| Summary: | Wheat (<i>Triticum aestivum</i> Linn.; Poaceae) is a very common and important food grain and ranks second in total cereal crop production. A large amount of wheat hull is produced after threshing that, as the non-food part of wheat, is agro-waste, accounting for 15~20% of the wheat. This study aimed at biologically and phytochemically investigating wheat hull for its valorization as a by-product. In our ongoing search for natural product-derived anti-inflammatory agents, <i>T. aestivum</i> hull was evaluated for its nitric oxide (NO) production inhibition in lipopolysaccharide (LPS)-activated RAW 264.7 cells, and the phytochemical investigation of the ethyl acetate fraction showing inhibitory effect led to the isolation of a flavone (<b>1</b>) and seven flavonolignans (<b>2</b>–<b>8</b>). Compounds <b>2</b>–<b>8</b> have not yet been isolated from <i>Triticum</i> species. All compounds were evaluated for their LPS-induced NO production inhibition, and <b>1</b>, <b>2</b>, <b>4</b>, <b>6</b>, and <b>8</b> exhibited inhibitory effects with IC<sub>50</sub> values ranging from 24.14 to 58.95 μM. These results suggest the potential of using <i>T. aestivum</i> hull as a source for producing anti-inflammatory components, enhancing its valorization as a by-product.
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