title: Cerebroprotective effect of isolated harmine alkaloids extracts of seeds of Peganum harmala L. on sodium nitrite-induced hypoxia and ethanol-induced neurodegeneration in young mice.
abstract: The aim of the study was to isolate the harmine alkaloids from the seeds of Peganum harmala (TAPH) and its cerebroprotective effect on cognitive deficit mice. The tested doses of TAPH were screened for Sodium nitrite induced hypoxia and Ethanol induced neurodegeneration using behavioral models. The TAPH was found to be non-neurotoxic and Psychoactive by preventing the motor impairment and increasing the locomotion activity of animals in Rota rod and Actophotometer respectively. TAPH (5, 2.5 and 1.25 mg kg(-1) p.o.) significantly (p < 0.001) protected the Sodium nitrite induced memory impairment by decreasing the time require to find the water bottle in special water bottle case model. In Elevated Plus Maze (EPM) and Passive Shock Avoidance paradigm (PSA) the TAPH shown improved acquisition and retention memory significantly (p < 0.001) by decreasing the Transverse Latency Time (TLT) and increasing the Step Down Latency (SDL), respectively in dose dependent manner. The results were well supported by biochemical parameters, by inhibiting the Acetylcholinestrase (p < 0.01) activity, increasing the GSH (p < 0.001) level and decreasing the TBARS (p < 0.001) level of whole brain. Moreover TAPH has shown the significant Monoamine oxidase-A (MAO-A) inhibition action (p < 0.001), hence it reduces the metabolism of epinephrine, 5-HT and other monoamines and enhances the action of these neurotransmitters indirectly; this adrenergic system plays an important role in learning and memory. Further, TAPH (5 mg kg(-1)) protect the DNA fragmentation of frontotemporal cortex of the brain from hypoxic effect induced by Sodium nitrite in Gel Electrophoresis studies. The results were comparable to their respective standards. Hence, harmine alkaloids are potential enough to utilize in the management of Neurodegenerative disorders of the type Alzheimer's diseases.
authors: Department of Pharmacology and Toxicology, Postgraduate Studies and Research Center, BLDEA's College of Pharmacy, Bijapur-586 103, India.
authors: S M
authors: SM
authors: Biradar
authors: Department of Pharmacognosy and Phytochemistry, Sarada Vilas College of Pharmacy, Mysore-570 004, Karnataka, India.
authors: Hanumanthachar
authors: H
authors: Joshi
authors: Department of Pharmacology and Toxicology, Postgraduate Studies and Research Center, SET's College of Pharmacy, Dharwad-580 002, India.
authors: K C
authors: KC
authors: Tarak
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D003071:Cognition / Q000187:drug effects; D003072:Cognition Disorders / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control* / Q000523:psychology; D019610:Cytoprotection; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D000431:Ethanol; D058851:GPI-Linked Proteins / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006247:Harmine / Q000302:isolation & purification / Q000494:pharmacology*; D002534:Hypoxia, Brain / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000523:psychology; D008297:Male; D051379:Mice; D008995:Monoamine Oxidase / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects; D009410:Nerve Degeneration; D018696:Neuroprotective Agents / Q000302:isolation & purification / Q000494:pharmacology*; D032443:Peganum / Q000737:chemistry; D008517:Phytotherapy; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D010946:Plants, Medicinal; D011930:Reaction Time / Q000187:drug effects; D012639:Seeds; D012977:Sodium Nitrite; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D013997:Time Factors
chemical_list: D058851:GPI-Linked Proteins; D018696:Neuroprotective Agents; D010936:Plant Extracts; D017392:Thiobarbituric Acid Reactive Substances; D000431:Ethanol; D006247:Harmine; D008995:Monoamine Oxidase; D000110:Acetylcholinesterase; C548245:Ache protein, mouse; D005978:Glutathione; D012977:Sodium Nitrite