Chromolaena odorata (C. odorata) (L.) R. King & H. Robinson is a perennial flowering shrub with diverse habitats, including crops, grasslands, and roadsides. This plant has been widely used in Vietnamese folk medicine for gastric ulcer treatment. Hence, the present study aimed to evaluate the acute toxicity and the anti-ulcer effect of the ethanol crude extract of C. odorata leaves and its fractions against the indomethacin-induced gastric ulcer model in mice, and investigate the chemical constituents of the most active fraction. According to in vivo results, the ethyl acetate residue with the highest anti-ulcer activity significantly reduced gastric lesions in theexperimental mice model with an ulcer index of 0.73 ± 0.39 and a percentage inhibition of 26.92%. Thus, this fraction was chosen for further chemical investigation. Four pure compounds (1-4) were extracted and isolated by using chromatographic methods. Based on the nuclear magnetic resonance spectroscopy, melting temperature, mass spectrometry analysis, and compared with thepublished literature, their structures were elucidated as 1-(4-hydroxy-3-methoxyphenyl)propane- 1,2-diol (1), kaempferol-7-O-α-L-rhamnopyranoside (2), naringenin-5,7-di-O-β-Dglucopyranoside (3), and rubrosterone (4). To our best knowledge, all of these compounds were isolated for the first time from C. odorata leaves. These findings contribute to providing scientific evidence for the traditional use and phytochemicals of C. odorata leaves. 
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