Cornus controversa Leaf and Stem Extract Attenuates LPS-Induced Inflammatory Responses in RAW 264.7 Macrophages via NF-κB/MAPK Inhibition and AMPK Activation
Year: 2025
Type: article
Abstract: IntroductionInflammation is an essential innate immune response triggered by various harmful stimuli, including pathogens, toxins, and tissue injury [1,2].Although it plays a crucial role in host defense and in maintaining homeostasis, excessive or prolonged inflammatory responses are strongly associated with the pathogenesis of various acute and chronic diseases, including arthritis, atherosclerosis, cardiovascular disease, and cancer [2-5].Thus, regulation of aberrant inflammatory signaling has been recognized as a key strategy for preventing and treating inflammatory disorders.Macrophages, which are key effector cells in inflammation and immunity, release a wide array of pro-inflammatory mediators (e.g., nitric oxide (NO) and prostaglandin E2 (PGE2)), enzymes (e.g., inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2)), and cytokines (e.g., tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6)) [6][7][8].Further, lipopolysaccharide (LPS), a component of the outer membrane of gram-negative bacteria that has been sufficiently characterized, activates macrophages via Toll-like receptor 4 (TLR4) [9].Specifically, LPS stimulation activates intracellular signaling cascades, including nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs), which in turn drive the transcription of proinflammatory genes as well as the release of inflammatory mediators [10,11].Therefore, LPS-stimulated RAW 264.7 macrophages have been extensively used as an established in vitro model for identifying potential antiinflammatory agents and elucidating their underlying mechanisms.On the one hand, among the signaling pathways that govern macrophage responses to inflammation, NF-κB 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.
Institution: Pusan National University
Language: English
Subfield: Complementary and alternative medicine
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Awards: G6846069856, G6857672969
OpenAlex ID: W4416765799