Discovery of Terpenoidal Trimers Gercadietanes A–G from <i>Commiphora</i> Resins Showing Potential Antidepressant Properties In Vivo

Novel sesqui-sesqui-diterpene trimers, gercadietanes A-G (<b>1</b>-<b>7</b>), were isolated from the resins of <i>Commiphora</i> and structurally characterized. These compounds feature a unique [4 + 2] Diels-Alder cycloaddition between the furan ring of a germacrene unit and the exocyclic double bond of cadinane-type sesquiterpenoids, followed by esterification with dehydroabietic acid or its derivatives on the cadinane skeleton. Inspired by chemical defense of plant resins, biological evaluation revealed that <b>1</b> demonstrated potent anti-inflammatory effects and significantly modulated cytokine profiles by reducing pro-inflammatory cytokines and elevating anti-inflammatory cytokines in vitro. In vivo, <b>1</b> mitigated LPS-induced depression-like behaviors in mice, suggesting its potential as a therapeutic agent for inflammation-associated depression.