Dihydromyricetin inhibits the M1 polarization of macrophage induced by oxidized low-density lipoprotein through JAK3/STAT5 signaling pathway / 中华老年医学杂志

ABSTRACT

Objective To observe the effect of dihydromyricetin(DMY) on the M1 polarization of macrophages induced by oxidized low-density lipoprotein(Ox-LDL) and to explore its mechanism.Methods RAW 264.7 cells were incubated in RPMI1640 medium containing Ox-LDL(50 mg/L) and DMY(40 μmol/L) for 24 h.The effect of JAK/STAT signaling pathway inhibitor AG-490 on DMY was observed.The levels of tumor necrosis factor-α(TNF-α),interferon-y(IFN-γ),transforming growth factor-β(TGF-β) and interleukin-10(IL-10) in the supernatant of cell culture medium were detected by enzyme-linked immunosorbent assay(ELISA).The protein expressions of inducible nitric oxide synthase(iNOS) and arginase 1(Arg1) were tested by Western blot.Results Compared with the control group,the Ox-LDL group showed that the protein expression in macrophage of iNOS and levels of TNF-α and IFN-γ in the supernatant of culture medium were significantly increased(t =4.12,2.89 and 3.44,P=0.023,0.036 and 0.031),while the protein expression of Arg1 in cells and levels of TGF-β and IL-10 in the supernatant of culture medium were significantly decreased(t =3.71,2.31 and 2.67,P =0.034,0.038 and 0.034),and the ratios of p-JAK3/JAK3 and p-STAT5/STAT5 in cells were significantly increased(t =3.93 and 2.65 and P =0.007 and 0.021).Compared with the OxLDL group,the Ox-LDL+DMY group showed that the protein expression of iNOS in cells and levels of TNF-α and IFN-γ in the supernatant of culture medium were significantly decreased(t =5.74,2.37and 3.07,P =0.022,0.031 and 0.033),while the protein expression of Arg1 in cells and levels of TGF-β and IL-10 in the supernatant of culture medium were significantly increased(t =3.94,2.19 and 2.44,P=0.025,0.047 and 0.035),and the ratios of p-JAK3/JAK3 and p-STAT5/STAT5 in cells were significantly decreased(t =3.41 and 2.32,P =0.015 and 0.023).Compared with the Ox-LDL+ DMY group,the Ox-LDL+-DMY + AG-490 group showed that the protein expression of iNOS and levels of TNF-α and IFN-γ in supernatant of culture medium were significantly increased (t =3.14,3.41 and 3.74,P =0.017,0.028 and 0.023),while the protein expression of Arg1 and levels of TGF-β and IL-10 were significantly decreased (t =2.87,2.85 and 3.47,P =0.025,0.035 and 0.028).Conclusions Dihydromyricetin inhibits the M1 polarization of macrophages induced by Ox-LDL,and the mechanism may be related with the activation of JAK3/STAT5 signaling pathway.