Naringin Reverses Neurobehavioral and Biochemical Alterations in Intracerebroventricular Collagenase-Induced Intracerebral Hemorrhage in Rats

Pharmacology. 2017;100(3-4):172-187. doi: 10.1159/000453580. Epub 2017 Jul 1.


Intracerebral hemorrhage (ICH) contributes to 10-15% of all strokes and is a high risk factor for morbidity and mortality as compared to other subtypes of stroke, that is, cerebral ischemia and subarachnoid hemorrhage. Oxidative stress (OS)-induced neuroinflammation and neuronal cell death contribute towards the hallmarks of ICH. Spared antioxidant levels, increased inflammatory cytokines and free radicals in ICH lead to neuronal death and exaggerate the hallmarks of ICH. Intracerebroventricular (ICV) collagenase (COL-induced neuronal cell damage and cognitive deficits form a widely recognized experimental model for ICH. Naringin (NGN), a natural antioxidant bioflavonoid, has shown potent neuroprotective effects in different neurodegenerative diseases. However, its potential is least explored in pathological conditions, such as hemorrhagic stroke. This study is aimed at exploring the protective effects of NGN against ICV-COL induced behavioral, neurological and memory deficits in rats. ICV-ICH was induced by single, unilateral intrastriatal injection of COL (1 IU in 2 µL, ICV) over 10 min. From 2nd day onwards, NGN was administered in three different doses (10, 20, and 40 mg/kg; p.o.). Animals were subjected to a battery of behavioral tests to assess behavioral changes, including neurological scoring tests (cylinder test, spontaneous motility, righting reflex, horizontal bar test, forelimb flexion), actophotometer, rotarod, Randall Selitto and von Frey. Poststroke depression and memory deficits were estimated using forced swim test and Morris water maze test, respectively. Poststroke depression, neurological and cognitive deficits were mitigated dose dependently by NGN administration. NGN administration also attenuated the nitro-OS and restored tumor necrosis factor-α and endogenous antioxidant levels. Our research demonstrates that NGN has a protective effect against ICH-induced neurocognitive deficits, along with mitigation of oxido-nitrosative and inflammatory stress.

Keywords: Collagenase; Intracerebral hemorrhage; Intracerebroventricular; Naringin; Stroke.

MeSH terms

  • Animals
  • Brain / drug effects
  • Brain / metabolism
  • Catalase / metabolism
  • Cerebral Hemorrhage / chemically induced
  • Cerebral Hemorrhage / drug therapy*
  • Cerebral Hemorrhage / metabolism
  • Cerebral Hemorrhage / physiopathology
  • Collagenases
  • Exploratory Behavior / drug effects
  • Female
  • Flavanones / pharmacology
  • Flavanones / therapeutic use*
  • Glutathione / metabolism
  • Hyperalgesia / drug therapy
  • Lipid Peroxidation
  • Locomotion / drug effects
  • Matrix Metalloproteinase 9 / metabolism
  • Maze Learning / drug effects
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use*
  • Rats, Wistar
  • Reflex, Righting / drug effects
  • Rotarod Performance Test
  • Superoxide Dismutase / metabolism
  • Tumor Necrosis Factor-alpha / metabolism


  • Flavanones
  • Neuroprotective Agents
  • Tumor Necrosis Factor-alpha
  • Catalase
  • Superoxide Dismutase
  • Collagenases
  • Matrix Metalloproteinase 9
  • Mmp9 protein, rat
  • Glutathione
  • naringin