NEUROPROTECTIVE AGENTS, NATURAL PLANT HERBS & DRUGS IN ISCHEMIC STROKE: A REVIEW

 

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ABOUT AUHTORS
Nesar Ahmad*,Zafar Khan, Noorul Hasan, Abdul Basit, Seikh Zohrameena
Department of Pharmacology,
Faculty of Pharmacy,
Integral University, Lucknow, UP, India
*nesar50@gmail.com

ABSTRACT 
Stroke is a destructive experience which can result in permanent disability in brain. There is no permanent drug which can improve the blood flow at infracted area and also improve the neurological deficit. Due to the lack of treatments available for stroke, many researchers will investigate the suitable plants or drugs for the treatment of this disease. Numerous medicinal plants and herbal drugs are available to treat stroke, some of the plants are Ginkgo biloba, Fructus Chebulae, Pomegranate, Rosa laevigata, Garlic, Leonurus heterophyllus, Olive, Grape, Allium cepa, drugs such as Pravastatin, Senkyunolide I, Phloretin, Mgso4, HAMI 3379, Oleoylethanolamie, scopolamine and mecamylamine, Nitric Oxide, N-nitro-L-arginine methyl ester (L-NAME), 3,5,6,7,8,3’,4’-Heptamethoxy flavones, Rosiglitazone, Puerarin, the activity was estimated by parameters like superoxide dismutase (SOD) activity, Hemispheric swelling index (cerebral edema), H2O2 induced cell injury, OGD-R induced cell injury, superoxide dismutase and glutathione peroxidises, mitochondrial membrane potential, Western blotting assay, ROS scavenging assays, Superoxide anion  scavenging assay, Hydroxyl radical  scavenging assay, H2O2 scavenging assay, Singlet oxygen scavenging assay, Peroxyl radical scavenging assay, Peroxynitrite anion scavenging assay, myeloperoxidase (MPO) activity, blood–brain barrier integrity, cerebral infarct size, in Situ Apoptosis Detection, Western blotting, SOD, GSH, glutathione peroxidase, and MDA levels, Reverse transcription polymerase chain reaction (RT-PCR), Lactate dehydrogenase activity assay, Determination of caspase activity, acetylcholinesterase (AChE) activity, Determination of choline acetyltransferase activity (ChAT), Cell viability, Oxygen glucose deprivation/reperfusion assay, Flow cytometry, Immunohistochemistry.  The present review focused on different medicinal plants and drugs that have been tested in Stroke in animal models.

REFERENCE ID: PHARMATUTOR-ART-2494

PharmaTutor (Print-ISSN: 2394 - 6679; e-ISSN: 2347 - 7881)

Volume 5, Issue 5

Received On: 14/02/2017; Accepted On: 23/02/2017; Published On: 01/05/2017

How to cite this article: Ahmad N, Khan Z, Hasan N, Basit A, Zohrameena S;Neuroprotective agents, Natural Plant Herbs & Drugs in Ischemic Stroke: A Review; PharmaTutor; 2017; 5(5); 29-36

INTRODUCTION
Stroke, the major cause of death and disability, is regarded as the important problem in developing countries [1]. Frequent incidences of cerebral ischemia are seen in age-related disorders, hypoxic–ischemic brain injury, carotid artery pathologies, asphyxiation and shock etc. It is a devastating event that is associated with great morbidity (Madl and Holzer, 2004). In certain clinical situations such as transient global cerebral ischemia anticipates or even induced iatrogenically during cardiac or thoracic surgery. Permanent ligation of bilateral common carotid arteries is a well known model used to study cerebral ischemia (Choe et al., 2001). Bilateral common carotid artery occlusion (BCCAO) causes moderate and most likely permanent reduction of cortical and cerebral blood flow in diverse areas of brain (Jeon et al., 2004).Despite the importance of stroke and the advances of technologies nowadays. The prophylactic protection against stroke with neuroprotective agents has gained much attention. Cerebral ischemia is characterized by a rapid onset of neurological injury due to interruption of blood flow to the brain [2]. This injury has been reported to be associated with the action and interaction of many factors such as excitatory amino acids, calcium overloading, and oxidative stress damage, periphery depolarization of infarction, neuroinflammation, and apoptosis [3–5]. However, accumulative lines of evidence in this decade point out to the crucial role of oxidative stress. It has been reported that the reduction of cerebral blood flow and the reperfusion period induce the elevation of oxidative stress and lipid peroxidation [6–9]. Interestingly, both in vitro and in vivo data have demonstrated that this injury can be protected by polyphenolics including flavonoids [7, 8, 10–13]. Ginkgo biloba belonging to the family Ginkgoaceae which can improve cerebral oxygen supply, decrease cerebral oxygen extraction rate and consumption, and reduce cerebral oxygen metabolic rate[14].Fructus Chebulae decreases the cerebral infarct volume and extent of hemisphere swelling[15]. Pomegranate decrease brain levels of NF-κB p65, TNF-α, caspase-3 and increased brain levels of IL-10, and cerebral ATP roduction[16]. Pravastatin drug which used for the proportion of viable neuronal cells after ischemia was greater in the pravastatin vs. control group, with greater expression of apoptotic cells in the control vs. pravastatin group. Bax protein expression was significantly decreased; Bcl-2 expression was increased, but not significantly [17]. Puerarin is a drug which is used for treatment significantly improved the phosphorylation level of AKT in dose-dependent, reduced the infarct volume, the number of Nissl body, and cleaved caspase-3 and GFAP positive cells increased [18].

