Therapeutic Polysaccharides - Essay Example

Therapeutic Polysaccharides I. Polysaccharide Importance Polysaccharides play a ubiquitous role in biological processes, with modern research continuing to demonstrate just how integral these compounds are in biochemical processes. Polysaccharides have been referred to as the “sleeping giant” in natural products research for bioactive compounds, representing pathways to new clinical treatments for a variety of conditions as well as shedding light on the compounds’ roles in disease (Shao-Ping 2011, p.1420). Because of their unique composition and structure, the important role that polysaccharides will play in the future of research is undeniable. On a fundamental level, polyssarcharides are defined as polymeric chains composed of mono- or di-saccharides bound together by glycosidic bonds, a special type of covalent bond. Carbohydrates possess a hemiacetal group that contains a reactive anomeric carbon that readily reacts in certain low pH cellular environments to form a stable glycosidic bond. While the ring structure of the carbohydrate subunits confers a rigid form, the glycosidic bonds allow for chain flexibility, conferring similar mechanical properties found in other semi-elastic polymers (Andre and Gushlbauer 1974, p.803-805). The unique properties yielded by this chemical structure allow polysaccharides to fulfill a variety of biological roles. II. The Butternut Squash (Cururbita moschata) The plant commonly referred to as the Butternut Squash, also commonly called the Winter Squash, Pumpkin Squash, and Field Pumpkin, is scientifically known as Cucurbita moschata, a member of the same family as gourds and cucumbers. Like its close relatives, the plant grows on a vine with soft, hairy stems and is found in both North and South America in growing zones USDA 8 through 11 (Saylor and Network Vista, Inc. 2008, p.4175). The plant is widely grown for foodstuffs and is a common home gardener favorite. The leaves of the plant are broad, with nearly orbicular structure, and few lobes are present in the vine. Annually, Cucurbita moschata produces yellow colored flowers with wide spreading and crinkled petal structures, of a monoecious variety possessing both male and female structures within a single plant. The fruit produced may vary in shape, but are broadly oblong or crookneck with a penduncle angle and wide apex. The oldest record of domestication of these plants is shown in excavated seed found in Mexico from about 5000 B.C as well as in Peru from 3000 B.C., demonstrating that the plant has been cultivated for a large period of human history (Saylor and Network Vista, Inc. 2008, p.4175). The butternut squash plays an important commercial and agricultural role based on its unique hardiness, making it both commercially interesting as well as interesting to researchers. Cucurbita moschata has long been a favorite in traditional medicine and has often been used by herbalists to treat a variety of conditions for hundreds years. The seeds of the plant are edible and contain phytosterols known best for their treatment of prostate disorders, expulsion of intestinal worms and parasites, and ability to prevent the formation of kidney stones. The yellow blooms of the plant have been used to stabilize and correct patients with symptoms of jaundice. Many herbalists also brew the leaves of the plant as a tea that is effective in treating stomach inflammation. The Cherokee American Indians and locals in Surinam have been known to apply the seeds as an anthelmintic and also as a pediatric urinary aid to reduce the symptoms of bed-wetting (Tropilab, Inc. 2011). Cucurbita moschata has a long history as plant of medicinal interest, and research has demonstrated the potent activity of some of the plants metabolites and secondary metabolites. III. Literature Review Cucurbita moschata, or the butternut squash, is a well known source of novel polysaccharides compound with unique bioactivity. The most common biologically important polysaccharides are composed of subunits of the pyranose ring structure, or a six-membered ring composed of five carbon atoms and one oxygen atom linked by single bonds. The pyranose structure provides a rigid backbone for each subunit, and commonly assumes the stable chair conformation. It is this conformation that has been demonstrated as responsible for the characteristic elasticity of many biological polysaccharides, as demonstrated by the change in