title: Neuroprotective effect of asiatic acid on rotenone-induced mitochondrial dysfunction and oxidative stress-mediated apoptosis in differentiated SH-SYS5Y cells.
abstract: Parkinson's disease (PD) is a chronic neurodegenerative disease, manifested due to the loss of dopaminergic neurons, which ultimately leads to impaired movement in elderly populations. The pathogenesis of PD is associated with numerous factors including oxidative stress, mitochondrial dysfunction and apoptosis. There is no effective therapy available to cure or halt the progression of this disease still now. Asiatic acid (AA) is a triterpene extracted from Centella asiatica has been reported as an antioxidant and anti-inflammatory agent, that offers neuroprotection against glutamate toxicity. Therefore, in this study, we have investigated the effect of AA in a rotenone (an inhibitor of mitochondrial complex I) induced in vitro model of PD. Following the exposure of SH-SY5Y cells to rotenone, there was a marked overproduction of ROS, mitochondrial dysfunction (as indexed by the decrease in mitochondrial membrane potential) and apoptosis (Hoechst and dual staining, comet assay; expressions of pro-apoptotic and anti-apoptotic indices). Pre-treatment with AA reversed these changes might be due to its antioxidant, mitoprotective and anti-apoptotic properties. However further extensive studies on in vivo models of PD are warranted to prove AA neuroprotective effect before entering into the clinical trial.
authors: a Department of Biochemistry and Biotechnology , Faculty of Science, Annamalai University , Annamalai Nagar , Tamilnadu 608 002 , India.
authors: Jagatheesan
authors: J
authors: Nataraj
authors: a Department of Biochemistry and Biotechnology , Faculty of Science, Annamalai University , Annamalai Nagar , Tamilnadu 608 002 , India.
authors: Thamilarasan
authors: T
authors: Manivasagam
authors: a Department of Biochemistry and Biotechnology , Faculty of Science, Annamalai University , Annamalai Nagar , Tamilnadu 608 002 , India.
authors: Arokiasamy
authors: A
authors: Justin Thenmozhi
authors: b Department of Food Science and Nutrition , CAMS, Sultan Qaboos University , Muscat , Oman.|c Ageing and Dementia Research Group , Sultan Qaboos University , Muscat , Oman.
authors: Musthafa Mohamed
authors: MM
authors: Essa
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D000978:Antiparkinson Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects; D015507:Drugs, Investigational / Q000494:pharmacology*; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D053978:Pentacyclic Triterpenes / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D012402:Rotenone / Q000633:toxicity; D014475:Uncoupling Agents / Q000633:toxicity
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D000978:Antiparkinson Agents; D051017:Apoptosis Regulatory Proteins; D015415:Biomarkers; D015507:Drugs, Investigational; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D053978:Pentacyclic Triterpenes; D017382:Reactive Oxygen Species; D014475:Uncoupling Agents; D012402:Rotenone; C017032:asiatic acid
keywords: Apoptosis; Mitochondrial dysfunction; Oxidative stress; Parkinson's disease; Rotenone