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Published on: January 10, 2025
Magnesium lithospermate B reduces inflammatory response in a mouse model of hepatic ischemia-reperfusion injury
Shaohua Song1, Wenyu Liu, Fang Liu
1Department of Organ Transplantation, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Huangpu District, Shanghai, 200003, China.
Abstract:
It has been well proved that acute inflammatory response and hepatocellular apoptosis contributed to the pathogenesis of liver ischemia reperfusion (IR) injury. A vast amount of research has demonstrated that magnesium lithospermate B (MLB) has potent anti-apoptosis and potential anti-inflammatory pharmacological properties. However, it has not previously been examined whether MLB can attenuate hepatic IR injury. Firstly, the optimal dose of MLB to protect against hepatic IR injury was determined using hepatic IR model in mice. Then, the effect of MLB on IR-induced inflammatory response was detected in detail. We found that MLB exhibited protective effect from the beginning of 50 mg/kg and culminated at the doses of 100 and 200 mg/kg. The alanine aminotransferase and aspartate aminotransferase levels in MLB group were markedly decreased. Severe hepatocellular swelling/necrosis, sinusoidal/vascular congestion and inflammatory cell infiltration were seen and a large number of apoptotic cells were found in the liver samples from Saline group, while minimal damage and very few apoptotic cells were noted in the samples from MLB group. Kuppfer cells infiltration, myeloperoxidase activity and mRNA level of CD11b in MLB group was significantly decreased. Serum TNF-a and IL-6, and mRNA expression of CXCL-10 and ICAM-1 was markedly decreased in the samples from MLB group. Inflammatory signaling pathway activation was largely prevented in MLB group. MLB can significantly attenuate IR-induced hepatocellular damage and hepatocellular apoptosis by preventing inflammatory signaling pathways activation, inflammatory mediators expression and macrophage and neutrophil infiltration.
Insights
Magnesium lithospermate B (MLB) protects against liver ischemia reperfusion (IR) injury by reducing inflammation and cell death. MLB treatment significantly decreased liver damage markers and inflammatory responses in a mouse model.
Area of Science:
- Hepatology
- Immunology
- Pharmacology
Background:
- Liver ischemia reperfusion (IR) injury involves acute inflammation and hepatocellular apoptosis.
- Magnesium lithospermate B (MLB) possesses known anti-apoptotic and anti-inflammatory properties.
Purpose of the Study:
- To investigate the efficacy of MLB in attenuating hepatic IR injury.
- To determine the optimal protective dose of MLB.
- To elucidate the underlying mechanisms of MLB's protective effects.
Main Methods:
- Establishment of a mouse model for hepatic IR injury.
- Administration of varying doses of MLB to assess protective effects.
- Evaluation of liver enzymes, histological damage, apoptosis markers, inflammatory cell infiltration, and cytokine/chemokine expression.
Main Results:
- MLB demonstrated protective effects starting at 50 mg/kg, with optimal results at 100 and 200 mg/kg.
- MLB significantly reduced liver enzyme levels (ALT, AST) and histological damage.
- MLB treatment decreased hepatocellular apoptosis, inflammatory cell infiltration (Kupffer cells, neutrophils), and key inflammatory mediators (TNF-α, IL-6, CXCL-10, ICAM-1).
Conclusions:
- Magnesium lithospermate B effectively attenuates liver IR injury.
- MLB exerts its protective effects by inhibiting inflammatory signaling pathways, reducing inflammatory mediator production, and limiting immune cell infiltration.
- MLB shows therapeutic potential for managing hepatic IR injury.
