functional food markets, where cultural factors, low levels of nutrition knowledge and income constraints limit the popularity of these health foods. Oligosaccharides are low molecular weight carbohydrates, containing sugar moieties with degrees of polymerization (DP) between 2 and 10, intermediate in nature between simple sugars and polysaccharides5. In the non-digestible oligosaccharides, the anomeric C-atoms (C1 or C2) of the monosaccharide units have configuration that makes their glycosidic bonds non- susceptible to the hydrolytic activity of human digestive enzymes6. The non-digestible oligosaccharides (NDOs) possess important physico-chemical and physiological properties and
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serve as dietary fibers and prebiotics. Enrichment of diet with NDOs improves gut microecology. Prebiotics are fermented in the colon by endogenous bacteria to release energy, metabolic substrates, lactic and short-chain carboxylic acids as end products of fermentation7. These compounds promote the proliferation of probiotics8. Probiotics are live microorganisms which when administered in adequate amounts colonize as commensal of the host conferring a health benefit on the host.
2. PHYSICO-CHEMICAL PROPERTIES OF OLIGOSACCHARIDES
The oligosaccharides are about 0.3-0.6 times as sweet as sucrose, this low sweetness attribute is exploited in food formulations as a replacement of sucrose. Further, the low caloric densities make the oligosaccharides useful as bulking agents in food formulations. They are used as humectants because of their high moisture-retaining capacity without increasing water activity. Based on their physiological properties, these carbohydrates are grouped as digestible or non-digestible. In addition, as compared to the solutions of mono- and disaccharides, higher molecular weights of oligosaccharides make them more viscous solutions. The stability of oligosaccharides depends on the sugar residue content, ring form, anomeric configuration and linkage types. Generally β-linkages are stronger than α-linkages and hexoses are more strongly linked than pentoses. Low pH and high temperature tend to impair the physico-chemical properties and reduce nutritional value of oligosaccharides. Such additives of moderate sweetness, organoleptic characteristics and stability over a wide range of pH and temperature are suitable for incorporation into foods. They show exceedingly high structural diversity than oligopeptides and oligonucleotides9. The functional oligosaccharides include Fructo- oligosaccharides10 (FOs), Gluco-oligosaccharides (GOs), Isomalto-oligosaccharides (IMOs), Soybean meal oligosaccharides (SMOs), Mannan-oligosaccharides (MOs), Galacto- oligosaccharides, Gentio-oligosaccharides, Isomaltulose, Lactosucrose, Malto-oligosaccharides11 (MOs), Xylo-oligosaccharides12 (XOs), Pectin-derived acidic oligosaccharides13 (PAOs), Cyclodextrins14.
3. TYPES AND SOURCES OF OLIGOSACCHARIDES
Functional oligosaccharides are found in varying concentrations in milk, honey, sugarcane juice, soyabean, lentils, mustard, fruits and vegetables such as onion, asparagus, sugar beet, artichoke, chicory, leek, garlic, artichoke, banana, rye, barley, yacon, wheat, tomato and bamboo shoots15. Xylo-oligosaccharides are extracted from gram husk, wheat bran, barley hulls, brewery spent grains, almond shells, bamboo, corn cob, staw, etc16. Oligosaccharides have been produced from plant cell wall polysaccharides viz. soy arabinogalactan, sugar beet arabinan, wheat flour arabinoxylan, polygalacturonan and rhamnogalacturonan fraction from apple17. Wichienchot et al. have isolated prebiotic oligosaccharides from unconventional sources like redflesh pitaya18 (dragon fruit) and Thammarutwasik et al. from jackfruit seed19. Two novel
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oligosaccharides, β-D-fructopyranosyl-(26)-β-D-glucopyranosyl-(13)-D-glucopyranose and β-D-fructopyranosyl-(26)-β-D-glucopyranosyl-(13)-D-glucopyranose have been isolated from a fermented beverage of 50 kinds of fruits and vegetables20. High levels of Raffinose family oligosaccharides (RFOs) are extracted from lupin species belonging to Leguminosae family. Algal-oligosaccharide lysates have been derived from algal polysaccharides21. Neoagaro- oligosaccharides (NAOs) have been obtained from enzymatic hydrolysis of agarose22. Functional properties of oligosaccharides from different sources vary due to their variable monomers, degree of polymerization and glycosidic bonds. Types and sources of common oligosaccharides are presented in Table 1.
