Article

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

ABSTRACT

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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    • "The anti-inflammatory activities of RvD1 and E1 have been reported both in vitro and in vivo mostly on peripheral cells. Their pro-resolving effects are widely described in macrophages in rodent models of inflammation (for reviews:Claria et al., 2011;Fredman and Serhan, 2011;Lee and Surh, 2012;Recchiuti, 2013;Seki et al., 2009;Serhan, 2014). In vitro studies report that RvD1 and RvE1 inhibit neutrophil transmigration and infiltration to the inflamed site (Arita et al., 2005;Wang et al., 2011). "

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    • "Given the promising results with RvE1 in animal models, RX-10045, a synthetic analog of RvE1, was tested in Phase II clinical trials for dry eye (NCT00799552). In the multicenter, double-blind, randomized, placebo-controlled 28-day trial involving 232 patients, RX-10045 treatment led to significant improvements in symptoms such as stinging, grittiness, and ocular discomfort compared with placebo[65]. However, corneal fluorescein staining results, the primary outcome measure, have not been published and Phase III trials have not officially commenced. "
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    ABSTRACT: Ocular surface diseases such as dry eye, allergic keratoconjunctivitis, and infection are very prevalent conditions and involve ocular surface stress and inflammation. Recently, various lipid-based therapies have been advocated for the modulation of ocular surface inflammation. Here we review the latest developments and challenges of these strategies. These include administration of essential fatty acids, cyclooxygenase (COX) inhibitors and resolvin analogs. Lipids form part of the tear film and are crucial for tear film stability; loss of tear film stability can aggravate ocular surface inflammation. Strategies to replenish tear film lipids - namely, eyelid warming and eye drops containing natural or synthetic lipids - are evaluated. Recent advances in the use of lipids as ocular drug delivery vehicles, antioxidants, and diagnostic markers are discussed.
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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.
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