Anti-inflammatory and analgesic monoterpenoid indole alkaloids of Kopsia officinalis.

Ethnopharmacological Relevance: "Ya gai", an important part of Dai medical theory, is traditionally recognized as an antidote. Kopsia officinalis Tsiang et P. T. Li is a "Ya gai" related medicine and has been widely used by Dai people for the treatment of pain and inflammation. Previous literature on title species suggested that monoterpenoid indole alkaloids (MIAs) could be its main bioactive components. However, the specific bioactive ingredients for inflammation-related treatment are still unrevealed, which inspired us to conduct a phytochemical and pharmacological investigation related to its traditional use.

Aim Of The Study: To support the traditional use of K. officinalis by assessing the anti-inflammatory and analgesic effects of its purified MIAs.

Material And Methods: Compounds were isolated and purified from the barks and leaves of K. officinalis using diverse chromatographic methods. The structures were established by means of extensive spectroscopic analyses and quantum computational technique. The anti-inflammatory activities of the purified MIAs were evaluated in vitro based on the suppression of lipopolysaccharide-activated inflammatory mediators (COX-2, IL-1β, and TNF-α) in RAW 264.7 macrophage cells. Anti-inflammatory and analgesic activities in vivo were assessed with carrageenan-induced paw edema and acetic acid-stimulated writhing in mice models.

Results: 23 MIAs including four new compounds were obtained and structurally established. Most of isolates showed significant anti-inflammatory effects in vitro by inhibiting inflammatory mediators (COX-2, IL-1β, and TNF-α). Further pharmacological evaluation in vivo revealed that 12-hydroxy-19(R)-hydroxy-ibophyllidine (1) and 11,12-methylenedioxykopsinaline N-oxide (5) remarkably decreased the number of writhing, while kopsinic acid (8), (-)-kopsinilam (12), and normavacurine-21-one (20) significantly relieved paw edema, respectively, even better than the positive control aspirin.

Conclusions: The in vitro and in vivo findings supported the traditional use of K. officinalis with respect to its anti-inflammatory and analgesic effect, as well as provided potent bioactive MIAs for further chemical modification and pharmacological investigation.