Table 1: Types, Sources and Biological Applications of Oligosaccharides S.N. Oligosaccharides Sources Biological Applications 1. Isomalto- Bacillus circulans T-3040 Prevent dental caries, increase cecal oligosaccharide23 Bifidobacterium population (IMOs) 2. Soybean meal Soybean seed Promote competitive exclusion of oligosaccharides10 potential pathogens, reduce oxidative (SMOs) stress, reverse cardio cerebrovascular disease 3. Fructo- Aspergillus, Fusarium, Improve gut absorption of Ca and Mg, oligosaccharides24 Arthrobacter, prevent urogenital infections, (FOs) Aureobasidum sweetener in beverages, acariogenic Gluconacetobacter, quality, effect on lipid metabolism, Bacillus chicory root, reduce risk of colon cancer fermented beverage of plant extract 4. Galacto- Bifidobacterium bifidum Used as prebiotics, lactulose is used in oligosaccharides NCIMB 41171, treatment of hyperammonemia and lactulose25 Kluyveromyces lactis portosystemic encephalopathy, as and Sulfolobus laxative, infant formulae, prebiotic solfataricus and low-calorie sweetener 5. Mannan- Cell wall fragments of Modulate gut microbiota of gilthead oligosaccharides26 yeast sea bream fish, alter lymphocyte (MOs) response in vitro, alternative to antibiotic growth promoters in broiler diets 6. Gluco- Leuconostoc Promote beneficial cutaneous flora, oligosaccharides27 mesenteroides NRRL B used in dermocosmetic industry (GOs) 1299 7. Gentio- Penicillium multicolor Useful as prebiotic and taste improver
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oligosaccharides28 of some beverages 8. Lactosucrose29 Pseudomonas aurantiaca Increase bifidobacteria population 9. Malto- From starch by the action Reduce the levels of Clostridium oligosaccharides30 of pullulanase, perfringens and family (MOs) isoamylase and amylases Enterobacteriaceae 10. Xylo- Aspergillus, Prebiotic, cosmetics, plant growth oligosaccharides Trichoderma, regulator, antioxidant, gelling agent, (XOs) or Feruloyl- Penicillium, Bacillus, treatment of diabetes, arteriosclerosis oligosaccharides31 Streptomyces, also from and colon cancer (FOs) Bengal gram husk, wheat bran and straw, aspen wood, barley hulls, brewery spent grains, almond shells, bamboo, corn cob 11. Chitosan Depolymerised products Antioxidant, anti-tumor, anti- oligosaccharides32 of chitosan hypertensive, anti-microbial and (COs) immunopotentiating activities, protect normal cells from apoptosis 12. Human milk Human breast milk Facilitate preferential growth of oligosaccharide7 bifidobacteria and lactobacilli in the (HMOs) colon of breast-fed neonates 13. β-Glucan Oat-based diet Exert better lactobacillogenic effect oligosaccharide33 14. Gentio- By digestion of starch Improves poebiotic profile oligosaccharides34 (GeOs) 15. Cyclodextrins14 Transformation of starch Stabilize deliquescent or volatile (CDs) by certain bacteria such compounds in foods and chemicals; as Bacillus macerans emulsify oils; protect against oxidation and photodegradation, mask bitterness in foods and drugs, enhance bioavailability of poorly soluble drugs 16. Algal- Polysaccharide extracts Antioxidant and health food prebiotic oligosaccharides (APEs) of Gracilaria effect lysate21 (AOL)
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4. STRUCTURES, GLYCOSIDIC LINKAGES OF COMMON OLIGOSACCHARIDES Nature of oligosaccharide, composition and glycosidic linkages between different monosaccharide units are presented in Table 2. Table 2: Monomer Composition and Glycosidic Linkages of Common Oligosaccharides S.N. Oligosaccharides Monomer composition Glycosidic Linkage 1. Soybean meal (Galactose)n-glucose- -(16)--(12)--fructose linked oligosaccharides10 fructose (SMO) (Raffinose and Stachyose) 2. Fructooligosaccharid (Fructose)n-glucose -(21) and -(12) linked es20 3. Galactooligosacchari (Galactose)n-glucose -(14) and -(16) linked des25 4. Xylooligosaccharide (Xylose)n -(14) linked s31 (XOS) 5. Gentiooligosacchari (Glucose)n -(16) linked des28 (GeOS) 6. Lactosucrose29 Galactose-glucose- -(14)--(12)-fructose linked fructose 7. Arabino- (Arabinose)n -(15) linked oligosaccharides35 (AOS) 8. Isomaltooligosaccha (Glucose)n -(16) linked ride30 9. Maltooligosaccharid (Glucose)n -(14) linked e30 (MOS) 10. Chitosan (2-Acetamido-D-glucose- -(1,4) linked oligosaccharides32 2-amino-D-glucose)n (COS) 11. Cyclodextrins14 Cyclic-D-glucose -(14) linked (CDs)
