Antioxidant and Anti‐Inflammatory Effects of Herbal Formula SC‐E3 in Lipopolysaccharide‐Stimulated RAW 264.7 Macrophages

Abstract

SC-E3 is a novel herbal formula composed of five oriental medicinal herbs that are used to treat a wide range of inflammatory diseases in Korean traditional medicine. In this study, we sought to determine the effects of SC-E3 on free radical generation and inflammatory response in lipopolysaccharide- (LPS-) treated RAW 264.7 macrophages and the molecular mechanism involved. The ethanol extract of SC-E3 showed good free radical scavenging activity and inhibited LPS-induced reactive oxygen species generation. SC-E3 significantly inhibited the production of the LPS-induced inflammatory mediators, nitric oxide and prostaglandin E2, by suppressing the expressions of inducible nitric oxide synthase and cyclooxygenase-2, respectively. SC-E3 also prevented the secretion of the proinflammatory cytokines, IL-1β, TNF-α, and IL-6, and inhibited LPS-induced NF-κB activation and the mitogen-activated protein kinase (MAPK) pathway. Furthermore, SC-E3 induced the expression of heme oxygenase-1 (HO-1) by promoting the nuclear translocation and transactivation of Nrf2. Taken together, these results suggest that SC-E3 has potent antioxidant and anti-inflammatory effects and that these effects are due to the inhibitions of NF-κB and MAPK and the induction of Nrf2-mediated HO-1 expression in macrophages. These findings provide scientific evidence supporting the potential use of SC-E3 for the treatment and prevention of various inflammatory diseases.

Indoxyl Sulfate Promotes Macrophage IL-1β Production by Activating Aryl Hydrocarbon Receptor/NF-κ/MAPK Cascades, but the NLRP3 inflammasome Was Not Activated

“…It is well-known that macrophage inflammation and apoptosis are enhanced by MAPK and NF-activation. For example, in vitro, LPS enhances the phosphorylation of mouse macrophage NF-κ p65, Ik-, ERK, JNK, and p38, which was inhibited by SC-E3, a novel herbal formula [ 25 ]. Macrophage-specific NF-κB knockout in apolipoprotein E-deficient mice reduced the high-fat-diet-induced acceleration of atherosclerosis [ 26 ].…”

Nepetoidin B from Salvia plebeia R. Br. Inhibits Inflammation by Modulating the NF-κB and Nrf2/HO-1 Signaling Pathways in Macrophage Cells

“…Therefore, this study investigated the potential of NeB isolated from S. plebeia to regulate inflammation by modulating oxidative stress alongside its effects on the NF-κB pathway. Chronic inflammation and excessive oxidative stress can cause chronic diseases, such that control of inflammation and oxidative stress is essential [ 1 ]. Oxidative stress occurs when the imbalance between the generation of free radicals and their degradation by antioxidants [ 23 , 24 ].…”

“…Interest in increased life expectancy and quality of life is growing. Homeostasis instability, chronic inflammation, and oxidative stress are linked to the majority of diseases [ 1 ]. Inflammation refers to the process by which the innate immune system defends itself against harmful stimuli, including pathogens, toxic compounds, and damaged cells [ 2 ].…”

In vitro Anti-inflammatory Evaluation of 6-Thioguanine and 6-Hydroxy-2-Mercaptopurine as A Potential Treatment for Rheumatoid Arthritis

“…LPS-stimulated RAW 264.7 macrophage is a model for anti-inflammatory drug screening and in the investigation of the signal pathways involved for the proinflammatory cytokines production and enzyme induction. (1) The immortalized rabbit synovial fibroblast HIG-82 cells line, which shares numerous characteristics of activated human rheumatoid synovium in the same concentrations, mimics the same conditions as rheumatoid arthritis pathogenesis. (2) The thiopurines antimetabolites, 6-mercaptopurine (6MP) or PurinetholTM and 6-thioguanine (6TG) or Thioguanine TabloidTM are structural purine analogues act as anti-cytotoxic agent which often used as anticancer drugs and acute leukemia treatment.…”