Therapeutic potential of resolvins in the prevention and treatment of inflammatory disorders

Tumor Microenvironment Global Core Research Center, College of Pharmacy, Seoul National University, Seoul 151-742, South Korea.
Biochemical pharmacology (Impact Factor: 5.01). 11/2012; 84(10):1340-50. DOI: 10.1016/j.bcp.2012.08.004
Source: PubMed


Acute inflammation, the primary response to harmful infection and injury, can be successfully completed through effective resolution and tissue repair. Resolution of inflammation requires the elimination of key inflammatory cells and the downregulation of pro-inflammatory mediators in the inflamed sites. This coordinated process is actively regulated by biochemical mediators which possess anti-inflammatory and/or pro-resolving effects. Resolvins, endogenous lipid mediators generated from omega-3 fatty acids, have emerged as a novel class of potent molecules that counteract excessive inflammatory responses and stimulate pro-resolving mechanisms; regulating the trafficking of leukocytes and stimulating non-phlogistic phagocytosis of apoptotic neutrophils by macrophages.The disruption of these anti-inflammatory and pro-resolving mechanisms can not only cause the initiation of unnecessary inflammation, but also lead to the persistence of inflammation which contributes to the pathogenesis and progression of chronic inflammatory diseases. Since inflammation can have the beneficial effect on host defense, the timely resolution of inflammation is better to avoid chronic inflammatory situation, rather than merely blocking inflammation at the beginning. In this regards, understanding of the mechanism underlying resolution of inflammation provides a novel therapeutic approach to prevent and treat chronic inflammatory disorders. This review will address therapeutic potential of resolvins for the successful management of inflammatory ailments.

