Prospect of antioxidants and antiproliferative substances in campomanesia adamantium (Myrtaceae): Aislan Cristina Rheder Fagundes Pascoal

Author(s)

Aislan Cristina Rheder Fagundes Pascoal

• Document type: Master's Dissertation
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia
• Defense date: 2012-02-23

Examining board members

Marcos José Salvador; Elaine Minatel; Elfriede Marianne Bacchi

• Advisor: Marcos José Salvador

Abstract

Campomanesia adamantium (Cambess.) O. Berg (Myrtaceae) is a plant popularly known as gabiroba or guaviroba, whose fruits are edible. Its leaves and bark are used in folk medicine as anti-inflammatory, antidiarrheal, antiseptic of the urinary tract and treatment of flu. As part of a bioprospecting program aimed at the discovery of bioactive natural products, this study aims at prospecting with phyto-derived antioxidant and antiproliferative activity accumulated in the ethanol extract from leaves of C. adamantium. To this end, it has adapted methods for in vitro evaluation of antioxidant activity (DPPH radical reduction and ORACFL assays) and antiproliferative activity against human tumor cell lines and proceeded to the phytochemical study, seeking to identify the major constituents active. Initially, we obtained the profile of the active extracts (HPLC-DAD and ESI-MS), identifying some known substances directly into the crude extract and fractions (dereplication). The active extracts were subjected to fractionation guided by the antioxidant and antiproliferative activities and the compound isolated and purified held structural elucidation using spectroscopic analysis (NMR (1D and 2D) and mass spectrometry). Still, we sought to assess whether the purified substance induces cell death by apoptosis front of the cell line of prostate cancer (PC-3) with analysis of mRNA expression by semiquantitative PCR of the genes BAX and BCL-2 and DNA fragmentation by flow cytometry. The results suggest that: (1) the crude ethanol extract of leaves of C. adamantium and its fractions in butanol and ethyl acetate showed antiproliferative activity against human tumor lines; (2) the crude ethanol extract of leaves of C. adamantium and its fractions butanol and ethyl acetate showed antioxidant activity proved both by DPPH method (based on mechanisms of electron transfer), and by the ORACFL assay (kinetic method based on mechanisms of hydrogen transfer). The antioxidant activity of these samples may be related to the high content of total soluble phenolic substances estimated by the Folin Ciocalteu colorimetric assay; (3) analysis employing HPLC-DAD, ESI-MS and MS-MS of extracts and fractions with antioxidant activity suggested the presence of flavonoids isoquercitrin (Ca1), quercitrin (Ca2), myricetin (Ca3), quercetin (Ca4) chalcones and 2 ', 4'-dihydroxy- 6'-metoxichalcona (Ca5), 2', 4'-dihydroxy-5'-methyl-6 '-metoxichalcona (Ca6) and 2', 4'-dihydroxy-3 ', 5'-dimethyl-6'-metoxichalcona (Ca7); (4) the phytochemical study of ethyl acetate fraction led to the isolation and identification of the chalcone Ca5 which showed promising antiproliferative activity against some human tumor cell lines studied; (5) analysis of gene expression of BAX and BCL-2 showed no changes, but DNA fragmentation can be observed apoptosis in cells that were treated with chalcone Ca5. Thus, we proceeded the study of C. adamantium to search of natural products with antioxidant and antiproliferative activities, to contribute to the chemoprevention of diseases related to oxidative stress (degenerative diseases, cancer, cardiovascular, inflammatory) and to obtain new sources of pharmaceutical products (AU)

• FAPESP's process: 09/11426-3 - Campomanesia adamantium: prospection of antioxidants and compounds with antiproliferative properties.
• Grantee: Aislan Cristina Rheder Fagundes Pascoal
• Support Opportunities: Scholarships in Brazil - Master