4. SYNTHESIS AND PURIFICATION OF OLIGOSACCHARIDES
The large scale application of functional oligosaccharides in foods, feed, pharmaceutical, cosmetics and agrochemical industries, make it imperative to develop scale-up synthesis methods. Oligosaccharides can be extracted from natural sources or synthesized by physical, chemical or enzymatic methods36. Commonly employed methods are hydrolysis of
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polysaccharides or synthesis from disaccharide substrates by enzymatic and chemical treatment15. Raffinose oligosaccharides are directly extracted from plant materials using water or aqueous methanol or ethanol solutions15. Mannose and rhamnose orthoesters readily undergo O- 2-(orthoester) C-bond cleavage and give a dioxolenium ion intermediate leading to synthesis of -(12) linked oligosaccharides37. Lactulose is synthesized by isomerization of lactose using catalyst as sodium hydroxide, sodium hydroxide, boric acid and sodium aluminate38. Oligosaccharides are synthesized by controlled enzymatic hydrolysis of polysaccharides. Xylo-oligosaccharides (XOS) are produced from xylan by hydrolysis with enzymatic treatment12. For preparing complex and highly pure oligosaccharides, application of microbial enzyme glycosyl-transferases and fructosyltransferases are currently recognized very effective. Glucansucrase, an extracellular enzyme secreted by Leuconostoc, Lactobacillus and Streptococcus catalyzes a primary reaction for synthesis of dextran from sucrose and a secondary reaction for oligosaccharide synthesis in presence of acceptors like maltose or isomaltose39 used microwave induced acid hydrolysis of glucans for oligosaccharides synthesis from the branched glucan of Leuconostoc mesenteroides NRRL B-742. For higher production of Inulo- oligosaccharides (IOS) from inulin, the endoinulinase gene of Pseudomonas sp. was cloned and expressed in Escherichia coli HB101. The endoinulinase from E. coli HB101 was constitutively expressed, producing a high yield of IOS (78%). Continuous production of IOS from inulin was also carried out using a bioreactor packed with the immobilized cells, which gave 150 g/l h for 17 days at 500C under the optimal operation conditions40. Galactosaccharides (GOS) can be prepared from lactose by enzymatic reaction using -galactosidases from Lactobacillus reuteri, Aspergillus oryzae, Kluveromyces lactis. GOS synthesis can be conducted in batch or continuous system using Membrane reactor with ultrafiltration ceramic membrane41. The continuous enzymatic production of Galactosyloligosaccharides (GOS) from lactose was carried out using a ceramic membrane reactor system42. Biosynthesis of Fructo-oligosaccharides (FOS) was observed during growth of thermophilic fungus Sporotrichum thermophile in high sucrose media submerged batch cultivation. Neutral branched Arabino-oligosaccharides were isolated from sugar beet arabinan by enzymatic degradation with mixtures of pure and well defined arabinohydrolases from Chrysosporium lucknowense35. Feruloyl Xylo-oligosaccharides (FeXOSs) were obtained from corn cobs by treatment with a Thermoascus aurantiacus family 10--D-endoxylanase16. Inverting cellobiose phosphorylase and cellodextrin phosphorylase from Clostridium thermocellum ATCC27405 belonging to glycoside hydrolase family 94 catalysed reverse phosphorolysis of -D-glucose 1-phosphate to produce -glucosyl oligosaccharides43. In contrast to prolific use of exoglycosidases as oligosaccharide synthesis tool, endoglycosidases have found very studies. Murata and Usui described an efficient synthetic method of functional oligosaccharides utilizing lysozyme, cellulase, and lacto-N-biosidase-mediated transglycosylations44. The various synthesis methods of oligosaccharides are presented in Table 3. For different applications, oligosaccharides of variable purity are required. Purified oligosaccharide mixtures have increased viscosity, reduced sweetness and hygroscopicity, and
