Curcumin alleviates hypertrophic scarring by inhibiting fibroblast activation and regulating tissue inflammation.

BACKGROUND: Hypertrophic scar (HS) that can lead to defects in appearance and function is often characterized by uncontrolled fibroblast proliferation and excessive inflammation. Curcumin has been shown to have anti-inflammatory and anti-oxidative effects and to play an anti-fibrotic role by interfering transforming growth factor-ß1 (TGF-ß1)/Smads signaling pathways. AIM: To study the effect and mechanism of curcumin on HS from the perspective of fibroblast activity and inflammation regulation. METHODS: Cell proliferation, migration and the expression of α-smooth muscle actin (α-SMA) of TGF-ß1-induced human dermal fibroblasts (HDFs) treated by curcumin were evaluated using Cell Counting Kit-8 assay, 5-ethynyl-2'-deoxyuridine staining, Transwell assay, Western blotting and immunofluorescence, respectively. The expression of TGF-ß1/Smad3 pathway-related molecules (TGF-ß1, TGFß-R1/2, p-Smad3, Smad4) was detected by Western blotting. In a rabbit ear model, hematoxylin and eosin and Masson's staining were conducted to assess scar elevation and collagen deposition, and immunohistochemistry was performed to detect the activation of fibroblasts and infiltration of inflammatory cells. RESULTS: Curcumin inhibited proliferation, migration and α-SMA expression of HDFs in a dose-dependent manner. Curcumin (25 µm mol/L) did not regulate the expression of endogenous TGF-ß1, but suppressed Smad3 phosphorylation and nuclear translocation, leading to lower α-SMA expression. Curcumin also reduced hypertrophic scarring of rabbit ear, accompanied by the inhibited TGF-ß1/Smad3 pathway, inflammatory infiltration and M2 macrophage polarization. CONCLUSION: Curcumin plays an anti-scar role through regulating fibroblast activation and tissue inflammation. Our findings provide scientific reference for the clinical use of curcumin in the treatment of HS.

Curcumin Protects Human Dermal Fibroblasts Exposed to Hydrogen Peroxide by Regulating Autophagy Level and Reactive Oxygen Species Generation.

Curcumin is getting more and more attention in wound healing and scar prevention because of its wide range of pharmacological effects, such as anti-inflammation, antioxidant, and anti-fibrosis. The activity of fibroblasts suffering from oxidative stress is reduced, affecting wound repair. In this study, we investigated whether curcumin treatment (10 µM, 24 hours) had protective effects on human dermal fibroblasts (HDFs) exposed to hydrogen peroxide (H2O2, 300 µM, 12 hours). We found that curcumin alleviated H2O2-induced accumulation of reactive oxygen species (ROS, the fold change relative to the untreated control was 1.75 [SD ± 0.21] vs 5.23 [SD ± 0.51], P < .001) and improved the expression and activities of antioxidant enzymes superoxide dismutase 1 (66.61 U [SD ± 7.47] vs 46.39 U [SD ± 6.82]/106 cells, P < .05) and catalase (9.77 U [SD ± 1.82] vs 4.61 U [SD ± 0.94]/106 cells, P < .01), accompanied with increased cell proliferation and migration but decreased senescence. In addition, we found that curcumin reduced the inhibition of autophagy by H2O2, as manifested in the increased autophagic vacuoles (P < .05) and higher expression of autophagy-related proteins including phosphoinositide-3-kinase class III (P < .001), light chain 3 form II (P < .001), and Beclin1 (P < .01). However, intracellular redox status deteriorated again and curcumin's protection effects were partially canceled after autophagy was inhibited by 3-methyladenine pretreatment. These data suggest that rescue of HDFs from oxidative damage by curcumin may related to the regulation of autophagy levels and ROS generation.