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Discovery of Terpenoidal Trimers Gercadietanes A-G from Commiphora Resins Showing Potential Antidepressant Properties
Wei-Fen Li1, Madhu Babu Sura1, Si-Si Zhu1
1Guangdong Provincial Key Laboratory of Chinese Medicine Ingredients and Gut Microbiomics, Marshall Laboratory of Biomedical Engineering, Institute for Inheritance-Based Innovation of Chinese Medicine, School of Pharmacy, Shenzhen University Medical School, Shenzhen University, Shenzhen 518060, China.
Abstract:
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.
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