This study aimed to investigate the effectiveness of anti-atherosclerosis of rosmarinic acid (RosA).This study used a parallel flow chamber to establish low shear stress (LSS)-induced endothelial (EC) dysfunction model.This study exposed EC to LSS (3 dyn/cm2) for 30 min and treated it by oridonin.the ROS and NO levels in EC were measured by DHE and DAF-FM DA assay.The mRNA and protein expression of ICAM-1 and VCAM-1 were assayed by qPCR and Westen blotting.This study fed zebrafish with high-cholesterol diet (HCD) to establish a zebrafish atherosclerosis (AS) model,and observed lipid accumulation and inflammation by a fluorescence microscope.Results found that RosA improved LSS-induced EC dysfunction,and inhibited HCD-induced lipid accumulation,oxidative stress and inflammation.Results indicated that RosA may be used for the treatment of AS,and primarily exhibited its protective role through improving LSS-induced EC dysfunction.

Observe the effect of naringenin on autophagy of THP-1 foam cells to explore its potential mechanism for the prevention and treatment of atherosclerosis.First of all,CCK8 experiment was used to test the effect of naringenin on cell viability at different concentrations.In the next steps,different concentrations of naringenin (0,10,25,50,100 μmol/L) were applied to foam cells,and Western blot was used to detect the expression of LC3,p62 and the content of total cholesterol in foam cells.Naringenin,rapamycin and 3MA were applied to foam cells respectively to analyze the protein expression levels of LC3 and p62 later.Ox-LDL,naringenin and compound C were applied to macrophages respectively to analyze the protein expression levels of LC3,p-AMPK,AMPK and the content of total cholesterol finally.The results showed as follows:Naringenin had no toxic effect on foam cells activity (P>0.05);Compared the naringenin group with the model group,the ratio of LC3II/LC3I was increased(P<0.05),and the expression of P62 was reduced (P<0.05),the content of total cholesterol was reduced otherwise(P<0.05);Compared the naringenin group with the model group,the ratio of LC3II/LC3I and the ratio of p-AMPK/AMPK were increased(P<0.05),and the content of total cholesterol was reduced(P<0.05).Naringenin could up-regulate the autophagy ability of foam cells,and reduce the content of total cholesterol in the cells to inhibit the formation of foam cells.Naringenin promoted the autophagy ability of foam cells by increasing the level of AMPK phosphorylation,which might be one of the molecular mechanisms of naringenin in preventing and treating atherosclerosis.

In order to investigate the effect of wogonin on atherosclerosis and arterial inflammation in ApoE^-/- mice fed with high fat diet,ApoE^-/- mice were divided into normal diet group (ND),high-fat diet group (HFD),high-fat diet + wogonin (10 mg/kg) group (HFD + wogonin 10 mg/kg) and high-fat diet + wogonin (20 mg/kg) group (HFD + wogonin 20 mg/kg).Mice were given high-fat diet and wogonin for 12 weeks and then the arterial tissues were collected.RT-qPCR was used to detect the mRNA expression of IL-6,TNF-α,ICAM-1 and VCAM-1.Immunofluorescence staining was used to detect the expression of Moma-2 and VCAM-1 in the aortic root.Oil red O staining and HE staining were used to detect the changes of the lipid deposition and pathological changes in the aortic root.Biochemical kits were used to detect the serum lipid levels.Western blot was used to detect the phosphorylation of NF-κB and the expression of IκB-α.The results showed that compared with HFD group,the area of atherosclerotic plaque in HFD+wogonin group was decreased (P<0.05),but the serum lipid levels do not change; moreover,monocyte/monocyte macrophage infiltration,the protein expression of VCAM-1,the mRNA expression level of TNF-α,IL-6,ICAM-1 and VCAM-1 and the activation of NF-κB signal pathway in HFD+wogonin group were significantly reduced (P<0.05).These findings indicated that wogonin could effectively alleviate arterial atherosclerosis and inhibit NF-κB-mediated arterial inflammation in ApoE^-/- mice induced by high-fat diet.

To explore the mechanism of gypenoside preventing and treating AS by affecting long non-coding RNA TUG1/miR-26a to interfere with mitochondrial apoptosis,thereby improving liver lipid deposition in ApoE^-/-AS mice.In this experiment,10 C57BL/6J mice were used as the normal control group,and 20 healthy ApoE-/-mice fed with high-fat diet for 12 weeks were randomly divided into model group and gypenoside group,given intragastrically for 4 weeks.Lipid deposition in mouse liver was observed by HE staining,blood lipid level was detected by automatic biochemical analyzer,and mRNA expression of long non-coding TUG1,miRNA-26a,Bcl2,Bax,Cytc,cleaved caspase-3,cleaved caspase-9 and cleaved PARP were detected by real-time q-PCR,and protein expression of Bcl2,Bax,Cytc,cleaved caspase-9 and cleaved PARP were detected by Wes automatic Western blotting quantitative analysis system.The results showed that the blood lipid level of ApoE-/- mice in the model group was disordered,liver cell volume increased,and fat vacuoles were obvious.The expression of Lnc-TUG1 in mouse liver was significantly increased,and miRNA-26a was significantly decreased (P<0.01);Bax,Cytc,cleaved caspase-3,cleaved PARP mRNA and protein expression significantly increased,Bcl2 mRNA and protein expression significantly decreased P<0.01 or P<0.05);cleaved caspase-9 protein expression significantly increased（P<0.05）,cleaved caspase-9 mRNA only has an upward trend.After the intervention of gypenoside,dyslipidemia was improved,the degree of liver cell steatosis was reduced,fatty vacuoles were significantly reduced.Lnc-TUG1 expression was decreased,miRNA-26a expression was increased (P<0.05),the mRNA and protein expressions of Bax,Cytc,cleaved caspase-3 and cleaved caspase-9 were significantly down-regulated,Bcl2 mRNA and protein was significantly up-regulated,the expressions of cleaved PARP protein were significantly down-regulated(P<0.01 or P<0.05),and cleaved PARP mRNA showed only a downregulation trend.The results suggested that the effect of gypenoside in preventing and treating atherosclerosis may be to interfere with mitochondrial apoptosis by affecting long non-coding RNA TUG1/miR-26a,thereby improving liver lipid deposition in ApoE^-/-AS mice.

Panax notoginseng saponins (PNS) is an active ingredient extracted from the roots of Panax notoginseng,which is widely used in the treatment of atherosclerotic diseases.However,its related mechanism is not completely clear.In this study,we found that PNS has the function of improving blood lipid and inhibiting the formation of atherosclerotic plaque in ApoE^-/- mice.Its molecular mechanism is related to TLR4/SYK signaling pathway.Furthermore,in vitro cell experiments showed that PNS could inhibit macrophage phagocytosis and CD36 expression in mouse plaques.Therefore,we believe that PNS can inhibit the formation of foam cells in ApoE^-/- mice by inhibiting TLR4/SYK signaling so as to inhibiting the progression of atherosclerosis.