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Dual anti-inflammatory activities of COX-2/5-LOX driven by kratom alkaloid extracts in lipopolysaccharide-induced RAW 264.7 cells. | LitMetric

AI Article Synopsis

  • Cyclooxygenase (COX) and lipoxygenase (LOX) enzymes are crucial in creating inflammatory compounds like prostaglandins and leukotrienes during inflammation.
  • The study found that a kratom alkaloid extract, rich in mitragynine, can inhibit both COX-2 and LOX enzymes without causing cell toxicity at low concentrations, while a methanolic extract had no inhibitory effect.
  • The kratom alkaloid extract also significantly reduced key inflammatory markers and showed strong binding affinity to COX-2 and LOX enzymes, suggesting it could serve as a safer alternative to traditional non-steroidal anti-inflammatory drugs (NSAIDs).

Article Abstract

Cyclooxygenase (COX) and lipoxygenase (LOX) enzymes play a pivotal role in producing pro-inflammatory eicosanoids, including prostaglandins (PGs) and leukotrienes (LTs), in the inflammation process. Mitragynine is a primary alkaloid contained in the kratom's leaves and has been reported to show anti-inflammatory activity by suppressing COX-2 mRNA translation to lowering PGs synthesis. In this study, the Kratom's alkaloid extract containing ~ 46% mitragynine was found to exhibit dual inhibition activity towards COX-2/5-LOX enzymes at concentrations below 25 ppm in the LPS-induced RAW 264.7 macrophage cells. At these levels, no cell toxicity was observed while the cells became death (e.g., 10-46% viability at 50-100 ppm) and only COX-2 inhibition activity was observed after exposed with more than 25 ppm of alkaloid extract. In contrast, the methanolic-crude extract of Kratom's leaf containing ~ 5% mitragynine showed no inhibition toward COX-2/5-LOX enzymes and did not toxic onto the cells, even after treated at 100 ppm. The alkaloid extract suppressed several antiinflammation parameters, including ROS (64% reduction at 25 ppm), NO (30% reduction at 25 ppm), TNF-α (~ 50% reduction at 25 ppm), and IL-6 production (60% reduction at 6.25 ppm). In silico molecular studies indicated strong binding affinity of Kratom alkaloids to COX-2 and 5-LOX active sites, supporting the Kratom's alkaloids to have great potential dual inhibition activity towards COX-2/5-LOX enzymes and to be developed as a safer NSAIDs with fewer side effects.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11584675PMC
http://dx.doi.org/10.1038/s41598-024-79229-xDOI Listing

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