Emerging evidence indicates the inhibition of neuroinflammation is an important and promising strategy for managing Alzheimer's disease. Anti-neuroinflammatory agents are potential drug leads. In this work, seventeen diterpenoids (1-17) including ten previously undescribed ones, named excoaglolides A-J (1-10) were isolated from the stems and twigs of the mangrove plant, Excoecaria agallocha L. The undescribed diterpenoids could be categorized into four subclasses, viz., ent-isopimaranes (1-4), ent-beyeranes (5-7), ent-atisanes (8-9), and ent-labdane (10). Their structures including absolute configurations were unambiguously characterized by spectroscopic methods, single crystal X-ray diffraction analyses, ECD calculations, and modified Mosher's method. Notably, compound 1 was a rare 3,4-seco-3,11-lactone-ent-isopimarane, whereas compound 2 was the first 2,3-seco-2,11-lactone-ent-isopimarane
compound 5 represents the first example of 2,3-seco-2-nor-1,3-lactone-ent-beyerane, compound 8 was the first member of 18(4→3)-abeo-ent-atisane forming through a Wagner-Meerwein rearrangement, compound 9 was an unusual rearranged 3,4-seco-ent-atisane possessing a cyclobutane ring, and compound 10 featuring a rare chlorine substitution at C-15. In addition, the stereochemistry of the known diterpenoid excoagallochaol D (11) with a unique 6/7/4-fused ring system was firstly determined by single crystal X-ray diffraction analyses in this study. Compounds 1, 12, 15, and 16 showed significant nitric oxide production inhibition in lipopolysaccharide-induced BV-2 microglial cells with IC