This study aims to investigate the mechanism by which modified Xiangsha Liujunzi Decoction regulates liver inflammatory responses through apolipoprotein A-I(ApoA-I)-mediated modulation of activating transcription factor 3(ATF3). After 16 ApoA-I~(-/-) mice and 24 C57BL/6J mice were adaptively fed for one week, the 16 ApoA-I~(-/-) mice were randomly divided into high-fat diet(HFD) group and modified Xiangsha Liujunzi Decoction [traditional Chinese medicine(TCM) treatment] group. The 24 C57BL/6J mice were randomized into blank control group, HFD control group, and TCM treatment control group. The blank control group was fed standard diet, while the remaining groups received high-fat diet. After eight weeks, the TCM treatment groups(both ApoA-I~(-/-) and C57BL/6J mice) were administered modified Xiangsha Liujunzi Decoction via oral gavage. The levels of total cholesterol(TC), triglycerides(TG), low-density lipoprotein cholesterol(LDL-C), high-density lipoprotein cholesterol(HDL-C), alanine aminotransferase(ALT), and aspartate aminotransferase(AST) in serum of mice were measured by using an automated biochemical analyzer. Pathomorphological changes in liver tissue were evaluated via hematoxylin-eosin(HE) and oil red O staining. The levels of interleukin(IL)-1β, IL-6, and tumor necrosis factor-α(TNF-α) in liver tissue were detected by enzyme-linked immunosorbent assay(ELISA), and the expression levels of ApoA-I, ATF3, Toll-like receptor 4(TLR4), and nuclear factor-κB(NF-κB) mRNAs and proteins were measured by reverse-transcription quantitative polymerase chain reaction(RT-qPCR) and Western blot. Compared with the blank control group, the HFD control group exhibited significantly elevated levels of TC, TG, HDL-C, LDL-C, ALT, and AST in serum of mice(P<0.01), significantly increased levels and expressions of IL-1β, IL-6, and TNF-α mRNAs in serum and liver tissue(P<0.01), significantly reduced expressions of ApoA-I and ATF3 mRNAs and proteins in liver tissue(P<0.01), and significantly upregulated expressions of TLR4 and NF-κB mRNAs and proteins(P<0.01). Compared with the HFD control group, the TCM treatment control group showed significantly reduced levels of TC, TG, HDL-C, LDL-C, ALT, and AST in the serum of mice(P<0.05, P<0.01), significantly decreased levels and expressions of IL-1β, IL-6, and TNF-α mRNAs in serum and liver tissue(P<0.05, P<0.01), upregulated expressions of ApoA-I and ATF3 mRNAs and proteins in liver tissue(P<0.05, P<0.01), and significantly downregulated expressions of TLR4 and NF-κB mRNAs and proteins(P<0.05, P<0.01). Compared with the HFD control group, the HFD group displayed significantly elevated levels of TC, TG, LDL-C, ALT, and AST in serum of mice(P<0.01), significantly reduced level of HDL-C(P<0.01), significantly increased levels and expressions of IL-1β, IL-6, and TNF-α mRNAs in serum and liver tissue(P<0.05, P<0.01), significantly reduced expressions of ATF3 mRNA and protein(P<0.05, P<0.01), and significantly elevated TLR4 and NF-κB mRNAs and proteins(P<0.05, P<0.01). Compared with the TCM treatment control group, the TCM treatment group showed significantly elevated levels of TC, TG, LDL-C, ALT, and AST in the serum of mice(P<0.05, P<0.01), significantly reduced levels of HDL-C(P<0.01), significantly increased levels and expressions of IL-1β, IL-6, and TNF-α mRNAs in serum and liver tissue(P<0.05, P<0.01), significantly downregulated expression of ATF3 mRNA and protein(P<0.01), and significantly upregulated expressions of TLR4 and NF-κB mRNAs and proteins(P<0.05, P<0.01). Modified Xiangsha Liujunzi Decoction may ameliorate dyslipidemia-induced liver inflammation by upregulating the expression of ApoA-I, activating ATF3, and subsequently inhibiting the TLR4/NF-κB signaling pathway.
