Total phenolic content, antioxidant activity and pre-clinical safety evaluation of an Anacardium occidentale stem bark Portuguese hypoglycemic traditional herbal preparation

Abstract

Anacardium occidentale L. (cashew tree) has been traditionally used to treat type 2 diabetes. Hereby we present results of free radical scavenging activity assay and in vivo toxicity and genotoxicity tests on red and white cashew stem bark Portuguese traditional herbal preparations (CSBTHPs) used to control type 2 diabetes, standardized on the basis of the total phenolic content.A 2-week repeated dose toxicity study was performed with three doses (40.2, 127, 402mg/kg/day) of each CSBTHP, administered by gavage to CD-1 mice (n=28). Micronucleus test and comet assay were performed in CD-1 mice (n=18) which received a single dose of 2000mg/kg (p.o.) of each CSBTHP or cyclophosphamide 50mg/kg (i.p.) or water (p.o.).The total phenolic content was 58.0±0.4mg gallic acid equivalents (GAE)/g cashew stem bark (CSB) in white CSBTHP and 51.3±1.6mg GAE/g CSB in red CSBTHP. Both red and white CSBTHPs exhibited concentration-dependent radical scavenging activity with IC50 values of 180.7±6.7μg/mL and 143.8±2.8μg/mL, respectively. No treatment-related effects on relative organ weights, biochemical parameters and food intake were observed in the repeated dose toxicity study with both CSBTHPs. In the mice micronucleus test both CSBTHPs showed absence of bone marrow suppression and a similar frequency of micronuclei in immature erythrocytes between treated and negative control groups. The comet assay revealed both CSBTHPs to be non-genotoxic.Concluding, both red and white CSBTHPs, standardized on the basis of the total phenolic content, revealed to be sources of natural antioxidants and devoid of a genotoxic risk. The daily oral administration of doses up to 402mg/kg of those CSBTHPs did not induce relevant signs of toxicity in mice.