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

Novel sesqui-sesqui-diterpene trimers, gercadietanes A-G (1-7), were isolated from the resins of Commiphora 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 1 demonstrated potent anti-inflammatory effects and significantly modulated cytokine profiles by reducing pro-inflammatory cytokines and elevating anti-inflammatory cytokines in vitro. In vivo, 1 mitigated LPS-induced depression-like behaviors in mice, suggesting its potential as a therapeutic agent for inflammation-associated depression.