The inhibition of 5-Lipoxygenase (5-LO) products leukotriene B4 (LTB 4 ) and cysteinyl leukotrienes (cysLTs) modulates the inflammatory response and improves cutaneous wound healing

Inhibition of Proinflammatory Enzymes and Attenuation of IL-6 in LPS-Challenged RAW 264.7 Macrophages Substantiates the Ethnomedicinal Use of the Herbal Drug Homalium bhamoense Cubitt & W.W.Sm

“…The enzyme catalyzes the initial steps in the conversion of arachidonic acid to leukotrienes [27]. The biosynthesis of lipidic mediators is also related to an increased production of ROS [27] and underlies the inflammatory response in wound healing, with the disruption of 5-LOX being found to improve cutaneous healing [10,28]. Furthermore, classical symptoms of inflammation such as pain, reddening and edema of the surrounding tissue during cutaneous wound healing are caused by the release of eicosanoids [29].…”

“…Wound healing is an utterly complex process involving an array of finely tuned steps, from initial injury to the final reconstituted tissue, with inflammatory mediators orchestrating a series of events throughout most of the process [9]. For example, the metabolic products of hyaluronidase and 5-lipoxygenase (5-LOX) function as microenvironmental cues, actively participating in the regulation of healing processes and inflammation [10,11]. Nitric oxide (NO) acts as a mediator of skin homeostasis and wound repair, influencing collagen deposition and the strength of incisional wounds [12].…”

Eicosanoids in tissue repair

“…Indeed, multiple studies have implicated the 5‐LOX‐LTB 4 ‐BLT1 axis in aberrant neutrophil recruitment and impaired tissue repair in experimental models of skin wound healing. In particular, 5‐LOX deficiency or pharmacological targeting of the 5‐LOX pathway resulted in accelerated cutaneous healing, likely by reducing the production of reactive oxygen species (ROS) as well as of proinflammatory cytokines and chemokines in wounded skin . Similarly, 5‐LOX‐deficient mice and mice treated with LT‐modifying drugs were protected against acute inflammatory lung injury in a model of bacterial sepsis .…”

“…In particular, 5-LOX deficiency or pharmacological targeting of the 5-LOX pathway resulted in accelerated cutaneous healing, likely by reducing the production of reactive oxygen species (ROS) as well as of proinflammatory cytokines and chemokines in wounded skin. 6,29 Similarly, 5-LOX-deficient mice and mice treated with LT-modifying drugs were protected against acute inflammatory lung injury in a model of bacterial sepsis. 17 However, these studies also suggested that in addition to the LTB 4 -BLT1 axis, cysteinyl LTs contributed to 5-LOX-driven inflammatory tissue damage and aberrant tissue repair.…”

“…prostaglandin E 2 ) can accelerate repair, whereas LTs produced via the 5lipoxygenase (5-LOX) pathway can impair tissue repair and instead cause aberrant inflammation and tissue ( Table 1). [4][5][6][7] In contrast to the detrimental role of proinflammatory 5-LOX metabolites, anti-inflammatory metabolites of 12/15-LOX (e.g. LXA 4 ) can reduce inflammation and promote tissue repair.…”