METHOD: Antioxidant activities were determined. Phytochemical analysis was performed by gas chromatography mass spectrometry (GCMS). In the in vivo study, Sprague Dawley rats were pretreated with C. nudiflora (150, 300, and 450 mg kg body weight (b.wt.)) once daily for 14 days followed by two doses of CCl4 (1 ml/kg b.wt.). After 2 weeks, the rats were sacrificed and hepatoprotective analysis was performed.

RESULTS: In vitro studies have shown that the extract possessed strong antioxidant activity and has ability to scavenge 2,2-diphenyl-2-picrylhydrazyl-free radicals effectively. GCMS analysis of the C. nudiflora extract revealed the presence of various bioactive compounds. Administration of C. nudiflora significantly reduced the impact of CCl4 toxicity on serum markers of liver damage, serum aspartate transaminase (AST), and alanine transaminase (ALT). C. nudiflora also increased antioxidant levels of hepatic glutathione (GSH) and antioxidant enzymes and ameliorated the elevated hepatic formation of malondialdehyde (MDA) induced by CCl4 in rats. Histopathological examination indicated that C. nudiflora protect the liver from the toxic effect of CCl4 and healed lesions such as necrosis, fatty degeneration, and hepatocyte injury as irregular lamellar organization and dilations in the endoplasmic reticulum. The immunohistochemical studies revealed that pretreatment of C. nudiflora decreased the formation of 4-hydroxy-2-nonenal (HNE)-modified protein adducts and 8-hydroxy-2'-deoxyguanosine (8-OHdG). Furthermore, overexpression of the proinflammatory cytokines TNF-α, IL-6, and prostaglandin E2 is also reduced.

METHODOLOGY/PRINCIPAL FINDINGS: The hexane extract of C. cassia demonstrated high anti-proliferative activity against MCF-7 and MDA-MB-231 cells (IC50, 34 ± 3.52 and 32.42 ± 0.37 μg/ml, respectively). Oxidative stress due to disruption of antioxidant enzyme (SOD, GPx and CAT) activity is suggested as the probable cause for apoptosis initiation. Though the main apoptosis pathway in both cell lines was found to be through caspase-8 activation, caspase-9 was also activated in MDA-MB-231 cells but suppressed in MCF-7 cells. Gene expression studies revealed that AKT1, the caspase-9 suppressor, was up-regulated in MCF-7 cells while down-regulated in MDA-MB-231 cells. Although, AKT1 protein expression in both cell lines was down-regulated, a steady increase in MCF-7 cells was observed after a sharp decrease of suppression of AKT1. Trans-cinnamaldehyde and coumarin were isolated and identified and found to be mainly responsible for the observed anti-proliferative activity of CE (Cinnamomum cassia).