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

Abstract

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 h) had protective effects on human dermal fibroblasts (HDFs) exposed to hydrogen peroxide (H2O2, 300 μM, 12 h). 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 < 0.001) and improved the expression and activities of antioxidant enzymes superoxide dismutase 1 (SOD1, 66.61 U (SD ± 7.47) vs. 46.39 U (SD ± 6.82) /10 6 cells, p < 0.05) and catalase (CAT, 9.77 U (SD ± 1.82) vs. 4.61 U (SD ± 0.94) /10 6 cells, p < 0.01), 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 < 0.05) and higher expression of autophagy-related proteins including PI3KC3 (p < 0.001), LC3-II (p < 0.001) and Beclin1 (p < 0.01). However, intracellular redox status deteriorated again and curcumin’s protection effects were partially canceled after autophagy was inhibited by 3-MA pretreatment. These data suggest that rescue of HDFs from oxidative damage by curcumin may related to the regulation of autophagy levels and ROS generation.

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

“…25 Our team has recently reported that the cultivation of fibroblasts with curcumin at 10 μmol/L can promote autophagy and defend cells against ROS attack after hydrogen peroxide exposure. 26 More curcumin concentrations and fibroblasts from different phases of wound repair need to be studied to elaborate the effect of curcumin on the oxidant-antioxidant balance of fibroblasts, which determines whether it is applied for wound healing or scar treatment. In addition, high-dose oral curcumin is considered safe for clinical use, which also indicates its poor systemic bioavailability.…”

“…However, high concentrations of curcumin induce fibroblast apoptosis by increasing the generation of reactive oxygen species (ROS), while low concentrations improve heme oxygenase‐1 activity and protect cells from oxidative injury 25 . Our team has recently reported that the cultivation of fibroblasts with curcumin at 10 μmol/L can promote autophagy and defend cells against ROS attack after hydrogen peroxide exposure 26 . More curcumin concentrations and fibroblasts from different phases of wound repair need to be studied to elaborate the effect of curcumin on the oxidant‐antioxidant balance of fibroblasts, which determines whether it is applied for wound healing or scar treatment.…”