Management of chronic anterior uveitis relapses: efficacy of oral phospholipidic curcumin treatment. Long-term follow-up

Pia Allegri, Antonio Mastromarino, Piergiorgio Neri, Pia Allegri, Antonio Mastromarino, Piergiorgio Neri

Abstract

Curcumin has been successfully applied to treat inflammatory conditions in experimental research and in clinical trials. The purpose of our study is to evaluate the efficacy of an adjunctive-to-traditional treatment with Norflo tablets (curcumin-phosphatidylcholine complex; Meriva) administered twice a day in recurrent anterior uveitis of different etiologies. The study group consisted of 106 patients who completed a 12-month follow-up therapeutic period. We divided the patients into three main groups of different uveitis origin: group 1 (autoimmune uveitis), group 2 (herpetic uveitis), and group 3 (different etiologies of uveitis). The primary end point of our work was the evaluation of relapse frequency in all treated patients, before and after Norflo treatment, followed by the number of relapses in the three etiological groups. Wilcoxon signed-rank test showed a P < 0.001 in all groups. The secondary end points were the evaluation of relapse severity and of the overall quality of life. The results showed that Norflo was well tolerated and could reduce eye discomfort symptoms and signs after a few weeks of treatment in more than 80% of patients. In conclusion, our study is the first to report the potential therapeutic role of curcumin and its efficacy in eye relapsing diseases, such as anterior uveitis, and points out other promising curcumin-related benefits in eye inflammatory and degenerative conditions, such as dry eye, maculopathy, glaucoma, and diabetic retinopathy.

Keywords: anterior recurrent uveitis; curcumin; phosphatidylcholine-bound-curcumin (Meriva).

Figures

Figure 1
Figure 1
A) Total number of patients with relapses before and after Norflo therapy. B) Total relapse number before and after Norflo therapy. Note: Wilcoxon signed-rank test: P < 0.001.

