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[Effect of matrine on mouse hepatitis and tumor necrosis factor production induced by Propionibacterium
1Research Laboratory of Natural and Synthetic Drugs, College of Pharmacy, Changhai Hospital, Second Military Medical University, Shanghai.
Abstract:
The effect of matrine (Mat) on lipopolysaccharides (LPS)-induced fatal hepatitis and tumor necrosis factor (TNF) production in Propionibacterium acnes (PA)-primed mice were studied. Mice were injected i.p. LPS (10 micrograms/mouse) 7 d after i.p. PA (0.5 ml/mouse) to induce fatal hepatitis. After i.p. LPS, serum TNF activity rose to 1657 +/- 406 kU.L-1 at 1.5 h and ALT activity increased up to 1,496 +/- 890 U.L-1 at 5 h. Six of 8 mice died within 5 h and the massive hemorrhagic necrosis of the liver was observed in all mice. Administration of Mat (10, 50 mg.kg-1, i.p., bid x 3 d) before the LPS injection markedly reduced the elevation of serum TNF and ALT activity in a dose-dependent manner, and diminished the mortality induced by LPS. Liver congestion and necrosis induced by LPS in PA-primed mice were ameliorated markedly by Mat pretreatment. Mat (62.5-250 mg.L-1) inhibited LPS-induced TNF release from PA-primed mouse peritoneal macrophage in vitro in a concentration-dependent manner. These results seggest that Mat protected PA-primed mice from the development of fatal hepatitis induced by LPS due to inhibition of TNF production.
Insights
Matrine (Mat) effectively protected mice from fatal hepatitis induced by lipopolysaccharides (LPS) and Propionibacterium acnes (PA) priming. This protection was linked to Matrine
Area of Science:
- Hepatology
- Immunology
- Pharmacology
Background:
- Lipopolysaccharides (LPS) can induce fatal hepatitis in mice primed with Propionibacterium acnes (PA).
- Tumor necrosis factor (TNF) plays a key role in the pathogenesis of LPS-induced liver injury.
Purpose of the Study:
- To investigate the protective effects of matrine (Mat) against LPS-induced fatal hepatitis in PA-primed mice.
- To determine the impact of matrine on TNF production in this model.
Main Methods:
- PA-primed mice were injected with LPS to induce hepatitis.
- Matrine was administered intraperitoneally before LPS challenge.
- Serum TNF and ALT levels, mortality, and liver pathology were assessed.
- In vitro studies examined matrine's effect on TNF release from macrophages.
Main Results:
- LPS injection led to high mortality, elevated serum TNF and ALT levels, and severe liver necrosis.
- Matrine administration significantly reduced mortality, TNF and ALT levels, and liver damage in a dose-dependent manner.
- Matrine inhibited LPS-induced TNF release from macrophages in vitro.
Conclusions:
- Matrine exhibits significant protective effects against LPS-induced fatal hepatitis in PA-primed mice.
- The hepatoprotective mechanism of matrine involves the inhibition of TNF production.