A series of 22 stilbene derivatives based on resveratrol were synthesized incorporating acetoxy-, benzyloxy-, carboxy-, chloro-, hydroxy- and methoxy functional groups. We examined the cytotoxicity of these 22 stilbenes in human K562 chronic myelogenous leukemia cells. Only four compounds were cytotoxic namely 4'-hydroxy-3-methoxystilbene (15), 3'-acetoxy-4-chlorostilbene (19), 4'-hydroxy-3,5-dimethoxystilbene or pterostilbene (3) and 3,5-dibenzyloxy-4'-hydroxystilbene (28) with IC(50)s of 78 µM, 38 µM, 67 µM and 19.5 µM respectively. Further apoptosis assessment on the most potent compound, 28, confirmed that the cells underwent apoptosis based on phosphatidylserine externalization and loss of mitochondrial membrane potential. Importantly, we observed a concentration-dependent activation of caspase-9 as early as 2 hr with resultant caspase-3 cleavage in 28-induced apoptosis. Additionally, a structure-activity relationship (SAR) study proposed a possible mechanism of action for compound 28. Taken together, our data suggests that the pro-apoptotic effects of 28 involve the intrinsic mitochondrial pathway characterized by an early activation of caspase-9.
Reactive oxygen species (ROS) play an important role in ageing and age-related neurodegenerative changes including Parkinson's disease (PD). PD is characterized by signs of major oxidative stress and mitochondrial damage in the pars compacta of the substantia nigra. Present study was designed to investigate whether the Centella asiatica extract (CAE) would prevent 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity in aged Sprague-Dawley rats. Adult, male Sprague-dawley rats of 300-350 g were divided into control, C. asiatica alone, MPTP alone (20 mg/kg, for 21 days) and MPTP with C. asiatica (300 mg/kg for 21 days) groups. Effect of aqueous extract of C. asiatica on oxidative biomarker levels in corpus striatum and hippocampus homogenate was examined. MPTP-challenged rats elicited a significant increase in lipid hydroperoxides (LPO) (p < 0.01), protein-carbonyl-content (PCC) (p < 0.01) and xanthine oxidase (XO) (p < 0.01) when compared with control rats. There was a significant decrease in total antioxidants (TA) (p < 0.001), superoxide dismutase (SOD) (p < 0.001), glutathione peroxidase (GPx) (p < 0.01) and catalase (CAT) (p < 0.001) levels with MPTP treatment. Supplementation of CAE reduced LPO and PCC and significantly increased (p < 0.01) TA and antioxidant enzyme levels (p < 0.01) in corpus striatum and hippocampus. These results show that administration of C. asiatica was effective in protecting the brain against neurodegenerative disorders such as Parkinsonism.
Lead is known to disrupt the biological systems by altering the molecular interactions, cell signaling, and cellular function. Exposure to even low levels of lead may have potential hazardous effects on brain, liver, kidneys and testes. The efficacy of Etlingera elatior (torch ginger) to protect hepatotoxicity induced by lead acetate was evaluated experimentally in male Sprague - Dawley rats. Rats were exposed to lead acetate in drinking water (500 ppm) for 21 days and the effects of concurrent treatment with extract of E. elatior on hepatic lipid hydroperoxides (LPO), protein carbonyl content (PCC), total antioxidants (TA), superoxide dismutase (SOD), glutathione peroxidase (GPX) and glutathione S- Transferase (GST) levels and histopathological changes in liver were evaluated. There was a significant decrease in TA and other antioxidant enzymes (p < 0.05) and increase in LPO and PCC (p < 0.05) with lead acetate ingestion. Concurrent treatment with E. elatior extract significantly reduced the LPO and PCC (p < 0.05) in serum and increased the antioxidant enzyme levels (p < 0.05) in the liver. Significant histopathological changes were seen in hepatic tissue with chronic lead ingestion. Treatment with E. elatior significantly reduced these lead-induced changes in hepatic architecture. E. elatior has also reduced the blood lead levels (BLL). Thus, there has been extensive biochemical and structural alterations indicative of liver toxicity with exposure to lead and E. elatior treatment significantly reduced these oxidative damage. Our results suggest that E. elatior has a powerful antioxidant effect against lead-induced hepatotoxicity.