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cause fewer Maillard reactions during heat processing. The absence of simple sugars lowers cariogenicity and calorific value, and allows the non-digestible oligosaccharides (NDOs) to be used as diabetic foods. Contaminating sugars in the form of unreacted substrates and monosaccharides, present after oligosaccharide formation, are removed by membrane filtration or chromatographic methods30. Immobilised cells of Zymomonas mobilis were used to remove glucose, fructose and sucrose from food-grade oligosaccharide mixtures. This immobilization technique proved more effective for better oligosaccharide yield and purity than conventional chromatographic techniques. The oligosaccharide of interest is generally isolated from the mixture by size-exclusion chromatography. Cross-flow nanofiltration has the potential of purifying oligosaccharide from mixtures containing contaminant monosaccharides45. Spiral wound nanofiltration membranes were applied to separate galactose-oligosaccharide from sugar solution. Ultrafiltration based on commercial thin-film polymeric membranes was used to purify the xylo-oligosaccharides obtained by autohydrolysis of almond shells. Liquors from rice husk autohydrolysis were refined by membrane processing, hydrolyzed with commercial enzymes and subjected to ion exchange processing to yield pure xylo-oligosaccharides46.
Table 3: Various Methods of Synthesis of Oligosaccharides S.N. Methods Examples of synthesis methods Oligosaccharide produced 1. Physical Autohydrolysis of brewery’s spent Xylo-oligosaccharides47 grain with water at 1900C
Guar gum at 180-2400C Oligosaccharides48 Hydrothermal processing of wheat Feruloylatedarabinoxylo- bran oligosaccharides49 2. Chemical O-2-(orthoester) C-bond cleavage -(12)-linked oligosaccharides37 Isomerization reaction of lactose Lactulose38 Extraction by water or aqueous Raffinose oligosaccharides15 methanol or ethanol solutions
Hydrolysis of rice bran by Feruloylated oligosaccharides13 trifluoroacetic acid Microwave induced acid hydrolysis Glucoligosaccharides39 of glucan 3. Enzymati Action of -galactosidases on Galactosaccharides41 c lactose Endoinulinase gene of Inulo-oligosaccharides40 Pseudomonas sp. was cloned and expressed in Escherichia coli HB101
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During culture of fungus Fructo-oligosaccharides16 Sporotrichum thermophile Degradation of arabinan with Arabino-oligosaccharides35 arabinohydrolases Treatment of corn cobs by Feruloyl xylo-oligosaccharides16 endoxylanase Transgalactosylation of lactose by Galactosyl-oligosaccharides42 -galactosidase Reverse phosphorolysis of -D- -Glucosyl oligosaccharides43 glucose 1-phosphate by cellobiose phosphorylase and cellodextrin phosphorylase
6. STRUCTURAL ANALYSIS AND QUANTIFICATION OF OLIGOSACCHARIDES To understand the relations between physico-chemical properties and the functionality of oligosaccharides, it is important to characterize their structure. Structural analysis requires determination of monosaccharides, their sequence, type of linkages, branching and anomeric configuration. Thin Layer Chromatography (TLC) can reveal the degree of polymerization of oligosaccharides. Among the prevalent analytical methods, mass spectrometry (MS) is the best because of its precise results, analytical versatility and very high sensitivity. Over the past decade, the fast atom bombardment (FAB) technique has been replaced by the more sensitive techniques of electrospray ionization (ESI) and matrix-assisted laser desorption/ionization (MALDI)50. Methylation analysis, MALDITOF-MS and NMR are some other well-known methods for structure analysis of oligosaccharides20. The oligosaccharides are isolated using carbon-Celite column chromatography and preparative high performance liquid chromatography. To quantify oligosaccharides in reaction mixture products the most common methods employed are: capillary electrophoresis with a UV-Diode Array detector, high-performance anion- exchange chromatography with pulsed amperometric detection, high-performance chromatography with a refractive index detector, thin layer chromatography, mass spectrometry and UV spectrophotometry combined with artificial neural networks (ANN)51.