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    • "Treatment of inflammation requires removal of key inflammatory cells and down regulation of proinflammatory mediators in the inflamed sites. This twoway control process is actively regulated by biochemical mediators possessing anti-inflammatory effect (Lee and Surh, 2012). Some chronic inflammatory diseases remain one of the world's major health problems. "
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    ABSTRACT: Investigations for anti-inflammatory potential and categorization of Sudanese medicinal plants according to their potency. Anti-inflammatory effect of plants' extracts of 17 genera were studied using the carrageenan induced inflammation in rats' paws. The plant extracts were obtained using methanol and dichloromethane as solvent and administered intra peritoneally at the concentration of 2g/kg body weight. The results obtained in this experiment strongly support and validate the traditional uses of these Sudanese medicinal plants to treat various inflammatory diseases. 63.9% of plants extracts showed marked inhibition of inflammation induced by carrageenan (78.3% out of this percentage represented by methanolic extract), 27.8% showed no activity and 8.3% enhanced the carrageenan induced inflammation. The anti-inflammatory effect of many of these plants has not been reported previously, yet they have been extensively used in Sudanese folkloric medicine. The result of this study justify the traditional medicinal use of the evaluated plants species in treating inflammatory disorders and helped in categorizing the investigated plants into most useful, moderately useful and least useful category for inflammatory diseases. Out of the 17 investigated plant species 05 belongs to most useful and 06 belongs to moderately useful category. However, toxicity studies are required to prove the safety of these plant materials.
    Pakistan journal of pharmaceutical sciences 01/2015; · 0.68 Impact Factor
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    • "Production of these metabolites peaks at 24 hours after an inflammatory stimulus and likely serves as a secondary means of resolving inflammation when other mechanisms fail to adequately do so [32]. Furthermore, the rHypoE-7 cell line exhibits undetectable levels of lipoxygenase 5 (LOX5), an enzyme involved in the formation of resolvins as shown by qRT-PCR (data not shown) [33]. Although the rHypoE-7 cell model does express PPARγ (data not shown) and thus has the ability to mediate PPARγ-dependent reduction in of inflammation by oxidative DHA products, this situation is unlikely to come into play during our short experimental protocol as DHA oxidative products peak at 10 hours after the inflammatory response [34]. "
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    ABSTRACT: Overnutrition and the ensuing hypothalamic inflammation is a major perpetuating factor in the development of metabolic diseases, such as obesity and diabetes. Inflamed neurons of the CNS fail to properly regulate energy homeostasis leading to pathogenic changes in glucose handling, feeding, and body weight. Hypothalamic neurons are particularly sensitive to pro-inflammatory signals derived locally and peripherally, and it is these neurons that become inflamed first upon high fat feeding. Given the prevalence of metabolic disease, efforts are underway to identify therapeutic targets for this inflammatory state. At least in the periphery, omega-3 fatty acids and their receptor, G-protein coupled receptor 120 (GPR120), have emerged as putative targets. The role for GPR120 in the hypothalamus or CNS in general is poorly understood. Here we introduce a novel, immortalized cell model derived from the rat hypothalamus, rHypoE-7, to study GPR120 activation at the level of the individual neuron. Gene expression levels of pro-inflammatory cytokines were studied by quantitative reverse transcriptase-PCR (qRT-PCR) upon exposure to tumor necrosis factor alpha (TNFalpha) treatment in the presence or absence of the polyunsaturated omega-3 fatty acid docosahexaenoic acid (DHA). Signal transduction pathway involvement was also studied using phospho-specific antibodies to key proteins by western blot analysis. Importantly, rHypoE-7 cells exhibit a transcriptional and translational inflammatory response upon exposure to TNFalpha and express abundant levels of GPR120, which is functionally responsive to DHA. DHA pretreatment prevents the inflammatory state and this effect was inhibited by the reduction of endogenous GPR120 levels. GPR120 activates both AKT (protein kinase b) and ERK (extracellular signal-regulated kinase); however, the anti-inflammatory action of this omega-3 fatty acid (FA) receptor is AKT- and ERK-independent and likely involves the GPR120-transforming growth factor-beta-activated kinase 1 binding protein (TAB1) interaction as identified in the periphery. Taken together, GPR120 is functionally active in the hypothalamic neuronal line, rHypoE-7, wherein it mediates the anti-inflammatory actions of DHA to reduce the inflammatory response to TNFalpha.
    Journal of Neuroinflammation 03/2014; 11(1):60. DOI:10.1186/1742-2094-11-60 · 5.41 Impact Factor
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    • "pro-inflammatory mediators in the inflamed sites. This coordinated process is actively regulated by biochemical mediators which possess anti-inflammatory and/or pro-resolving effects [1] . Chronic inflammatory diseases remain one of the world's major health problems. "
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    ABSTRACT: Objective: To develop HPTLC fingerprint profile of anti-inflammatory active extract fractions of Tribulus terrestris (family Zygophyllaceae). Methods: The anti-inflammatory activity was tested for the methanol and its fractions (chloroform, ethyl acetate, n-butanol and aqueous) and chloroform extract of Tribulus terrestris (aerial parts) by injecting different groups of rats (6 each) with carrageenan in hind paw and measuring the edema volume before and 1, 2 and 3 h after carrageenan injection. Control group received saline i.p. The extracts treatment was injected i.p. in doses of 200 mg/kg 1 h before carrageenan administration. Indomethacin (30 mg/kg) was used as standard. HPTLC studies were carried out using CAMAG HPTLC system equipped with Linomat IV applicator, TLC scanner 3, Reprostar 3, CAMAG ADC 2 and WIN CATS-4 software for the active fractions of chloroform fraction of methanol extract. Results: The methanol extract showed good antiedematous effect with percentage of inhibition more than 72%, indicating its ability to inhibit the inflammatory mediators. The methanol extract was re-dissolved in 100 mL of distilled water and fractionated with chloroform, ethyl acetate and n-butanol. The four fractions (chloroform, ethyl acetate, n-butanol and aqueous) were subjected to anti-inflammatory activity. Chloroform fraction showed good anti-inflammatory activity at dose of 200 mg/kg. Chloroform fraction was then subjected to normal phase silica gel column chromatography and eluted with petroleum ether-chloroform, chloroform-ethyl acetate mixtures of increasing polarity which produced 15 fractions (F1-F15). Only fractions F1, F2, F4, F5, F7, F9, F11 and F14 were found to be active, hence these were analyzed with HPTLC to develop their finger print profile. These fractions showed different spots with different Rf values. Conclusions: The different chloroform fractions F1, F2, F4, F5, F7, F9, F11 and F14 revealed 4, 7, 7, 8, 9, 7, 7 and 6 major spots, respectively. The results obtained in this experiment strongly support and validate the traditional uses of this Sudanese medicinal plant.
    Asian Pacific Journal of Tropical Biomedicine 03/2014; 4(3). DOI:10.1016/S2221-1691(14)60232-X
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