Abstract
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-κB and inducible nitric oxide synthase (iNOS), and mRNA levels of mitogen-activated protein kinase (8, 9, and 14), iNOS, tumor necrosis factor-α, and interleukin-1β. 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.
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Abbreviations
- CLP:
-
Cecal ligation and puncture
- GAPDH:
-
Glyceraldehyde 3-phosphate dehydrogenase
- GPx:
-
Glutathione peroxidase
- GR:
-
Glutathione reductase
- GSH:
-
Glutathione
- IL-1β:
-
Interleukin-1β
- iNOS:
-
Inducible nitric oxide synthase
- MDA:
-
Malondialdehyde
- MPO:
-
Myeloperoxidase
- MAPK:
-
Mitogen-activated protein kinase
- MOD:
-
Multi-organ dysfunction
- NADPH:
-
Reduced nicotinamide adenine dinucleotide phosphate
- NF-κB:
-
Nuclear factor-κB
- NO:
-
Nitric oxide
- ROS:
-
Reactive oxygen species
- TNF-α:
-
Tumor necrosis factor-α
- ZSC:
-
Ziziphus spina-christi (L.)
- ZSCLE:
-
Ziziphus spina-christi leaf extract
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Acknowledgement
The authors would like to express their appreciation to the Deanship of Scientific Research at King Saud University for funding this study through the research group project No. RG-198.
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10787_2017_439_MOESM1_ESM.jpg
Supplementary Figure: Effects of Ziziphus spina-christi leaf extract (ZSCLE) administration on the scoring index of histopathological evaluation in mice with cecal ligation and puncture (CLP)-induced sepsis. Values represent the mean ± SEM (n = 7). aSignificantly different from sham (p < 0.05); bSignificantly different from CLP (p < 0.05). (JPEG 189 kb)
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Dkhil, M.A., Al-Quraishy, S. & Moneim, A.E.A. Ziziphus spina-christi leaf extract pretreatment inhibits liver and spleen injury in a mouse model of sepsis via anti-oxidant and anti-inflammatory effects. Inflammopharmacol 26, 779–791 (2018). https://doi.org/10.1007/s10787-017-0439-8
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DOI: https://doi.org/10.1007/s10787-017-0439-8