Therapeutic Effect Of Curcumin On Hypertrophic Scar And Its Possible Mechanism

Hypertrophic scarring generally occurs following trauma, burns and surgery, which is a common disorder in plastic surgery. Although the worldwide prevalence of hypertrophic scar is not known, hypertrophic scar represent an overhealing state involved repair cells, extracellular matrix, cytokine. Fibroblast, collagen, TGF-β1 was reported importantly. Traditional Chinese medicine have become popular in recent years, whose active ingredients are being investigated widely. Curcumin, the active ingredient in turmeric(Curcuma longa), is a highly pleiotropic molecule with anti-inflammatory, anti-oxidant, chemopreventive, chemosensitization, and radiosensitization activities, multitargeting by curcumin as revealed by molecular interaction studies. We investigate the therapeutic effects of curcumin on hypertrophic scars and explore the possible mechanism.Part Ⅰ Effects of curcumin on reducing hypertrophic scar in rabbit ears[Objective] To investigate the effects of curcumin on reducing hypertrophic scar in rabbit ears.[Methods] Hypertrophic scars in rabbit ears was established over the ventral surface. Experimental group contains normal skin(A group), hypertrophic scar(B group), contractubex ® positive control(C group), 2.5% curcumin w/w(D group), 5% curcumin w/w(E group), 10% curcumin w/w(F group). Each group contains 16 hypertrophic scar specimens.(A group contains 16 normal skin tissues in the corresponding position.) Drug was applied once daily to the scars for 28 days. The specimens were collected after continuous dosing 28 days. HE and Masson staining were performed. The hypertrophic index(HI), numerical density on area(NA), area density on area(AA) were measured.[Results] Curcumin could reduce the degree of hyperplasia scar and make it smaller, softer, flatter. The number of excessive fibroblasts was lower and the collagen fibers were decreased, more regularly ranged in curcumin group. Curcumin dose dependently reduced the HI significantly(P<0.05). The NA and AA were decreased significantly(P<0.05).[Conclusion] Curcumin has therapeutic effect to hypertrophic scar in rabbit ears. With further pharmacological mechanism research, the development of new dosage forms, curcumin is expected to become the effective drugs for the treatment of hypertrophic scar.Part Ⅱ Effect of curcumin on collagen synthesis and catabolism of hypertrophic scar in rabbit ears[Objective] To investigate the effects of curcumin on the expression of collagen Ⅰ、collagen Ⅲ、 MMP-1 、 TIMP-1 mRNA and the expression of TGF-β1 prot in the hypertrophic scar of rabbit ears.[Methods] Hypertrophic scars in rabbit ears was established over the ventral surface. Experimental group contains normal skin(A group), hypertrophic scar(B group), contractubex ® positive control(C group), 2.5% curcumin w/w(D group), 5% curcumin w/w(E group), 10% curcumin w/w(F group). Each group contains 16 hypertrophic scars specimens.(A group contains 16 normal skin tissues in the corresponding position.) Drug was applied once daily to the scars for 28 days. The specimens were collected after continuous dosing 28 days. Real-time PCR method was used to detect the mRNA expression of Collagen Ⅰ、Collagen Ⅲ、MMP-1、TIMP-1. The protein expression of TGF-β1 was detected with Western blot assessment.[Results] Real-time PCR showed that the expression of Collagen Ⅰ mRAN. The expression of Collagen Ⅲ mRAN was lower in curcumin group. The expression of MMP-1 mRNA was increased in E and F group. Curcumin decreased the expression of TIMP-1 mRNA. Western blot showed that curcumin dose dependently reduced the protein expression of TGF-β1.[Conclusion] Curcumin decreased the expression of Collagen Ⅰ、Collagen Ⅲ mRAN, increased the expression of MMP-1 mRNA and decreased the expression of TIMP-1 mRNA. At the same time, curcumin decreased the expression of TGF-β1 protein. This maybe one of the mechanisms that curcumin possesses the therapeutic effects on hypertrophic scar in the rabbit ears.Part Ⅲ Curcumin induces hypertrophic scar fibroblasts apoptosis by regulating Bcl-2/Bax protein[Objective] To investigate the effects of curcumin on cell apoptosis in hypertrophic scar fibroblasts and the related mechanism.[Methods] In vitro hypertrophic scar fibroblasts were treated with curcumin of 10 μmol/L, 20 μmol/L, 40 μmol/L. MTT assay was used to detect the inhibitory effects of curcumin on proliferation of hypertrophic scar fibroblasts. The apoptosis rate was analyzed by using flow cytometry with Annexin V-FITC/PI double staining. The activities of Caspase-9 and Caspase-3 was detected with spectrophotometric method. The protein expression of Bcl-2 and Bax was detected with Western blot assessment.[Results] MTT assay showed that curcumin could inhibit hypertrophic scar fibroblasts proliferation and the inhibitory rate increased with the concentration of Curcumin(P<0.05). Annexin V-FITC/PI double staining showed that curcumin could induce apoptosis of fibroblasts and the apoptosis rate increased with the concentration of Curcumin(P<0.05). The activities of caspase-9 and caspase-3 was significantly increased(P<0.05). Western Blot assessment showed that curcumin reduced the Bcl-2 protein expression, increased the Bax protein expression and increased the ratio of Bax/Bcl-2(P<0.05).[Conclusion] Curcumin inhibits proliferation and induces apoptosis of hypertrophic scar fibroblasts. Its mechanism may be associated with increasing the activities of caspase-3 and caspase-9 by inhibiting the expression of Bcl-2 protein and promoting the expression of Bax protein.