Knockout of NLRP3 enhances hypolipidemic effect and anti-inflammative effect of apigenin in Triton-WR 1339-induced hyperlipidemia mice / 中国药理学通报

ABSTRACT

Aim To investigate the role and mechanism of NLRP3 on hypolipidemic effect and anti-inflammative effect of apigenin. Methods Triton-WR 1339-induced hyperlipidemia was applied to wide type C57BL/6 and NLRP3"'" mice, which was treated with apigenin of 6.25 mg • kg"1 • day"1 for five days. Blood and liver tissueswere collected for detecting TC, TG, HDL, LDL, IL-1B, IL-6, MCP-1 and the liver underwent HE staining. The expressions of NLRP3, I L 4, ASC, CD36, CYP7A1 and FGF21 were tested using RT-qPCR. Results Compared with NLRP3 "'" model group, serum contents of TC, TG, HDL, LDL, IL-1B, IL-6, MCP-1 were reduced in NLPR3"'" treated with apigenin of 6. 25 mg • kg"1 (P < 0. 05). The percentage of hepatic steatosis wasdown-regulated by apigenin in pathogenesis observation. However, all these phenotype changes were not observed in WT mice treated with apigenin. Moreover, up-regulation of CD36 and vLDLR and down-regualtion of ASC and IL-4 were founded in both WT and NLRP3"'" model group (P < 0. 05), while down-regulation of FGF21 and up-regulation of CYP7A1 were only seen in NLRP3"/ _ model group but not in WT group. Conclusions Knockout of NLRP3 enhances hypolipidemic effect and anti-inflammative effect of apigenin in triton-1339 IP-induced hyperlipidemia mice, which may be associated with apigenin-regulated FGF21/CYP7A1 pathway without NLRP3 inflammasome interruption.