Effects of Apocynin and Ethanol on Intracerebral Haemorrhage‐induced Brain Injury in Rats

Titova, Elena; Ostrowski, Robert P.; Sowers, Lawrence C.; Zhang, Junyi; Tang, Jiping

doi:10.1111/j.1440-1681.2007.04664.x

Cited by 30 publications

(23 citation statements)

References 52 publications

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“…Apocynin (5 mg/kg, i.p., 3 times daily for 2 days after surgery) attenuated vasospasm and reduced neurological deficits after experimental subarachnoid hemorrhage in rats (49). However, apocynin treatment (3, 10 and 30 mg/kg, i.p., 2 h after surgery) did not improve the outcome after intracerebral hemorrhage in rat (50).…”

Section: Stroke and Brain Injuriesmentioning

confidence: 99%

The neuroprotective effects of apocynin

Simonyi¹

2012

Front Biosci

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The recognition of health benefits of phytomedicines and herbal supplements lead to an increased interest to understand the cellular and molecular basis of their biological activities. Apocynin (4-hydroxy-3-methoxy-acetophenone) is a constituent of the Himalayan medicinal herb Picrorhiza kurroa which is regarded as an inhibitor of nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase, a superoxide-producing enzyme. NADPH oxidase appears to be especially important in the modulation of redox-sensitive signaling pathways and also has been implicated in neuronal dysfunction and degeneration, and neuroinflammmation in diseases ranging from stroke, Alzheimer's and Parkinson's diseases to psychiatric disorders. In this review, we aim to give an overview of current literature on the neuroprotective effects of apocynin in the prevention and treatment of neurodegenerative disorders. Particular attention is given to in vivo studies. KeywordsApocynin; NADPH oxidase; NOX2; Neurodegeneration; Animal models; Review INTRODUCTIONApocynin (4-hydroxy-3-methoxy-acetophenone) was first isolated from Apocynum species. Two North American species of Apocynum, A. androsaemifolium and A. cannabinum, were widely used by Native American tribes as medicine (1). In addition, Apocynum venetum is used as a tea in north China and Japan and reported to have hepatoprotective effects (2). Apocynin may also be obtained from other plants, e.g. from the rhizome of Iris species.Apocynin was discovered during activity-guided isolation of immunomodulatory constituents from Picrorhiza kurroa, an endangered medicinal plant native to the mountains of India, Nepal, Tibet and Pakistan. Picrorhiza kurroa has been used to treat liver diseases, upper respiratory tract disorders, chronic diarrhea, scorpion sting and fever in the Ayurvedic system of medicine (3). In traditional Chinese medicine, Picrorhiza has been used to treat Send correspondence to: Agnes Simonyi, Department of Biochemistry, 117 Schweitzer Hall, University of Columbia, MO 65211, simonyia@missouri.edu. NIH Public Access Author ManuscriptFront Biosci (Elite Ed It is important to note that no adverse side effects of Picrorhiza extract/apocynin have been reported (3). Apocynin has a very good safety profile in animal studies as well (4), and several studies used long-term treatment without any signs of ill-health effects (see the studies with transgenic mice of Alzheimer's disease, for an example). Our recent study on the bioavailability of apocynin showed that apocynin is rapidly metabolized into glucuronic conjugate (5). At 30 min and 1 h after injection (5 mg/kg body wt, i.p.), approximately 50% of apocynin was converted to its glycosyl derivative and was distributed in plasma, liver and brain. Apocynin appeared in plasma as early as 30 min, peaked at 1 h and declined to low levels after 2 h (5). Following intragastric administration, apocynin is shown to undergo rapid absorption and excretion; with urinary excretion containing the unchanged form, the glucuronide, demethylat...

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Section: Stroke and Brain Injuriesmentioning

confidence: 99%

The neuroprotective effects of apocynin

Simonyi¹

2012

Front Biosci

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“…In almost all studies described in Table 2, the compound has been administered (in concentrations ranging from 0.4 to 300 mg/kg) as preventive treatment ranging from more than 2 months before disease onset in the case of ALS [54] to a few minutes before ischemic stroke [27]. It is clear that a curative approach would be more relevant, although the outcome of such studies is sometimes disappointing, as for hemorrhagic stroke [151]. In the case of ALS, chronic treatment with apocynin in the drinking water led to extremely variable results: a first study described an increase of survival (113 days) in SOD G93A mice, a real hope for a potential treatment in patients with ALS [54].…”

Section: Natural Compoundsmentioning

confidence: 99%

Targeting NOX enzymes in the central nervous system: therapeutic opportunities

Sorce

Krause

Jaquet

2012

Cell. Mol. Life Sci.

