Effect of L-pGlu-(1-benzyl)-l-His-l-Pro-NH2against in-vitro and in-vivo models of cerebral ischemia and associated neurological disorders.
Central nervous system plays a vital role in regulation of most of biological functions which are abnormally affected in various disorders including cerebral ischemia, Alzheimer's and Parkinson's (AD and PD) worldwide. Cerebral stroke is an extremely fatal and one of the least comprehensible neurological disorders due to limited availability of prospective clinical approaches and therapeutics. Since, some endogenous peptides like thyrotropin-releasing hormone have shown substantial neuroprotective potential, hence present study evaluates the newer thyrotropin-releasing hormone (TRH) analogue L-pGlu-(1-benzyl)-l-His-l-Pro-NH2for its neuroprotective effects against oxygen glucose deprivation (OGD), glutamate and H2O2induced injury in pheochromocytoma cell lines (PC-12 cells) and in-vivo ischemic injury in mice. Additionally, the treatment was further analyzed with respect to models of AD and PD in mice. Cerebral ischemia was induced by clamping both bilateral common carotid arteries for ten minutes. Treatment was administered to the mice five minute after restoration of blood supply to brain. Consequential changes in neurobehavioural, biochemical and histological parameters were assessed after a week. L-pGlu-(1-benzyl)-l-His-l-Pro-NH2showed significant reduction in glutamate, H2O2and OGD -induced cell death in concentration and time dependent manner. Moreover, L-pGlu-(1-benzyl)-l-His-l-Pro-NH2resulted in a substantial reduction in CA1 (Cornus Ammonis 1) hippocampal neuronal cell death, inflammatory cytokines, TNF-α, IL-6 and oxidative stress in hippocampus. In addition, L-pGlu-(1-benzyl)-l-His-l-Pro-NH2was found to be protective in two acute models of AD and PD as well these findings demonstrate the neuroprotective potential of L-pGlu-(1-benzyl)-l-His-l-Pro-NH2in cerebral ischemia and other diseases, which may be mediated through reduction of excitotoxicity, oxidative stress and inflammation.
Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Sector-67, S.A.S. Nagar, Mohali, Punjab, 160062, India; Amity Institute of Pharmacy, Amity University, Noida, Uttar Pradesh, 201303, India. Electronic address: neuropharmacology2015@gmail.com.
Satyendra K
SK
Rajput
Amity Institute of Pharmacy, Amity University, Noida, Uttar Pradesh, 201303, India.
Arun K
AK
Sharma
Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Sector-67, S.A.S. Nagar, Mohali, Punjab, 160062, India.
Chhuttan L
CL
Meena
In Vitro Toxicology Laboratory, Indian Institute of Toxicology Research, Lucknow, Uttar Pradesh, 226001, India.
Aditya B
AB
Pant
Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Sector-67, S.A.S. Nagar, Mohali, Punjab, 160062, India.
Rahul
R
Jain
Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Sector-67, S.A.S. Nagar, Mohali, Punjab, 160062, India.
Shyam S
SS
Sharma
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D002545:Brain Ischemia / Q000150:complications* / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D002375:Catalepsy / Q000150:complications / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D016923:Cell Death / Q000187:drug effects; D004195:Disease Models, Animal; D005947:Glucose / Q000172:deficiency; D018698:Glutamic Acid / Q000633:toxicity; D006220:Haloperidol; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology; D018836:Inflammation Mediators / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008569:Memory Disorders / Q000150:complications / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008954:Models, Biological; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D010100:Oxygen / Q000633:toxicity; D016716:PC12 Cells; D051381:Rats; D012601:Scopolamine; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use
D018836:Inflammation Mediators; C547125:L-pGlu-(1-benzyl)-L-His-L-ProNH2; D018698:Glutamic Acid; D013973:Thyrotropin-Releasing Hormone; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D012601:Scopolamine; D005947:Glucose; D006220:Haloperidol; D010100:Oxygen
Glutamate; Neurotransmitters; OGD; Peptide; Stroke; TRH analog