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Neuroprotection by trans-resveratrol against collagenase-induced neurological and neurobehavioural deficits in rats involves adenosine A1 receptors

Abd Aziz NAW, Iezhitsa I, Agarwal R, Abdul Kadir RF, Abd Latiff A, Ismail NM

Neurol Res, 2020 Mar;42(3):189-208.
PMID: 32013788 DOI: 10.1080/01616412.2020.1716470

Objective:Trans-resveratrol has been shown to have neuroprotective effects and could be a promising therapeutic agent in the treatment of intracerebral haemorrhage (ICH). This study aimed to investigate the involvement of the adenosine A1 receptor (A1R) in trans-resveratrol-induced neuroprotection in rats with collagenase-induced ICH.Methods: Sixty male Sprague-Dawley rats weighing 330-380 g were randomly divided into five groups (n = 12): (i) control, (ii) sham-operated rats, (iii) ICH rats pretreated with vehicle (0.1% DMSO saline, i.c.v.), (iv) ICH rats pretreated with trans-resveratrol (0.9 µg, i.c.v.) and (v) ICH rats pretreated with trans-resveratrol (0.9 µg) and the A1R antagonist, DPCPX (2.5 µg, i.c.v.). Thirty minutes after pretreatment, ICH was induced by intrastriatal injection of collagenase (0.04 U). Forty-eight hours after ICH, the rats were assessed using a variety of neurobehavioural tests. Subsequently, rats were sacrificed and brains were subjected to gross morphological examination of the haematoma area and histological examination of the damaged area.Results: Severe neurobehavioural deficits and haematoma with diffuse oedema were observed after intrastriatal collagenase injection. Pretreatment with trans-resveratrol partially restored general locomotor activity, muscle strength and coordination, which was accompanied with reduction of haematoma volume by 73.22% (P < 0.05) and damaged area by 60.77% (P < 0.05) in comparison to the vehicle-pretreated ICH group. The trans-resveratrol-induced improvement in neurobehavioural outcomes and morphological features of brain tissues was inhibited by DPCPX pretreatment.Conclusion: This study demonstrates that the A1R activation is possibly the mechanism underlying the trans-resveratrol-induced neurological and neurobehavioural protection in rats with ICH.

Matched MeSH terms: Neuroprotective Agents/administration & dosage*
Cognitive effects of vanillic acid against streptozotocin-induced neurodegeneration in mice

Singh JC, Kakalij RM, Kshirsagar RP, Kumar BH, Komakula SS, Diwan PV

Pharm Biol, 2015 May;53(5):630-6.
PMID: 25472801 DOI: 10.3109/13880209.2014.935866

Vanillic acid (VA), a flavoring agent used in food and drug products, obtained naturally from the plant Angelica sinensis (Oliv.) Diels (Apiaceae), used in the traditional Chinese medicine. It is reported to possess strong antioxidant, anti-inflammatory, and neuroprotective effects. However, the pharmacological effects on oxidative stress-induced neurodegeneration are not well investigated.

Matched MeSH terms: Neuroprotective Agents/administration & dosage*
Fulltext Oil palm phenolics confer neuroprotective effects involving cognitive and motor functions in mice

Leow SS, Sekaran SD, Tan Y, Sundram K, Sambanthamurthi R

Nutr Neurosci, 2013 Sep;16(5):207-17.
PMID: 23433062 DOI: 10.1179/1476830512Y.0000000047

Phenolics are important phytochemicals which have positive effects on chronic diseases, including neurodegenerative ailments. The oil palm (Elaeis guineensis) is a rich source of water-soluble phenolics. This study was carried out to discover the effects of administering oil palm phenolics (OPP) to mice, with the aim of identifying whether these compounds possess significant neuroprotective properties.

Matched MeSH terms: Neuroprotective Agents/administration & dosage*
Protective effect of magnesium acetyltaurate against endothelin-induced retinal and optic nerve injury

Arfuzir NN, Lambuk L, Jafri AJ, Agarwal R, Iezhitsa I, Sidek S, et al.

Neuroscience, 2016 06 14;325:153-64.
PMID: 27012609 DOI: 10.1016/j.neuroscience.2016.03.041

