Effect of lycopene on glycolipid metabolism and pancreatic tissue through regulation of TLR4/MyD88/NF-κB signaling pathway in high-fat diet induced obese mice / 中草药

Objective: To investigate the effects of lycopene on glycolipid metabolism and pancreatic tissue inflammation in obese mice and its underlying mechanism. Methods: The obese mouse model was induced by a high-fat diet (HFD). The effects of lycopene on body weight, blood glucose, blood lipid and body fat were observed after 8 weeks of administration. Pathological changes of pancreas were observed by HE staining. Protein expressions involved in TLR4/MyD88/NF-κB signaling pathway were detected by Western blotting, and the degree of macrophage infiltration in the pancreatic tissues of obese mice were detected by IHC. Results: Lycopene significantly inhibited body weight gain and reduced fasting blood glucose, as well as improved glucose tolerance and blood lipid level in obese mice. In addition, lycopene also reduced vacuolization, edema degeneration, islet hypertrophy and other inflammatory lesions in pancreatic tissues. Moreover, the protein expression levels of TLR4, MyD88 and NF-κB in pancreatic tissue were decreased and the inflammatory infiltration was reduced. Conclusion: Lycopene can improve blood glucose, lipid metabolism and pancreatic inflammation in obese mice, and its mechanism may be related to the regulation of TLR4/MyD88/NF-κB signaling pathway.

Intervention Effects of Berberine on Mice Macrophage Polarization Based on TLR 4/MyD88/NF-κB Signaling Pathway / 中国药房

OBJECTIVE：To study the effects of berberine on mic e macrophage polarization based on TLR 4-MyD88-NF-κB signaling pathway. METHODS ：Using mice RAW 264.7 macrophage as the object ，atorvastatin calcium as positive control ， inflammatory cell model was induced by lipopolysaccharide （LPS）；ELISA method was used to detect the contents of TNF-α，IL-6 and NF-κB in cell culture medium after treated with low，medium and high doses of berberine （5，10，20 μmol/L）for 24 h. The real-time fluorescence quantitative PCR was conducted to determine the mRNA expression of TLR 4 and MyD 88 in cells. Western blotting assay was used to detect the protein expression of TLR 4，MyD88，iNOS and CD 206 in cells. RESULTS ：Compared with blank control group ，the contents of TNF-α，IL-6 and NF-κB in cell culture medium，mRNA expression of TLR 4 and MyD 88， protein expression of TLR 4，MyD88 and iNOS in cells were increased significantly in LPS induction group （P＜0.05）. Compared with LPS induction group ，the contents of TNF-α and IL-6，mRNA and protein expression of TLR 4 and MyD 88 in atorvastatin calcium group ，berberine medium-dose and high-dose groupsas well as the content of NF-κ B and protein expression of iNOS in administration groups were decreased significantly ， while the content of NF-κB in berberine high-dose group was significantly lower than atorvastatin calcium group （P＜0.05）. The protein expressions of CD206 in atorvastatin calcium group and berberine high-dose group were increased significantly ，while the protein expression of CD 206 in berberine high-dose group was significantly higher than atorvastatin calcium group （P＜0.05）. CONCLUSIONS ：Different doses of berberine can intervene in mice macrophage polarization to different extents ，the mechanism of which may be associated with the regulation of TLR4/MyD88/NF-κB signaling pathway.

Effects of Anzi Mixture on TLR4/MyD88/NF-κB Signaling Pathway of Antiphospholipid Antibodies Posi-tive Abortive Mice / 中国药房

OBJECTIVE:To study the effects of Anzi mixture on Toll like receptor 4(TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear facter-κB(NF-κB)signaling pathway of antiphospholipid antibodies(APA)positive abortive mice,and to inves-tigate the mechanism of anti-APA positive abortion. METHODS:BALB/c mice(female)were randomly divided into blank control group,model group,aspirin group (positive control,0.0195 g/kg) and Anzi mixture low-dose,medium-dose and high-dose groups (37.7,75.4,150.8 g/kg,calculated by crude drug),with 10 mice in each group. Except for blank control group,other groups were given human β2-glycoprotein Ⅰ as derivant to establish APA positive abortion model. From the first day of pregnancy, treatment groups were given relevant medicine intragastrically,and blank control group and model group were given constant vol-ume of normal saline intragastrically,once a day,for consecutive 9 d. mRNA and protein levels of TLR4,myeloid differentiation 2 (MD2),MyD88 and NF-κB in placental tissue of mice were determined by RT-PCR and immunohistochemical method. RE-SULTS:Compared with blank control group,mRNA and protein expression of TLR4,MD2,MyD88 and NF-κB in placental tis-sue were increased markedly in the model group(P<0.01). Compared with model group,mRNA and protein expression of TLR4, MD2 and MyD88 in aspirin group and Anzi mixture low-dose and medium-dose groups were decreased significantly as well as the protein expression of TLR4 in Anzi mixture high-dose group and the protein expression of NF-κB in all medicine groups(P<0.05 or P<0.01). mRNA expression of TLR4 and MD2 and the protein expression of MD2 and MyD88 in Anzi mixture low-dose groups were lower than those in aspirin group (P<0.05 or P<0.01). CONCLUSIONS:Anzi mixture can inhibit TLR4/MyD88/NF-κB signaling pathway of APA positive abortive mice,which may be one of anti-APA positive abortion mechanisms.