7. INDUSTRIAL APPLICATIONS OF OLIGOSACCHARIDES
Functional oligosaccharides of various origins have been used extensively as food ingredients, prebiotic supplements, drug delivery, immunostimulators, cosmetics, animal feed and agrochemicals8. Because of the multiple beneficial health effects attributed to functional oligosaccharides, they are used widely in food products as anticariogenic agents and low- sweetness humectants. As nutraceuticals, oligosaccharides are used in beverages (fruit drinks,
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coffee, cocoa, tea, soda, soya milk, soft drinks, health drinks and alcoholic beverages) and milk products (fermented milk, instant powders, powdered milk, yoghurt and ice cream). Also, the functional oligosaccharides are amended in desserts (puddings and sherbets), table spreads (jellies, jams, marmalades, honey products), confectionary (candy, cookies, biscuits, chocolate, sweets), bakery products (breads and pastries), breakfast cereals, meat products (fish paste and tofu) and food for infants, elders and diabetics. Algal-oligosaccharide-lysates have anti-oxidative potential owing to their high polyphenol content21. Rao et al. reported the synergistic effect of lysozyme and chitooligosaccharides (COS), the combination treatment resulted in complete elimination of Escherichia coli, Pseudomonas fluorescens and Bacillus cereus and reduced the load of Staphylococcus aureus in meat model system52. Wrapping materials are manufactured in Japan using antibacterial Allylisothiocyanate (AITC) and cyclodextrin complex53. The functional oligosaccharides, act as nutrients for the probiotic Bifidobacteria and Lactobacilli. Isomaltooligosaccharides increase cecal Bifidobacterium population and soybean meal oligosaccharides (SMO) promote competitive exclusion of potential pathogens10. The Bifidogenic bacteria transform soluble indigestible oligosaccharides to organic acids, mainly short-chain fatty acids (SCFA) such as acetic, propionic and n-butyric acids, which being fermentable, improve gastrointestinal health54. Acetate and propionate show anticholesterolemic effect; while butyrate prevents the proliferation of gut epithelial cells, showing anticarcinogenic property. Recent development of commercial prebiotic oligosaccharides and probiotic bacteria has generated the synbiotic concept. Probiotic yogurts are fortified with prebiotic oligosaccharides to benefit gut health. Probiotics suppress pathogenic microbes by lowering pH of the large intestine, produce vitamins (B-complex, folic acid) and stimulate the immune system54. Lactobacilli form a biofilm on the surface of the vaginal mucosa and protect it against pathogens. Qualified prebiotics as fructooligosaccharides (FOS) and glucooligosaccharides (GOS) avoid the urogenital infections by promoting proliferation of lactobacilli24. A controlled administration of xylooligosaccharides, help suppress pathogenic bacteria and avoid intestinal disorders such as constipation, inflammatory bowel, diarrhoea and gastritis. As ingredients of pharmaceutical products, the oligosaccharides control constipation, hyperlipidemia and encephalopathy55. Xylooligosaccharides in pharmaceutical preparations exhibit antiallergy, antimicrobial, anti-infection and anti-inflammatory properties, selective cytotoxicity and immunomodulatory action12. Feruloyl xylooligosaccharides have potential antioxidative capacity in ultraviolet induced oxidative damage to cells. Savic et al. carried out conductometric studies on copper complexes with pullulan or dextran oligosaccharides and