PHYTIC ACID (MYO-INOSITOL HEXAPHOSPHATE)- A PROMISING PHARMACEUTICAL AGENT: A REVIEW

  • Radhakrishnan Narayanaswamy Bio Incubator and Lab, Vel Tech Technology Incubator, Vel Tech Rangarajan Dr. Sagunthala R and D Institute of Science and Technology, 400 Feet Outer Ring Road, Avadi, Chennai, Tamil Nadu, India.
  • Norhaizan Mohd Esa Department of Nutrition and Dietetics, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia.

Abstract

Phytic acid (myo-inositol hexaphosphate) has gained much attention among researchers for its therapeutic value. This review focuses on pharmacological activities of phytic acid, which have been demonstrated by pre-clinical studies. Anti-carcinogenic, antioxidant, antidiabetic, hypolipidemic, anti-angiogenic, and immunomodulation are the most extensively studied pharmacological activities of phytic acid. In addition to these, phytic acid and its derivatives also possess enzyme inhibitory activities against few key enzymes such as 5-alpha reductase, aldose reductase, cyclooxygenase, lipase, matrix metalloproteinase-2 & 9, pepsin, polyphenol oxidase, protease, β-secretase, tyrosinase, and xanthine oxidase were emphasized. The profound pharmacological activities of phytic acid have proven to be a good therapeutic agent and could be employed in preventing as well as treating such diseases.

Keywords: Phytic acid (myo-inositol hexaphosphate), Anticarcinogenic, Hypoallergenic, 5-alpha reductase (type-2), β-Secretase (type-1).

References

1. Oatway L, Vasanthan T, Helm JH. Phytic acid. Food Rev Int 2001;17:419-31.
2. Valli SA, Gowrie SU. A study on the bioactive potential of fresh and dried sprouts of Cocos nucifera L. An in vitro and in silico approach. Int J Pharm Pharm Sci 2017;9:129-42.
3. Tyagi P, Kumar Y, Gupta D, Singh H, Kumar A. Therapeutic advancements in management of iron over load-a review. Int J Pharm Pharm Sci 2015;7:35-44.
4. Graf E, Empson KL, Eaton JW. Phytic acid. A natural antioxidant. J Biol Chem 1987;262:11647-50.
5. Reddy NR. Occurrence, distribution, content, and dietary intake of phytate. In: Reddy NR, Sathe SK, editors. Food Phytates. Boca Raton: CRC; 2002. p. 25-51.
6. Shamsuddin AM. Metabolism and cellular functions of IP6: A review. Anticancer Res 1999;19:3733-6.
7. Wawszczyk J, Kapral M, Hollek A, Weglarz L. The effect of phytic acid on the expression of NF-kappaB, IL-6 and IL-8 in IL-1beta-stimulated human colonic epithelial cells. Acta Pol Pharm 2012;69:1313-9.
8. Tsao GT, Zheng Y, Lu J, Gong CS. Adsorption of heavy metal ions by immobilized phytic acid. Appl Biochem Biotechnol 1997;63 65:731- 41.
9. Graf E, Eaton JW. Antioxidant functions of phytic acid. Free Radic Biol Med 1990;8:61-9.
10. Hue JJ, Li L, Lee YE, Lee KN, Nam SY, Yun YW, et al. Antibacterial activity of sodium phytate and sodium phosphates against Escherichia coli O157: H7 in meats. J Fd Hyg Saf 2007;22:37-44.
11. Han BK, Choi HJ, Park YS. Antimicrobial and antioxidative activities of phytic acid in meats. Food Eng Prog 2012;16:145-50.
12. Yoon JH, Thompson LU, Jenkins DJ. The effect of phytic acid on in vitro rate of starch digestibility and blood glucose response. Am J Clin Nutr 1983;38:835-42.
13. Larsson O, Barker CJ, Sjöholm A, Carlqvist H, Michell RH, Bertorello A, et al. Inhibition of phosphatases and increased ca2+ channel activity by inositol hexakisphosphate. Science 1997;278:471- 4.
14. Barker CJ, Berggren PO. Inositol hexakisphosphate and beta-cell stimulus-secretion coupling. Anticancer Res 1999;19:3737-41.
