Protective effects of Moringa oleifera L. Leaves extract against ethylene glycol–induced lung injury: An integrated In Vivo and In Silico study

Abstract

Ethylene glycol (EG) intoxication induces multi-organ toxicity characterized by oxidative stress, inflammation, and pulmonary injury secondary to metabolic acidosis and renal damage. This study aimed to evaluate the protective effect of Moringa oleifera L. leaves extract against EG-induced lung damage using integrated in vivo and in silico approaches. Twenty-five male Wistar rats were randomly divided into five groups: negative control, EG control (265 mg/kg BW/day), and three treatment groups receiving EG followed by M. oleifera extract at doses of 200, 316, and 500 mg/kg BW for 21 days. Lung tissues were examined histopathologically using hematoxylin and eosin staining to assess alveolar congestion and interalveolar septal thickening. Molecular docking analysis was performed to evaluate interactions between major phytoconstituents and apoptosis- and inflammation-related targets, namely Caspase-3 and Tumor Necrosis Factor Receptor 1 (TNFR1). EG exposure significantly increased congestion and septal thickening compared to the negative control (p < 0.05). Administration of M. oleifera extract produced dose-dependent improvement. The 500 mg/kg BW dose showed the greatest protective effect, reducing alveolar congestion by 48% and septal thickening by 78.3%, with no significant difference compared to the negative control (p > 0.05). Phytochemical screening identified quercetin, kaempferol, β-carotene, tocopherol, and ascorbic acid as potential bioactive compounds. Docking results demonstrated strong binding affinities of β-carotene (−8.1 kcal/mol) toward Caspase-3 and flavonoids toward TNFR1 (−6.4 to −6.5 kcal/mol), suggesting inhibition of apoptotic and inflammatory pathways. In conclusion, M. oleifera L. leaves extract, particularly at 500 mg/kg BW, exhibits significant protective effects against EG-induced pulmonary injury. The integrated in vivo and in silico findings support its potential as a natural therapeutic candidate targeting oxidative stress–mediated lung damage.