Asiaticoside induces human collagen I synthesis through TGFbeta receptor I kinase (TbetaRI kinase)-independent Smad signaling.
Skin aging appears to be principally related to a decrease in the levels of type I collagen, the primary component of the skin dermis. Asiaticoside, a saponin component isolated from Centella asiatica, has been shown to induce type I collagen synthesis in human dermal fibroblast cells. However, the mechanism underlying asiaticoside-induced type I collagen synthesis, especially at a molecular level, remains only partially understood. In this study, we have attempted to characterize the action mechanism of asiaticoside in type I collagen synthesis. Asiaticoside was determined to induce the phosphorylation of both Smad 2 and Smad 3. In addition, we detected the asiaticoside-induced binding of Smad 3 and Smad 4. In a consistent result, the nuclear translocation of the Smad 3 and Smad 4 complex was induced via treatment with asiaticoside, pointing to the involvement of asiaticoside in Smad signaling. In addition, SB431542, an inhibitor of the TGFbeta receptor I (TbetaRI) kinase, which is known to be an activator of the Smad pathway, was not found to inhibit both Smad 2 phosphorylation and Type 1 collagen synthesis induced by asiaticoside. Therefore, our results show that asiaticoside can induce type I collagen synthesis via the activation of the TbetaRI kinase-independent Smad pathway.
Biospectrum Life Science Institute, Gunpo City, Gyunggi Do, Korea.
Jongsung
J
Lee
Eunsun
E
Jung
Youngji
Y
Kim
Junho
J
Park
Jinil
J
Park
Sungtaek
S
Hong
Jieun
J
Kim
Changgu
C
Hyun
Yeong Shik
YS
Kim
Deokhoon
D
Park
D015153:Blotting, Western; D028041:Centella; D024042:Collagen Type I / Q000096:biosynthesis / Q000187:drug effects*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007641:Keratolytic Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta; D015398:Signal Transduction; D015595:Skin Aging; D051900:Smad3 Protein / Q000378:metabolism; D051901:Smad4 Protein / Q000378:metabolism; D014315:Triterpenes / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use
D024042:Collagen Type I; D007641:Keratolytic Agents; D010936:Plant Extracts; D018125:Receptors, Transforming Growth Factor beta; D051900:Smad3 Protein; D051901:Smad4 Protein; D014315:Triterpenes; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; C004446:asiaticoside