Ethanol-Extracted Brazilian Propolis Exerts Protective Effects on Tumorigenesis in Wistar Hannover Rats

PLoS One. 2016 Jul 8;11(7):e0158654. doi: 10.1371/journal.pone.0158654. eCollection 2016.


The present study was conducted over a course of 104 weeks to estimate the carcinogenicity of ethanol-extracted Brazilian green propolis (EEP). Groups of 50 male and 50 female Wistar Hannover rats, 6-week-old at commencement were exposed to EEP at doses of 0, 0.5 or 2.5% in the diet. Survival rates of 0.5% and 2.5% EEP-treated male and female rats, respectively, were significantly higher than those of respective control groups. Overall histopathological evaluation of neoplasms in rat tissues after 2 years showed no significant increase of tumors or preneoplastic lesions in any organ of animals administered EEP. Significantly lower incidences of pituitary tumors in 0.5% EEP male and 2.5% EEP female groups, malignant lymphoma/leukemia in both 2.5% EEP-treated males and females and total thyroid tumors in 0.5% EEP male group were found. Administration of EEP caused significant decreases of lymphoid hyperplasia of the thymus and lymph nodes in 2.5% EEP-treated rats, tubular cell hyperplasia of kidneys in all EEP groups, and cortical hyperplasia of adrenals in EEP-treated females. In the blood, significant reduction of neutrophils in all EEP-treated males and band neutrophils in 2.5% EEP-treated females was found indicating lower levels of inflammation. Total cholesterol and triglicerides levels were significantly lower in the blood of 2.5% EEP-treated female rats. In conclusion, under the conditions of the 2-year feeding experiment, EEP was not carcinogenic, did not induce significant histopathological changes in any organ, and further exerted anti-inflammatory and antitumorigenic effects resulting in increase of survival of Wistar Hannover rats.

MeSH terms

  • Animals
  • Body Weight / drug effects
  • Carcinogenesis / drug effects*
  • Carcinogens / toxicity
  • Cell Transformation, Neoplastic
  • Ethanol / chemistry*
  • Female
  • Male
  • Mutagenicity Tests
  • Plant Extracts / chemistry*
  • Propolis / chemistry*
  • Rats
  • Rats, Wistar


  • Carcinogens
  • Plant Extracts
  • Ethanol
  • Propolis

Grant support

This research was supported by a grant from the Ministry of Health, Labor and Welfare of Japan (grant title: Research on genotoxicity and carcinogenicity of food additives and health foods). No number existed.