Effects of curcumin-liposome formulation on inflammatory cascade activated by oxidative stress in primary human corneal epithelial cells

Abstract

Curcumin is a naturally occurring polyphenol extracted from turmeric, that exhibits several challenging properties such as anti-inflammatory, antioxidant, lipid-modulating, anti-thrombotic, immunomodulatory, neuroprotective, hepatoprotective and anti-tumor activities. Dry eye disease (DED) is recognized as a multifactorial disorder of the tears and ocular surface, associated with different symptoms, visual disturbance, and tear film instability, accompanied by inflammation of the ocular surface. Inflammation contributes to dry eye disese and in turn dry eyes can lead to worsening inflammation. Protective effects of curcumin have been proved in different eye diseases such as uveitis, idiopathic orbital inflammation, glaucomatous optic neuropathy and diabetes. Considering this background, the aim of the present study was to investigate the effects of curcumin loaded liposomes on human corneal epithelial culture cells subjected to oxidative stress, in order to detect cells’ defensive response to the oxidative stress in presence of curcumin and to determine the optimal concentration of curcumin loaded liposomes for ophthalmic topical therapy in ocular surface disorders. Results obtained demonstrated that curcumin was able to protect cells from oxidative stress induced by hydrogen peroxide by reducing inflammation and activation of TNF-α (p < 0.01 vs H₂O₂ cells), NF-kB (p < 0.01 vs H₂O₂ cells) and NLRP3 (p < 0.01 vs H₂O₂ cells) pathways. Moreover, our results evidenced that curcumin reduced the levels of Bax (p < 0.01 vs H₂O₂ cells), a well known proapoptotic protein, and enhanced Bcl-2 protein (p < 0.01 vs H₂O₂ cells), thus exerting protection against apoptosis in corneal cells. All together, these results confirm the neutralizing effects of curcumin on the oxidative stress induced changes in corneal epithelial cells that might prevent cells damage and death with successive promoting of the inflammatory cascade.