Efeitos anti-inflamatório e tumoral da erva-de-passarinho (Passovia ovata)

Abstract

Chronic inflammation can be associated with several diseases including breast cancer, which represents one of the main causes of death in the world. Current antineoplastic therapy has several side and deleterious effects, thus, phytotherapy represents a path to new adjuvant treatments. Mistletoe is a group of plants with recognized anti-inflammatory and antitumor effects, however, only a few studies have been done regarding neotropical species Passovia ovata pharmacological properties. This research aimed to determine the extraction yield, the phytochemical composition, and to evaluate the anti-inflammatory, antioxidant, and antitumor effects of the hydroethanolic extract of P. ovata (POH), and its hexane (FHE), ethyl acetate (FEA) and aqueous (FW) fractions. For this, qualitative phytochemical assays, high-performance liquid chromatography (HPLC), thin-layer chromatography (TLC), and quantification of flavonoids were carried out, in addition to cytotoxicity assays in RAW 264.7 macrophages and CCD-1072Sk fibroblasts, in vitro and in vivo anti-inflammatory assays, antioxidant assays by DPPH, ABTS and FRAP methodologies and in vitro antitumor assay. Yields were 25%, 17.48%, 3.98% and 0.31% for POH, FW, FEA and FHE, respectively. In the extract POH, were identified anthraquinones, tannins, anthocyanins, anthocyanidins, flavonols, catechins, and flavanones. FHE presented the highest content of flavonoids with 36.044±0.733 mg of quercetin (QE)/gram, and in FHE and FEA, phenolic compounds were detected by TLC and HPLC. In the in vitro assay, the extract POH showed low cytotoxicity in RAW 264.7 macrophages and significantly reduced (p < 0.01) the quantification of nitrite, IL-1􀈕, IL-6 and TNF-α at a concentration of 500 μg/mL after 48 hours of treatment in macrophages stimulated with LPS. In the in vivo study, the concentration of 500 mg/kg of POH after 4 hours from treatment, administered orally, reduced edema, inflammatory infiltrate, and the number of mast cells in the footpad of BALB/c mice stimulated with carrageenan. In BALB/c peritonitis model, POH did not influence cytokine levels or cell counts in the tested concentrations. FEA was the fraction with the highest antioxidant activity in ABTS, DPPH and FRAP assays. POH and fractions 15 demonstrated low cytotoxicity against CCD-1072Sk fibroblasts cell line. POH, FHE and FEA had cytotoxic effects against breast cancer cells MCF7 and MDA-MB-231, with FHE having the greatest effect at all times tested. Our results showed that P. ovata leaves have great therapeutic effects, acting through immunomodulatory, antioxidant and antitumor pathways, which may determine a promising source of new therapeutic compounds for drug production