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Five new clerodane diterpenoids from Callicarpa integerrima and their anti-inflammatory activity
Muhammad Aurang Zeb1, Jian-Lin Lai1, Xing-Jie Zhang1
1Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, Yunnan Characteristic Plant Extraction Laboratory Co., Ltd., Yunnan Key Laboratory of Research and Development for Natural Products, School of Chemical Science and Technology, School of Pharmacy, and School of Life Sciences, Yunnan University, Kunming 650500, PR China.
None:
Five previously undescribed clerodane diterpenoids named calintegerinoids A-E (1-5), featuring 5/6 and 6/6 fused ring systems, were isolated from Callicarpa integerrima. Their structures were determined using modern spectroscopic techniques, including NMR, HR-ESI-MS, IR, UV, specific rotations, and ECD, supplemented by quantum chemical calculations and DP4+ analysis. Compared with the standard drug Andrographolide (IC50 8.01 ± 0.46 μM), compound 3 demonstrated potent inhibition of LDH release with an IC50 value of 1.27 ± 0.05 μM. It also dose-dependently suppressed IL-1β release and potently blocked NLRP3 inflammasome activation triggered by LPS and Nigericin, leading to decreased pyroptosis. In addition, compound 3 decreased ASC speck formation in a dose-dependent manner, suggesting its significant anti-inflammatory potential by inhibiting NLRP3 inflammasome assembly.
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