15. Kuppusamy A, Muthusamy U, Thirumalaisamy SA, Varadharajan S, Ramasamy K, Ramanathan S. In vitro (α-glucosidase and α-amylase inhibition) and in vivo antidiabetic property of phytic acid (IP6) in streptozotocin-nicotinamide-induced Type 2 diabetes mellitus (NIDDM) in rats. J Complement Integr Med 2011;8:1483.
16. Kunyanga CN, Imungi JK, Okoth MW, Biesalski HK, Vadivel V. Antioxidant and Type 2 diabetes related functional properties of phytic acid extract from Kenyan local food ingredients: Effects of traditional processing methods. Ecol Food Nutr 2011;50:452-71.
17. Maldonado-Rojas W, Olivero-Verbel J. Potential interaction of natural dietary bioactive compounds with COX-2. J Mol Graph Model 2011;30:157-66.
18. Radhakrishnan N, Lam KW, Intan SI. In silico analysis of selected honey constituents as human neutrophil elastase (HNE) and matrix metalloproteinases (MMP 2 and 9) inhibitors. Int J Food Prop 2015;18:2155-64.
19. Sudheer Kumar M, Sridhar Reddy B, Kiran Babu S, Bhilegaonkar PM, Shirwaikar A, Unnikrishnan MK, et al. Antiinflammatory and antiulcer activities of phytic acid in rats. Indian J Exp Biol 2004;42:179-85.
20. Bozsik A, Kökény S, Olah E. Molecular mechanisms for the antitumor activity of inositol hexakisphosphate (IP6). Cancer Genomics Proteomics 2007;4:43-51.
21. Kumar V, Sinha AK, Makkar HP, Becker K. Dietary roles of phytate and phytase in human nutrition: A review. Food Chem 2010;120:945- 59.
22. McFadden DW, Riggs DR, Jackson BJ, Cunningham C. Corn-derived carbohydrate inositol hexaphosphate inhibits Barrett’s adenocarcinoma growth by pro-apoptotic mechanisms. Oncol Rep 2008;19:563-6.
23. Hussein MR, Abd El-Aziz MA, Ahmad NS, Omran F, Abdulhameed M. The biochemical changes associated with phytic acid on induced breast proliferative lesions in rats: Preliminary findings. Cancer Biol Ther 2006;5:1129-33.
24. Norazalina S, Norhaizan ME, Hairuszah I, Norashareena MS. Anticarcinogenic efficacy of phytic acid extracted from rice bran on azoxymethane-induced colon carcinogenesis in rats. Exp Toxicol Pathol 2010;62:259-68.
25. Nurul-Husna S, Norhaizan ME, Hairuszah I, Abdah MA, Norazalina S, Norsharina I. Rice bran phytic acid (IP6) induces growth inhibition, cell cycle arrest and apoptosis on human colorectal adenocarcinoma cells. J Med Plants Res 2010;4:2283-9.
26. Karmakar S, Banik NL, Ray SK. Molecular mechanism of inositol hexaphosphate-mediated apoptosis in human malignant glioblastoma T98G cells. Neurochem Res 2007;32:2094-102.
27. Dorsey M, Benghuzzi H, Tucci M, Cason Z. Growth and cell viability of estradiol and IP-6 treated hep-2 laryngeal carcinoma cells. Biomed Sci Instrum 2005;41:205-10.
28. Janus SC, Weurtz B, Ondrey FG. Inositol hexaphosphate and paclitaxel: Symbiotic treatment of oral cavity squamous cell carcinoma. Laryngoscope 2007;117:1381-8.
29. Somasundar P, Riggs DR, Jackson BJ, Cunningham C, Vona-Davis L, McFadden DW, et al. Inositol hexaphosphate (IP6): A novel treatment for pancreatic cancer. J Surg Res 2005;126:199-203.
30. Agarwal C, Dhanalakshmi S, Singh RP, Agarwal R. Inositol hexaphosphate inhibits constitutive activation of NF- kappa B in androgen-independent human prostate carcinoma DU145 cells. Anticancer Res 2003;23:3855-61.
31. Gupta KP, Singh J, Bharathi R. Suppression of DMBA-induced mouse skin tumor development by inositol hexaphosphate and its mode of action. Nutr Cancer 2003;46:66-72.
32. Graf E, Mahoney JR, Bryant RG, Eaton JW. Iron-catalyzed hydroxyl radical formation. Stringent requirement for free iron coordination site. J Biol Chem 1984;259:3620-4.
33. Canan C, Delaroza F, Casagrande R, Baracat MM, Shimokomaki M, Ida EI. Antioxidant capacity of phytic acid purified from rice bran. Acta Sci Technol 2012;34:457-63.
