Des-O-MethyllasiodiplodinIsolated from <i>Xanthostemon chrysanthus</i> Ameliorates Inflammationby Regulating Autophagy

Abstract Xanthostemon chrysanthus (F.Muell.) Benth. is a species from the Myrtaceae family with limited phytochemical and pharmacological studies. In this study, ten compounds (1–10) were isolated and purified from X. chrysanthus, among which compound 2, identified as des-O-methyllasiodiplodin (DML), exhibited the most potent anti-inflammatory activity. This is the first report of DML being isolated from this species. DML significantly inhibited lipopolysaccharide (LPS)-induced inflammation in RAW264.7 macrophages by reducing the expression of TNF-α, IL-1β, and IL-6, as well as nitric oxide (NO) and reactive oxygen species (ROS) production. Moreover, DML promoted autophagy by increasing LC3 II/LC3 I conversion and decreasing p62 expression, accompanied by suppression of the PI3K/AKT/mTOR signaling pathway. The autophagy inhibitor chloroquine (CQ) reversed these effects, confirming that DML exerts its anti-inflammatory action through autophagy activation. In a mouse ear edema model, DML effectively reduced inflammation, showing even greater efficacy than indomethacin. Collectively, this study provides the first evidence that DML isolated from X. chrysanthus exerts strong anti-inflammatory effects by promoting autophagy and modulation of the PI3K/AKT/mTOR pathway. These findings enrich the chemical and pharmacological understanding of X. chrysanthus and highlight DML as a promising natural candidate for the development of novel anti-inflammatory therapeutics.