Anti-inflammatory metabolites from the leaves of Ohwia caudata

Abstract

Ohwia caudata, a significant traditional Chinese medicine, exhibits anti-inflammatory properties and is clinically used to treat dysentery, gastroenteritis, and other inflammatory conditions. However, the bioactive constituents responsible for its anti-inflammatory activity remain poorly understood. In the study, a phytochemical investigation of O. caudata leaves led to the isolation and structural elucidation of twenty-one previously undescribed compounds, including ohcanosides A–T (1–20) and (1R)-1,2,3,4-tetrahydro-7,8-dihydroxy-1-isoquinolinecarboxylic acid (21), along with three known isolates (22–24). All the known compounds were reported from the Ohwia genus for the first time. To assess the anti-inflammatory potential of these isolates, a LPS-stimulated RAW264.7 macrophage model was employed. The results demonstrated that compounds 3, 7–10, 14, 15, 17, 19, 20, and 22–24 significantly inhibited nitric oxide (NO) production in a concentration-dependent manner (3, 10, and 30 μM). Molecular docking studies further revealed strong binding affinities between compounds 9, 10, 14, and 17 and phosphatidylinositol 3-kinase (PI3K), with binding energy values below −5 kcal/mol, suggesting stable receptor-ligand interactions. Additionally, Western blot analysis confirmed that these compounds exert their anti-inflammatory effects by downregulating key proteins (PI3K, Akt, and p-Akt) in the PI3K/Akt signaling pathway. These findings provide valuable insights into the anti-inflammatory mechanisms of O. caudata and highlight its potential as a source of novel anti-inflammatory agents.