The present study illustrated that curcumin suppresses H
2O
2 generation in a dose-dependent manner in a cell-free system. These findings are in line with the known antioxidant property of curcumin.
43 We also showed that curcumin inhibits phosphorylation of Smad3. Interestingly, in the absence of TGFβ1, curcumin also reduced collagen production without affecting basal level of H
2O
2 generation, suggesting that curcumin has an additional mechanism to regulate collagen production in the cells. In addition, curcumin inhibits p300HAT,
27 a key coactivator enzyme required for activation of several transcription factors such as Smad and NF-κB. We have recently shown that inhibition of p300 HAT activity with pharmacologic inhibitors such as garcinol and curcumin, or p300-specific siRNA, reduces both expression and activity of Nox4 in human endothelial cells.
29,31 Consistent with our previous study, we demonstrated for the first time that curcumin reduces TGFβ1 induction of Nox4 gene expression by conjunctival fibroblasts, which would in turn attenuate H
2O
2 generation. Recently, TGFβ1 has been shown to increase Nox4 protein expression by human gingival fibroblasts, and such response is inhibited by a similar concentration of curcumin that is used in our study.
44 Collectively, the present study suggests that curcumin inhibits phosphorylation of Smad3, scavenges H
2O
2 generation, and suppresses expression of Nox4, which appears to be the main Nox isoform activated by TGFβ1; and these inhibitory effects of curcumin would decrease the subsequent release of collagen by these cells. The protective effect of curcumin appears to result from a combination of its antioxidant, anti-inflammatory, antiangiogenic, and antifibrotic properties and is attributable to the pleiotropic effects of curcumin on genes and effector molecules involved in these signaling pathways.
26,28 Therefore, it would be of great interest to further explore the effect of curcumin in ocular fibrotic disorders in postsurgical complications and chemical burn injuries.
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