Abstract

Andrographis paniculata is a grass-shaped medicinal herb, traditionally used in Southeast Asia. The aim of this study was to evaluate the chemoprotective effects of A. paniculata on colorectal cancer. A. paniculata ethanol extract was tested on azoxymethane (AOM)-induced aberrant crypt foci (ACF) in vivo and in vitro. A. paniculata treated groups showed a significant reduction in the number of ACF of the treated rats. Microscopically, ACF showed remarkably elongated and stratified cells, and depletion of the submucosal glands of AOM group compared to the treated groups. Histologically, staining showed slightly elevated masses above the surrounding mucosa with oval or slit-like orifices. Immunohistochemically, expression of proliferating cell nuclear antigen (PCNA) and β-catenin protein were down-regulated in the A. paniculata treated groups compared to the AOM group. When colon tissue was homogenized, malondialdehyde (MDA) and nitric oxide (NO) levels were significantly decreased, whereas superoxide dismutase (SOD) activity was increased in the treated groups compared to the AOM group. A. paniculata ethanol extract showed antioxidant and free radical scavenging activity, as elucidated by the measure of oxidative stress markers. Further, the active fractions were assessed against cell lines of CCD841 and HT29 colon cancer cells.

Highlights

  • Colorectal cancer continues to afflict several thousands of males and females per year, accounting for about 10% of cancer-related deaths and weighed as the third commonest malignancy in Malaysia as reported in 2007 [1]. Therapeutic modalities such as chemotherapy and radical colostomy are considered curative for localized manageable cases, they are acknowledged for the noticed increase in the five-year survival [2]

  • Studying specific natural product molecules selected on the basis of the inhibition of multiple processes responsible for the production of proinflammatory mediators and stimulating the transcriptional machinery necessary for mitochondrial biosynthesis may be a feasible approach for the prevention and treatment of numerous types of cancer

  • Acute toxicity No mortalities were observed in the treated animal groups

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Summary

Introduction

Colorectal cancer continues to afflict several thousands of males and females per year, accounting for about 10% of cancer-related deaths and weighed as the third commonest malignancy in Malaysia as reported in 2007 [1]. Therapeutic modalities such as chemotherapy and radical colostomy are considered curative for localized manageable cases, they are acknowledged for the noticed increase in the five-year survival [2]. The fluoropyrimidine 5-fluorouracil (5-FU) is an anti-tumour agent widely used in the treatment of solid tumours, including colorectal cancers [3]. Studying specific natural product molecules selected on the basis of the inhibition of multiple processes responsible for the production of proinflammatory mediators and stimulating the transcriptional machinery necessary for mitochondrial biosynthesis may be a feasible approach for the prevention and treatment of numerous types of cancer

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