ABSTRACT
BACKGROUND: Saraca asoca (SA) (Roxb.) is one of the folk medicinal plants found in India, Bangladesh, and Sri Lanka. Its major biological activity appears due to the presence of flavonoid group of compounds in its bark extract. OBJECTIVE: In this study, our research aims to analyze the chemopreventive effect of flavonoids, especially a natural phenol catechin present in the bark methanolic extract of SA on acute myeloid leukemia (AML) mice. MATERIALS AND METHODS: The total bark extract was partitioned and analyzed on thin-layer chromatography (TLC) plate. The yellow-brown material of spot 4 was analyzed and identified as catechin. The yellowish brown material (YBM) was tested for their chemopreventive potential. An in vivo AML mice model was used to test the efficacy. Hematological parameters (Hb %, red blood cell, and white blood cell count), expression of cell cycle regulatory proteins, and DNA fragmentation analysis were performed. RESULTS: After treatment of benzene-exposed mice with the major flavonoid compound, namely catechin, the above parameters increase significantly (P < 0.05). There was an upregulation of p53 and p21, caspase 11 myeloperoxidase, bcl2, and CYP2EI in catechin-treated group. DNA was less fragmented in flavonoid-treated group compared to that of control (P ≤ 0.05). The present study indicates that the secondary metabolites of SA methanolic bark extract, comprising flavonoid catechin as major constituents, have modulatory effect in cell cycle deregulation and hematological abnormalities induced by benzene in mice. CONCLUSIONS: Our data suggest that catechin from methanolic bark extract of SA effectively attenuates benzene-induced secondary AML in bone marrow, which is likely associated with the anticell cycle deregulation properties of this flavan-3-ol. This study was supported by the observation that catechin (YBM), like doxorubicin, can act as the neutralizer and protector of mortality in cancer cases. SUMMARY: The catechin from methanolic bark extract of Saraca asoca has chemoprotective activity in benzene-induced secondary acute myeloid leukemia.(AML) in bone marrowHematological parameters, structural analysis of DNA showed that the purified catechin attenuates the conditions responsible for the development of AMLThe purified flavonol, catechin has a modulatory effect on different cell cycle deregulations induced by benzene in AML model.
ABSTRACT
Benzene, designated as environmental and occupational carcinogen and hematotoxin, has been associated with secondary leukemia. To develop a toxicokinetic model of AML, benzene can be used as leukemogenic agent. The aim of the present study was to optimize the dose, period and time of cumulative benzene exposure of Swiss Albino mice and to analyze survival rate; alteration in cell cycle regulation and other clinical manifestations in mice exposed to benzene vapour at a dose 300 ppm × 6 h/day × 5 days/week for 2 weeks, i.e., 9000(a)ppm cumulative dose. Analyzing physiological parameters like plasma enzyme profile, complete hematology (Hb %, RBC indices and WBC differentials), hematopoietic cells morphology, expression of cell cycle regulatory proteins, tissue histology and analysis of DNA fragmentation, optimum conditions were established. Down regulation of p53 and p21 and up regulation of CDK2, CDK4, CDK6, cyclin D1 and E in this exposed group were marked as the optimum conditions of cellular deregulation for the development of secondary AML. Elevated level of Plasma AST/ALT with corresponding changes in liver histology showing extended sinusoids within the hepatocytic cell cords in optimally exposed animals also confirmed the toxicokinetic relation of benzene with leukemia. It can be concluded from the above observations that the 9000(a)ppm exposed animals can serve as the induced laboratory model of secondary acute myeloid leukemia.
