Chemical modification of curcumin: Solubility and antioxidant capacity

ABSTRACT

The aim of this study was to develop a chemical method for demythylation of curcumin. The methoxy groups reduced solubility and low bioavailability of curcumin. The treatment of curcumin with hydrogen bromide or choline chloride increased cucumin water solubility from 1 mg/mL to 30 or 25 mg/mL, respectively. ¹HNMR spectra showed that the chemical shift of O-methoxy groups at 3.9 ppm disappeared upon chemical treatment of curcumin, and indicated that these groups were removed especially after hydrogen bromide treatment. The antioxidant activity of treated curcumin and untreated curcumin was measured using different in vitro assays (i.e., 1,1-diphenyl-2-picrylhydrazyl and 2,2’-azino-bis (3-ethylbenzo-thiazoline-6-sulfonic acid) radical scavenging, and phosphomolybdenum complex formation). A remarkable increase in 1,1-diphenyl-2-picrylhydrazyl and 2,2’-azino-bis (3-ethylbenzo-thiazoline-6-sulfonic acid) radical scavenging was observed as curcumin-hydrogen bromide > curcumin-Choline chloride > curcumin. The formation of phosphomolybdenum complex was found to increase in the order of curcumin-choline cloride > curcumin-hydrogen bromide > curcumin with EC₅₀ 30, 41, and 114 µg/mL, respectively. In conclusion, hydrogen bromide-treated curcumin could be used as potential antioxidant in new functional foods.

KEYWORDS:

• Curcumin
• Demethylation
• Acid treatment
• Water solubility
• Antioxidant activities

Funding

This article was funded by the Deanship of Scientific Research (DSR), King Abdulaziz University, Jeddah, under grant Number 36-130-D1432. The authors are grateful to DSR for the technical and financial support.

