Antioxidant-Rich Fraction of Urtica dioica Mediated Rescue of Striatal Mito-Oxidative Damage in MPTP-Induced Behavioral, Cellular, and Neurochemical Alterations in Rats.
Parkinson's disease (PD) having a complex and multi-factorial neuropathology includes mainly the degeneration of the dopaminergic nigrostriatal pathway, which is a cumulative effect of depleted endogenous antioxidant enzymes, increased oxidative DNA damage, mitochondrial dysfunction, excitotoxicity, and neuroinflammation. The present study was designed to investigate the neuroprotective effect of a potent antioxidant from Urtica dioica in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of parkinsonism. MPTP was administered intranigrally for the induction of PD in male Wistar rats. Behavioral alterations were assessed in between the study period. Animals were sacrificed immediately after behavioral session, and different biochemical, cellular, and neurochemical parameters were measured. Intranigrally repeated administration of MPTP showed significant impairment of motor co-ordination and marked increase of mito-oxidative damage and neuroinflammation in rats. Intranigral MPTP significantly decreases the dopamine and its metabolites with impairment of dopaminergic cell density in rat brain. However, post-treatment with the potent antioxidant fraction of Urtica dioica Linn. (UD) (20, 40, 80 mg/kg) improved the motor function, mito-oxidative defense alteration significantly and dose dependently in MPTP-treated rats. In addition, the potent antioxidant fraction of UD attenuated the pro-inflammatory cytokines (TNF-α and IL-β) and restored the level of dopamine and its metabolites in MPTP-induced PD in rats. Moreover, minocycline (30 mg/kg) with lower dose of UD (20 mg/kg) had significantly potentiated the protective effect of minocycline as compared to its effect with other individual drug-treated groups. In conclusion, Urtica dioica protected the dopaminergic neurons probably by reducing mito-oxidative damage, neuroinflammation, and cellular alteration along with enhanced neurotrophic potential. The above results revealed that the antioxidant rich fraction of UD contain flavonoids and phenolic compounds, which have a promising approach in therapeutics of PD.
Department of Pharmacology, ISF College of Pharmacy, Moga, 142001, Punjab, India.
Rohit
R
Bisht
Department of Pharmacology, ISF College of Pharmacy, Moga, 142001, Punjab, India.
Bhuwan Chandra
BC
Joshi
Department of Pharmacology, ISF College of Pharmacy, Moga, 142001, Punjab, India.
Ajudhiya Nath
AN
Kalia
Department of Pharmacology, ISF College of Pharmacy, Moga, 142001, Punjab, India. aprakas6@jhmi.edu.|Division of Pediatric Infectious Diseases, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Ross Building, Level 11, Room 1109, Baltimore, MD, 21205, USA. aprakas6@jhmi.edu.
Atish
A
Prakash
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D003342:Corpus Striatum / Q000187:drug effects; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D026982:Urtica dioica / Q000187:drug effects*
D000975:Antioxidants; D018696:Neuroprotective Agents; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Dopamine; MPTP; Mitochondrial dysfunction; Neuroinflammation; Oxidative stress; Parkinson’s disease; Urtica dioica