Allyl methyl disulfide attenuates liver injury induced by concanavalin A by suppressing M1 polarization of macrophages and NLRP3 inflammasome activation.

The rising prevalence of autoimmune hepatitis (AIH) and its intricate pathogenesis has escalated it to a global health issue. This study centered on investigating the effects of allyl methyl disulfide (AMDS) against concanavalin A (ConA)-induced AIH in mice and elucidate the possible mechanisms. Histopathology and blood biochemistry were performed to assess the protective effects of AMDS on ConA-challenged liver injury in C57BL/6 male mice. Then, Immunohistochemistry, Immunofluorescence, RT-qPCR, ELISA and Western blot assays were performed to test changes in the M1 polarization of macrophage and NLRP3 inflammasome activation. Additionally, J774A.1 and AML12 cells were co-cultured to further investigate protective mechanism of AMDS against AIH. We found that AMDS pretreatment significantly alleviated the elevation of the levels of liver injury marker enzymes, and liver pathological changes triggered by ConA. Additionally, AMDS antagonized liver neutrophil infiltration, liver macrophage M1 polarization, and the increase in serum IL-6 and TNF-α levels induced by ConA. Furthermore, the changes in protein and mRNA levels of crucial molecules in the NF-κB and NLRP3 inflammasome pathways after ConA challenge were restored by AMDS. Additionally, AMDS significantly ameliorated the ConA-induced morphological alterations, the release of IL-6 and TNF-α, and the activation of NLRP3 inflammasome pathway in J774A.1 macrophages. Lastly, in a conditioned co-culture system of AML12 and J774A.1 cells, administration of AMDS at a concentration of 25 μM prominently inhibited the mRNA levels of Tnf and Nos2 in AML12 cells. Collectively, AMDS ameliorates ConA-induced AIH by alleviating hepatic neutrophil infiltration, inhibiting M1-type macrophage polarization, and antagonizing NLRP3 inflammasome activation.