Cornus controversa Leaf and Stem Extract Attenuates LPS-Induced Inflammatory Responses in RAW 264.7 Macrophages via NF-κB/MAPK Inhibition and AMPK Activation

Abstract

Inflammation is a fundamental immune response that protects the host against infection and tissue injury. However, it can also contribute to the pathogenesis of various chronic diseases. In this study, we investigated the anti-inflammatory effects of Cornus controversa leaf and stem (CC-LS) extract in RAW 264.7 macrophages as well as the underlying mechanisms. Our results showed that CC-LS attenuated lipopolysaccharide (LPS)-induced inflammatory responses in RAW 264.7 macrophages in a dose-dependent manner without cytotoxicity even at high concentrations. Specifically, CC-LS significantly suppressed nitric oxide production and downregulated the expression of inducible nitric oxide synthase and cyclooxygenase-2 in the LPS-stimulated cells. It also attenuated intracellular reactive oxygen species accumulation, inhibited NF-κB p65 phosphorylation, and downregulated the expression of pro-inflammatory cytokines, including tumor necrosis factor-α, interleukin-6, and interleukin-1β. Moreover, it inhibited the phosphorylation of mitogen-activated protein kinases, ERK, JNK, and p38, while promoting the activation of AMP-activated protein kinase (AMPK) and its downstream substrate, acetyl-CoA carboxylase. These findings indicate that CC-LS exerts potent anti-inflammatory effects in macrophages by targeting the NF-κB, MAPK, and AMPK signaling pathways, suggesting its potential as a natural source for developing anti-inflammatory therapeutic agents.