 

Natural plants Herbs & drug used as a neuroprotection in ischemic stroke

Name of plant Herbs

Dose

Model

Parameters

Result

Ginkgo biloba

1 mg/kg

Hypoperfusin in

elderly patients

CaO2, SjvO2 and CEO2, Glua, Laca, superoxide dismutase (SOD) activity.

Ginkgo biloba extract can improve cerebral oxygen supply, decrease cerebral oxygen extraction rate and consumption, and reduce cerebral oxygen metabolic rate [14].

Fructus Chebulae

 

300, 500 mg/kg.

MCAO, 90min, reperfusion 24hr

Hemispheric swelling index (cerebral edema), H2O2 induced cell injury, OGD-R induced cell injury.

 

 

 

Fructus Chebulae extract increases the PC12 cell survival against OGD-R and H2O2.  Fructus Chebulae also decreases the cerebral infarct volume and extent of hemisphere swelling [15].

 

 

Pomegranate

250, 500 mg/kg.

BCCAO,

60 min, Reperfusion 60 min

Determination of brain nitric oxide, superoxide dismutase and glutathione peroxidises, glutathione reductase, brain cytokines.

 Reduction in brain contents of MDA, and NO, in addition to enhancement of SOD, GPX, and GRD. Pomegranate extract decreased brain levels of NF-κB p65, TNF-α, caspase-3 and increased brain levels of IL-10, and cerebral ATP roduction. Comet assay showed less brain DNA damage [16].

Rosa laevigata

50, 100 and 200 mg/kg

MCAO reperfusion 24hr

DAPI staining, TUNEL assay, Determination of mitochondrial membrane potential, Western blotting assay, Immunohistochemisty

 Prevented I/R-induced disability and histological damage, significantly decreased DNA fragmentation, up-regulated the expression of Bcl-2, and down-regulated the expressions of p53, 37 Apaf1, Fas, FasL, Bax, Bid, cytochrome C and active Caspase-3. Moreover, decreased the expressions of NF-jB, iNOS, MMP-9, COX-2, TNF-a, IL-1b, IL-4, IL-6, and down-regulated the levels of p-JNK, p-ERK and in MAPK pathways [19].

Garlic

360 mg/kg. i.p.

MCAO for 2hr

ROS scavenging assays, Superoxide anion  scavenging assay, Hydroxyl radical  scavenging assay, H2O2 scavenging assay, Singlet oxygen scavenging assay, Peroxyl radical scavenging assay, Peroxynitrite anion scavenging assay

Extracts decreased mRNA expression of NR1- and NR2B-NMDA-receptor subunits and prevented ischemia-induced reduction in mitochondrial potential and in ATP synthesis. Antioxidants present in garlic extracts may regulate ROS concentrations during ischemia, favour pro-survival pathways, and attenuate mitochondrial dysfunction [20].

 

Leonurus heterophyllus

3.6,   7.2, 14.4 mg/kg

MCAO for 2 hr, reperfusion 24hr

Measurement of myeloperoxidase (MPO) activity, Measurement of NO metabolite in the brain, The apoptosis ratio of nerve fiber in the brains mensurate,

LHAE significantly decreasing neurological deficit scores, reducing the infarct volume and MPO content.  LHAE at 14.4 mg/kg significantly decreased the NO level. In addition, LHAE significantly decreased the apoptosis ratio of nerve fiber [21].

Olive

50, 75 and 100 mg/kg

MCAO for 30 min, reperfusion 24hr

Behavioural Parameter- Normal motor function, failure to extend forepaw; loss of righting reflex; no spontaneous motor activity. Biochemical parameters, Lipid profiles, Assessment of brain water content, blood–brain barrier integrity

Oral administration of olive leaf extract reduces infarct volume, brain edema, blood–brain barrier permeability, and improves neurologic deficit scores [22].

 

 

 

 

 

Grape

30 mg/ml

BCCAO for 5 min, reperfusion 4 days

Behavioural parameters-Assessment of locomotor activity, Biochemical parameters- Assessment of neurons, astrocytes and microglial cells, DAPI staining to assess nuclear DNA damage, 8-OHdG immunohistochemistry to identify oxidized DNA

GPE resulted in hyperlocomotion, extensive DND, oxidative and fragmented DNA damage, and an increase in reactive astrocytes and microglial cells in the hippocampal CA1 region[23].

Allium cepa

100 and 200 mg/kg

 BCCAO for 10 min, reperfusion 24 hr

Behavioural parameters-Elevated plus maze, Inclined beam walking test, Lateral push test Biochemical parameters- Estimation of thiobarbituric acid reactive substance (TBARS), Assessment of cerebral infarct size,

 

A. cepa bulb markedly reduced cerebral infarct size and attenuated impairment in short-term memory and motor coordination. marked decrease in mitochondrial TBARS [24].

 

 

 

 

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