the enthalpic component of elasticity for such materials upon cleavage of the pyranose rings in such biological compounds as amylose, dextran and pullulan (Marszalek and Oberhauser et al. 1998, p.661). As such is can be demonstrated that the unique properties, which play a critical role in the polysaccharides’ behavior(s) in vivo, are conferred by the composition of its subunits. Polysaccharides, such as those found in Cucurbita moschata stems and seeds, play a role, particularly in plant cells, as storage components and structural components, necessary to both organism growth and reproduction. In fact, the key structural element, the cell wall, is strengthened by polysaccharides. The compounds can broadly be categorized into storage polysaccharides, such as starches and glycogen, and structural polysaccharides, such as arabinoxylans, cellulose, chitin, and pectins (ISCID 2011, p.1). Polysaccharides have a diverse set of roles of undeniable importance to the growth and proliferation of many organisms. Infectious disease accounts for over one third of deaths worldwide, and with resistant pathogen strains on the rise, the search for new bioactive compounds from natural products has become an increasingly prolific area of research. Polysaccharides isolated from plants, particularly certain algae strains, have been demonstrated to have antiviral and antibiotic properties, treating such well known conditions as HIV and providing potential leads for the treatment of a variety of other clinical conditions (Martinez and Del Olmoet al. 2005, p.393). Isolation of novel bioactive compounds from natural products is necessary to combat disease resistance and to develop new and more effective treatments for chronic conditions, such as HIV and cancer. Isolated from have been shown to have cytotoxic properties that may be useful in cancer treatment, as well as many other conditions (Caili and Huan et al. 2006, p.73-74). Polysaccharides play a particularly important role in the fields of glycobiology, and were recognized as early as 1908 by the Committee on Protein Nomenclature of the American Society for Biochemist for their importance in complexing with proteins in biological systems. Modern research has expanded the scientific knowledge of glycoprotiens and glycoconjugates incorporating polysaccharides as important intelligent structures involves in cellular functions (Dumitriu 1996, p.265-266). These compounds also play an important role in intercellular communication and interaction. Glycobiology has shown that polysaccharide chains are crucial in specific ligand cell-cell interactions as well as specific ligand cell-microbe interactions, impacting a variety of processes completed by eukaryotic cells. The first intrinsic glycan receptors were shown to mediate such functions as cellular clearance, turnover, and intracellular trafficking of soluble blood-plasma. One of the most well documented examples is regulation of mannose-6-phosphate (Man-6-P) in direction of lysosomal enzymes within the lysosome body, were receptors specifically are able to recognize terminal and subterminal polysaccharides in order to initiate a cellular activity (Varki and Cummings et al. 2008, p.I-6). Many other examples of specific ligand interactions involving polysaccharides exist, and are yet to be characterized, leaving a wide body of research to be explored by new researchers. In plants, polysaccharides serve as structural elements in the cellular wall and other structures. Randomly oriented cellulose microfibrils are randomly oriented along these structural walls, and many undergo a secondary thickening process wherein additional polysaccharide chains are added. These chains undergo additional lignifications in situ as a result of phenolic polymerization, resulting in the hard “woody structure seen in many plants and food materials such as brand (Stephen and Phillips 2006, p.633-634). Many of the polysaccharides isolated from plant material play structural roles; however, the more interesting bioactive polysaccharides are often those involved with intracellular and cell-microbe communication and interaction. A number of researchers have isolated and explored the properties of novel pectic polysaccharides, particularly those of the Cucurbita moschata seed. Pectic plyssacharides are a family of complex polysaccharides that contain 1,4-linked α-D-galactosyluronic acid residues, generally found in the primary plant cell wall and other