References

    1. Bengmark S. Curcumin an atoxic antioxidant and natural NFkappab, cycclooxygenase-2, lipooxygenase and inducible nitric oxide synthase inhibitor: a shield against acute and chronic diseases. J Par Ent Nutr. 2006;30(1):61–62.
    1. Bright JJ. Curcumin and autoimmune disease. Adv Exp Med Biol. 2007;595:425–451.
    1. Jacob A, Rongqian W, Zhou M, Wang P. Mechanism of the anti-inflammatory effect of curcumin: PPAR-γ activation. PPAR Res. 2007;89369
    1. Nonn L, Duong D, Preehl DM. Chemopreventive anti-inflammatory activities of curcumin and other phytochemicals mediated by MAP kinase phosphatase-5 in prostate cells. Carcinogenesis. 2007;28:1188–1196.
    1. Shakibaei M, John T, Schulze–Tanzil G, Lehmann I, Mobasheri A. Suppression of NF-kappaB activation by curcumin leads to inhibition of expression of cyclo-oxygenase-2 and matrix-metalloproteinase-9 in human articular chondrocytes: implications for the treatment of osteoarthritis. Biochem Pharmacol. 2007;73:1434–1445.
    1. Strimpakos AS, Sharma RA. Curcumin: preventive and therapeutic properties in laboratory studies and clinical trials. Antioxid Redox Signal. 2008;10:511–545.
    1. Holt PR, Katz S, Kirshoff R. Curcumin therapy in inflammatory bowel disease: a pilot study. Dig Dis Sci. 2005;50:2191–2193.
    1. Jobin C, Bradham CA, Russo MP, et al. Curcumin blocks cytokine-mediated NF-kappaB Activation pro-inflammatory gene expression by inhibiting inhibitory factor I-kappaB kinase activity. J Immunol. 1999;15:3474–3483.
    1. Mohan R, Sivak J, Ashton P, et al. Curcuminoids inhibit the angiogenic response stimulated by fibroblast growth-factor-2, including expression of matrix metalloproteinase gelatinase B. J Biolog Chem. 2000;275(14):10405–10412.
    1. Goel A, Kunnumakkara AB, Aggarwal BB. Curcumin as “curecumin”: from kitchen to clinic. Biochem Pharmacol. 2008;75(4):787–809.
    1. Biswas S, Rahman I. Modulation of steroid activity in chronic inflammation: a novel anti-inflammatory role for curcumin. Mol Nutr Food Res. Epub 2008 Mar 10.
    1. Yadav VS, Mishra KP, Singh DP, Mehrotra S, Singh VK. Immunomodulatory effects of curcumin. Immunopharmacol Immunotoxicol. 2005;27(3):485–497.
    1. Malchiodi-Albedi F, Matteucci A, Bernardo A, Minghetti L. PPAR-γ, microglial cells, and ocular inflammation: new venues for potential therapeutic approaches. PPAR res . 2008:295784.
    1. Murata T, He S, Hangai M, et al. Peroxisome proliferator-activated receptor-gamma ligands inhibit choroidal neovascularization. Invest Ophthalmol Vis Sci. 2000;41(8):2309–2317.
    1. Bonne C. PPAR gamma: a novel pharmacological target against retinal and choroidal neovascularization. J Fr Ophtalmol. 2005;28(3):326–330.
    1. Siddiqui AM, Cui X, Wu R, et al. The anti-inflammatory effect of curcumin in an experimental model of sepsis is mediated by upregulation of peroxisome proliferator-activated receptor-γ. Critical Care Med. 2006;34(7):1874–1882.
    1. Jiang C, Ting T, Seed B. PPAR-γ agonists inhibit production of monocyte inflammatory cytokines. Nature. 1998;391:82–86.
    1. Cuomo J, Chernyshev V. Preliminary report–comparative bioavailability of curcuminoids from Meriva® vs 95% curcumin extract. Salt Lake City, UT: Usana Health Sciences, Inc; 2009.
    1. Wan YJ, Pan MH, Cheng AL, et al. Stability of curcumin in buffer solutions and characterization of its degradation products. J Pharm Biomed Anal. 1997;15(12):1867–1876.
    1. Anand P, Kunnumakkara AB, Newman RA, Aggarwal BB. Bioavailability of curcumin: problems and promises. Mol Pharm. 2007;4(6):807–818.
    1. Marczylo TH, Verschoyle RD, Cooke DN, Morazzoni P, Steward WP, Gescher AJ. Comparison of systemic availability of curcumin with that of curcumin formulated with phosphatidylcholine. Cancer Chemoter Pharmacol. 2007;60:171–177.
    1. Lal B, Kapoor AK, Asthana OP, et al. Efficacy of curcumin in the management of chronic anterior uveitis. Phytother Res. 1999;13:318–322.
    1. Bloch-Michel E, Nussenblatt RB International Uveitis Study Group. Recommendations for the evaluation of intraocular inflammatory diseases. Am J Ophthalmol. 1987;103:234–235.
    1. Li L, Braiteh FS, Kurzrock R. Liposome-encapsulated curcumin. In vitro and in vivo effects on proliferation, apoptosis, signaling and angiogenesis. Cancer. 2005;104(6):1322–1331.
    1. Jurenka J. Anti-inflammatory properties of curcumin, a major constituent of Curcuma longa: a review of preclinical and clinical research. Alt Med Rev. 2009;14(2):141–153.
    1. Marczylo TH, Steward WP, Gesher AJ. Rapid analysis of curcumin and curcumin metabolites in rat biomatrices using a novel ultraperformance liquid chromatography method. J Agric Food Chem. 2009;57(3):797–803.
    1. Lal B, Kapoor K, Agrawal PK, Asthana OP, Srimal RC. Role of curcumin in idiopathic inflammatory orbital pseudotumours. Phytother Res. 2000;14(6):443–447.
    1. Passos E, Grinstead RL, Khoobehi B. Effectiveness of curcumin, an angiogenesis inhibitor, in experimental choroidal neovascularization in rats. Invest Ophthalmol Vis Sci. 2002;43 E-Abstract 1274.
    1. Chen M, Hu D-N, Pan Z, Lu CW, Xue CY, Aass I. Curcumin protects against hyperosmoticity-induced IL-1β elevation in human corneal epithelial cell via MAPK pathways. Exp Eye Res. 2010;90(3):437–443.
    1. Kumar PA, Suryanarayana P, Reddy PY, Reddy GB. Modulation of α-crystallin chaperone activity in diabetic rat lens by curcumin. Mol Vision. 2005;11:561–568.
    1. Hata M, Sasaki E, Ota M, et al. Allergic contact dermatitis from curcumin (turmeric) Contact Dermatol. 1997;36:107–108.
    1. Swierczynska MK, Krecisz B. Occupational skin changes in persons working in contact with food spices. Med Pr. 1998;49:187–190.
    1. Sharma RA, Steward WP, Gesher AJ. Pharmacokinetics and pharmacodynamics of curcumin. Adv Exp Med Biol. 2007;595:453–470.
    1. Lao CD, Ruffin MT, Normolle D, et al. Dose escalation of a curcuminoid formulation. BMC Complement Altern Med. 2006;6:10.
    1. Bisht S, Feldmann G, Soni S, et al. Polymeric nanoparticle-encapsulated curcumin: a novel strategy for human cancer therapy. J Nanobiotechnology. 2007;5:3.
    1. Maiti K, Mukherjee K, Gantait A, Saha BP, Mukherjee PK. Curcumin-phospholipid complex: preparation, therapeutic evaluation and pharmacokinetic study in rats. Int J Pharm. 2007;330:155–163.
    1. Aggarwal BB, Sung B. Pharmacological basis for the role of curcumin in chronic diseases: an age-old spice with modern targets. Trends Pharmacol Sci. 2009;30(2):85–94.
    1. Barry J, Fritz M, Brender JR. Determining the effects of lipophillic drugs on membrane structure by solid-state NMR spectroscopy–The case of the antioxidant curcumin. J Am Chem Soc. 2009;131(12):4490–4498.
    1. Aggarwal BB, Harikumar KB. Potential therapeutic effects of curcumin, the anti-inflammatory agent against neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases. Int J Biochem Cell Biol. 2009;41(1):40–59.
    1. Jeong SJ, Koh W, Lee EO, et al. Antiangiogenic phytochemicals and medical herbs. Phytotherapy Res. 2010 Jun 17; [Epub ahead of print]
    1. Arbiser JL, Klauber N, Rohan R, et al. Curcumin is an in vivo inhibitor of angiogenesis. Mol Med. 1998;4(6):376–383.
    1. Kowluru RA, Kanwar M. Effect of curcumin on retinal oxidative stress and inflammation in diabetes. Nutr Metab. 2007;4:8.

Source: PubMed

3
구독하다