Neuroprotective effect of total flavonoids from Ilex pubescens against focal cerebral ischemia/reperfusion injury in rats

Abstract

Ilex pubescens is commonly used in traditional Chinese medicine to treat cardiovascular and cerebrovascular diseases, such as coronary artery disease and stroke. However, the underlying mechanisms remain to be fully elucidated. The aim of the present study was to investigate the effects of Ilex pubescens total flavonoids (IPTF) on neuroprotection and the potential mechanisms in a rat model of focal cerebral ischemia/reperfusion (I/R) injury. Rats were pretreated with intragastric administration of IPTF at doses of 200 and 100 mg/kg for 5 days; middle cerebral artery occlusion surgery was then performed to induce cerebral I/R injury. Neurological deficits were determined using the 5-point neurological function score evaluation system, brain infarct sizes were determined by 2,3,5-triphenyltetrazolium chloride staining and alterations in brain histology were determined by hematoxylin and eosin staining. The neurological deficit score, the infarcted area and the brain tissue pathological injury were significantly reduced when the rats were pretreated with IPTF. In addition, inflammatory mediators and neurotrophic factors in the brain were investigated. IPTF pretreatment decreased the activities of total nitric oxide synthase (TNOS), induced NOS (iNOS) and constitutive NOS (cNOS), and the levels of nitric oxide (NO), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), however, it increased the levels of IL-10 in brain tissues. Furthermore, pretreatment with IPTF also increased the protein expressions of brain-derived neurotrophic factor, glial cell-derived neurotrophic factor and vascular endothelial growth factor, when compared with the model group. In conclusion, the results of the present study demonstrated that IPTF has a neuroprotective effect against focal cerebral I/R injury in rats. The mechanism may be associated with the decreased production of certain proinflammatory cytokines including NO, IL-1β, TNF-α, TNOS, iNOS and cNOS, the increased production of the anti-inflammatory cytokine IL-10 and the increased secretion of neurotrophic factors.

Stress Response Simulated by Continuous Injection of ACTH Attenuates Lipopolysaccharide-Induced Inflammation in Porcine Adrenal Gland

“…Many studies have demonstrated that activated TLRs in organ injury are associated with oxidative stress ( 41 , 42 ). NO (nitric oxide) is an important inflammatory mediator derived from NOS, including induced NOS (iNOS) and constitutive NOS (cNOS) ( 43 ). Actually, the regulation of NO production by cNOS and iNOS was a complex issue, and it was reported that the activity of cNOS was regulated by LPS and some cytokines in the mouse vascular endothelial cell line ( 44 ).…”

“…These results indicate that the strong inflammatory reaction induced by LPS may decrease cNOS activity in local adrenal gland tissue although ACTH pretreatment alleviates the effect of LPS. NO is predominantly produced by iNOS in the late phase of inflammation ( 43 , 46 ). Here, we found LPS treatment increased levels of iNOS protein secretion in the adrenal gland but decreased T-SOD activity without an ACTH × LPS effect.…”

Antioxidant Therapies for Neuroprotection—A Review

“…Specifically, the administration of 2′-methoxy-6-methylflavone increases GABA A receptor tonic currents, which are elevated following stroke, through the δ-containing GABA A receptors, decreases infarct volume, and improves functional recovery [141]. Additionally, the administration Ilex Pubescens total flavonoids on neuroprotection using a rat model of focal cerebral ischemia/reperfusion injury has led to a reduction of the neurological deficit score, infarcted area, and brain tissue pathological injury, an increase of the brain-derived neurotrophic factor, glial cell-derived neurotrophic factor and vascular endothelial growth factor expression levels, and a decrease of various proinflammatory cytokines [142].…”

Anti-inflammatory Effects of Traditional Chinese Medicines on Preclinical in vivo Models of Brain Ischemia-Reperfusion-Injury: Prospects for Neuroprotective Drug Discovery and Therapy

“…Ilex pubescens was found to reduce IRI in brain’s hippocampus and cortex by down regulation of NO and stimulation of Ca 2+ dependent ATP enzyme activation ( Yan et al, 2017 ). Fang et al (2017) , reported that Ilex pubescens can attenuate the cerebral IRI in MCAO rats. Ilex pubescens inhibited the production of NO due to inhibition of iNOS, cNOS and decreased production of IL-1β and TNF-α.…”