ABSTRACT
Hydroxychavicol (HC), a major phenolic derivative isolated from the leaves of Piper betle L. is well known for its antibacterial, antifungal and antimutagenic properties. The present study evaluated the in vivo antitumor activity of HC against Ehrlich Ascites Carcinoma (EAC) cells in Swiss albino mice and in silico interaction of HC with the receptors involved in the cancer. Hydroxychavicol (200 and 400 mg/kg bw) was orally administered for 21 consecutive days and was effective in inhibiting the tumor growth in ascitic mouse model. HC consistently reduced the tumor volume, viable cell count, lipid peroxidation and elevated the life span of HC treated mice. Besides the hematological profiles, SGOT and SGPT levels reverted back to normal and oxidative stress markers GSH, SOD and CAT also increased in HC treated groups. In silico docking analysis revealed that HC possessed potent antagonist activity against all the cancer targets demonstrating its inhibitory activity.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Carcinoma, Ehrlich Tumor/drug therapy , Eugenol/analogs & derivatives , Animals , Antineoplastic Agents, Phytogenic/administration & dosage , Carcinoma, Ehrlich Tumor/pathology , Catalase/metabolism , Computer Simulation , ErbB Receptors/antagonists & inhibitors , ErbB Receptors/metabolism , Eugenol/administration & dosage , Eugenol/chemistry , Eugenol/pharmacology , Female , Glutathione/metabolism , Lipid Peroxidation/drug effects , Mice , Molecular Docking Simulation , Oxidative Stress/drug effects , Piper betle/chemistry , Plant Extracts/pharmacology , Receptors, CXCR4/antagonists & inhibitors , Receptors, CXCR4/metabolism , Superoxide Dismutase/metabolismABSTRACT
Tephrosia tinctoria, a perennial under shrub of Fabaceae family, is endemic to Western Ghats. In this study, friable whitish yellow callus was developed after 45 days using Murashige and Skoog medium supplemented with 2,4-dichlorophenoxyacetic acid (2.0 mg/l) + 6-benzylaminopurine (0.5 mg/l) in various explants of T. tinctoria. The ethyl acetate extracts of leaf (LE), stem (SE), and root (RE) were compared with leaf (LCE), stem (SCE), and root (RCE) derived callus, for antioxidant and antiproliferative activities. The SE possessed the highest phenolic and flavonoid content among all the extracts tested and showed a significant antioxidant assays. The study of anticancer activity on human hepatocellular carcinoma (HepG2) cell line revealed that the callus extracts especially RCE possessed significant inhibition of cell growth (IC50 20 µg/ml) at 72 h treatment period on analysis with MTT assay. The apoptotic cell death was observed through DNA fragmentation analysis in HepG2 cells treated with the T. tinctoria extracts. The gas chromatography-mass spectrometry finger printing profile showed that more than 60 % percentage of metabolites are similar in both SE and SCE. The higher percentage area of antioxidant compound (stigmast-4-en-3-one) was observed in SE (2.01 %) and higher percentage area of anticancer compound (phenol, 2,4-bis(1,1-dimethylethyl)) in SCE (0.91 %). In addition to that, callus extracts contain squalene, which is used for target deliver and also used as anticancer drug. Thus, the present study revealed that the T. tinctoria has potent antioxidant and antiproliferative activity and the callus culture can be used for the production of the bioactive compounds due to the endemic nature of this plant.