References

• Cheng, K.K.; Yeung, C.F.; Ho, S.W.; Chow, S.F.; Chow, A.H.; Baum, L. Highly Stabilized Curcumin Nanoparticles Tested in an in Vitro Bloodebrain Barrier Model and in Alzheimer’s Disease Tg2576 Mice. AAPS Journal 2012, 15, 324–336.
   PubMed Web of Science ®Google Scholar
• Olszanecki, R.; Jawien, J.; Gajda, M.; Mateuszuk, L.; Gebska, A.; Korabiowska, M.; Chlopicki, S.; Korbut, R. Effect of Curcumin on Atherosclerosis in Apoe/LDLR-Double Knockout Mice. Journal of Physiology and Pharmacology 2005, 56, 627–635.
   PubMed Web of Science ®Google Scholar
• Shin, S.K.; Ha, T.Y.; McGregor, R.A.; Choi, M.S. Longterm Curcumin Administration Protects Against Atherosclerosis Via Hepatic Regulation of Lipoprotein Cholesterol Metabolism. Molecular Nutrition and Food Research 2011, 55, 1829–1840.
   Google Scholar
• Bar-Sela, G.; Epelbaum, R.; Schaffer, M. Curcumin as an Anti-Cancer Agent: Review of the Gap Between Basic and Clinical Applications. Current Medicinal Chemistry 2010, 17, 190–197.
   PubMed Web of Science ®Google Scholar
• Duvoix, A.; Blasius, R.; Delhalle, S.; Schnekenburge, M.; Morceau F.; Henry, E.; Dicato, M.; Diederich, M. Chemopreventive and Therapeutic Effects of Curcumin. Cancer Letters 2005, 223, 181–190.
   PubMed Web of Science ®Google Scholar
• Anand, P.; Sundaram, C.; Jhurani, S.; Kunnumakkara, A.B.; Aggarwal, B.B. Curcumin and Cancer: An “Old-Age” Disease with an “Age-Old” Solution. Cancer Letters 2008, 267, 133–164.
   PubMed Web of Science ®Google Scholar
• Ravindran, J.; Prasad, S.; Aggarwal, B.B. Curcumin and Cancer Cells: How Many Ways Can Curry Kill Tumor Cells Selectively. AAPS Journal 2009, 11, 495–510.
   PubMed Web of Science ®Google Scholar
• Anantharaman, A.; Subramanian, B.; Chandrasekaran, R.; Seenivasan, R.; Siva, R. Colorants and Cancer: A Review. Industrial Crops and Products 2014, 53, 167–186.
   Web of Science ®Google Scholar
• El-Sayed, E.M.; El-azeem, A.S.A.; Afify, A.A.; Shabana, M.H.; Ahmed, H.H. Cardioprotective Effects of Curcuma Longa L. Extracts Against Doxorubicininduced Cardiotoxicity in Rats. Journal of Medicinal Plant Reserach 2011, 5, 4049–4058.
   Google Scholar
• Naksuriya, O.; Okonogi, S.; Schiffelers, R.M.; Hennink, W.E. Curcumin Nanoformulations: A Review of Pharmaceutical Properties and Preclinical Studies and Clinical Data Related to Cancer Treatment. Biomaterials 2014, 35, 3365–3383.
   PubMed Web of Science ®Google Scholar
• Torchilin, V.P. Recent Advances with Liposomes as Pharmaceutical Carriers. Nature Review. Drug Discovery 2005, 4, 145–160.
   PubMed Web of Science ®Google Scholar
• Sun, M.; Su, X.; Ding, B.; He, X.; Liu, X.; Yu, A.; Lou, H.; Zhai, G. Advances in Nanotechnology Based Delivery Systems for Curcumin. Nanomedicine UK 2012, 7, 1085–1100.
   PubMed Web of Science ®Google Scholar
• Kataoka, K.; Harada, A.; Nagasaki, Y. Block Copolymer Micelles for Drug Delivery: Design, Characterization and Biological Significance. Advanced Drug Delivery Reviews 2001, 47, 113–131.
   PubMed Web of Science ®Google Scholar
• Parvathy, K.; Negi, P.; Srinivas, P. Curcumineamino Acid Conjugates: Synthesis, Antioxidant and Antimutagenic Attributes. Food Chemistry 2010, 120, 523–530.
   Web of Science ®Google Scholar
• Esmaili, M.; Ghaffari, S.M.; Moosavi-Movahedi, Z.; Atri, M.S.; Sharifizadeh, A.; Farhadi, M.; Youefi, R.; Chobert, J-M.; Haertle T.; Moosavi-Movahedi A.A. Beta Casein-Micelle as a Nano Vehicle For Solubility Enhancement of Curcumin; Food Industry Application. LWT Food Science and Technology 2011, 44, 2166–2172.
   Web of Science ®Google Scholar
• Loftsson, T.; Duchêne, D. Cyclodextrins and Their Pharmaceutical Applications. International Journal of Pharmacology 2007, 329, 1–11.
   PubMed Web of Science ®Google Scholar
• Ford, J.L. The Current Status of Solid Dispersions. Pharmaceutica Acta Helvetiae 1986, 61, 69–88.
   PubMedGoogle Scholar
• Mohanty, C.; Sahoo, S.K. The in Vitro Stability and in Vivo Pharmacokinetics of Curcumin Prepared as an Aqueous Nanoparticulate Formulation. Biomaterials 2010, 31, 6597–6611.
   PubMed Web of Science ®Google Scholar
• Tapal, A.; Tiku, P.K. Complexation of Curcumin with Soy Protein Isolate and Its Implications on Solubility and Stability of Curcumin. Food Chemistry 2012, 130, 960–965.
   Web of Science ®Google Scholar
• Abbott, A.P.; Capper, G.; McKenzie, K.J.; Ryder, K.S. Electrodeposition of Zinc-Tin Alloys from Deep Eutectic Solvents Based on Choline Chloride. Journal of Electroanalytical Chemistry 2007, 599, 288–294.
   Web of Science ®Google Scholar
• Ao, C.; Li, A.; Elzaawely, A.A.; Xuan, T.D.; Tawata, S. Evaluation of Antioxidant and Antibacterial Activities of Ficus microcarpa L. Fil. Extract. Food Control 2008, 19, 940–948.
   Web of Science ®Google Scholar
• Shirwaikar, A.; Shirwaikar, A.; Rajendran, K.; Punitha, I.S. In Vitro Antioxidant Studies on the Benzyl Tetra Isoquinoline Alkaloid Berberine. Biological and Pharmaceutical Bulletin 2006, 29, 1906–1910.
   Google Scholar
• Re, R.; Pellegrini, N.; Proteggente, A.; Pannala, A.; Yang, M.; Rice-Evans, C. Antioxidant Activity Applying an Improved ABTS Radical Cation Decolorization Assay. Free Radical Biology and Medicine 1999, 26, 1231–1237.
   PubMed Web of Science ®Google Scholar
• Prieto, P.; Pineda, M.; Aguilar, M. Spectrophotometric Quantitation of Antioxidant Capacity Through the Formation of a Phosphomolybdenum Complex: Specific Application to the Determination of Vitamin E. Analytical Biochemistry 1999, 269, 337–341.
   PubMed Web of Science ®Google Scholar
• Wichitnithad, W.; Nimmannit, U.; Wacharasindhu, S.; Rojsitthisak, P. Synthesis, Characterization and Biological Evaluation of Succinate Prodrugs of Curcuminoids for Colon Cancer Treatment. Molecules 2011, 16, 1888–1900.
   Google Scholar
• Ozcelik, B.; Lee, J.H.; Min, D.B. Effects of Light, Oxygen and pH on the 2,2-Diphenyl-1-Picrylhydrazyl (DPPH) Method to Evaluate Antioxidants. Journal of Food Science 2003, 68, 487–490.
   Web of Science ®Google Scholar
• Matthaus, B. Antioxidant Activity of Extracts Obtained from Residues of Different Oilseeds. Journal of Agriculture Food Chemistry 2002, 50, 3444–3452.
   PubMed Web of Science ®Google Scholar
• Kaviarasan, S.; Naik, G.H.; Gangabhagirathi, R.; Anuradha, C.V.; Priyadarsini, K. I. In Vitro Studies on Antiradical and Antioxidant Activities of Fenugreek (Trigonella Foenum Graecum) Seeds. Food Chemistry 2007, 103, 31–37.
   Google Scholar
• D’abrosca, D.; Pacifico, S.; Cefarelli, G.; Mastellone, C.; Fiorentino, A. Limoncella’ Apple, an Italian Apple Cultivar: Phenolic and Flavonid Contents and Antioxidant Activity. Food Chemistry 2007, 104, 1333–1337.
   Web of Science ®Google Scholar

Additional information

Funding

This article was funded by the Deanship of Scientific Research (DSR), King Abdulaziz University, Jeddah, under grant Number 36-130-D1432. The authors are grateful to DSR for the technical and financial support.