Enhancement of wound healing by the alkaloid taspine defining mechanism of action.
Taspine (mol wt 369,000) is an alkaloid extracted from trees of Croton (family Euphorbiaceae) of the western Amazon region that has been used by natives and others as a vulnerary agent. Taspine was purified from tree sap to test its healing properties using different topical concentrations in the paired rat surgical incision model. Wound tensile strength and histology were evaluated. Samples treated with 250 micrograms, but not those treated with 50 micrograms or 10 micrograms, had significant higher values for MBS than paired controls (26%, P < 0.005, and 30%, P < 0.001, by Days 5 and 7, respectively). Taspine did not modify MBS at Day 12. Sample treated with 250 micrograms had significantly greater mononuclear cellular infiltration at Days 5 and 7 but not at Day 12. To better understand the effect of taspine as an enhancer of wound healing, we conducted in vitro studies in cell cultures. Taspine stimulated chemotaxis for fibroblasts. Taspine did not have an effect on specific assays for macrophage chemotaxis, neutrophil activation, fibroblast proliferation, or matrix assembly. Taken together, the data suggest that taspine promotes early phases of wound healing in a dose-dependent manner with no substantial modification thereafter. Its mechanism of action is probably related to its chemotactic properties on fibroblasts and is not mediated by changes in extracellular matrix.
Porras-Reyes
B H
BH
Division of Plastic Surgery, Washington University School of Medicine, Saint Louis, Missouri 63110.
Lewis
W H
WH
Roman
J
J
Simchowitz
L
L
Mustoe
T A
TA
D000470:Alkaloids / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000627:therapeutic use; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002633:Chemotaxis / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D004261:DNA Replication / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D007249:Inflammation; D008168:Lung; D008264:Macrophages / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D010587:Phagocytosis / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013481:Superoxides / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology*; D014947:Wounds and Injuries / Q000473:pathology / Q000503:physiopathology*
D000470:Alkaloids; D000894:Anti-Inflammatory Agents, Non-Steroidal; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; D013755:Tetradecanoylphorbol Acetate; C018394:taspine; D013936:Thymidine