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Among the pathogenic mechanisms underlying central nervous system (CNS) diseases, oxidative stress is almost invariably described. For this reason, numerous attempts have been made to decrease reactive oxygen species (ROS) with the administration of antioxidants as potential therapies for CNS disorders. However, such treatments have always failed in clinical trials. Targeting specific sources of reactive oxygen species in the CNS (e.g. NOX enzymes) represents an alternative promising option. Indeed, NOX enzymes are major generators of ROS, which regulate progression of CNS disorders as diverse as amyotrophic lateral sclerosis, schizophrenia, Alzheimer disease, Parkinson disease, and stroke. On the other hand, in autoimmune demyelinating diseases, ROS generated by NOX enzymes are protective, presumably by dampening the specific immune response. In this review, we discuss the possibility of developing therapeutics targeting NADPH oxidase (NOX) enzymes for the treatment of different CNS pathologies. Specific compounds able to modulate the activation of NOX enzymes, and the consequent production of ROS, could fill the need for disease-modifying drugs for many incurable CNS pathologies.

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“…Apocyanin has been widely used as a NADPH oxidase inhibitor in vitro and in vivo experimental models of PD [21]. Earlier, it was used to prevent oxidative stress-mediated cell damage in several disease models, but recently it has been proved to improve neurological function and can be used as a neuroprotective agent [22][23][24][25][26]. Therefore, considering the pharmacological properties of apocyanin in neurological disorders, the present study is designed to establish the neuroprotective efficacy of apocyanin in LPS-induced PD model.…”

Section: Introductionmentioning

confidence: 99%

Apocyanin, a Microglial NADPH Oxidase Inhibitor Prevents Dopaminergic Neuronal Degeneration in Lipopolysaccharide-Induced Parkinson’s Disease Model

Sharma

Nehru

2015

Mol Neurobiol

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Microglia-associated inflammatory processes have been strongly implicated in the development and progression of Parkinson's disease (PD). Specifically, microglia are activated in response to lipopolysaccharide (LPS) and become chronic source of cytokines and reactive oxygen species (ROS) production. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex is responsible for extracellular as well as intracellular production of ROS by microglia and its expression is upregulated in PD. Therefore, targeting NADPH oxidase complex activation using an NADPH oxidase inhibitor, i.e., apocyanin seems to be an effective approach. The aim of present study was to investigate the neuroprotective effects of apocyanin in a LPS-induced PD model. LPS (5 μg) was injected intranigral and apocyanin was administered daily at a dose of 10 mg/kg b.wt (i.p.) during the experiment. LPS when injected into the substantia nigra (SN) reproduced the characteristic hallmark features of PD in rats. It elicited an inflammatory response characterized by glial cell activation (Iba-1, GFAP). Furthermore, LPS upregulated the gene expression of nuclear factor-κB (NFκB), iNOS, and gp91PHOX and resulted in an elevated total ROS production as well as NADPH oxidase activity. Subsequently, this resulted in dopaminergic loss as depicted by decreased tyrosine hydroxylase (TH) expression with substantial loss in neurotransmitter dopamine and its metabolites, whereas treatment with apocyanin significantly reduced the number of glial fibrillary acidic protein (GFAP) and Iba-1-positive cells in LPS-treated animals. It also mitigated microglial activation-induced inflammatory response and elevation in NADPH oxidase activity, thus reducing the extracellular as well as intracellular ROS production. The present study indicated that targeting NADPH oxidase can inhibit microglial activation and reduce a broad spectrum of toxic factors generation (i.e., cytokines, ROS, and reactive nitrogen species [RNS]), thus offering a hope in halting the progression of PD.

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Effects of Apocynin and Ethanol on Intracerebral Haemorrhage‐induced Brain Injury in Rats

Cited by 30 publications

References 52 publications

The neuroprotective effects of apocynin

The neuroprotective effects of apocynin

Targeting NOX enzymes in the central nervous system: therapeutic opportunities

Apocyanin, a Microglial NADPH Oxidase Inhibitor Prevents Dopaminergic Neuronal Degeneration in Lipopolysaccharide-Induced Parkinson’s Disease Model

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