34. Zajdel A, Wilczok A, Węglarz L, Dzierżewicz Z. Phytic acid inhibits lipid peroxidation in vitro. Biomed Res Int 2013;2013:147307.
35. Norhaizan ME, Ng SK, Norashareena MS, Abdah MA. Antioxidant and cytotoxicity effect of rice bran phytic acid as an anticancer agent on ovarian, breast and liver cancer cell lines. Malays J Nutr 2011;17:367- 75.
36. Vucenik I, Podczasy JJ, Shamsuddin AM. Antiplatelet activity of inositol hexaphosphate (IP6). Anticancer Res 1999;19:3689-93.
37. Vucenik I, Passaniti A, Vitolo MI, Tantivejkul K, Eggleton P, Shamsuddin AM, et al. Anti-angiogenic activity of inositol hexaphosphate (IP6). Carcinogenesis 2004;25:2115-23.
38. Otake T, Shimonaka H, Kanai M, Miyano K, Ueba N, Kunita N, et al. Inhibitory effect of inositol hexasulfate and inositol hexaphosphoric acid (phytic acid) on the proliferation of the human immunodeficiency virus (HIV) in vitro. Kansenshogaku Zasshi 1989;63:676-83.
39. Otake T, Mori H, Morimoto M, Miyano K, Ueba N, Oishi I, et al. Anti-HIV-1 activity of myo-inositol hexaphosphoric acid (IP6) and myo-inositol hexasulfate(IS6). Anticancer Res 1999;19:3723-6.
40. Mcclure FJ. The cariostatic effect in white rats of phosphorus and calcium supplements added to the flour of bread formulas and to bread diets. J Nutr 1960;72:131-6.
41. Mcclure FJ. Cariostatic effect of phosphates. Science 1964;144:1337-8.
42. Englander HR, Keyes PH. Effect of phosphate supplements on cavitation in hamsters infected with caries-conducive streptococci. J Dent Res 1970;49:140-4.
43. Kaufman HW, Kleinberg I. Effect of pH on calcium binding by phytic acid and its inositol phosphoric acid derivatives and on the solubility of their calcium salts. Arch Oral Biol 1971;16:445-60.
44. Vasca E, Materazzi S, Caruso T, Milano O, Fontanella C, Manfredi C, et al. Complex formation between phytic acid and divalent metal ions: A solution equilibria and solid state investigation. Anal Bioanal Chem 2002;374:173-8.
45. Eberhard M, Föller M, Lang F. Effect of phytic acid on suicidal erythrocyte death. J Agric Food Chem 2010;58:2028-33.
46. Chung SY, Champagne ET. Effects of phytic acid on peanut allergens and allergenic properties of extracts. J Agric Food Chem 2007;55:9054- 8.
47. Katayama T. Hypolipidemic action of phytic acid (IP6): Prevention of fatty liver. Anticancer Res 1999;19:3695-8.
48. Lee SH, Park HJ, Chun HK, Cho SY, Jung HJ, Cho SM, et al. Dietary phytic acid improves serum and hepatic lipid levels in aged ICR mice fed a high-cholesterol diet. Nutr Res 2007;27:505-10.
49. Kang MY, Kim SM, Rico CW, Lee SC. Hypolipidemic and antioxidative effects of rice bran and phytic acid in high fat-fed mice. Food Sci Biotechnol 2012;21:123-8.
50. Weglarz L, Parfiniewicz B, Mertas A, Kondera-Anasz Z, Jaworska-Kik M, Dzierzewicz Z. Effect of inositol hexaphosphate on lipopolysaccharide-stimulated release of TNF-alpha from human mononuclear cells. Pol J Environ Stud 2008;17:283-90.
51. Xu Q, Kanthasamy AG, Reddy MB. Neuroprotective effect of the natural iron chelator, phytic acid in a cell culture model of Parkinson’s disease. Toxicology 2008;245:101-8.
52. Lv Y, Zhang Z, Hou L, Zhang L, Zhang J, Wang Y, et al. Phytic acid attenuates inflammatory responses and the levels of NF-κB and p-ERK in MPTP-induced Parkinson’s disease model of mice. Neurosci Lett 2015;597:132-6.
53. Grases F, Garcia-Gonzalez R, Torres JJ, Llobera A. Effects of phytic acid on renal stone formation in rats. Scand J Urol Nephrol 1998;32:261-5.
