Mutagenic potential of Cordia ecalyculata alone and in association with Spirulina maxima for their evaluation as candidate anti-obesity drugs

Abstract

ABSTRACT. Obesity is one of the most important nutritional disorders, and can be currently considered as an epidemic. Although there are few weight reduction drugs available on the market, some new drug candidates have been proposed, including Cordia ecalyculata, a Brazilian plant with anorectic properties, and Spirulina maxima, a cyanobacterium with antioxidant and anti-genotoxic activity. In this study, we evaluated the mutagenic potential of C. ecalyculata at doses of 150, 300, and 500 mg/kg alone and in association with S. maxima at doses of 75, 150, and 250 mg/kg, respectively, through an in vivo micronucleus test, using mice of both sexes, and an in vitro micronucleus test and comet assay, using human peripheral blood. For all tests, cyclophosphamide was used as a positive control. The results showed that treatment of 300 mg/kg C. ecalyculata and the combination treatment of 500 mg/kg C. ecalyculata with 250 mg/kg S. maxima resulted in anorectic effects. The mutagenic tests did not reveal any clastogenic or genotoxic activity for any treatment, indicating that these candidates could be marketed as weight-reduction drugs. Moreover, the drugs contain chemo-preventive substances that can protect against tumorigenesis, which has been associated with obesity.

Can Spirulina maxima reduce the mutagenic potential of sibutramine?

“…Although the cyanobacterium is described as an antioxidant and anti-mutagenic due the presence of alfa-tocopherol and beta-carotene (Araldi et al, 2014), it was not able to significantly reduce the frequency of micronuclei. Genotoxicity conferred by sibutramine can lead to serious risks for overweight and obese patients.…”

“…Among the different tests, the PCEMNT and CBMNT are common as part of the battery of tests required for these agencies (Fenech, 2000(Fenech, , 2011Araldi et al, 2014Araldi et al, , 2015. This is because these techniques are simple, versatile, low cost and quick to perform.…”

“…Current studies have also demonstrated the antioxidant and anti-inflammatory potential of S. maxima (Miranda et al, 1998;Gutiérrez-Rebolledo et al, 2015). Moreover, studies have already shown that S. maxima is anti-mutagenic and is compatible with other anorexiant drugs, such as Pholia magra (Araldi et al, 2014).…”

“…The mutagenic potential of S. maxima alone was not evaluated by the PCEMNT. The protocol of CBMNT was done according the technical recommendations proposed by Araldi et al (2014) and Araldi et al (2015). Briefly, 0.2 mL peripheral blood was transferred to a culture flask containing 5 mL RPMI 1640 media supplemented with 15% fetal bovine serum, 0.1 mL L-glutamine, and 0.1 mL phytohemagglutinin A (PHA).…”

“…S. maxima is composed of 65% protein and 30% essential amino acids (Delay, 2002). In addition, this cyanobacterium has chelated minerals (iron, potassium and magnesium), vitamins (biotin, cyanocobalamin, calcium pantothenate, folic acid, inositol, thiamine, alpha-tocopherol, pyridoxine and riboflavin), phenolic acids, beta-carotene and fatty acids (linoleic and gamma-linolenic acids) (Delay, 2002;Araldi et al, 2014). S maxima is considered the greatest discovery of the 21st century in the nutrition field (Ponce-Canchihuamán et al, 2010).…”