Macrophages are important immune cells in innate immunity, and have remarkable heterogeneity and polarization. Under pathological conditions, in addition to the resident macrophages, other macrophages are also recruited to the diseased tissues, and polarize to various phenotypes (mainly M1 and M2) under the stimulation of various factors in the microenvironment, thus playing different roles and functions. Liver diseases are hepatic pathological changes caused by a variety of pathogenic factors (viruses, alcohol, drugs, etc.), including acute liver injury, viral hepatitis, alcoholic liver disease, metabolic-associated fatty liver disease, liver fibrosis, and hepatocellular carcinoma. Recent studies have shown that macrophage polarization plays an important role in the initiation and development of liver diseases. However, because both macrophage polarization and the pathogenesis of liver diseases are complex, the role and mechanism of macrophage polarization in liver diseases need to be further clarified. Therefore, the origin of hepatic macrophages, and the phenotypes and mechanisms of macrophage polarization are reviewed first in this paper. It is found that macrophage polarization involves several molecular mechanisms, mainly including TLR4/NF-κB, JAK/STATs, TGF-β/Smads, PPARγ, Notch, and miRNA signaling pathways. In addition, this paper also expounds the role and mechanism of macrophage polarization in various liver diseases, which aims to provide references for further research of macrophage polarization in liver diseases, contributing to the therapeutic strategy of ameliorating liver diseases by modulating macrophage polarization.

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Liver fibrosis is a chronic pathological process that various pathogenic factors lead to abnormal hyperplasia of hepatic connective tissue, and its main feature is the excessive deposition of extracellular matrix. However, there are currently no drugs approved for the treatment of liver fibrosis. Phillygenin (PHI), a lignan isolated from Forsythiae Fructus, showed potential anti-inflammatory and anti-fibrosis effects but the mechanisms remain unknown. In view of the vital role of gut microbiota in the development of liver fibrosis, this study aimed to explore whether PHI could protect intestinal epithelial barrier and attenuate liver fibrosis by maintaining the homeostasis of intestinal microbiota. Therefore, the liver fibrosis model was induced by intraperitoneal injection of olive oil containing 10% carbon tetrachloride (CCl4) for 4 weeks in C57BL/6J mice. Histological analysis including Hematoxylin-Eosin, Masson, Sirius red, and immunohistochemistry staining were carried out to detect the histopathology and collagen deposition of mice liver tissues. The biochemical indexes related to liver function (ALT, AST, AKP, γ-GT), fibrosis (HYP, HAase, LN, PC III, IV-C) and inflammation (TNF-α, MIP-1, LPS) were determined by specific commercial assay kits. In vivo experimental results showed that PHI could improve liver histopathological injury, abnormal liver function, collagen deposition, inflammation and fibrosis caused by CCl4. Moreover, PHI restored the intestinal epithelial barrier by promoting the expression of intestinal barrier markers, including ZO-1, Occludin and Claudin-1. More importantly, the corrective effect of PHI on the imbalance of gut microbiota was confirmed by sequencing of the 16 S rRNA gene. In particular, PHI treatment enriches the relative abundance of Lactobacillus, which is reported to alleviate inflammation and fibrosis of damaged liver. Collectively, PHI attenuates CCl4-induced liver fibrosis partly via modulating inflammation and gut microbiota.

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