Studies On The Antiatherogenic Effects And Its Mechanism Of The Ethanol Extract Of Usnea

Objective Studies on the antiatherogenic effects and its mechanism of the ethanol extract of Usnea.Method A high fat diet and VD₃ were used to establish the atherosclerotic rat model,with0.004 g/kg/d of simvastatin as a positive control,fed with 0.7,1.4,and 2.8 g/kg/d of Usnea ethanol extract for 21 days to investigate the antiatherogenic activity and mechanism of Usnea ethanol extract.The blood,liver,and aorta samples from each rat were collected after the last administration.Pharmacodynamic effects,including body weight,serum and liver lipid levels,calcium ion(Ca²⁺),oxidized low-density lipoprotein?ox-LDL?,aspartate aminotransferase?AST?,alanine aminotransferase?ALT?,atherosclerotic index?AI?,liver index,hepatic and aorta morphological changes were evaluated.To explore the mechanisms,the inflammation related factors,including C-reactive protein?CRP?,intercellular adhesion molecule-1?ICAM-1?,tumor necrosis factor-??TNF-??,interleukin-1??IL-1??,interleukin-1?15??IL-1?15??and monocyte chemoattractant protein-1?MCP-1?,were detected by enzyme-linked immunosorbent assay?ELISA?.In addition,the gene expressions of Toll-like receptor 5?TLR5?,myeloid differentiating factor 88?MyD88?,and nuclear factor-?B?NF-?B?were detected by real-time PCR?RT-PCR?.Result The atherosclerotic rat model was successfully established after 9 weeks on the high-fat diet.The aortic intima was significantly thickened in atherosclerotic model rats,and ripe atherosclerotic plaques can be clearly observed in the aorta.During the administration,the body weights of the rats in the high-fat diet groups were slightly lower than those in the normal diet group,but there was no significant difference in body weight between the groups?P>0.05?.Compared with the model group,simvastatin and ethanol extract of Usnea can significantly reduce the serum levels of triglyceride?TG?,low-density lipoprotein cholesterol?LDL-C?,Ca²⁺,AST,ALT,the liver contents of total cholesterol?TC?and TG,AI and liver index,as well as significantly increase the contents of high-density lipoprotein cholesterol?HDL-C?both in serum and liver?P<0.01 or P<0.05?.The serum level of ox-LDL can be significantly reduced by simvastatin,low and medium Usnea ethanol extract doses?P<0.01?.In addition,simvastatin and low dosage of Usnea ethanol extract can significantly reduce the liver content of LDL-C?P<0.01?.Liver and aorta tissues pathological observation showed that simvastatin and ethanol extract of Usnea can improve degeneration to a certain extent.Atherosclerotic score,middle membrane thickness and plaque area were significantly decreased compared to the model group?P<0.05 or P<0.01?.Furthermore,simvastatin and ethanol extract of Usnea can significantly reduce the serum levels of CRP?ICAM-1?TNF-??IL-1?and MCP-1?P<0.05 or P<0.01?,as well as the gene expressions of TLR5,MyD88 and NF-?B?P<0.05 or P<0.01?.And low dosage of Usnea ethanol extract can significantly increase the serum level of IL-10?P<0.01?.Conclusion The ethanol extract of Usnea can promote lipid metabolism and reduce the plaque area in atherosclerotic model rats,which shows a positive antiatherogenic effect of Usnea ethanol extract.And the mechanism may be related to the promotion of the expression of serum IL-10 and inhibition of TLR5/NF-?B signaling pathway,consequently down-regulating the inflammatory related factor levels of CRP,ICAM-1,TNF-?,IL-1?and MCP-1.