Asiaticoside suppresses collagen expression and TGF-β/Smad signaling through inducing Smad7 and inhibiting TGF-βRI and TGF-βRII in keloid fibroblasts
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Asiaticoside (ATS) isolated from the leaves of Centella asiatica possesses strong wound-healing properties and reduces scar formation. However, the specific effects of asiaticoside on the formation of keloidal scars remain unknown. In the present study, we evaluated the in vitro effects of asiaticoside on the proliferation, collagen expression, and transforming growth factor (TGF)-β/Smad signaling of keloid-derived fibroblasts. Fibroblasts isolated from keloid tissue and normal skin tissues were treated with asiaticoside at different concentrations. Afterwards, they were subjected to RT-PCR and Western blot analyses. The inhibitory effects of asiaticoside on fibroblast viability were assayed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Asiaticoside decreased fibroblast proliferation in a time- and dose-dependent manner. It also inhibited type I and type III collagen protein and mRNA expressions. In addition, asiaticoside reduced the expression of both TGF-βRI and TGF-βRII at the transcriptional and translational level. Moreover, it increased the expression of Smad7 protein and mRNA. However, asiaticoside did not influence the expression of Smad2, Smad3, Smad4, phosphorylated Smad2, and phosphorylated Smad3. Taken together, these results suggest that asiaticoside could be of potential use in the treatment and/or prevention of hypertrophic scars and keloids.
KeywordsAsiaticoside Transforming growth factor-β Smad Collagen Keloid
- 7.Dong MS, Jung SH, Kim HJ, Kim JR, Zhao LX, Lee ES, Lee EJ, Yi JB, Lee N, Cho YB, Kwak WJ, Park YI (2004) Structure-related cytotoxicity and anti-hepatofibric effect of asiatic acid derivatives in rat hepatic stellate cell-line, HSC-T6. Arch Pharm Res 27:512–517Google Scholar
- 33.Yun K-J, Kim J-Y, Kim J-B, Lee K-W, Jeong S-Y, Park H-J, Jung H-J, Cho Y-W, Yun K, Lee K-T (2008) Inhibition of LPS-induced NO and PGE2 production by asiatic acid via NF-kappa B inactivation in RAW 264.7 macrophages: possible involvement of the IKK and MAPK pathways. Int Immunopharmacol 8:431–441PubMedCrossRefGoogle Scholar