Journal of Literature Pharmacy Sciences

.: REVIEW
Hiyalüronik Asit ve Tıbbi Önemi
Hyaluronic Acid and Medicinal Importance
Büşra FENDOĞLUa, Didem ŞÖHRETOĞLUa, Ayşe KURUÜZÜM UZa
aFarmakognozi AD, Hacettepe Üniversitesi Eczacılık Fakültesi, Ankara, TÜRKİYE
J Lit Pharm Sci. 2019;8(1):76-84
doi: 10.5336/pharmsci.2018-62742
Article Language: TR
Full Text
ÖZET
Hiyalüronik asit; omurgalıların epitelyal, nöral ve bağ dokularının hücre dışı matrisinde bulunan bir polisakkarittir. Yüksek nem tutma, biyouyumluluk ve viskoelastisite özellikleri nedeni ile dünya çapında yüksek ticari değeri olan çeşitli farmasötik, biyomedikal ve kozmetik ürünlerin önemli bir bileşeni hâline gelmiştir. Günümüzde antiinflamatuar ve antiödem özelliklerinden dolayı oftalmoloji, dermatoloji, ortopedi ve romatoloji alanlarında sıklıkla kullanılmakta olup, son zamanlarda diş hekimliğinde de kullanımı bulunmaktadır.

Anahtar Kelimeler: Hiyalüronik asit; biyolojik ürün; glikozaminoglikan
ABSTRACT
Hyaluronic acid is a polysaccharide found in the extracellular matrix of the epithelial, neural, and connective tissues of the vertebrates. Because of its high moisture retention, biocompatibility and viscoelastic properties, this polymer has become a major component of major pharmaceutical, biomedical and cosmetic products with high commercial value worldwide. Due to its antiinflammatory and anti-edematous properties today, it is frequently used in ophthalmology, dermatology, orthopedics and rheumatology fields and has also recently been used in dentistry.

