Chenopodium ambrosioides Linn. induces mitochondrial-dependent cell death via activation of mPT pore opening, caspases and apoptotic machinery

Abstract Objectives Mitochondrion is an organelle involved in cellular energy generation and cell death. The mitochondrial permeability transition (mPT) pore plays a crucial role in the execution of mitochondrial-dependent cell death. Several medicinal plants evoke their therapeutic potential against tumor and cancer by instigating mitochondrial-dependent cell death. This research consequently explored the effect of chloroform fraction of Chenopodium ambrosioides (CFCA) on mitochondrial-dependent cell death via mPT pore. Methodology Rats were equally assigned into four groups; A (control), B (50), C (100) and D (200) mg/kg CFCA. Mitochondria were isolated by differential centrifugation. The mPT pore opening, mitochondrial ATPase (mATPase) activity and mitochondrial-lipid peroxidation (mLPO) were assessed spectrophotometrically. Caspases 9 and 3 levels, hepatic DNA fragmentation, histology and immunohistochemical analysis of Bax, Cytochrome c , P53 and anti-apoptotic Bcl-2 proteins were determined. Gas Chromatography-Mass Spectrometry (GC-MS) analysis of CFCA was carried out. Results The CFCA dose-dependently induced mPT pore opening, enhanced mATPase activity, reduced malondialdehyde generation, increased Caspases 9 and 3 levels and effected hepatic DNA fragmentation. The histological assessment showed mild to moderate steatosis and infiltration of the hepatocytes. The CFCA upregulated the expression of Bax, Cytochrome c and P53 proteins while anti-apoptotic Bcl-2 protein was downregulated. The GC-MS analysis revealed the presence of certain pharmacologically reactive compounds including Tridecanoic acid, 12-methyl ester, Hexadecanoic acid methyl ester, 11-Octadecadienoic acid, methyl ester, Pyrido2,3-dpyrimidine and 6-Undecyl-5,6-dihydro-2H-pyran-2-one. Conclusions This study suggests the presence of phytochemicals in CFCA that could execute mitochondrial-mediated apoptosis via induction of mPT pore opening, caspases and apoptotic machinery.