Cytogenotoxic and antihyperplastic effects of the aqueous extracts of <i>Cymbopogon citratus</i> (Poaceae) and <i>Citrus medica</i> (Rutaceae) Cytogenotoxic and antihyperplastic effects

Abstract

Cymbopogon citratus and Citrus medica are commonly consumed in combination as an herbal tea to prevent or treat various conditions including cancers. This study evaluated the cytogenotoxic and antihyperplastic effects of aqueous extracts of C. citratus (AECC) and C. medica (AECM). Both extracts were chemically screened for the quantification of phytochemicals with genotoxic properties, and their antioxidant activities were evaluated in vitro. The cytogenotoxicity was evaluated on Allium cepa exposed to increasing concentrations (0.25, 0.5, and 1 mg/mL) of AECC and AECM and to mixtures of the two extracts [Mix 1 (AECC 0.25 + AECM 0.25), Mix 2 (AECC 0.5 + AECM 0.5) and Mix 3 (AECC 1 + AECM 1)] for 96 h. They were then examined macroscopically and microscopically for evaluation of mitotic index and chromosomal aberrations. The antihyperplastic effects of the two extracts were evaluated on the endometrium of ovariectomized rats. Endometrial hyperplasia was induced with tamoxifen (10 mg/kg; ip). Plant extracts were administrated orally for 37 days at the doses of 8, 40 and 200 mg/kg BW for AECC; 34, 170 and 850 mg/kg BW for AECM. The co-administration of the two extracts was carried out according to the following scheme: Mix 1: AECC 8 + AECM 34; Mix 2: AECC 40 + AECM 170; and Mix 3: AECC 200 + AECM 850. Animals were then sacrificed for biological analyses. Results showed that the contents of phenols, flavonoids, and tannins were lower in AECM than in AECC. AECC was also found to have greater antioxidant capacity than AECM. Both extracts induced chromosomal aberrations and reduced mitotic index (p < 0.001) in meristematic cells of A. cepa. These extracts also inhibited the hyperplastic effect of tamoxifen by reducing the uterine epithelium to a single cell layer (p < 0.001). This effect was associated with decreased serum estradiol levels, uterine oxidative stress and increased cytotoxicity. In conclusion, C. citratus and C. medica are endowed with genotoxic, mitodepressant, and antihyperplastic properties, justifying at least in part their use against cancers. The joint use of the two medicinal plants has proven to be more effective than their separate use.