18β-Glycyrrhetinic acid mitigates radiation-induced skin damage via NADPH oxidase/ROS/p38MAPK and NF-κB pathways.

Radiation-induced inflammation plays an important role in radiation-induced tissue injury. 18β-glycyrrhetinic acid (18β-GA) has shown an anti-inflammatory activity. This study aimed to assess the activity of 18β-GA against radiation-induced skin damage, and explore the underlying mechanisms. In vitro assay revealed 18β-GA treatment decreased the production of IL-1β, IL-6, PGE2 and decreased p38MAPK phosphorylation, DNA-binding activity of AP-1, and NF-κB activation in irradiated RAW264.7 macrophages. Additionally, 18β-GA suppressed NF-κB activation by inhibiting NF-κB/p65 and IκB-α phosphorylation and alleviated ROS overproduction in irradiated RAW264.7 macrophages. In vivo assay showed 18β-GA alleviated severity of radiation-induced skin damage, reduced inflammatory cell infiltration and TNF-α, IL-1β and IL-6 levels in cutaneous tissues. Our findings demonstrate that 18β-GA exhibits anti-inflammatory actions against radiation-induced skin damage probably by inhibiting NADPH oxidase activity, ROS production, activation of p38MAPK and NF-κB signaling, and the DNA binding activities of NF-κB and AP-1, consequently suppressing pro-inflammatory cytokine production.

Su L ，Wang Z ，Huang F ，Lan R ，Chen X ，Han D ，Zhang L ，Zhang W ，Hong J ... -  《-》

Urolithin A attenuates pro-inflammatory mediator production by suppressing PI3-K/Akt/NF-κB and JNK/AP-1 signaling pathways in lipopolysaccharide-stimulated RAW264 macrophages: Possible involvement of NADPH oxidase-derived reactive oxygen species.

Urolithin A, a gut microbial metabolite of ellagic acid, is reported to exert anti-inflammatory effects in vitro and in vivo. However, complete mechanisms underlying the regulation of inflammatory responses by urolithin A remain unclear. This study aimed to evaluate the anti-inflammatory potential of urolithin A and its underlying mechanisms in lipopolysaccharide (LPS)-stimulated RAW264 macrophages. Urolithin A significantly attenuated the pro-inflammatory mediator production in LPS-stimulated RAW264 and mouse peritoneal macrophages. This compound significantly suppressed the LPS-elicited nuclear factor-κB (NF-κB) and activator protein-1 (AP-1) activation. The phosphorylation of Akt and c-Jun N-terminal kinase (JNK) was also inhibited by the treatment with urolithin A. Through experiments using kinase inhibitors, urolithin A abolished the LPS-induced phosphatidylinositol 3-kinase (PI3-K)/Akt/NF-κB and JNK/AP-1 signaling pathways, resulting in suppression of pro-inflammatory mediator production. Furthermore, treatment with this compound significantly reduced the intracellular accumulation of reactive oxygen species, which are known to act as secondary messengers in the activation of redox-sensitive transcription factors NF-κB and AP-1. Urolithin A treatment also diminished the LPS-evoked activation of NADPH oxidase (NOX), which is the main source of reactive oxygen species in activated macrophages. The inhibition of this activity by urolithin A led to the prevention of LPS-elicited NF-κB and AP-1 activation as well as Akt and JNK phosphorylation, resulting in the reduction of pro-inflammatory mediator production. Collectively, these results indicate that urolithin A treatment attenuates pro-inflammatory mediator production by suppressing NOX-derived reactive oxygen species-mediated PI3-K/Akt/NF-κB and JNK/AP-1 signaling pathways in LPS-stimulated macrophages.

Komatsu W ，Kishi H ，Yagasaki K ，Ohhira S ... -  《-》

Oregano Essential Oil Attenuates RAW264.7 Cells from Lipopolysaccharide-Induced Inflammatory Response through Regulating NADPH Oxidase Activation-Driven Oxidative Stress.

Cheng C ，Zou Y ，Peng J 《MOLECULES》

18β-Glycyrrhetinic acid inhibits IL-1β-induced inflammatory response in mouse chondrocytes and prevents osteoarthritic progression by activating Nrf2.

Chen B ，Zhu D ，Xie C ，Shi Y ，Ni L ，Zhang H ，Li S ，Lu J ，Xiao J ，Xia W ，Huang C ，Wang X ... -  《-》

Cnidilide, an alkylphthalide isolated from the roots of Cnidium officinale, suppresses LPS-induced NO, PGE(2), IL-1β, IL-6 and TNF-α production by AP-1 and NF-κB inactivation in RAW 264.7 macrophages.

Cnidilide, an alkyl phthalide isolated from the rhizome of Cnidium officinale, has been reported to possess antispasmodic and sedative effects. However, the anti-inflammatory capacity and molecular mechanism of cnidilide have not been studied to date. In the present study, we investigated the inhibitory effects of cnidilide on LPS-induced pro-inflammatory mediators and the underlying molecular mechanisms in RAW 264.7 macrophages. Our results indicated that cnidilide potently inhibits inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression at the protein and mRNA levels and their promoter activities, causing attendant decreases in the production of nitric oxide (NO) and prostaglandin E2 (PGE2). In addition, cnidilide reduced LPS-induced production and mRNA expression of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) in a dose-dependent manner. Molecular data revealed that cnidilide inhibited LPS-induced transcriptional activity of activator protein-1 (AP-1) by reducing the phosphorylation and nuclear translocation of c-Fos and c-Jun. In addition, cnidilide attenuated LPS-induced transcriptional activity of nuclear factor-κB (NF-κB), and this reduction was accompanied by parallel reduction in the phosphorylation, but not in the translocation of p65 NF-κB. In addition, cnidilide inhibited LPS-induced phosphorylation of p38 mitogen-activated protein kinase (MAPK) and mitogen- and stress-activated protein kinase 1(MSK-1), a downstream kinase. Moreover, the phosphorylation of c-Jun N-terminal kinase (JNK) was suppressed by cnidilide in a concentration-dependent manner, whereas it did not inhibit the extracellular signal-regulated kinase (ERK) phosphorylation in LPS-stimulated RAW 264.7 macrophages. Taken together, our findings suggest that cnidilide has anti-inflammatory properties by inhibiting p38 MAPK, JNK, AP-1, and the NF-κB pathway in LPS-stimulated RAW 264.7 macrophages.

Lee WS ，Shin JS ，Jang DS ，Lee KT ... -  《-》