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Scripta Scientifica Pharmaceutica


Surh Young-Joon, Yum Hye-Won, Na Hye-Kyung


Docosahexaenoic acid (DHA), a representative ω-3 polyunsaturated fatty acid derived from fish oil, has been reported to possess a wide spectrum of health beneficial effects. We have previously reported that topical application of DHA prior to UVB irradiation attenuated the expression of cyclooxygenase-2 and NAD(P)H:oxidase-4 in hairless mouse skin. DHA pretreatment also attenuated UVB-induced DNA binding of nuclear factor-kappaB (NF-κB) through inhibition of phosphorylation of IκB kinase-α/β, phosphorylation and degradation of IκBα and phosphorylation and nuclear translocation of p65, a functionally active subunit of NF-κB. When topically applied to mouse skin or treating mouse epidermal cells with it, DHA induced the activation of Nrf2 that plays a pivotal role in cellular defence against oxidative stress and inflammatory damage. DHA also inhibited experimentally induced colitis in mice. Timely resolution of inflammation at the early stage is important in preventing further progression to chronic inflammation and related disorders including cancer. Resolution of inflammation is an active coordinated process regulated by distinct endogenous lipid mediators, such as resolvins and lipoxins that have anti-inflammatory and pro-resolving effects. Our recent studies have revealed that DHA enhances the efferocytic activity of macrophages, an essential event in the resolution of inflammation. Moreover, DHA induced M2 macrophage polarization through peroxisome proliferator-activated receptor γ activation. DHA undergoes oxidation to produce 17-hydroxy-DHA that is converted to an electrophilic 17-oxo metabolite. The 17-oxo-DHA induced activation of Nrf2 and upregulation of its target proteins, such as heme oxygenase-1 with anti-inflammatory activity. Further, transgenic mice harbouring fat-1 gene capable of generating spontaneously n-3 polyunsaturated fatty acids including DHA were found to be less susceptible to experimentally induced colitis and skin carcinogenesis.



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About The Authors

Surh Young-Joon

Yum Hye-Won

Na Hye-Kyung

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