Caffeine - rich infusion from Cola nitida (kola nut) inhibits major carbohydrate catabolic enzymes; abates redox imbalance; and modulates oxidative dysregulated metabolic pathways and metabolites in Fe2+-induced hepatic toxicity

Biomed Pharmacother. 2017 Dec:96:1065-1074. doi: 10.1016/j.biopha.2017.11.120. Epub 2017 Dec 6.

Abstract

The antioxidative and antidiabetic effects and toxicity of caffeine-rich infusion of Cola nitida were investigated using in vitro, ex vivo and in silico models. C. nitida was infused in boiling water and allowed to cool before concentrating at <50°C. HPLC analysis of the infusion revealed a caffeine content of 80.08%. The infusion showed potent in vitro antioxidant activity by significantly (p<0.05) scavenging 2,2'-diphenyl-1-picrylhydrazyl (DPPH). It significantly (p<0.05) inhibited α-glucosidase and α-amylase activities. Treatment of Fe2+ induced oxidative hepatic tissues with the infusion led to increase Superoxide Dismutase (SOD) and catalase activities, and glutathione (GSH) level as well as decreased malondialdehyde (MDA) level. FTIR spectroscopy of hepatic metabolite revealed restoration of oxidative-induced depleted functional groups by the infusion. LC-MS analysis of the metabolite also revealed restoration of most depleted metabolites with concomitant generation of 4-O-Methylgallic, (-)-Epicatechin sulfate, L-Arginine, L-tyrosine, Citric acid and Decanoic acid in infusion-treated tissues. Pathway analysis of the identified metabolites revealed the presence of 21 metabolic pathways involved in normal hepatic tissues, 12 in oxidative injured tissues and 17 in the treated tissues. Treatment with the infusion restored 4 metabolic pathways common to the normal tissue and further activated 4 additional pathways. Prediction of oral toxicity of caffeine showed it to belong to class 3, with a LD50 of 127mg/kg. Its toxicity target was predicted as Adenosine Receptor A2a. It was also predicted to be an inhibitor of CYP1A2. These results suggest the antioxidative and antidiabetic properties of C. nitida infusion, with caffeine as the major constituent.

Keywords: Antioxidative; Cola nitida; Kola nuts; Metabolomics; Type 2 diabetes.

MeSH terms

  • Animals
  • Antioxidants / administration & dosage
  • Antioxidants / isolation & purification
  • Caffeine / administration & dosage*
  • Caffeine / isolation & purification
  • Carbohydrate Metabolism / drug effects
  • Carbohydrate Metabolism / physiology*
  • Cola*
  • Ferrous Compounds / toxicity*
  • Liver / drug effects
  • Liver / metabolism*
  • Male
  • Oxidation-Reduction / drug effects
  • Oxidative Stress / drug effects
  • Oxidative Stress / physiology
  • Plant Extracts / administration & dosage*
  • Plant Extracts / isolation & purification
  • Rats
  • Seeds

Substances

  • Antioxidants
  • Ferrous Compounds
  • Plant Extracts
  • ferrous sulfate
  • Caffeine