In vivo and in vitro toxicological evaluation of the hydroalcoholic leaf extract of Ageratum conyzoides L. (Asteraceae)

J Ethnopharmacol. 2014 Sep 11;155(2):1214-8. doi: 10.1016/j.jep.2014.07.005. Epub 2014 Jul 15.

Abstract

Ethnopharmacological relevance: In African traditional medicine, Ageratum conyzoides has been used as purgative, febrifuge, anti-ulcer and wound dressing. To date there is no safety information about long term use of Ageratum conyzoides which contains pyrrolizidine alkaloids, a class of hepatotoxic and carcinogenic phytochemicals. This study aims to evaluate the 90 days subchronic toxicity and in vitro toxicity of Ageratum conyzoides.

Materials and methods: Three groups of 8 rats (4 males and 4 females) received distilled water (control), 500 and 1000 mg/kg of the extract daily for 90 consecutive days by oral gavage. The animals were observed daily for abnormal clinical signs and death. Body weight, relative organ weight, haematological and biochemical parameters of blood as well as heart, kidney, liver and spleen tissues histology were evaluated.

Results: After 90 days administration, Ageratum conyzoides increased significantly (p<0.05) the relative weight of the liver, the spleen and kidney as compared to control group. Ageratum conyzoides increased also significantly (p<0.05) ALP, ALT, AST and blood glucose. Furthermore, an increase in the number of platelets associated with a normocytic and normochromic anaemia was observed. The cytotoxicity, determined by the MTT test and neutral red assay, has shown that the cytotoxicity of hydroalcoholic extract of Ageratum conyzoides and its total alkaloids was very close.

Conclusions: Our results have shown that Ageratum conyzoides at 500 and 1000 mg/kg can induce liver, kidney and haematological disorders. These toxics effects can be attributed to its total alkaloids especially to pyrrolizidine alkaloids which are present in this plant.

Keywords: Ageratum conyzoides; Cytotoxicity; Oral toxicity; Pyrrolizidine alkaloids; Total alkaloids.

MeSH terms

  • Administration, Oral
  • Ageratum* / chemistry
  • Anemia / blood
  • Anemia / chemically induced
  • Anemia / diagnosis
  • Animals
  • Biomarkers / blood
  • Blood Platelets / drug effects
  • Blood Platelets / metabolism
  • Blood Platelets / pathology
  • Caco-2 Cells
  • Cell Survival / drug effects
  • Chemical and Drug Induced Liver Injury / blood
  • Chemical and Drug Induced Liver Injury / diagnosis
  • Chemical and Drug Induced Liver Injury / etiology
  • Ethanol / chemistry*
  • Female
  • Humans
  • Inhibitory Concentration 50
  • Kidney / drug effects
  • Kidney / metabolism
  • Kidney / pathology
  • Kidney Diseases / blood
  • Kidney Diseases / chemically induced
  • Kidney Diseases / diagnosis
  • Liver / drug effects
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Phytotherapy
  • Plant Extracts / administration & dosage
  • Plant Extracts / chemistry
  • Plant Extracts / isolation & purification
  • Plant Extracts / toxicity*
  • Plant Leaves
  • Plants, Medicinal
  • Rats, Wistar
  • Risk Assessment
  • Solvents / chemistry*
  • Time Factors
  • Toxicity Tests, Subchronic

Substances

  • Biomarkers
  • Plant Extracts
  • Solvents
  • Ethanol