reported higher pharmaceutical stability and promising application in veterinary and human medicine as antiviral, antitumor and anti-inflammatory agent. Novel oligosaccharides containing galactoses and one glucosamine (or N-acetylglucosamine) residues with -(14), -(16) and -(16) glycosidic bonds suppressed the proliferation of human leukemia K562 cells. Iwata et al. investigated the effects of chitosan oligosaccharides on the femur trabecular structure in ovariectomized rats by three-dimensional imaging analysis using micro-computed tomography (CT). Chitosan oligosaccharides prevented decrease in bone volume, trabecular number,
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thickness and connectivity, establishing itself as bone-inducing substance for use as biocompatible bone graft material. An oligosaccharide fraction AVF3, purified from a preparation of dried leaves of Artemisia species promoted survival of the mouse thymocytes in culture. A mouse gene array study suggested AVF3 induced suppression of Fas/FasL gene expression and modulation of apoptotic cell death. Johnstone et al. reported that linking of modified peptides with oligosaccharide dramatically increases the stability, membrane permeability and bioavailability of the peptides rendering it suitable for drug-delivery applications56. Du et al. reported that linoleic acid (LA)-grafted chitosan oligosaccharide (CSO) (CSO-LA) were able to self-assemble and form spherical shape polymeric micelles Loaing anticancer drug doxorubicin (DOX) on the CSO-LA micelles, the drug encapsulation efficiencies (EE) were found about 75% higher. The in vitro release studies indicated the possible utilization of the amphiphilic micellar chitosan derivatives as carriers for hydrophobic drugs for improving their delivery and release properties. The mitogenic activity of acidic fibroblast growth factor (a- FGF) is potentiated by the highly sulfated hexasaccharide isolated after digestion of pancreas heparan sulfate with heparitinase I. Isolaflavone derivative exert prophylactic effect against breast and prostate cancer. Inclusion complex of isolaflavone derivative with cyclodextrin shows reduction in its bitter taste and improvement in water solubility, absorption from gut and physiological property. Raspberry ketone when added to cyclodextrin, shows better solubility and improved anti-obesity effect53. Polysulfated oligosaccharide glycosides synthesized as heparan sulfate (HS) mimetics, bound tightly to angiogenic growth factors (FGF-1, FGF-2, and VEGF) and strongly inhibited heparanase activity. They also showed good antitumor activity in vivo in a mouse melanoma model demanding further investigation of these oligosaccharides as potential antiangiogenic and anticancer therapeutics56. The aqueous extract of Orchis latifolia rich in fructooligosaccharides showed ameliorative effect on sexual dysfunction in hyperglycaemic male rats57. The oligosaccharides are commonly used in cosmetics as stabilizers and bulking agents. Adachi and Vallee evaluated the skin emollient efficacy of various oligosaccharides, obtained by a controlled enzymatic depolymerization of membranous polysaccharides agarose, carrageenan, alginate and fucoidan extracted from brown seaweed58. The high molecular oligosaccharide applied to skin protected cells from cigarette smoke, pesticides and heavy metals. Low molecular oligosaccharide has antiinflammation effect which mechanisms are inhibition of interlukin-1a release from keratinocytes and cycrooxygenase activity. Also, low molecular oligosaccharide chelated with zinc showed sebum-regulation, anti- bacterial action. Finally, oligosaccharide chelated with manganese and magnesium inhibited free radical activity and prevented langerhans cell from UVB rays. Minoru and Yoshio discovered that oligosaccharides trehalose influence the water-holding properties of lipid multilamellar structure existing in the stratum corneum59. Owing to the skin moisturizing effect, trehalose may be implicated in cosmetics. Cyclodextrins are used in cosmetics to solubilise fragrance, suppress their volatility and facilitate spraying as micropowders. Cyclodextrins are used in deodorant to neutralize smoke, mold, cooking, stale and pet odours emanating from clothes. Cyclodextrains are implicated in skin-care products as soaps and shampoos, to stabilize antibacterial