Keywords: Hyaluronic acid; biological products; glycosaminoglycans
REFERENCES:
  1. Meyer K, Palmer JW. The polysaccharide of the vitreous humor. J Biol Chem. 1934;107:629-34.
  2. Balazs EA, Laurent TC, Jeanloz RW. Nomenclature of hyaluronic acid. Biochem J. 1986;235(3):903. [Crossref] [PMC]
  3. Scott JE, Heatley F. Hyaluronan forms specific stable tertiary structures in aqueous solution: a C-13 NMR study. Proc Natl Acad Sci U S A. 1999;96(9):4850-5. [Crossref]
  4. Beasley KL, Weiss MA, Weiss RA. Hyaluronic acid fillers: a comprehensive review. Facial Plast Surg. 2009;25(2):86-94. [Crossref]
  5. Tsepilov RN, Beloded AV. Hyaluronic acid-an ? old ? molecule with ? new ? functions: biosynthesis and depolymerization of hyaluronic acid in bacteria and vertebrate tissues including during carcinogenesis. Biochem (Mosc). 2015;80(9):1093-108. [Crossref]
  6. Heldermon C, DeAngelis PL, Weigel PH. Topological organization of the hyaluronan synthase from Streptococcus pyogenes. J Biol Chem. 2001;276(3):2037-46. [Crossref]
  7. Bernstein EF, Underhill CB, Hahn PJ, Brown DB, Uitto J. Chronic sun exposure alters both the content and distrbution of dermal glicosaminoglicans. Br J Dermatol. 1996;135(2): 255-62. [Crossref]
  8. Leach JB, Schmidt CE. Hyaluronan. In: Wnek GE, Bowlin GL, eds. Encyclopedia of Biomaterials and Biomedical Engineering. 1 st ed. New York: Marcel Dekker; 2004. p.779-89.
  9. Mio K, Stern R. Inhibitors of the hyaluronidases. Matrix Biol. 2002;21(1):31-7. [Crossref]
  10. Ponnuraj K, Jedrzejas MJ. Mechanism of hyaluronan binding and degradation: structure of Streptococcus pneumoniae hyaluronate lyase in complex with hyaluronic acid disaccharide at 1.7 A resolution. J Mol Biol. 2000;299(4):885-95. [Crossref]
  11. Lokeshwar VB, Schroeder GL, Carey RI, Soloway MS, Iida N. Regulation of hyaluronidase activity by alternative mRNA splicing. J Biol Chem. 2002;277(37):33654-63. [Crossref]
  12. El Hajjaji H, Cole AA, Manicourt DH. Chondrocytes, synoviocytes and dermal fibroblasts all express PH-20, a hyaluronidase active at neutral pH. Arthritis Res Ther. 2005;7(4): R756-68. [Crossref]
  13. Girish KS, Kemparaju K. Inhibition of Naja naja venon hyaluronidase: role in the management of poisonous bite. Life Sci. 2005;78(13):1433-40. [Crossref]
  14. Kim E, Baba D, Kimura M, Yamashita M, Kashiwabara S, Baba T. Identification of a hyaluronidase, Hyal5, involved in penetration of mouse sperm through cumulus mass. Proc Nat Acad of Sci U S A. 2005;102(50):1802833. [Crossref]
  15. Senni K, Pereira J, Gueniche F, DelbarreLadrat C, Sinquin C, Ratiskol J, et al. Marine polysaccharides: a source of bioactive molecules for cell therapy and tissue engineering. Mar Drugs. 2011;9(9):1664-81. [Crossref]
  16. Giji S, Arumugam M. Isolation and characterization of hyaluronic acid from marine organisms. Adv Food Nutr Res. 2014;72:61-77. [Crossref]
  17. Balazs EA, Band P. Hyaluronic acid: its structure and use. Cosmet Toilet. 1984;99:65-72.
  18. Brown MB, Jones SA. Hyaluronic acid: a unique topikal vehicle for the localized delivery of drugs to the skin. J Eur Acad Dermatol Venereol. 2005;19(3):308-18. [Crossref]
  19. Kang DY, Kim WS, Heo IS, Park YH, Lee S. Extraction of hyaluronic acid (HA) from rooster comb and characterization using flow fieldflow fractionation (FlFFF) coupled with multiangle light scattering (MALS). J Sep Sci. 2010;33(22):3530-6. [Crossref]
  20. Hadidian Z, Pirie NW. The preparation and some properties of hyaluronic acid from human umbilical cord. Biochem J. 1948;42(2):260-5. [Crossref]
  21. Balazs EA, Watson D, Duff IF, Roseman S. Hyaluronic acid in synovial fluid. I. molecular parameters of hyaluronic acid in normal and arthritic human fluids. Artritis Rheum. 1967;10(4):357-76. [Crossref]
  22. Nishikawa S, Tamai M. Ultrastructure of hyaluronic acid and collagen in the human vitreous. Curr Eye Res. 1996;15(1):37-43. [Crossref]
  23. Postlethwaite AE, Smith GN Jr, Lachman LB, Endres RO, Poppleton HM, Hasty KA, et al. Stimulation of glycosaminoglycan synthesis in cultured human dermal fibroblasts by interleukin 1. Induction of hyaluronic acid synthesis by natural and recombinant interleukin 1s and synthetic interleukin 1 beta peptide 163-171. J Clin Invest. 1989;83(2):629-36. [Crossref]
  24. Akiyama H, Saito M, Qiu G, Toida T, Imanari T. Analytical studies on hyaluronic acid synthesis by normal human epidermal keratinocytes cultured in a serum-free medium. Biol Pharm Bull. 1994;17(3):361-4. [Crossref]
  25. Toyoda H, Motoki K, Tanikawa M, Shinomiya K, Akiyama H, Imanari T. Determination of human urinary hyaluronic acid, chondroitin sulphate and dermatan sulphate as their unsaturated disaccharides by high-performance liquid chromatography. J Chromatogr. 1991;565(1-2):141-8. [Crossref]
