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Abstract
This study investigates the effect of Phyllanthus amarus leaf extract on apoptotic and cytokine activity in 1,2-dimethylhydrazine (DMH)-induced colon carcinoma in Swiss albino rats. Colon cancer remains a major global health burden, and the exploration of plant-derived bioactive compounds for safer chemoprevention has gained increasing attention. Phyllanthus amarus, a medicinal plant known for its antioxidant, anti-inflammatory, and anticancer properties, was evaluated for its potential to mitigate colon carcinogenesis. Colon cancer was induced in rats through subcutaneous administration of DMH (20 mg/kg body weight) once weekly for 10 weeks. Experimental groups received oral doses of ethanol leaf extract of P. amarus at concentrations of 250, 350 and 450 mg/kg body weight throughout the treatment period. Biochemical, histological, and molecular assessments were performed to determine oxidative stress status, apoptotic activity, and cytokine modulation. Treatment with P. amarus significantly decreased oxidative stress by enhancing the activities of antioxidant enzymes such as superoxide dismutase and catalase, and reducing lipid peroxidation levels. Histopathological analysis revealed restoration of normal colon tissue architecture and reduced dysplasia in treated rats compared to the DMH control group. Molecular findings showed that P. amarus extract enhanced apoptosis by upregulating the expression of caspase-3 and caspase-9, while downregulating the anti-apoptotic protein Bcl-2. Furthermore, cytokine assays demonstrated that P. amarus modulated inflammatory signaling by lowering pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) and elevating the anti-inflammatory cytokine IL-10. These outcomes indicate that P. amarus confers chemoprotective effects through suppression of oxidative damage, activation of the intrinsic apoptotic pathway via caspase-9 and caspase-3, and regulation of cytokine balance
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