Des-O-Methyllasiodiplodin Isolated from Xanthostemon chrysanthus Ameliorates Inflammation by Regulating Autophagy.

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.