  26. Deutsch HF. Some properties of a human serum hyaluronic acid. J Biol Chem. 1957;224(2):767-74.
  27. Nettelbladt O, Bergh J, Schenholm M, Tengblad A, Hällgren R. Accumulation of hyaluronic acid in the alveolar interstitial eritissue in bleomycin-induced alveolitis. Am Rev Respir Dis. 1989;139(3):759-62. [Crossref]
  28. Hallgren R, Gerdin B, Tufveson G. Hyaluronic acid accumulation and redistribution in rejecting rat kidney graft. Relationship to the transplantation edema. J Exp Med. 1990;171(6): 2063-76. [Crossref]
  29. Bignami A, Asher R. Some observations on the localization of hyaluronic acid in adult, newborn and embryonal rat brain. Int J Develop Neurosci. 1992;10(1):45-57. [Crossref]
  30. Fraser JR, Alcorn D, Laurent TC, Robinson AD, Ryan GB. Uptake of circulating hyaluronic acid by the rat liver. Cellular localization in situ. Cell Tissue Res. 1985;242(3):505-10. [Cross ref]
  31. Kuhlman RE, Kaufman HE. A microchemical study of the aqueous humor enzyme-protein interrelations. Arch Ophthalmol. 1960;63(1):41-6. [Crossref]
  32. Cleland RL, Sherblom AP. Isolation and physical characterization of hyaluronic acid prepared from bovine nasal septum by cetylpyridinium chloride precipitation. J Biol Chem. 1977; 252(2):420-6.
  33. Fraser JR, Kimpton WG, Pierscionek BK, Cahill RN. The kinetics of hyaluronan in normal and acutely inflamed synovial joints: observations with experimental arthritis in sheep. Semin Arthritis Rheum. 1993;6 Suppl 1:9-17. [Crossref]
  34. Dicker SE, Franklin CS. The isolation of hyaluronic acid and chondroitin sulphate from kidneys and their reaction with urinary hyaluronidase. J Physiol. 1996;186(1):110-20. [Crossref]
  35. Lebel L, Smith L, Risberg B, Gerdin B, Laurent TC. Effect of increased hydrostatic pressure on lymphatic elimination of hyaluronan from sheep lung. J App Physiol. (1985) 1988;64(4):1327-32. [Crossref]
  36. Farber SJ, vag Praag D. Composition of glycosaminoglycans (mucopolysaccharides) in rabbit renal papillae. Biochim Biophys Acta. 1970;208(2):219-26. [Crossref]
  37. Necas J, Bartosikova L, Brauner P, Kolar J. Hyaluronic acid (hyaluronan): a review. Vet Med. 2008;53(8):397-411. [Crossref]
  38. Dwyer TM, Banks SA, Alonso-Galicia M, Cockrell K, Carroll JF, Bigler SA, et al. Distribution of renal medullary hyaluronan in lean and obese rabbits. Kidney Int. 2000;58(2):7219. [Crossref]
  39. Takagaki K, Nakamura T, Majima M, Endo M. Isolation and characterization of a chondroitin sulfate-degrading endo-beta-glucuronidase from rabbit liver. J Biol Chem. 1988;263(15): 7000-6.
  40. Laurent UB, Fraser JR. Turnover of hyaluronate in the aqueous humour and vitreous body of the rabbit. Exp Eye Res. 1983;36(4):493-503. [Crossref]
  41. Seastone CV. The virulence of group C haemolytic streptococci of animal origin. J Exp Med. 1939;70(4):361-78. [Crossref]
  42. Aslan M, Simsek G, Dayi E. The effect of hyaluronic acid-supplemented bone graft in bone healing: experimental study in rabbits. J Biomater Appl. 2006;20(3):209-20. [Crossref]
  43. Çakır O, Kazancıoğlu HO, Ak G. [Hyaluronic acid in dentistry]. Istanbul Univ Dishekim Fak Derg. 2011;45(1):37-41.
  44. Turley EA, Noble PW, Bourguignon LY. Signaling properties of hyaluronan receptors. J Biol Chem. 2002;277(7):4589-92. [Crossref]
  45. Hascall VC, Majors AK, De la Motte CA, Evanko SP, Wang A, Drazba JA, et al. Intra cellular hyaluronan: a new frontier for inflammation? Biochim Biophys Acta. 2004; 1673(1-2):3-12. [Crossref]
  46. Sutherland IW. Novel and established applications ofmicrobial polysaccharides. Trends Biotechnol. 1998;16(1):41-6. [Crossref]
  47. Liao YH, Jones SA, Forbes B, Martin GP, Brown MB. Hyaluronan: pharmaceutical characterization and drug delivery. Drug Deliv. 2005;12(6):327-42. [Crossref]
  48. Simon A, Safran A, Revel A, Aizenman E, Reubinoff B, Porat-Katz A, et al. Hyaluronic acid can successfully replace albumin as the sole macromolecule in a human embryo transfer medium. Fertil Steril. 2003;79(6):1434-8. [Crossref]
  49. Gardner DK, Rodriegez-Martinez H, Lane M. Fetal development after transfer is increased by replacing protein with the glycosaminoglycan hyaluronan for mouse embryo culture and transfer. Hum Reprod. 1999;14(10):2575-80. [Crossref]
  50. Balazs EA, Denlinger JL. Viscosupplementation: a new concept in the treatment of osteoarthritis. J Rheumatol Suppl. 1993;20:3-9.
  51. Ghosh S, Jassal M. Use of polysaccharide fibres for modem wound dressings. Ind J Fibre Textile Res. 2002;27:434-50.
  52. Lequeux I, Ducasse E, Jouenne T, Thebault P. Addition of antimicrobial properties to hyaluronic acid by grafting of antimicrobial peptide. Eur Polym J. 2014;51:182-90. [Crossref]
