Camu-camu (Myrciaria dubia) seed extracts as a novel source of bioactive compounds with promising antioxidant, antimutagenic, cytotoxic, antimalarial and antischistosomicidal properties

Abstract

Bioactive compounds are associated with decreased in oxidative stress, inflammation and consequently in risk of non-communicable diseases. Phenolic compounds have demonstrated potential biological activity in many diseases, such as cancer, diabetes, inflammation, obesity-related diseases, neurodegenerative disorders, parasitic diseases, bacterial and viral infections or cardiovascular diseases due to antioxidant and prooxidant capacities. Indeed, these compounds may still have many applications in the pharmaceutical and food industries, with potential functional properties in vivo. The camu-camu seeds, which comprehend about 20% of the fruit weight, is discarded without taking benefit of their chemical components and potential application by the industry. In the current study, we characterized the phenolic composition, the in vitro chemical antioxidant effects, cytotoxic and anti-hemolytic activities, antimalarial and antischistosomicidal properties, besides the inhibition of induced cisplatin chromosomal aberrations of five camu-camu seed extracts obtained with different proportions of water (H2O) and ethyl alcohol (EtOH). The 50% H2O+50% EtOH was the most promising extract because it presented higher total phenolic content (4802 mg GAE/100 g), antioxidant capacity (DPPH = 3694 mg AAE/100 g; FRAP=6604 mg AAE/100 g; FCRC=4918 mg GAE/100 g) and inhibited the cell growth of four cancer cell lines (GI50=7.49 μg GAE/mL A549; 13.3 μg GAE/mL Caco-2; 15.57 μg GAE/mL HepG2 and 14.89 μg GAE/mL HCT8) without cytotoxic effects against normal cells (GI50 IMR90 > 43.2 μg GAE/mL). The cytotoxic effects presented high correlation with the (−)-epicatechin and methylvescalagin contents, while gallic and 2,5-dihydroxybenzoic acids were associated with cytoprotective effects of HCT8 cancer cell line. The 50% H2O+50% EtOH extract also presented protective effect by decreasing 37% of the induced-cisplatin chromosomal breaks index, suggesting its antimutagenic potential, which may be associated to its antioxidant and cytotoxic activities. Moreover, the extracts exhibited antischistosomicidal (ED50 values from 418.4 to >1000.0 µg/mL) and antimalarial activities (IC50 values from 24.2 to 240.8 µg/mL) for both W2 and 37 strains in all intra-erythrocytic stages. According to the correlation analysis, this toxic effects may mainly be attributed to methylvescalagin (r= -0.548 to -0.951, p <0.05) and 2,4-dihydroxybenzoic acid (r= -0.612 to -0.917, p<0.05) contents. Moreover, the anti-hemolytic effect was associated to methylvescalagin (r= -0.597, p<0.05). No toxic effects were observed for leishmaniasis and IMR90 normal cells. In this case, methylvescalagin was the bioactive compound of greatest interest once it presented simultaneous relation with antiparasitic and anti-hemolytic activities.