title: New monocyte locomotion inhibitory factor analogs protect against cerebral ischemia-reperfusion injury in rats.
abstract: Monocyte locomotion inhibitory factor (MLIF) is an oligopeptide with anti-inflammatory properties. The carboxyl-terminal end group Cys-Asn-Ser serves as the pharmacophore of MLIF. The aim of this study was to investigate the neuroprotective effects of two new synthetic analogs, Arg-Cys-Asn-Ser and D-Cys-Asn-Ser, on focal cerebral ischemia, which were designed and synthesized to increase the penetrability and enzymatic stability of Cys-Asn-Ser. Ninety-one male Sprague-Dawley rats were randomly divided into six groups: I - Sham; II - Ischemia-reperfusion (I/R); III - Nimodipine; IV - Cys-Asn-Ser; V - D-Cys-Asn-Ser; and VI - Arg-Cys-Asn-Ser. The rats in groups II-VI were subjected to middle cerebral artery occlusion. After 24 hours of reperfusion, the neurological deficit, cerebral infarct volume, and levels of the pro-inflammatory factors interleukin-1β (IL-1β) and tumor necrosis factor-alpha in brain tissue homogenates were assessed. Compared with the sham group, the mean neurological deficit scores were significantly higher in groups II-VI (p ≤ 0.019 for all). The mean infarct volumes were significantly higher in I/R and Cys-Asn-Ser groups compared with the sham group (both p ≤ 0.046). The mean IL-1β level was significantly lower in D-Cys-Asn-Ser and Arg-Cys-Asn-Ser groups compared with I/R group (both p ≤ 0.046). In conclusion, the results showed that Arg-Cys-Asn-Ser and D-Cys-Asn-Ser have the potential for protective effects against focal cerebral ischemia injury.
authors.affiliation: Department of Pharmacy, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China; Department of Respiratory Medicine, The Second Hospital of Lanzhou University, Lanzhou, China. wxiaoping08@sina.com.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Wang
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.forename: Yan
authors.initials: Y
authors.lastname: Yang
authors.forename: Jingman
authors.initials: J
authors.lastname: Ni
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000473:pathology / Q000517:prevention & control*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology / Q000517:prevention & control; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D008970:Molecular Weight; D009422:Nervous System Diseases / Q000139:chemically induced / Q000503:physiopathology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D009553:Nimodipine / Q000494:pharmacology; D009842:Oligopeptides / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D002121:Calcium Channel Blockers; D053583:Interleukin-1beta; D018696:Neuroprotective Agents; D009842:Oligopeptides; D014409:Tumor Necrosis Factor-alpha; C430647:monocyte locomotion inhibitory factor; D009553:Nimodipine