  53. Barbucci R, Magnani A, Casolaro M, Marchettini N, Rosi C, Bosco M. Modification of hyaluronic acid by insertion of sulfate groups to obtain a heparinlike molecule. Part I. Characterization and behavior in aqueous solution towards H+ and Cu2+ ions. Gazz Chim Ital. 1995;125:169-80.
  54. Wu RL, Huang L, Zhao HC, Geng XP. Hyaluronic acid in digestive cancers. J Cancer Res Clin Oncol. 2017;143(1):1-16. [Crossref]
  55. Kim JH, Moon MJ, Kim DY, Heo SH, Jeong YY. Hyaluronic acid-based nanomaterials for cancer therapy. Polymers. 2018;10(10):1133. [Crossref]
  56. Scaife CL, Shea JE, Dai Q, Firpo MA, Prestwich GD, Mulvihill SJ. Synthetic extracellular matrix enhances tumor growth and metastasis in an orthotopic mouse model of pancreatic adenocarcinoma. J Gastrointest Surg. 2008;12(6):1074-80. [Crossref]
  57. Seufferlein T, Ducreux M, Hidalgo M, Prager G, Van Cutsem E. More than a gelhyaluronic acid, a central component in the microenvironment of pancreatic cancer. European Oncology & Haematology. 2018;14(1):40-4. [Crossref]
  58. Golshani R, Lopez L, Estrella V, Kramer M, Iida N, Lokeshwar VB. Hyaluronic acid synthase-1 expression regulates bladder cancer growth, invasion, and angiogenesis through CD44. Cancer Res. 2008;68(2):483-91. [Crossref]
  59. Bullard KM, Kim HR, Wheeler MA, Wilson CM, Neudauer CL, Simpson MA, et al. Hyaluronan synthase-3 is upregulated in metastatic colon carcinoma cells and manipulation of expression alters matrix retention and cellular growth. Int J Cancer. 2003;107(5):739-46. [Crossref]
  60. Kim HR, Wheeler MA, Wilspn CM, Iida J, Eng D, Simpson MA, et al. Hyaluronan facilitates invasion of colon carcinoma cells in vitro via interaction with CD44. Cancer Res. 2004;64(13):4569-76. [Crossref]
  61. Gao F, Liu Y, He Y, Yang C, Wang Y, Shi X, et al. Hyaluronan oligosaccharides promote excisional wound healing through enhanced angiogenesis. Matrix Biol J. 2010;29(2):107-16. [Crossref]
  62. Liu D, Pearlman E, Diaconu E, Guo K, Mori H, Haqqi T, et al. Expression of hyaluronidase by tumor cells induces angiogenesis in vivo. Proc Natl Acad Sci U S A. 1996;93(15):7832-7. [Crossref]
  63. Guo LX, Zou K, Ju JH, Xie H. Hyaluronan promotes tumor lymphangiogenesis and intralymphantic tumor growth in xenografts. Acta Biochim Biophys Sin (Shanghai). 2005;37(9): 601-6. [Crossref]
  64. Termeer CC, Hennies J, Voith U, Ahrens T, Weiss JM, Prehm P, et al. Oligosaccharides of hyaluronan are potent activators of dendritic cells. J Immunol. 2000;165(4):1863-70. [Crossref] [PubMed]
  65. David-Raoudi M, Tranchepain F, Deschrevel B, Vincent JC, Bogdanowicz P, Boumediene K, et al. Differential effects of hyaluronan and its fragments fibroblasts: relation to wound healing. Wound Repair Regen. 2008;16(2):274-87. [Crossref] [PubMed]
  66. Sugahara KN, Hirata T, Hayasaka H, Stern R, Murai T, Miyasaka M. Tumor cells enhance their own CD44 cleavage and motility by generating hyaluronan fragments. J Biol Chem. 2006;281(9):5861-8. [Crossref]
  67. Kultti A, Zhao C, Singha NC, Zimmerman S, Osgood RJ, Symons R, et al. Accumulation of extracellular hyaluronan by hyaluronan synthase 3 promotes tumor growth and modulates the pancreatic cancer microenvironment. BioMed Res Int. 2014;2014:817613. [Crossref]
  68. Shen YN, Shin HJ, Joo HY, Park ER, Kim SH, Hwang SG, et al. Inhibition of HAS2 induction enhances the radiosensitivity of cancer cells via persistent DNA damage. Biochem Biophys Res Commun. 2014;443(3):796-801. [Crossref]
  69. Ju SY, Chiou SH, Su Y. Maintenance of the stemness in CD44(+) HCT-15 and HCT-116 human colon cancer cells requires miR-203 suppression. Stem Cell Res. 2014;12(1):86-100. [Crossref]
  70. Kavasi RM, Berdiaki A, Spyridaki I, Corsini E, Tsatsakis A, Tzanakakis G, at al. HA metabolism in skin homeostasis and inflammatory disease. Food Chem Toxicol. 2017;101:128-38. [Crossref]
  71. de Maio M. The minimal approach: an innavation in facial cosmetic prosedures. Aesthetic Plast Surg. 2004;28(5):295-300. [Crossref]
  72. Jansen K, van der Werff JF, van Wachem PB, Nicolai JP, de Leij LF, van Luyn MJ. A hyaluronan-based nerve guide: in vitro cytotoxicity, subcutaneous tissue reactions, and degradation in the rat. Biomaterials. 2004;25(3):483-9. [Crossref]
  73. Amarnath LP, Srinivas A, Ramamurthi A. In vitro hemocompatibility testing of UV-modified hyaluronan hydrogels. Biomaterials. 2006; 27(8):1416-24. [Crossref]
  74. Lim YJ, Sim WS, Kim YC, Lee SC, Choi YL. The neurotoxicity of epidural hyaluronic acid in rabbits: a light and electron microscopic examination. Anesth Analg. 2003;97(6):1716-20. [Crossref]

