Siti Irma Rahmawati text Jawa Barat,Indonesia National Research and Innovation Agency (BRIN) 2024 Scientific Reports, 2024, ? 1

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13 : ill Cyclooxygenase (COX) and lipoxygenase (LOX) enzymes play a pivotal role in producing proinflammatory 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-? (~ 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 COX2/5-LOX enzymes and to be developed as a safer NSAIDs with fewer side effects. Siti Irma Rahmawati MITRAGYNA SPECIOSA CELLULAR OXIDATIVE STRESS DUAL INHIBITION COX-2/5-LOX ANTI-INFLAMMATORY ARTVET2512 ARTVET2512 SIT d 250310 20250310012932 INLIS000000000019339 Converted from MARCXML to MODS version 3.5 using MARC21slim2MODS3-5.xsl (Revision 1.106 2014/12/19)