Amelioration of apoptotic events in the skeletal muscle of intra-nigrally rotenone-infused Parkinsonian rats by Morinda citrifolia--up-regulation of Bcl-2 and blockage of cytochrome c release.

Parkinson's disease is a progressive neurodegenerative movement disorder with the cardinal symptoms of bradykinesia, resting tremor, rigidity, and postural instability, which lead to abnormal movements and lack of activity, which in turn cause muscular damage. Even though studies have been carried out to elucidate the causative factors that lead to muscular damage in Parkinson's disease, apoptotic events that occur in the skeletal muscle and a therapeutical approach to culminate the muscular damage have not been extensively studied. Thus, this study evaluates the impact of rotenone-induced SNPc lesions on skeletal muscle apoptosis and the efficacy of an ethyl acetate extract of Morinda citrifolia in safeguarding the myocytes. Biochemical assays along with apoptotic markers studied by immunoblot and reverse transcription-polymerase chain reaction in the current study revealed that the supplementation of Morinda citrifolia significantly reverted alterations in both biochemical and histological parameters in rotenone-infused PD rats. Treatment with Morinda citrifolia also reduced the expression of pro-apoptotic proteins Bax, caspase-3 and caspase-9 and blocked the release of cytochrome c from mitochondria induced by rotenone. In addition, it augmented the expression of Bcl2 both transcriptionally and translationally. Thus, this preliminary study paves a way to show that the antioxidant and anti-apoptotic activities of Morinda citrifolia can be exploited to alleviate skeletal muscle damage induced by Parkinsonism.

EGCG mediated downregulation of NF-AT and macrophage infiltration in experimental hepatic steatosis.

SCOPE: Increased fat consumption in industrialized countries has resulted in hepatic steatosis that upregulates atherogenic aspirant genes, leading to atherosclerosis and mortality. Although extensive studies have been carried out to elucidate the atheroprotective efficacy of epigallocatechin-3-gallate (EGCG), the effect of EGCG on hepatic steatosis has not been studied comprehensively. Hence, the current study was designed to find out the effect of EGCG on hepatic events that prelude atherosclerosis with special reference to macrophage infiltration. METHODS AND RESULTS: Male albino rats of Wistar strain were used in this study. Basic biochemical assays along with the protein expression of CAMs, NF-κB, TNF-α and NF-AT were assayed in the current study. EGCG supplementation significantly reverted the alterations in both biochemical and histological parameters and is shown to reduce the TNF-α mediated NF-AT expression and thereby its downstream targets like ICAM-1 and E-selectin expression to a greater extent than NF-κB mediated downstream targets like VCAM-1 and P-selectin in hypercholesterolemic rat liver. CONCLUSION: Our results suggest that EGCG influences the early events of atherosclerosis that occur; thereby modulating the NF-AT pathway and thereby mitigating the hypercholesterolemic stress.

Epigallocatechin-3-gallate restores the Bcl-2 expression in liver of young rats challenged with hypercholesterolemia but not in aged rats: an insight into its disparity of efficacy on advancing age.

Advanced age significantly increases cholesterol levels, however, when combined with a high cholesterol diet it not only leads to life-threatening conditions like atherosclerosis, but also plays a central role in the pathogenesis of hepatic damage and its complications. Even though extensive studies have been carried out to elucidate the causative factors that lead to hepatic steatosis associated with liver damage in young rats due to hypercholesterolemia, events that occur in aged rats where a different milieu is presented by up and down regulation of various genes co-existing, has not been extensively studied. Hence, this study comparatively evaluates the impact of hypercholesterolemic stress induced liver damage in young and aged rats and the efficacy of epigallocatechin-3-gallate to protect the liver in both young and aged rats with special reference to apoptosis. Moreover, the work has been designed to investigate whether aged rats act as better models for studying the efficacy of atheroprotective drugs. Male albino rats of the Wistar strain were used in this study. Basic biochemical assays along with apoptotic markers assayed in the current study revealed that treatment with EGCG significantly reverted the alterations in both biochemical and histological parameters in young and aged hypercholesterolemic rats when compared to their respective controls. However, the extent of reversion was far superior in young rats, when compared to aged rats. EGCG reduced hepatic Bax expression in both young and aged hypercholesterolemic rats. On the other hand, Bcl-2 expression was up regulated significantly in young hypercholesterolemic rats, but not in aged hypercholesterolemic rats on treatment with EGCG. This throws light on the efficacy of the treatment differing in young and aged rats as well; atheroprotective drugs shall be tested for their efficacy in aged hypercholesterolemic models.