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Turkish Law will be applied in practicing, interpreting the hereby "Terms of Use" and managing the emerging legal relationships within this "Terms of Use" in case of finding element of foreignness, except for the rules of Turkish conflict of laws. Ankara Courts and Enforcement Offices are entitled in any controversy happened or may happen due to hereby contract.

9. CLOSING AND AGREEMENT

Hereby "Terms of Use" come into force when announced in the "SITE" by "Turkiye Klinikleri". The users are regarded to agree to hereby contract terms by using the "SITE". "Turkiye Klinikleri" may change the contract terms and the changes will be come into force by specifying the version number and the date of change on time it is published in the "SITE".

 

30.03.2014

Privacy Policy

We recommend you to read the terms of use below before you visit our website. In case you agree these terms, following our rules will be to your favor. Please read our Terms of Use thoroughly.

www.turkiyeklinikleri.com website belongs to Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. and is designed in order to inform physicians in the field of health

www.turkiyeklinikleri.com cannot reach to user’s identity, address, service providers or other information. The users may send this information to the website through forms if they would like to. However, www.turkiyeklinikleri.com may collect your hardware and software information. The information consists of your IP address, browser type, operating system, domain name, access time, and related websites. www.turkiyeklinikleri.com cannot sell the provided user information (your name, e-mail address, home and work address, phone number) to the third parties, publish it publicly, or keep it in the website. Gathered information has a directing feature to be a source for the website’s visitor profile, reporting and promotion of the services.

www.turkiyeklinikleri.com uses the taken information:

-To enhance, improve and maintain the quality of the website

-To generate visitor’s profile and statistical data

-To determine the tendency of the visitors on using our website

-To send print publications/correspondences

-To send press releases or notifications through e-mail

-To generate a list for an event or competition

By using www.turkiyeklinikleri.com you are considered to agree that;

-Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. cannot be hold responsible for any user’s illegal and immoral behavior,

-Terms of use may change from time to time,

-It is not responsible for other websites’ contents it cannot control or the harms they may cause although it uses the connection they provided.

Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. may block the website to users in the following events:

-Information with wrong, incomplete, deceiving or immoral expressions is recorded to the website,

-Proclamation, advertisement, announcement, libelous expressions are used against natural person or legal identity,

-During various attacks to the website,

-Disruption of the website because of a virus.

Written, visual and audible materials of the website, including the code and the software are under protection by legal legislation.

Without the written consent of Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. the information on the website cannot be downloaded, changed, reproduced, copied, republished, posted or distributed.

All rights of the software and the design of the website belong to Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc.

Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. will be pleased to hear your comments about our terms of use. Please share the subjects you think may enrich our website or if there is any problem regarding our website.

info@turkiyeklinikleri.com