Regulation of Concanavalin A-induced Immune Hepatitis in Mice by Dihydromyricetin at the M1/M2 Type Macrophage Level.

Abstract

Background: Autoimmune hepatitis (AIH) is an autoimmune disease accompanied by an autoimmune inflammatory response that often leads to severe liver damage. In addition, it may further lead to complications such as liver fibrosis, cirrhosis and liver failure. Dihydromyricetin (DHM) possesses various pharmacological properties, such as being anti-inflammatory, antioxidant, and antibacterial. In this experiment, we investigated the effect of DHM on autoimmune hepatitis mice based on the level of M1/M2 type macrophages.

Methods: An autoimmune hepatitis mouse model was established by the administration of DHM followed by tail vein injection of Concanavalin A (Con A). Liver tissues were examined for pathological and morphological changes. Interleukin-1β (IL-1β), interleukin-10 (IL-10), interleukin-6 (IL-6), and interleukin-4 (IL-4) levels in liver tissues were assessed. Serum hepatic function indexes were measured, including alanine aminotransferase (ALT), aspartate transaminase (AST), and lactatedehydrogenase (LDH). Oxidative stress indexes, malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and Nitric oxide (NO), were quantified. Additionally, tumor necrosis factor-α (TNF-α) and nuclear factor kappa-B (NF-κB) p65 mRNA and protein expression polarization were determined. The presence of M1/M2-type macrophages was also investigated.

Results: Compared to the model group, mice in the DHM group exhibited a significant reduction in serum hepatic function indexes (p < 0.05). Liver tissues from the DHM group showed a noteworthy decrease in MDA and NO levels, along with a significant increase in SOD and GSH-Px levels (p < 0.05). Furthermore, in the liver tissues of mice from the DHM group, there was a notable reduction in the count of M1-type macrophages and a considerable elevation in the M2-type macrophages (p < 0.05). IL-1β and IL-6 expression levels exhibited a significant decrease, whereas IL-10 and IL-4 levels displayed a significant increase (p < 0.05). Additionally, both TNF-α and NF-κB p65 mRNA levels and protein expression experienced a noteworthy decrease (p < 0.05).

Conclusion: DHM mitigates the inflammatory response in AIH mice by reducing oxidative stress and modulating macrophage polarization and the TNF-α/NF-κB pathway.