Resveratrol activates AMPK and suppresses LPS-induced NF-κB-dependent COX-2 activation in RAW 264.7 macrophage cells

Abstract

AMP-activated protein kinase (AMPK), an enzyme involved in energy homeostasis, regulates inflammatory responses, but its precise mechanisms are not fully understood. Recent evidence has shown that resveratrol (RES), an AMPK activator, reduces prostaglandin E2 production in lipopolysaccharide (LPS)-treated microglia. Here, we examined the effect of RES on nuclear factor kappa B (NF-κB) dependent cyclooxygenase (COX)-2 activation in LPS-treated RWA 264.7 macrophages. We found that treatment with RES increased AMPK activation. AMPK and acetyl CoA carboxylase phosphorylation were attenuated in cells treated with LPS+RES, compared to cells treated with LPS alone. RES inhibited tumor necrosis factor (TNF)-α and TNF receptor 1 in LPS-treated cells. Finally, RES inhibited LPS-induced NF-κB translocation into the nucleus and COX-2 expression. Moreover, the effects of 5-aminoimidazole-4-carboxamide ribose and compound C were consistent with the effects of RES in LPS-treated cells. Taken together, these results suggest that the anti-inflammatory action of RES in RAW 264.7 macrophages is dependent on AMPK activation and is associated with inhibition of the LPS-stimulated NF-κB-dependent COX-2 signaling pathway.

Involvement of AMPK, IKβα-NFκB and eNOS in the sildenafil anti-inflammatory mechanism in a demyelination model

“…Also, Steinberg et al (2006) observed that TNF-α suppresses AMPK activity by up-regulating the expression of protein phosphatase 2C, an inhibitor of AMPK signaling, thus contributing to the inflammatory process. In addition to its central mediatory function in cytokine expression, NFkB in myeloid cells may be induced by physical as well as oxidative stress of cells, or in other words via the iNOS (Carling et al, 2012;Zhang et al, 2008) or cyclooxygenase-2 (COX-2) (Yi et al, 2011). The present study found that sildenafil reduces IL-1β, TNF-α and iNOS expression.…”

YAP Inhibition by Resveratrol via Activation of AMPK Enhances the Sensitivity of Pancreatic Cancer Cells to Gemcitabine

“…Previous studies have established that resveratrol can activate the AMPK pathway [31]. The activation of AMPK leads to the suppression of YAP expression [32].…”

Resveratrol significantly inhibits the occurrence and development of cervical cancer by regulating phospholipid scramblase 1

“…In recent years, studies have found that resveratrol has a strong role in cancer prevention and treatment, and its regulatory effect can occur in various processes of tumor cell growth, division, and apoptosis . Resveratrol can play a significant role in inhibiting the progression of various cancers, including skin cancer, breast cancer, lung cancer, pancreatic cancer, and gastric cancer . In addition, the anticancer effect of resveratrol has been extensively studied at the molecular and cellular levels, such as cell signaling pathway, enzyme pathway, and p53 interface, leading to apoptosis …”