HYDROXYLATED DOCOSAHEXAENOIC ACID.

HDHA, like its precursor Docosahexaenoic Acid (DHA), actively participates in the skin's immune response by moderating inflammatory cascades. Its mechanisms include attenuating delayed-type hypersensitivity responses by reducing T-lymphocyte proliferation and the expression of intercellular adhesion molecules. It specifically suppresses the proinflammatory enzyme cyclooxygenase (COX)-2 and inhibits the activation of toll-like receptors (TLR2 and TLR4). This action helps to reduce the production of proinflammatory eicosanoids while simultaneously increasing the synthesis of inflammation-resolving lipid mediators. HDHA also competes with omega-6 polyunsaturated fatty acid derivatives, such as arachidonic acid, to diminish inflammation and allergic responses in cutaneous tissue. Furthermore, HDHA acts as a ligand for peroxisome proliferator-activated receptors (PPARs), which are transcription factors vital for regulating inflammation, immune responses, and metabolic processes. Topical application of DHA has also demonstrated an ability to accelerate skin wound healing, potentially through activating the GPR120 receptor, which possesses anti-inflammatory activity, thereby reducing interleukin (IL) 1β expression and increasing IL-6 and transforming growth factor β (TGF-β). It also improves epidermal keratinocyte differentiation and mitigates inflammation, possibly by functioning as a dual PPARα/γ agonist. It is noted that 2-hydroxy-docosahexaenoic acid (DHA-H) has a distinct metabolic pathway, undergoing α-oxidation to generate heneicosapentaenoic acid (HPA) rather than sharing metabolic routes with natural DHA.