Objective To study the protective effects and mechanism of aqueous extract of arctium lappa root on vas?cular endothelial cell injury in hypertensive rats. Methods The hypertensive rat model was induced by N-nitro-L-argi?nine. Rats were randomly divided into normal control group, model control group, positive control group (aptopril 15 mg/kg), low concentration of aqueous extract of arctium lappa root (0.5 g/kg), medium concentration of (1 g/kg) and high concentra?tion of (2 g/kg) groups. After six weeks of continuous intragastric administration, the systolic blood pressure levels at tail ar?tery were measured at 1, 4, 7, 10, 13, 16, 19, 22, 29, 36 and 42 d after treatment. And other indicators related to inflammato?ry factors were detected including C-reactive protein (CRP) and interleukin (IL)-6. The intercellular adhesion molecule-1 (ICAM-1) level was detected by taking samples of thoracic aorta. Results (1) The systolic blood pressure level at tail ar?tery was significantly lower in aqueous extract of arctium lappa root group than that of model control group ( P<0.05). (2) The aqueous extract of arctium lappa root can significantly improve the vascular endothelial cell injury, suppress vascular endo?thelial cell loss and blood cell adhesion, and cell proliferation with collagen fibers in muscle membrane. ( 3) The serum levels of IL-6, CRP and vascular endothelial ICAM-1 were significantly reduced in aqueous extract of arctium lappa root group than that of model control group (P<0.05). Conclusion Aqueous extract of arctium lappa root can significantly improve vascular endothelial cell injury in hypertensive rats. The mechanism may be related to the inhibition of inflammatory cyto?kines like IL-6, CRP and the expression of ICAM-1, and the improvement of chronic inflammatory response in vascular en?dothelium of hypertensive rats.

OBJECTIVETo explore the anti-inflammatory mechanisms of high density lipoprotein (HDL) by observing the effects of apoprotein (apo)AI, a major protein component of HDL, on the inflammatory macrophage cell polarity.

METHODSCultured mice marrow-derived macrophages were stimulated with lipopolysaccharide and interferon after 10 µg/ml of apoAI were added to the macrophages for 24 hours. The expression of membrane molecules CD16/32, CD206 were detected by fluorescence activated cell sorting (FACS). ELISA was used to detect the secretion of IL-10 and IL-12. Real-time quantitative PCR was used to detect the mRNA expression of TLR4, MyD88 and IRF5.

RESULTSCompared to macrophages stimulated by interferon and lipopolysaccharide but without pretreatment with apoAI, pre-incubation with apoAI significantly downregulated the expression of CD16/32 (91.17% ± 1.99% vs.50.47% ± 1.02%, P < 0.05), IL-12 [(747.27 ± 3.74)pg/ml vs. (73.80 ± 4.56)pg/ml, P < 0.05], upregulated the expression of CD206(0.33% ± 0.12% vs. 3.00% ± 0.36%, P < 0.05), IL -10 expression [(23.56 ± 4.30) pg/ml vs.(32.91 ± 2.47) pg/ml, P < 0.05], and reduced the mRNA expression of TLR4 (1.000 ± 0.025 vs.0.708 ± 0.003, P < 0.05) , MyD88 (1.591 ± 0.005 vs. 1.341 ± 0.005, P < 0.05) , IRF5 (0.954 ± 0.005 vs. 0.463 ± 0.003, P < 0.05) .

CONCLUSIONApoAI enhances the switch of inflammatory macrophages to anti-inflammatory macrophages possibly through inhibiting TLR4-MyD88-IRF5 pathway.

Animals ; Apolipoprotein A-I ; pharmacology ; Cell Line ; Female ; Interferon Regulatory Factors ; metabolism ; Interleukin-10 ; metabolism ; Interleukin-12 ; metabolism ; Lectins, C-Type ; metabolism ; Macrophages ; drug effects ; immunology ; metabolism ; Mannose-Binding Lectins ; metabolism ; Mice ; Mice, Inbred C57BL ; Myeloid Differentiation Factor 88 ; metabolism ; Receptors, Cell Surface ; metabolism ; Receptors, IgG ; metabolism ; Toll-Like Receptor 4 ; metabolism