Escin, a novel triterpene, mitigates chronic MPTP/p-induced dopaminergic toxicity by attenuating mitochondrial dysfunction, oxidative stress, and apoptosis.
Parkinson's disease (PD) is a common, chronic, and debilitating neurodegenerative disorder characterized by progressive loss of nigrostriatal dopaminergic neurons due to unknown factors. In the present study, we have evaluated if escin, a triterpene saponin from seeds of horse chestnut tree (Aesculus hippocastanum), offers neuroprotection against chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/probenecid (MPTP/p)-induced toxicity using a mouse model. Chronic administration of MPTP/p deteriorated the loss of TH immunoreactivity in striatum. Subsequently, MPTP/p also enhanced oxidative stress by mitochondrial complex I inhibition, thereby ensuing dopaminergic denervation via modulation of Bcl-2, Bax, Cyto-C, and cleaved caspases expressions. However, we observed that pretreatment with escin (4 mg/kg) significantly attenuated MPTP/p-induced mitochondrial dysfunction, oxidative stress, and apoptosis. Furthermore, behavioral studies and ultrastructural analysis of mitochondria and intracellular components were in support of these findings. Therefore, we speculate that escin might be a promising candidate for the prevention of mitochondrial dysfunction-induced apoptosis in neurodegenerative disorders such as PD.
Department of Biochemistry and Biotechnology, Annamalai University, Annamalai Nagar, 608 002, Tamil Nadu, India.
Govindasamy Pushpavathi
GP
Selvakumar
Department of Biochemistry and Biotechnology, Annamalai University, Annamalai Nagar, 608 002, Tamil Nadu, India. mani_pdresearchlab@rediffmail.com.
Thamilarasan
T
Manivasagam
Division of Biochemistry, Faculty of Medicine, Raja Muthaiah Medical College, Annamalai University, Annamalai Nagar, 608 002, Tamil Nadu, India.
Karamkolly R
KR
Rekha
Department of Biotechnology, Periyar University, Salem, 636011, Tamil Nadu, India.
Richard L
RL
Jayaraj
Department of Biotechnology, Periyar University, Salem, 636011, Tamil Nadu, India.
Namasivayam
N
Elangovan
D000818:Animals; D017209:Apoptosis; D004298:Dopamine / Q000633:toxicity; D004928:Escin / Q000494:pharmacology* / Q000627:therapeutic use; D020267:MPTP Poisoning / Q000188:drug therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress
D004928:Escin; D004298:Dopamine