Cyclooxygenase (COX), officially known as prostaglandin-endoperoxide synthase (PTGS), is an enzyme that is responsible for formation of important biological mediators called prostanoids, including prostaglandins, prostacyclin and thromboxane. Two cyclooxygenase isoforms have been identified and are referred to as COX-1 and COX-2. Under many circumstances the COX-1 enzyme is produced constitutively (i.e., gastric mucosa) whereas COX-2 is inducible (i.e., sites of inflammation). Common non-steroidal anti-inflammatory drugs (NSAIDs) inhibit both COX-1 and COX-2 isoforms. COX-2 is usually absent in most normal tissues, and is induced rapidly in response to pathological stimuli. There is abundant evidence to prove that COXs and 5-lipoxygenase (5-LOX) play a pivotal role in inflammation and organ dysfunction.

Psoralidin, a coumestan derivative, is a COX-2 and 5-LOX dual inhibitor with anti-cancer, anti-inflammatory and anti-bacterial properties.


In MDA-MB-231 cells, Psoralidin significantly downregulates NOTCH1 signaling, and this downregulation resulted in growth inhibition and induction of apoptosis in both ALDH and ALDH+ cells. In addition, Psoralidin facilitates inhibition of epithelial to mesenchymal transition (EMT) markers (β-catenin and vimentin) and upregulates E-cadherin expression.

Ionizing radiation (IR)-induced ROS activated COX-2 and 5-LOX pathway in human normal lung fibroblasts (HFL-1 and MRC-5 cells). However, Psoralidin inhibits the COX-2 through suppression of NF-kB activation at a step after Akt phosphorylation. Furthermore, Psoralidin blocks the 5-LOX activity by direct binding with the FLAP, and decreases fibroblast migration in IR-irradiated normal lung fibroblasts.
Also, Psoralidin blocks IR-induced LTB4 production and attenuates the IR-induced fibroblast migration. Moreover, in IR-induced pulmonary inflammation in mice, Psoralidin suppresses IR-induced expression of pro-inflammatory cytokines (TNF-α, TGF-β, IL-6 and IL-1 α/β) and ICAM-1.


In summary, Psoralidin is a COX-2 and 5-LOX dual inhibitor with anti-cancer, anti-inflammatory and anti-bacterial properties.

References:
[1] Hee Jung Yang, et al. Biochem Pharmacol. 2011 Sep 1;82(5):524-34.
[2] S Suman, et al. Br J Cancer. 2013 Nov 12;109(10):2587-96.