Ziziphus spina-christi leaf extract pretreatment inhibits liver and spleen injury in a mouse model of sepsis via anti-oxidant and anti-inflammatory effects

Sepsis is a systemic response to infection that can result in acute hepatic and splenic damage. Ziziphus spina-christi (L.) is a wild tree used as a medicinal plant by ancient Egyptians. However, little is known about the mechanism underlying its effects on sepsis. The current study investigated the protective effects of a Z. spina-christi leaf extract (ZSCLE) on liver and spleen damage in a male C57BL/6 mouse model of sepsis, induced by cecal ligation and puncture (CLP). Prior to CLP, ZSCLE was administered daily for five consecutive days via oral gavage at doses of 100, 200, or 300 mg/kg. The mice were euthanized 9 h after CLP, and oxidative stress markers were measured (myeloperoxidase, lipid peroxidation, nitric oxide, and reduced glutathione). In addition, we investigated histological changes, anti-oxidant enzyme activities (superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase), cytokine levels, protein expression of nuclear factor-kappa B and inducible nitric oxide synthase (iNOS), and mRNA levels of mitogen-activated protein kinase (8, 9, and 14), iNOS, tumor necrosis factor-alpha, and interleukin-1 beta. Our results indicated that ZSCLE significantly and dose-dependently inhibited sepsis-induced liver and spleen injury. These results suggest that ZSCLE could provide a therapeutic agent for sepsis by inducing anti-inflammatory and anti-oxidant effects.