Sesamin improves liver injury in nonalcoholic fatty liver disease mice by inhibiting M1 macrophage polarization

doi:10.12092/j.issn.1009-2501.2026.06.014

Abstract

Abstract:

AIM: To investigate whether Ses can improve liver injury in nonalcoholic fatty liver disease (NAFLD) mice by inhibiting M1 macrophages polarization. METHODS: A primary mouse bone marrow-derived macrophage (BMDMs) polarization model and a high-fat diet-fed NAFLD mouse model were used. After Ses treatment, the levels of inflammatory factors in BMDMs and mouse liver tissue, the expression of inducible nitric oxide synthase (iNOS, an M1 macrophage marker) and phosphorylated-signal transducer and activator of transcription1 (P-STAT1) were measured. Serum liver function indicators were also tested. Liver tissue sections were prepared for HE staining, F4/80 and P-STAT1 immunohistochemistry and immunofluorescence staining. RESULTS: Ses treatment reduced the levels of IL-1β and IL-6 in LPS-treated BMDMs and inhibited the expression of iNOS and P-STAT1. Ses treatment reduced the body weight of NAFLD mice and improved liver damage (P<0.01). In the Ses treatment group, the number of macrophages in the liver decreased, and the levels of IL-1β and IL-6, as well as the expression of iNOS and P-STAT1, were reduced(P<0.01). CONCLUSIONS: Ses improves liver damage in NAFLD mice. These effects may be associated with reduction of STAT1 phosphorylation and inhibition of M1 macrophage polarization.

Key words: sesamin, nonalcoholic fatty liver disease, M1 macrophage polarization

CLC Number:

R965.2

Junmin MA, Yue SUN, Yanhua TAO, Bei WEI, Qiuyun WANG, Cuiwei ZHANG, Guodong WANG, Xiang KONG, Haoran ZHANG. Sesamin improves liver injury in nonalcoholic fatty liver disease mice by inhibiting M1 macrophage polarization[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2026, 31(6): 844-850.

Figures/Tables 6

Fig.1 Effects of Ses treatment on the levels of inflammatory factors in BMDMs ($\bar x $±s) BMDMs were treated with 50 or 100 μmol/L Ses for 48 h and then treated with 100 ng/mL LPS for 24 h. A: inflammatory factor chip detection, n=3. The red box and yellow box represent IL-1β and IL-6, respectively. B and C: results of mRNA expression of IL-1β and IL-6, n=3. D and E: supernatant levels of IL-1β and IL-6 were quantified using ELISA assay, n = 3. **P<0.01.

Fig.2 Effects of Ses treatment on M1 macrophage polarization in BMDMs ($\bar x $±s) BMDMs were treated with 50 or 100 μmol/L Ses for 48 h and then treated with 100 ng/mL LPS for 24 h. A: representative immunofluorescence staining images of the iNOS protein in the BMDMs (scale bar=25 μm). B: results of mRNA expression of iNOS, n=3. C and D: the panel and histogram of iNOS protein expression, n=3. *P<0.05, **P<0.01.

Fig.3 Effects of Ses treatment on LPS-induced P-STAT1 expression in BMDMs ($\bar x $±s) BMDMs were treated with 50 or 100 μmol/L Ses for 48 h and then treated with 100 ng/mL LPS for 24 h. A-C: the panel and histogram of P-STAT1 Tyr701 and P-STAT1 Ser727 protein expression, n=3. *P<0.05, **P<0.01.

Fig.4 Effects of Ses treatment on liver injury in NAFLD mice ($\bar x $±s) A: body weight; B: liver weight; C: serum ALT level; D: serum AST level; E: serum TC level; F: serum TG level, n=6. *P<0.05, **P<0.01. G: representative HE staining images of mice liver tissue. The arrow indicates steatosis. (scale bar=100 μm).

Fig.5 Effects of Ses treatment on liver M1 macrophage polarization in NAFLD mice ($\bar x $±s) A: representative immunohistochemistry staining images of F4/80 in mice liver tissue (scale bar=50 μm). B: the number of F4/80 positive macrophages was calculated, n=3. C: results of mRNA expression of iNOS, n=3. D and E: levels of IL-1β and IL-6 in mice liver tissue were quantified using ELISA assay, n=6. **P<0.01.

Fig.6 Effects of Ses treatment on liver P-STAT1 expression in NAFLD mice ($\bar x $±s) A-C: the panel and histogram of P-STAT1 Tyr701 and P-STAT1 Ser727 protein expression in mice liver tissue, n=3, **P<0.01. D: representative immunofluorescence staining images of F4/80 and P-STAT1 Ser727 in mice liver tissue (scale bar=50 μm).

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