| Summary: | Our study investigates 16 medicinal plants via assessment of inhibition of proinflammatory enzymes such as cyclooxygenases (COX). The plants are used by traditional healers in the Greater Mpigi region in Uganda to treat inflammation and related disorders. We present results of diverse in vitro experiments performed with 76 different plant extracts, namely, (1) selective COX-2 and COX-1 inhibitor screening; (2) 15-LOX inhibition screening; (3) antibacterial resazurin assay against multidrug-resistant <i>Staphylococcus aureus</i>, <i>Listeria innocua</i>, <i>Listeria monocytogenes</i>, and <i>Escherichia coli</i> K12; (4) DPPH assay for antioxidant activity; and (5) determination of the total phenolic content (TPC). Results showed a high correlation between traditional use and pharmacological activity, e.g., extracts of 15 out of the 16 plant species displayed significant selective COX-2 inhibition activity in the PGH<sub>2</sub> pathway. The most active COX-2 inhibitors (IC<sub>50</sub> < 20 µg/mL) were nine extracts from <i>Leucas calostachys</i>, <i>Solanum aculeastrum, Sesamum calycinum</i> subsp. <i>angustifolium</i>, <i>Plectranthus hadiensis</i>, <i>Morella kandtiana</i>, <i>Zanthoxylum chalybeum</i>, and <i>Warburgia ugandensis</i>. There was no counteractivity between COX-2 and 15-LOX inhibition in these nine extracts. The ethyl acetate extract of <i>Leucas calostachys</i> showed the lowest IC<sub>50</sub> value with 0.66 µg/mL (COX-2), as well as the most promising selectivity ratio with 0.1 (COX-2/COX-1). The TPCs and the EC<sub>50</sub> values for DPPH radical scavenging activity showed no correlation with COX-2 inhibitory activity. This led to the assumption that the mechanisms of action are most likely not based on scavenging of reactive oxygen species and antioxidant activities. The diethyl ether extract of <i>Harungana madagascariensis</i> stem bark displayed the highest growth inhibition activity against <i>S. aureus</i> (MIC value: 13 µg/mL), <i>L. innocua</i> (MIC value: 40 µg/mL), and <i>L. monocytogenes</i> (MIC value: 150 µg/mL). This study provides further evidence for the therapeutic use of the previously identified plants used medicinally in the Greater Mpigi region.
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