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monoterpentoid Hinokitiol53. Oligosaccharides are widely being implicated in animal feeds. For commercial production of European turbot fish, formulation of a health-promoting diet is very important. Turbot larvae were weaned on diets containing cellulose, inulin and fructo- oligosaccharides or lactosucrose. Of the total load of bacterial isolates from turbot weaned on oligofructose, 14% consisted of probiotic Bacillus spp60. Dietary supplementation with chito- Oligosaccharide (COS) improved the average daily feed intake, nutrient digestibility and positive modulation of cecal microbial flora in gut of broiler chickens. Additionally, COS increased serum protein and high-density lipoprotein cholesterol and decreased serum triglyceride13. Though antibiotics have been widely used as feed additives for livestocks, the acquired antibiotic resistance to pathogens is a major concern61. Oligosaccharides afford potential substitute to antibiotics in animal feeds61. Soybean meal oligosaccharides (SMO) decrease the incidences of fatty liver of fish, enhance antioxidant enzymes and the immunity of broilers10. Mannan oligosaccharide (MOS500), derived from the cell wall of saccharomyces cerevisiae is an effective feed ingredient for poultry and livestocks. Cyclodextrins are crucial from agricultural point of view, as these oligosaccharides form inclusion complexes with herbicides, bug repellents, pheromones and growth hormones. The complex facilitates water solubility and reduces volatility53. The oligosaccharide cyclodextrin plays a crucial role in environment protection by forming soluble inclusion complexes with hydrophobic molecules and increasing degradation rate of hydrocarbons. Pectin-derived acidic oligosaccharides (PAOS) help in plant growth and development13. Mannan oligosaccharides (MO) either individually or in combination with ferulic acid, enhanced laccase levels in liquid cultures of three strains of white-rot fungi62.
8. STRATEGIES TO ENHANCE PRODUCTION OF FUNCTIONAL OLIGOSACCHARIDES
For large scale production of oligosaccharides, advancement in enzyme technology and development of recombinant microorganisms is of paramount importance. Usually, enzyme processes are cost intensive because of the high processing cost of production, purification and stabilization. Extraction of oligosaccharides from natural sources can also lead to the discovery of novel prebiotics. Use of low cost agro-residues as substrates for producing glucosyltransferases, amylases and xylanases capable of oligosaccharide synthesis, appears to be an economical approach. Recycling of immobilized enzymes can economise their industrial production. Optimization of hydrolysis conditions for oligosaccharides from polysaccharides through Response Surface Methodolgy (RSM) is also a promising method13.
9. CONCLUSION
Interest in functional oligosaccharides is motivated by their diverse industrial applications. The health benefits of functional oligosaccharides are well known and far reaching.
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Ranging from use in nutaceutical, pharmaceutical, prebiotics, cometics, animal feed and agriculture sector, oligosaccharides have benefits for everyone. Looking at their ever increasing demand, oligosaccharides have been subjected to an intensive and cutting-edge research during the last three decades. With galloping popularity of functional foods and environmental awareness, the future of oligosaccharides fortified products seems to be highly promising. Potential markets for oligosaccharides in future are expected to trigger a major boom across the globe.
10. REFERENCES
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