Biological Activities And Molecular Mechanism Of Fatty Acids,Derived From Dried Lucilia Sericata Larvae,Promote Cutaneous Wound Healing

Background: Recent studies have shown that fatty acids,as a natural product,possess various biological activities,including anti-bacterial,anti-cancer and promote cutaneouswound healing.Thereby,fatty acids have been considered as a promising candidate of new drug development.However,the underlying mechanisms of promote cutaneous wound healing still not fully elucidated.Objective: To investigate the effects and possible mechanisms of fatty acids,derived from dried Lucilia sericata larvae,promote acute cutaneous wound healing.Methods:(1)The fatty acids of moggot powder were extracted by the method of Soxhlet extraction.(2)The composition and content of fatty acids extracts were detected by gas chromatography-mass spectrometry.(3)The effect of local application fatty acids on acute cutaneous wound healing in vivo: 1)Wound area measurement was using high throughput transparency tracing sheet,2)H/E staining was used to observe the morphological changes of wound tissue and 3)Immunohistochemical staining was used to detect the proliferation of wound tissues.(4)The effects and possible mechanisms of fatty acids sodium salt solution(FASS)on human umbilical vein endothelial cells(HUVEC)was detected: 1)The pharmacodynamic and toxic effects of FASS were detected by cck-8,2)Hemocytometer-cell counting test FASS to promote cell proliferation,3)The effect of FASS on cell migration was detected by the wound healing test and Transwell test,4)In vitro capillary tube formation assay to detect the effect of FASS on angiogenesis,5)ELISA kit detects FASS promoting cell growth factor release,6)The effect of FASS on the expression of the protein in cells was detected by immunofluorescence detection,7)The signaling pathways of PI3K/AKT,ERK1/2,p38 MAPK and TGF/Smad3 were detected by Western blotting,8)RT-qPCR detects the expression of downstream genes after FASS activates the relevant signaling pathway.Results: The components of the fatty acids extracts are both medium-and long-chain fatty acids and up to 77.31% are unsaturated fatty acids.In vivo study,we discovered that local application of fatty acids effectively promotes cutaneous wound healing.Morphological evidence shows that fatty acid effectively promotes the formation of blood vessels in the wound surface and cell proliferation.Furthermore,in vitro assays,we found that FASS effectively promote endothelial cells proliferation,migration and angiogenesis;effectively enhance the growth factors release of VGEFA,PDGF and TGF-beta;effectively improve the expression of CD31 and alpha-SMA protein associated with neovascular stabilization;effectively activation the signaling pathways of AKT,ERK1/2,p38 MAPK,TGF-beta/Smads,which are promote cell proliferation,migration and angiogenesis,and downstream related genes associated with cell proliferation and vascular formation.Conclusion: Fatty acids effectively promote the formation of blood vessels on the cutaneous wound site,thereby promoting the cutaneous wound healing,which was achieved by improved the growth factors release of VGEFA,PDGF and TGF-beta,and trigger downstream signaling pathways of AKT?ERK1/2?p38 MAPK?TGF-?/Smads.In brief,our data showed that fatty acid has some medicinal research and development value in promoting cutaneous wound healing.