PMID- 18353310 OWN - NLM STAT- MEDLINE DCOM- 20080701 LR - 20220321 IS - 0014-2999 (Print) IS - 0014-2999 (Linking) VI - 584 IP - 2-3 DP - 2008 Apr 28 TI - Facilitating action of asiaticoside at low doses on burn wound repair and its mechanism. PG - 415-23 LID - 10.1016/j.ejphar.2008.02.036 [doi] AB - 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. FAU - Kimura, Yoshiyuki AU - Kimura Y AD - 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 FAU - Sumiyoshi, Maho AU - Sumiyoshi M FAU - Samukawa, Kei-Ichi AU - Samukawa K FAU - Satake, Noriko AU - Satake N FAU - Sakanaka, Masahiro AU - Sakanaka M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20080221 PL - Netherlands TA - Eur J Pharmacol JT - European journal of pharmacology JID - 1254354 RN - 0 (Ccl2 protein, mouse) RN - 0 (Centella asiatica extract) RN - 0 (Chemokine CCL2) RN - 0 (Cytokines) RN - 0 (Dermatologic Agents) RN - 0 (Interleukin-1beta) RN - 0 (Plant Extracts) RN - 0 (Triterpenes) RN - 0 (Vascular Endothelial Growth Factor A) RN - 0 (vascular endothelial growth factor A, mouse) RN - PKO39VY215 (asiaticoside) SB - IM MH - Administration, Cutaneous MH - Animals MH - Burns/*drug therapy/immunology/metabolism/physiopathology MH - Cell Line MH - Cell Proliferation/drug effects MH - Cell Survival/drug effects MH - Centella MH - Chemokine CCL2/metabolism MH - Cytokines/*metabolism MH - Dermatologic Agents/*pharmacology/therapeutic use MH - Disease Models, Animal MH - Dose-Response Relationship, Drug MH - Exudates and Transudates/drug effects/metabolism MH - Humans MH - Interleukin-1beta/metabolism MH - Keratinocytes/drug effects/immunology MH - Macrophages/drug effects/immunology MH - Male MH - Mice MH - Mice, Inbred BALB C MH - Neovascularization, Physiologic/drug effects MH - Plant Extracts MH - Signal Transduction/drug effects MH - Time Factors MH - Triterpenes/administration & dosage/*pharmacology MH - Vascular Endothelial Growth Factor A/metabolism MH - Wound Healing/*drug effects/immunology EDAT- 2008/03/21 09:00 MHDA- 2008/07/02 09:00 CRDT- 2008/03/21 09:00 PHST- 2007/05/25 00:00 [received] PHST- 2008/01/31 00:00 [revised] PHST- 2008/02/13 00:00 [accepted] PHST- 2008/03/21 09:00 [pubmed] PHST- 2008/07/02 09:00 [medline] PHST- 2008/03/21 09:00 [entrez] AID - S0014-2999(08)00167-2 [pii] AID - 10.1016/j.ejphar.2008.02.036 [doi] PST - ppublish SO - Eur J Pharmacol. 2008 Apr 28;584(2-3):415-23. doi: 10.1016/j.ejphar.2008.02.036. Epub 2008 Feb 21.