Antiinflammatory Steroidal Alkaloids from Sarcococca wallichii of Nepalese Origin

Bio-assay guided isolation from the plant Sarcococca wallichii Staph. yielded two new steroidal alkaloids: wallichimine A (1) and wallichimine B (2), and five known ones: sarcodinine (3), N-methylpachysamine A (4), alkaloid C (5), dictyophlebine (6), and sarcorine (7). The structures of the compounds were determined using mass spectrometry and NMR spectroscopy techniques. The immunomodulatory potential of compounds was evaluated on different parameters including production of intracellular reactive oxygen species (ROS), nitric oxide (NO) and on proinflammatory cytokine TNF-α. All compounds were found to be potent inhibitors of intracellular ROS produced from isolated neutrophils, except compound 5, which showed a moderate level of inhibition. Compounds 2 and 4 potently inhibited the production of NO (67.9% and 62.5% respectively). Compound 2 showed potent suppression on production of proinflammatory cytokine TNF-α (76.7%). Among all the tested compounds the new compound 2 was found to be the most potent immunosuppressive agent. This study shows that steroidal alkaloids could be lead compounds for anti-inflammatory drug discovery.