BACKGROUND: Parkinson's disease characterized by oxidative stress and mitochondrial damage in the pars compacta of substantia nigra remains a challenge to manage with an added disadvantage of side effects of L-levo dopa, the standard drug used for therapy. Thus, an alternative approach of utilizing natural components would be beneficial in the management of the disease. The present study was aimed to investigate the potential role of asiaticoside (As), a trisaccaride triterpene against1 - methyl 4 - phenyl 1,2,3,6 tetrahydropyridine (MPTP)-induced neurotoxicity in experimental mice. METHODS: Mice were divided into 4 groups: Group I received vehicle saline, group II was treated with 20 mg/kg of body weight of MPTP (2 doses with 2 h intervals), group III received MPTP along with 50 mg/kg body weight of As for the 21 consecutive days starting from the day of MPTP intoxication. Group IV received 50 mg/kg body weight of asiaticoside for the same period serving as drug control. Animals were sacrificed at the end of experimental period and the striatum and midbrain samples were analyzed for enzyme assays, transmission electron microscopic (TEM) analysis. Immunofluorescent assay was performed to study the expression of GFAP to detect astrocyte, which are activated due to neuronal damage. Imunohistochemical studies were carried out to quantify the expression of Bax and Bcl2, the molecular signatures that would provide clues of the extent of neurodegeneration. RESULTS: The activities of enzymes were increased on As administration when compared with those of group II animals. Expressions of Bax and Bcl2 along with GFAP did show significant variations (p < 0.05) on MPTP treatment when compared to control animals and the changes were found to be reversed significantly (p < 0.05) after treatment with asiaticoside. TEM analysis also showed attenuated degenerative architecture on As administration. The mice which received As alone (drug control IV) did not show significant variation from that of the control mice. CONCLUSION: The observations suggest that asiaticoside may be efficacious in protecting neurons from the oxidative damage caused by the insult of MPTP.
BACKGROUND:Parkinson's disease characterized by oxidative stress and mitochondrial damage in the pars compacta of substantia nigra remains a challenge to manage with an added disadvantage of side effects of L-levo dopa, the standard drug used for therapy. Thus, an alternative approach of utilizing natural components would be beneficial in the management of the disease. The present study was aimed to investigate the potential role of asiaticoside (As), a trisaccaride triterpene against1 - methyl 4 - phenyl 1,2,3,6 tetrahydropyridine (MPTP)-induced neurotoxicity in experimental mice. METHODS:Mice were divided into 4 groups: Group I received vehicle saline, group II was treated with 20 mg/kg of body weight of MPTP (2 doses with 2 h intervals), group III received MPTP along with 50 mg/kg body weight of As for the 21 consecutive days starting from the day of MPTP intoxication. Group IV received 50 mg/kg body weight of asiaticoside for the same period serving as drug control. Animals were sacrificed at the end of experimental period and the striatum and midbrain samples were analyzed for enzyme assays, transmission electron microscopic (TEM) analysis. Immunofluorescent assay was performed to study the expression of GFAP to detect astrocyte, which are activated due to neuronal damage. Imunohistochemical studies were carried out to quantify the expression of Bax and Bcl2, the molecular signatures that would provide clues of the extent of neurodegeneration. RESULTS: The activities of enzymes were increased on As administration when compared with those of group II animals. Expressions of Bax and Bcl2 along with GFAP did show significant variations (p < 0.05) on MPTP treatment when compared to control animals and the changes were found to be reversed significantly (p < 0.05) after treatment with asiaticoside. TEM analysis also showed attenuated degenerative architecture on As administration. The mice which received As alone (drug control IV) did not show significant variation from that of the control mice. CONCLUSION: The observations suggest that asiaticoside may be efficacious in protecting neurons from the oxidative damage caused by the insult of MPTP.
Authors: D Offen; P M Beart; N S Cheung; C J Pascoe; A Hochman; S Gorodin; E Melamed; R Bernard; O Bernard Journal: Proc Natl Acad Sci U S A Date: 1998-05-12 Impact factor: 11.205