Evaluation of non-clinical toxicity of extract and vouacapans from fruits ofPterodon pubescensBenth

Author(s)

da Silva Souza, Vanessa Helena ; Basting, Rosanna Tarkany ; de Oliveira Sousa, Ilza Maria ; Almeida Queiroz, Nubia de Cassia ; de Carvalho, Joao Ernesto ; Foglio, Mary Ann

• Document type: Journal article
• Source: DRUG AND CHEMICAL TOXICOLOGY; v. 45, n. 3, p. 14-pg., 2020-09-22.

Abstract

Pterodon pubescensBenth. is widely used in folk medicine for the treatment of inflammatory conditions, with the activity attributed to the compounds with a vouacapan moiety, however, few studies report the toxicological evaluation of the extract and safety issues related to the species. Herein the non-clinical toxicity, inin vivoandin vitrotests, of dichloromethane crude extract ofPterodon pubescensfruits (PPE) and vouacapan diterpene furan isomer ' s mixture (1:1) 6 alpha-hydroxy-7 beta-acetoxy-vouacapan-17 beta-oate methyl ester and 6 alpha-acetoxy-7 beta-hydroxy-vouacapan-17 beta-oate methyl ester isomers (VDFI mixture) is reported. Toxicological evaluation of 110-day repeated dose oral toxicity study, as hematological, biochemical, and histopathological parameters demonstrated that animals (male and female Wistar rats) treated with PPE presented no signs of toxicity, nevertheless daily high dose administration (500 mg/Kg) altered the metabolic homeostasis of animals that manifested microgoticular hepatic steatosis. Biochemical and histopathological results of animals (female Swiss mice) treated daily with VDFI mixture, at the highest dose (300 mg/Kg), indicated liver toxicity in one animal causing acute hepatotoxicity. Alkaline Comet assay demonstrated that PPE and VDFI mixture increased the percentage of DNA fragmentation without interfering with the tail moment parameter, but only VDFI mixture (30 mu g/mL) presented statistical difference. In the micronucleus induction test, PPE and VDFI mixture did not demonstrate mutagenic potential. Our data provide evidence for the safety use of PPE and VDFI mixture in lower doses enabling further clinical studies and the development of herbal medicine. (AU)

• FAPESP's process: 12/19661-4 - Vouacapans and geranilgeraniol synergic effect evaluation on nociceptive pain, pharmacokinetic and preclinical toxicological studies
• Grantee: Mary Ann Foglio
• Support Opportunities: Regular Research Grants