Ziziphus spina-christi (L.) leaf extract alleviates myocardial and renal dysfunction associated with sepsis in mice

Biomed Pharmacother. 2018 Jun:102:64-75. doi: 10.1016/j.biopha.2018.03.032. Epub 2018 Mar 15.

Abstract

Ziziphus spina-christi (L.), a traditional Arabian medicinal herb, has been used by Egyptians (Bedouin and Nubian) to treat inflammatory symptoms and swellings, pain, and heat since long. We aimed to investigate whether Ziziphus spina-christi leaf extract (ZSCLE) exerted a myocardial and renal protective effect on mice in which sepsis had been induced with cecal ligation and puncture (CLP). Male C57BL/6 mice were divided randomly into six groups (n = 7): sham-operated group, sham-operated mice treated with ZSCLE (300 mg/kg), CLP-induced sepsis group, ZSCLE (100 mg/kg)-treated group, ZSCLE (200 mg/kg)-treated group, and ZSCLE (300 mg/kg)-treated group. Pretreatment with ZSCLE (100, 200, and 300 mg/kg) restored the normal heart rate (HR); decreased the elevated levels of malondialdehyde; the activity of myeloperoxidase, nitric oxide (NO), and inducible NO synthase; and the expression of nuclear factor kappa B (NF-κB), but increased the content of glutathione and antioxidant enzyme activities in mice with sepsis. Moreover, the results of biochemical analyses and qRT-PCR indicated that ZSCLE treatment lowered the level of cytokines, including tumor necrosis factor alpha and interleukin (IL)-1β. Additionally, ZSCLE reduced myocardial and renal apoptosis by inducing the downregulation of caspase-3 and Bax mRNA and upregulation of the expression of Bcl-2. Based on these results, we suggest that ZSCLE has a protective effect against multiple-organ impairment that follows sepsis. This effect may be attributed to the antioxidant, anti-inflammatory, and anti-apoptotic activities of ZSCLE.

Keywords: Apoptosis; Inflammation; Oxidative stress; Sepsis; Ziziphus spina-christi.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / isolation & purification
  • Anti-Inflammatory Agents / pharmacology
  • Antioxidants / administration & dosage
  • Antioxidants / isolation & purification
  • Antioxidants / pharmacology
  • Apoptosis / drug effects*
  • Cytokines / metabolism
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Egypt
  • Gene Expression Regulation / drug effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Multiple Organ Failure / prevention & control
  • Myocardium / pathology
  • Plant Extracts / administration & dosage
  • Plant Extracts / pharmacology*
  • Plant Leaves
  • Renal Insufficiency / etiology
  • Renal Insufficiency / prevention & control
  • Sepsis / complications
  • Sepsis / drug therapy*
  • Ziziphus / chemistry*

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • Cytokines
  • Plant Extracts