| Summary: | <i>Tamarix aphylla</i> is a commonly grown plant in Saudi Arabia and its therapeutic potential is widely recognized. Here, in this study, the aim was to explore the role of <i>T. aphylla</i> leaf extract (TAE) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice and LPS-stimulated RAW 264.7 cells. The antioxidant and anti-inflammatory parameters of TAE were performed through in vitro assays by measuring H<sub>2</sub>O<sub>2</sub> free radical scavenging and protein denaturation inhibition. After LPS administration, broncho alveolar lavage fluid (BALF) and lung tissue were obtained to evaluate the pro-inflammatory cytokine levels, histopathological alterations, immunohistochemistry and TUNEL staining. The results designate that TAE shows anti-inflammatory activity through a decrease in pro-inflammatory cytokines, TNF-α and IL-6 in LPS-stimulated RAW 264.7 cells and BALF. The antioxidant enzyme level (SOD) decreased and MDA content was increased in the LPS-induced mice. However, TAE pretreatment markedly reversed these parameters compared to the group administered LPS only (<i>p</i> < 0.05). The histopathological analysis demonstrated that TAE maintained the lung tissue architecture by reducing LPS-induced inflammation and congestion. The expression pattern of the Cox-2 protein and apoptosis was high in the group administered LPS only, whereas TAE pretreatment showed a reduction in the expression pattern and apoptosis. Moreover, the in vitro assay of TAE demonstrated a concentration-dependent free radical scavenging and anti-inflammatory activity. In conclusion, our results advocate the health-promoting effects of <i>T. aphylla</i> on LPS-induced acute lung injury, which might be due to its antioxidative and anti-inflammatory potential.
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