Chemical Constituents from the Fruit of Melia azedarach and Their Anti-Inflammatory Activity

Phytochemical investigations of <i>Melia azedarach</i> fruits have led to the isolation of a novel tirucallane triterpenoid (<b>1</b>), four new limonoids (<b>2</b>-<b>5</b>), and four known limonoids (<b>6</b>-<b>9</b>). Their structures were clarified by comprehensive spectroscopic and spectrometric analyses. The anti-inflammatory activities of isolated compounds were assessed in vitro. Compound <b>2</b> exhibited the most potent anti-inflammatory effect, with an IC₅₀ value of 22.04 μM. Additionally, compound <b>2</b> attenuated LPS-induced reactive oxygen species (ROS) production and reduced the levels of inflammatory mediators IL-6 and TNF-<i>α</i>. A mechanistic study revealed that limonoid <b>2</b> 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.