Phytochemical investigations of Melia azedarach fruits have led to the isolation of a novel tirucallane triterpenoid (1), four new limonoids (2–5), and four known limonoids (6–9). Their structures were clarified by comprehensive spectroscopic and spectrometric analyses. The anti-inflammatory activities of isolated compounds were assessed in vitro. Compound 2 exhibited the most potent anti-inflammatory effect, with an IC50 value of 22.04 μM. Additionally, compound 2 attenuated LPS-induced reactive oxygen species (ROS) production and reduced the levels of inflammatory mediators IL-6 and TNF-α. A mechanistic study revealed that limonoid 2 suppresses the expression of iNOS and JAK2 and is implicated in the modulation of the NF-κB signaling cascade, which reveals its anti-inflammatory actions.