structural units. Analysis of these pectic polyssacharides indicates that they have strong antioxidant characteristics, which may yield important nutritional and medicinal benefits (Kostalova and Hromadkova et al. 2010, p.370). One research study demonstrates that polyssacharide and peptide compounds in the plant effectively limit liver damage caused by alcohol consumption (Park and Lee et al 2002, p.1451). Another study indicates that a novel ribosome-inactivating protein with bound polyssacharides, designated Moschatin, isolated from the mature seeds of pumpkin has a strong cytotoxic effect and may be useful in treating cancer patients (Heng and Feng et al. 2002, p.369-370). Additionally, researchers have isolated pumpkin polysaccharides that effectively inhibit H2O2, a primary cause of decrease in cell viability lactate dehydrogenase leakage, and malondialdehyde formation. Reduced H2O2 levels caused by these compounds were shown to cause decline in superoxide dismutase activity and glutathione depletion in mice macrophages cultured in vitro, confirming that the pumpkin seed contains polysaccharide compounds linked to antioxidative activity, as well as indicating that these compounds may play a cytoprotective role in the cell (Yang and Zhao et al. 2007, p. 4684). Because of their cytoprotective role, the polyssacharides found in Cucurbita moschata seed, and other areas of the plant, are of particular interest to medical researchers. While isolation techniques vary, most researchers choose to begin with classical extraction techniques and develop a method appropriate based on the compound they are attempting to isolate. The most common challenge facing those researchers working with isolation of polysaccharide compounds in Cucurbita moschata is the separation of pepides for the polysaccharides and the high phenolic count in purified samples, that may interfere with ability to elucidate the structure of unknown compounds. In fact, many major researchers list peptide contamination in the final samples as inevitable or difficult to avoid (Kostalova and Hromadkova et al. 2010, p.370). Purification generally begins with solvent extraction and sonification, after which a variety of methods may be used. Some researchers choose to hydrolyze target polyssacharides into component monosaccharides by acid treatment, a process which can make to easier to remove peptide impurities (Heng and Feng et al. 2002, p.369-370). Structural elucidation may be accomplished by a variety of methods including LC and GC Mass Spectrometry and crystallography. References Andre, A and Guschlbauer, W 1974. ‘Nucleoside conformations: 15. Flexibility of natural pyrimidine nucleosides around the glycosidic bond’, Nucleic Acids Res, vol.1, no.6, pp.803–807. Caili, Fu; Huan, Shi; and Quanhong, Li 2006. A Review on Pharmacological Activities and Utilization Techniques of Pumpkin, Plant Food for Human Nutrition, vol.61, p.73-80. Dumitriu, Severian 1996. Polysaccharides in Medical Applications, Marcel Decker, Inc., New York, NY. Heng, Chuan; Feng, Li; Zhen, Li; and Zu Chuan, Zhang 2002. Purification and characterization of Moschatin, a novel type I ribosome-inactivating protein from the mature seeds of pumpkin (Cucurbita moschata), and preparation of its immunotoxin against human melanoma cells, Cell Research, vol.13, pp.369-374. ISCID 2011. ISCID Encyclopedia: Polysaccharides, International Society for Complexity, Information, and Design. Kostalova, Zuzana; Hromadkova, Zdenka; and Ebrinerova, Anna 2010. 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Shao-ping, Li 2011, Special Issue: Natural Polysaccharides: Chemistry, Bioactivity and Analysis, Molecules, Special Issue. Stephen, Alistair M.; Phillips, Glyn O.; and Williams, Peter A. 2006. Food Polysaccharides and Their Applications, 2nd Edition, Talyor and Francis Group, Baton Rouge, FL. Tropilab, Inc. 2011. Cucurbita Moschata - Calabaza, Export and Wholesale of Medicinal Plants, Herbs, and Tropical Seeds, Saint Petersburg, FL. Varki, A; Cummings, R; Esko, J; Freeze, H; Stanley, P; Bertozzi, C; Hart, G; and Etzler, M 2008. Essentials of Glycobiology, 2nd edition, The Consortium of Glycobiology Editors, La Jolla, CA. < http://www.ncbi.nlm.nih.gov/books/NBK1908> Yang, X; Zhao, Y; and Lv Y 2007. Chemical composition and antioxidant activity of an acidic polysaccharide extracted from Cucurbita moschata Duchesne ex Poiret, Journal of Agric Food Chem, vol.55, no.12, pp. 4684–4690. Read More