title: Ursolic acid attenuates oxidative stress in nigrostriatal tissue and improves neurobehavioral activity in MPTP-induced Parkinsonian mouse model.
abstract: Parkinson's disease (PD) is characterized by a slow and progressive degeneration of dopaminergic neurons in substantia nigra pars compacta (SNpc) region of brain. Oxidative stress and inflammation plays important role in the neurodegeneration and development of PD. Ursolic Acid (UA: 3β-hydroxy-urs-12-en-28-oic acid) is a natural pentacyclic triterpenoid found in various medicinal plants. Its anti-inﬂammatory and antioxidant activity is a well-established fact. In this paper, the neuroprotective efficiency of UA in MPTP induced PD mouse model has been explored. For this purpose, we divided 30 mice into 5 different groups; first was control, second was MPTP-treated, third, fourth and fifth were different doses of UA viz., 5 mg/kg, 25 mg/kg, and 50 mg/kg body weight (wt) respectively, along with MPTP. After 21 days of treatment, different behavioral parameters and biochemical assays were conducted. Tyrosine hydroxylase (TH) immunostaining of SN dopaminergic neurons as well as HPLC quantification of dopamine and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanilic acid (HVA) were also performed. Our results proved that, UA improves behavioral deficits, restored altered dopamine level and protect dopaminergic neurons in the MPTP intoxicated mouse. Among three different doses, 25 mg/kg body wt was the most effective dose for the PD. This work reveals the potential of UA as a promising drug candidate for PD treatment.
authors.affiliation: Department of Biochemistry, Faculty of Science, Banaras Hindu University, Varanasi 221005, Uttar Pradesh, India. Electronic address: raibiochem@gmail.com.
authors.forename: Sachchida Nand
authors.initials: SN
authors.lastname: Rai
authors.affiliation: Department of Biochemistry, Faculty of Science, Banaras Hindu University, Varanasi 221005, Uttar Pradesh, India. Electronic address: satyndra_yadav@yahoo.co.in.
authors.forename: Satyndra Kumar
authors.initials: SK
authors.lastname: Yadav
authors.affiliation: Department of Biochemistry, Faculty of Science, Banaras Hindu University, Varanasi 221005, Uttar Pradesh, India. Electronic address: singhdivakar686@gmail.com.
authors.forename: Divakar
authors.initials: D
authors.lastname: Singh
authors.affiliation: Department of Biochemistry, Faculty of Science, Banaras Hindu University, Varanasi 221005, Uttar Pradesh, India. Electronic address: suryasingh@hotmail.com.
authors.forename: Surya Pratap
authors.initials: SP
authors.lastname: Singh
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006719:Homovanillic Acid / Q000378:metabolism; D008297:Male; D051379:Mice; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D018384:Oxidative Stress / Q000187:drug effects*; D010300:Parkinson Disease / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000523:psychology; D065842:Pars Compacta / Q000187:drug effects / Q000378:metabolism; D013378:Substantia Nigra / Q000187:drug effects* / Q000378:metabolism; D014315:Triterpenes / Q000494:pharmacology* / Q000627:therapeutic use; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D000097245:Ursolic Acid
chemical_list: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D015102:3,4-Dihydroxyphenylacetic Acid; D004298:Dopamine; D006719:Homovanillic Acid; D018696:Neuroprotective Agents; D014315:Triterpenes; D014446:Tyrosine 3-Monooxygenase; D000097245:Ursolic Acid
keywords: 3,4-Dihydroxyphenylacetic acid; Dopaminergic neuron; Homovanilic acid; Substantia nigra; Tyrosine hydroxylase; Ursolic acid