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

Abstract

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.

Mechanisms of Oxidative Stress and Therapeutic Targets following Intracerebral Hemorrhage

“…Danhong-a traditional Chinese medicine extracted from 2 herbs (Salviae miltiorrhiza Bunge (Danshen, China) and Carthamus tinctorius L (Honghua, China))-contains flavonoids and phenolic compounds and was reported to increase the expression of peroxiredoxin (Prx) 1 in astrocytes, thereby preventing severe brain injury following ICH in aged rats [102]. In addition, carnosine [103], COA-Cl (a novel synthesized nucleoside analog) [104], AE1-259-01 EP2 receptor agonists [105], green tea and red tea [57], protocatechuic acid (PCA) [106], nebivolol [107], 14Adiponectin (APN) [108], metformin [109], C1q/tumor necrosis factor-related protein 3 (CTRPs) [15], gastrodin [110], Naringin (NGN) [111], and Parthenolide (PN) [112] are all effective antioxidants in ICH animal models.…”

Naringin inhibits ovarian tumor growth by promoting apoptosis: An in�vivo study

“…Chinese herbal medicines are extensively reported to kill tumor cells, as well as to not be susceptible to drug resistance and to have few adverse effects ( 8 ). Naringin is a bioflavonoid and polyphenolic compound that is located in grapefruit ( 9 ). Previous studies have indicated that naringin has a number of pharmacological activities, including anti-inflammation, anti-oxidative stress, myocardial protection, and the regulation of glucose and lipid metabolism ( 10 ).…”

Scopoletin Attenuates Intracerebral Hemorrhage-Induced Brain Injury and Improves Neurological Performance in Rats

“…Due to the high BP in the cranium, herniation in the brain occurs, which is characteristic of ischemic stroke [3], resulting in neurological deficits or loss of neurological functions in the brain [26]. To evaluate this, we have tested the animals for their functional and neurological deficits by a series of tests such as spontaneous motility, forelimb suspension, Rotarod test, plane righting reflex, negative geotaxis reflex, and cliff avoidance [27].…”

“…Besides, CH often results in dysfunction of the cerebral nervous system and people affected would be forced to be away from social functioning and depend on others for their self-care [1,2]. The primary effects of CH are an increase in intracranial pressure owing to blood leak and its related mechanical shear of harmful neurons and glial cells [3]. Erythrocyte lysis products and damaged microg-lia would complicate into secondary brain injury with oxidative stress and increased inflammation [4] triggering a series of events involving inflammatory and oxidative stress pathways accounting for the pathophysiological processes [5][6][7].…”