Facilitating action of asiaticoside at low doses on burn wound repair and its mechanism.
Some reports published from 1967 to 1999 describe the use of ointments containing high doses (0.1 to 0.2%, w/w) C. asiataica herb extracts to enhance wound repair. Lower doses at which burn wound repair is enhanced by such topical applications have not been established yet. We found that the application of asiaticoside at low doses of 10(-8) to 10(-12)% (w/w) facilitated burn wound repair. To clarify the accelerating mechanisms of asiaticoside on burn wound repair, we examined the effects of asiaticoside on the levels of various cytokines produced at the site of the burn wound. The topical application of a low dose (10 pg, 1 ng, or 100 ng/wound area) of asiaticoside increased monocyte chemoattractant protein-1 (MCP-1), vascular endothelial growth factor (VEGF), and interleukin (IL)-1beta levels in burn wound exudates. Asiaticoside (10 pg to 100 ng/ml) enhanced MCP-1 production in HaCaT cells, but it had no direct effect on VEGF production. Furthermore, asiaticoside (10 pg to 100 ng/ml) increased the IL-1beta production in THP-1 macrophages with MCP-1, but it had no effect on IL-1beta production without MCP-1 or with lipopolysaccharide (LPS). These findings suggest that the enhancement of burn wound healing by asiaticoside might be due to the promotion of angiogenesis during skin wound repair as a result of the stimulation of VEGF production caused by the increase in MCP-1 expression in keratinocytes and the increase in IL-1beta expression in macrophages induced cooperatively by asiaticoside plus MCP-1.
Kimura
Yoshiyuki
Y
Division of Biochemical Pharmacology, Department of Basic Medical Research, Ehime University Graduate School of Medicine, Shitsukawa, Toon City, 791-0295, Japan. yokim@m.ehime-u.ac.jp
Sumiyoshi
Maho
M
Samukawa
Kei-Ichi
K
Satake
Noriko
N
Sakanaka
Masahiro
M
D000279:Administration, Cutaneous; D000818:Animals; D002056:Burns / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D028041:Centella; D018932:Chemokine CCL2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D003879:Dermatologic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005122:Exudates and Transudates / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D015603:Keratinocytes / Q000187:drug effects / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010936:Plant Extracts; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014315:Triterpenes / Q000008:administration & dosage / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects* / Q000276:immunology
C491768:Ccl2 protein, mouse; C526146:Centella asiatica extract; D018932:Chemokine CCL2; D016207:Cytokines; D003879:Dermatologic Agents; D053583:Interleukin-1beta; D010936:Plant Extracts; D014315:Triterpenes; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; C004446:asiaticoside