Vascular dysregulation has long been recognized as an important pathophysiological factor underlying the development of glaucomatous neuropathy. Endothelin-1 (ET1) has been shown to be a key player due to its potent vasoconstrictive properties that result in retinal ischemia and oxidative stress leading to retinal ganglion cell (RGC) apoptosis and optic nerve (ON) damage. In this study we investigated the protective effects of magnesium acetyltaurate (MgAT) against retinal cell apoptosis and ON damage. MgAT was administered intravitreally prior to, along with or after administration of ET1. Seven days post-injection, animals were euthanized and retinae were subjected to morphometric analysis, TUNEL and caspase-3 staining. ON sections were stained with toluidine blue and were graded for neurodegenerative effects. Oxidative stress was also estimated in isolated retinae. Pre-treatment with MgAT significantly lowered ET1-induced retinal cell apoptosis as measured by retinal morphometry and TUNEL staining. This group of animals also showed significantly lesser caspase-3 activation and significantly reduced retinal oxidative stress compared to the animals that received intravitreal injection of only ET1. Additionally, the axonal degeneration in ON was markedly reduced in MgAT pretreated animals. The animals that received MgAT co- or post-treatment with ET1 also showed improvement in all parameters; however, the effects were not as significant as observed in MgAT pretreated animals. The current study showed that the intravitreal pre-treatment with MgAT reduces caspase-3 activation and prevents retinal cell apoptosis and axon loss in ON induced by ET1. This protective effect of ET1 was associated with reduced retinal oxidative stress.

Matched MeSH terms: Neuroprotective Agents/administration & dosage*
Neuroprotective effect of poly(lactic-co-glycolic acid) nanoparticle-bound brain-derived neurotrophic factor in a permanent middle cerebral artery occlusion model of ischemia in rats

Kamarudin SN, Iezhitsa I, Tripathy M, Alyautdin R, Ismail NM

Acta Neurobiol Exp (Wars), 2020;80(1):1-18.
PMID: 32214270

Poly (lactide‑co‑glycolide) (PLGA) nanoparticles (NPs) are biodegradable carriers that participate in the transport of neuroprotective drugs across the blood brain barrier (BBB). Targeted brain‑derived neurotrophic factor (BDNF) delivery across the BBB could provide neuroprotection in brain injury. We tested the neuroprotective effect of PLGA nanoparticle‑bound BDNF in a permanent middle cerebral artery occlusion (pMCAO) model of ischemia in rats. Sprague‑Dawley rats were subjected to pMCAO. Four hours after pMCAO, two groups were intravenously treated with BDNF and NP‑BDNF, respectively. Functional outcome was assessed at 2 and 24 h after pMCAO, using the modified neurologic severity score (mNSS) and rotarod performance tests. Following functional assessments, rats were euthanized blood was taken to assess levels of the neurobiomarkers neuron‑specific enolase and S100 calcium‑binding protein β (S100β), and the brain was evaluated to measure the infarct volume. The NP‑BDNF‑treated group showed significant improvement in mNSS compared with pMCAO and BDNF‑treated groups and showed improved rotarod performance. The infarct volume in rats treated with NP‑BDNFs was also significantly smaller. These results were further corroborated by correlating differences in estimated NSE and S100β. NP‑BDNFs exhibit a significant neuroprotective effect in the pMCAO model of ischemia in rats.

Matched MeSH terms: Neuroprotective Agents/administration & dosage
Ficus deltoidea: Potential inhibitor of pro-inflammatory mediators in lipopolysaccharide-induced activation of microglial cells

Zolkiffly SZI, Stanslas J, Abdul Hamid H, Mehat MZ

J Ethnopharmacol, 2021 Oct 28;279:114309.
PMID: 34119609 DOI: 10.1016/j.jep.2021.114309

ETHNOPHARMACOLOGICAL RELEVANCE: Ficus deltoidea Jack (FD) is widely consumed in traditional medicine as a treatment for various diseases in Malaysia. Each part of the plant such as its leave, stem, fruit and root are used traditionally to treat different types of diseases. Vitexin and isovitexin are bioactive compounds abundantly found in the leaves of FD that possessed many pharmacological properties including neuroprotection. Nonetheless, its effects on key events in neuroinflammation are unknown.
AIM OF THE STUDY: To determine the inhibitory properties of FD aqueous extract on pro-inflammatory mediators involved in lipopolysaccharide (LPS)-induced microglial cells.
METHODS: Vitexin and isovitexin in the extract were quantified via high performance liquid chromatography (HPLC). The extract was evaluated for its cytotoxicity activity via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Pre-treatment with the extract on LPS-induced microglial cells was done to determine its antioxidant and anti-neuroinflammatory properties by measuring the level of reactive oxygen species (ROS), nitric oxide (NO), tumour necrosis factor alpha (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) via 2'-7'-dichlorofluorescin diacetate (DCFDA) assay, Griess assay and Western blot respectively.
RESULTS: The extract at all tested concentrations (0.1 μg/mL, 1 μg/mL, 10 μg/mL, 100 μg/mL) were not cytotoxic as the percentage viability of microglial cells were all above ~80%. At the highest concentration (100 μg/mL), the extract significantly reduced the formation of ROS, NO, TNF-α, IL-1β and IL-6 in microglial cells induced by LPS.
CONCLUSION: The extract showed neuroprotective effects by attenuating the levels of pro-inflammatory and cytotoxic factors in LPS-induced microglial cells, possibly by mediating the nuclear factor-kappa B (NF-κB) signalling pathway.

Matched MeSH terms: Neuroprotective Agents/administration & dosage