Red propolis exhibits chemopreventive effect associated with antiproliferative and anti-inflammatory activities

Abstract

Introduction: Red propolis is synthetized from exudates of Dalbergia ecastophyllum (L) Taub. and Symphonia globulifera L.f., presents isoflavones, guttiferone E, xanthochymol, and oblongifolin B and has anti-inflammatory, antioxidant, and antiproliferative activities.

Objectives: This study aimed to evaluate the antigenotoxic and anticarcinogenic potential of red propolis hydroalcoholic extract (RPHE) in rodents.

Methods: The influence of RPHE in doxorubicin (DXR)-induced genotoxicity was investigated through the micronucleus test in Swiss mice. Blood samples were also collected to investigate oxidative stress, hepatotoxicity, and nephrotoxicity. Was investigated the influence of RPHE in 1,2-dimethylhydrazine (DMH)-induced aberrant crypt foci, as well as its influence in proliferating cell nuclear antigen (PCNA) and the cyclooxygenase-2 (COX-2) expression in colon of rats, by immunohistochemistry.

Results: The results showed that RPHE (48 mg/kg) reduced DXR-induced genotoxicity. Animals treated with DXR showed significantly lower GSH serum levels in comparison to the negative control. RPHE treatments did not attenuated significantly the DXR-induced GSH depletion. No difference was observed in cytotoxicity parameters of mice hematopoietic tissues between the treatment groups, as well as the biochemical parameters of hepatotoxicity and nephrotoxicity. RPHE (12 mg/kg) reduced the DMH-induced carcinogenicity and toxicity, as well as DMH-induced PCNA and COX-2 expression in colon tissue.

Conclusion: Therefore, was observed that the RPHE has chemopreventive effect, associated to antiproliferative and anti-inflammatory activities.

Keywords: anti-inflammatory; anticarcinogenic; antiproliferative; chemoprevention; propolis.

Fig. 1

Frequencies of MNPCE in peripheral blood of Swiss mice treated with RPHE and DXR, and their respective controls. NC, negative control (water); DMSO, dimethyl sulfoxide (2.5%); RPHE, red propolis hydroalcoholic extract (12, 24, and 48 mg/kg b.w.); DXR, doxorubicin (10 mg/kg b.w.). Values are mean ± standard deviation (n = 5). ^aSignificantly different from the NC group (P < 0.05). ^bSignificantly different from the DXR group (P < 0.05).

Fig. 2

GSH levels in peripheral blood of Swiss mice treated with RPHE and DXR, and their respective controls. NC, negative control (water); DXR, doxorubicin (10 mg/kg b.w.); DMSO, dimethyl sulfoxide (2.5%); RPHE, red propolis hydroalcoholic extract (48 mg/kg b.w.); GSH, reduced glutathione. Values are mean ± standard deviation (n = 5). ^aSignificantly different from the NC group (P < 0.05).

Fig. 3

OD values of PCNA and COX-2 immunostaining in colon of Wistar Hannover rats treated with RPHE and DMH (a). Photomicrographs of immunohistochemical staining in colon sections from the DMSO+DMH and RPHE 12 + DMH (PCNA – B and c, respectively; COX-2 – D and e, respectively). (Nikon E200 microscope; 400× magnification; 3,3′- diaminobenzidine immunostaining [brown]; counterstain with hematoxylin [blue]; scale bar: 50 μm). DMSO, dimethyl sulfoxide (2.5%); DMH, 1,2-dimethylhydrazine (40 mg/kg b.w.); RPHE, red propolis hydroalcoholic extract (12 mg/kg b.w.); PCNA, proliferative cell nuclear antigen; COX-2, cyclooxygenase-2. Values are mean ± standard deviation (n = 3). ^aSignificantly different from the RPHE group (P < 0.05); ^bSignificantly different from the DMSO+DMH group (P < 0.05).