54. Selvam R. Calcium oxalate stone disease: Role of lipid peroxidation and antioxidants. Urol Res 2002;30:35-47.
55. Narayanaswamy R, Wai LK, Esa NM. Molecular docking analysis of phytic acid and 4-hydroxyisoleucine as cyclooxygenase-2, microsomal prostaglandin E synthase-2, tyrosinase, human neutrophil elastase, matrix metalloproteinase-2 and -9, xanthine oxidase, squalene synthase, nitric oxide synthase, human aldose reductase, and lipoxygenase inhibitors. Pharmacogn Mag 2017;13:S512-S518.
56. Sharma S. Screening of Natural Inhibition of 5-Alpha Reductase Type 2 for Treatment of Prostate Cancer - An in Silico Approach. Master Thesis 2010 Submitted to Mehsana Urban Institute of Sciences, Ganpat University, Gujrat, India.
57. Ruf JC, Ciavatti M, Gustafsson T, Renaud S. Effect of D-myo-inositol on platelet function and composition and on cataract development in streptozotocin-induced diabetic rats. Biochem Med Metab Biol 1992;48:46-55.
58. Saad N, Esa NM, Ithnin H. Suppression of β-catenin and cyclooxygenase-2 expression and cell proliferation in azoxymethane-induced colonic cancer in rats by rice bran phytic acid (PA). Asian Pac J Cancer Prev 2013;14:3093-9.
59. Knuckles BE. Effect of phytate and other myo-inositol phosphate esters on lipase activity. J Food Sci 1988;53:250-2.
60. Kapral M, Wawszczyk J, Jurzak M, Dymitruk D, Weglarz L. Evaluation of the expression of metalloproteinases 2 and 9 and their tissue inhibitors in colon cancer cells treated with phytic acid. Acta Pol Pharm 2010;67:625-9.
61. Kapral M, Wawszczyk J, Hollek A, Dymitruk D, Weglarz L. Inhibitory effect of inositol hexaphosphate on metalloproteinases transcription in colon cancer cells stimulated with phorbol-12-myristate 13-acetate. Acta Pol Pharm 2012;69:1307-12.
62. Yu S, Cowieson A, Gilbert C, Plumstead P, Dalsgaard S. Interactions of phytate and myo-inositol phosphate esters (IP1-5) including IP5 isomers with dietary protein and iron and inhibition of pepsin. J Anim Sci 2012;90:1824-32.
63. Du Y, Dou S, Wu S. Efficacy of phytic acid as an inhibitor of enzymatic and non-enzymatic browning in apple juice. Food Chem 2012;135:580- 2.
64. Khan A, Ghosh K. Evaluation of phytase production by fish gut bacterium, Bacillus subtilis, for processing of Ipomea aquatica leaves as probable aquafeed ingredient. J Aquat Food Prod Technol 2013;22:508 19.
65. Abe TK, Taniguchi M. Identification of myo-inositol hexakisphosphate (IP6) as a β-secretase 1 (BACE1) inhibitory molecule in rice grain extract and digest. FEBS Open Bio 2014;4:162-7.
66. Levy JL, Pons F, Agopian L, Besson R. A double-blind controlled study of a nonhydroquinone bleaching cream in the treatment of melasma. J Cosmet Dermatol 2005;4:272-6.
67. Muraoka S, Miura T. Inhibition of xanthine oxidase by phytic acid and its antioxidative action. Life Sci 2004;74:1691-700.
68. Graf E. Applications of phytic acid. J Am Oil Chem Soc 1983;60:1861- 7.
69. Ravichandran R, Seitz V, Venugopal JR, Sridhar R, Sundarrajan S, Mukherjee S, et al. Mimicking native extracellular matrix with phytic acid-crosslinked protein nanofibers for cardiac tissue engineering. Macromol Biosci 2013;13:366-75.
Statistics
208 Views | 218 Downloads
Citatons
How to Cite
Narayanaswamy, R., and N. Mohd Esa. “PHYTIC ACID (MYO-INOSITOL HEXAPHOSPHATE)- A PROMISING PHARMACEUTICAL AGENT: A REVIEW”. Asian Journal of Pharmaceutical and Clinical Research, Vol. 11, no. 11, Nov. 2018, pp. 42-46, doi:10.22159/ajpcr.2018.v11i11.27843.
Section
Review Article(s)