| Summary: | Natural products have served as primary remedies since ancient times due to their cultural acceptance and outstanding biodiversity. To investigate whether <i>Tamarix aphylla</i> L. modulates an inflammatory process, we carried out bioassay-guided isolation where the extracts and isolated compounds were tested for their modulatory effects on several inflammatory indicators, such as nitric oxide (NO), reactive oxygen species (ROS), proinflammatory cytokine; tumour necrosis factor (TNF-<i>α</i>), as well as the proliferation of the lymphocyte T-cells. The aqueous ethanolic extract of the plant inhibited the intracellular ROS production, NO generation, and T-cell proliferation. The aqueous ethanolic crude extract was partitioned by liquid-liquid fractionation using <i>n</i>-hexane (<i>n</i>-C<sub>6</sub>H<sub>6</sub>), dichloromethane (DCM), ethyl acetate (EtOAc), <i>n</i>-butanol (<i>n</i>-BuOH), and water (H<sub>2</sub>O). The DCM and <i>n</i>-BuOH extracts showed the highest activity against most inflammatory indicators and were further purified to obtain compounds <b>1</b>–<b>4</b>. The structures of 3,5-dihydroxy-4’,7-dimethoxyflavone (<b>1</b>) and 3,5-dihydroxy-4-methoxybenzoic acid methyl ester (<b>2</b>) from the DCM extracts; and kaempferol (<b>3</b>), and 3-hydroxy-4-methoxy-(<i>E</i>)-cinnamic acid (<b>4</b>) from the <i>n</i>-BuOH extract were elucidated by different spectroscopic tools, including MS, NMR, UV, and IR. Compound <b>2</b> inhibited the production of ROS and TNF-<i>α</i>, whereas compound <b>3</b> showed inhibitory activity against all the tested mediators. A better understanding of the potential aspect of <i>Tamarix aphylla</i> L. derivatives as anti-inflammatory agents could open the door for the development of advanced anti-inflammatory entities.
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