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      Effects of caffeic acid phenethyl ester in reducing cerebral edema in rat subjects experiencing brain injury: An in vivo study

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          Abstract

          Background

          A head injury is a very dangerous condition that threatens human life. This study examines the use of caffeic acid phenethyl ester (CAPE) in reducing cerebral edema in cases of head injury. The purpose of this study is to demonstrate whether CAPE can improve various parameters related to the expression of Aquaporin-4 (AQP4) mRNA and the serum AQP4 levels in rat subjects.

          Methods

          This is a randomized controlled study using a posttest-only control group design that uses experimental animals—specifically, male Rattus norvegicus ( Sprague Dawley strain) rats aged 10–12 weeks and weighing 200–300 g. This study used a head injury model according to Marmarou (1994) with minor modifications to the animal model fixation tool. The parameters of the AQP4 mRNA were examined with real-time PCR, while serum AQP4 levels were examined with sandwich ELISA.

          Results

          The AQP4 mRNA expression in rats that were given CAPE was lower than those not given CAPE, both on the fourth and seventh days; serum AQP4 levels in rats that were given CAPE were also lower than those not given CAPE, both on the fourth and seventh days.

          Conclusion

          Administration of CAPE in a rat model with head injury can reduce cerebral edema, mediated by AQP4.

          Highlights

          • Head injury is a major cause of mechanical brain cell injury and also catalyzes secondary damage.

          • Caffeic Acid Phenethyl Ester (CAPE) can reduce inflammatory processes, brain lipid peroxidation, and free radical damage.

          • CAPE treatment can cause a decrease in cerebral edema, mediated by Aquaporin-4 (AQP4).

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          Most cited references27

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          Time course of aquaporin expression after transient focal cerebral ischemia in mice.

          Cerebral edema contributes to morbidity and mortality in stroke. Aquaporins (AQPs)-1, -4, and -9 have been identified as the three main water channels in the brain. To clarify their role in water movement, we have compared their expression patterns with brain swelling after transient focal brain ischemia. There were two peaks of maximal hemispheric swelling at 1 hr and at 48 hr after ischemia, coinciding with two peaks of AQP4 expression. At 1 hr after occlusion, AQP4 expression was significantly increased on astrocyte endfeet in the core and in the border of the lesion. At 48 hr, AQP4 expression was increased in astrocytes in the border of the lesion over the whole cell. AQP9 showed a significant induction at 24 hr that increased gradually with time, without correlation with the swelling. The expression of AQP1 remained unchanged. These results suggest that AQP4, but not AQP1 or AQP9, may play an important role in water movement associated with the pathophysiology of edema after transient cerebral ischemia in the mouse. Copyright 2006 Wiley-Liss, Inc.
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            Therapeutic potential of caffeic acid phenethyl ester and its anti-inflammatory and immunomodulatory effects (Review).

            Caffeic acid phenethyl ester (CAPE), a naturally occurring compound isolated from propolis extract, has been reported to have a number of biological and pharmacological properties, exerting antioxidant, anti-inflammatory, anticarcinogenic, antibacterial and immunomodulatory effects. Recent in vivo and in vitro study findings have provided novel insights into the molecular mechanisms involved in the anti-inflammatory and immunomodulatory activities of this natural compound. CAPE has been reported to have anti-inflammatory properties involving the inhibition of certain enzyme activities, such as xanthine oxidase, cyclooxygenase and nuclear factor-κB (NF-κB) activation. Since inflammation and immune mechanisms play a crucial role in the onset of several inflammatory diseases, the inhibition of NF-κB represents a rationale for the development of novel and safe anti-inflammatory agents. The primary goal of the present review is to highlight the anti-inflammatory and immunomodulatory activities of CAPE, and critically evaluate its potential therapeutic effects.
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              Caffeic acid phenethyl ester reduces neurovascular inflammation and protects rat brain following transient focal cerebral ischemia.

              Ischemic stroke is a neurovascular disease treatable by thrombolytic therapy, but the therapy has to be initiated within 3 h of the incident. This therapeutic limitation stems from the secondary injury which results mainly from oxidative stress and inflammation. A potent antioxidant/anti-inflammatory agent, caffeic acid phenethyl ester (CAPE) has potential to mitigate stroke's secondary injury, and thereby widening the therapeutic window. We observed that CAPE protected the brain in a dose-dependent manner (1-10 mg/kg body weight) and showed a wide therapeutic window (about 18 h) in a rat model of transient focal cerebral ischemia and reperfusion. The treatment also increased nitric oxide and glutathione levels, decreased lipid peroxidation and nitrotyrosine levels, and enhanced cerebral blood flow. CAPE down-regulated inflammation by blocking nuclear factor kappa B activity. The affected mediators included adhesion molecules (intercellular adhesion molecule-1 and E-selectin), cytokines (tumor necrosis factor-alpha and interleukin-1beta) and inducible nitric oxide synthase. Anti-inflammatory action of CAPE was further documented through reduction of ED1 (marker of activated macrophage/microglia) expression. The treatment inhibited apoptotic cell death by down-regulating caspase 3 and up-regulating anti-apoptotic protein Bcl-xL. Conclusively, CAPE is a promising drug candidate for ischemic stroke treatment due to its inhibition of oxidative stress and inflammation, and its clinically relevant wide therapeutic window.
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                Author and article information

                Contributors
                Journal
                Ann Med Surg (Lond)
                Ann Med Surg (Lond)
                Annals of Medicine and Surgery
                Elsevier
                2049-0801
                15 August 2020
                September 2020
                15 August 2020
                : 57
                : 328-333
                Affiliations
                [a ]Department of Neurosurgery, Pelamonia Hospital, Makassar, Indonesia
                [b ]Department of Neurosurgery, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia
                [c ]Clinical Microbiologist Program, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia
                [d ]Department of Surgery Faculty of Medicine, Hasanuddin University, Makassar, Indonesia
                [e ]Doctoral Program of Medical Sciences, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia
                [f ]Department of Interna Medicine, Pelamonia Hospital, Makassar, Indonesia
                [g ]Departement of Microbiology, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia
                [h ]Departement of Neurosurgery, Putri Hijau Hospital, Medan, Indonesia
                Author notes
                []Corresponding author. Department of Neurosurgery, Pelamonia Hospital, Jalan Jend. Sudirman No.27, Makassar, 90157, Indonesia. rizha_nst@ 123456yahoo.com
                Article
                S2049-0801(20)30250-8
                10.1016/j.amsu.2020.08.016
                7452142
                9aa0f2b6-9327-4aaf-844f-e04e33e288b4
                © 2020 Published by Elsevier Ltd on behalf of IJS Publishing Group Ltd.

                This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

                History
                : 30 June 2020
                : 5 August 2020
                : 5 August 2020
                Categories
                Original Research

                experimental traumatic brain injury,caffeic acid phenethyl ester,blood serum,aqp4,rat model

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