Nano-gold displayed anti-inflammatory property via NF-kB pathways by suppressing COX-2 activity

Abstract

Rheumatoid arthritis (RA) is an autoimmune inflammatory disease, affecting almost 1% of world population. Although the exact cause of RA is not known but the complex interaction between inflammatory mediators like tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β), cyclooxygenase-2 (COX-2) and nitric oxide (NO) is accountable for cartilage destruction in joints. Gold is used for arthritis treatment since long without knowing its mechanism of action. Hence, the present study was designed to assess antiarthritic activity of nanogold (AuNGs) in collagen-induced arthritic (CIA) rat model by virtue of decreasing inflammatory mediators and oxidative stress. After induction CIA rats were treated with AuNGs in phosphate buffer at a dose of 20 μg/kg body weight for 20 days and found a significant decrease in the level of inflammatory mediators like TNF-α, IL-1β, COX-2 and transcription factor NF-kB (Nuclear factor-kB), which was found to be elevated in CIA rats. Additionally imbalance in oxidant and antioxidant status were determined and perceived that AuNGs remarkably attenuates the imbalance in level of antioxidant and oxidant near to normal. In consistent to biochemical results, mRNA expression of NF-kB, TNF-α, COX-2, and iNOS were also up-regulated in CIA rats, which were considerably down regulated by AuNGs treatment. These findings were positively correlated with the histological results of joints, displayed reduced inflammation and bone erosion in treated group. This study demonstrates the ability of AuNGs to ameliorate production of inflammatory mediators and oxidative stress in CIA rats. Induction of arthritis in rats showed increased inflammation, which activate the transcription factor NF-kB through activation of of IkB kinases (IKK) and ubiquination/proteosome degradation of IKB and transportation of activated NF-kB from cytoplasm to nucleus. In nucleus activated NF-kB bind to the promoter region of target gene and up regulate the production of pro-inflammatory cytokines, COX-2 and other inflammatory mediators that leads to cartilage destruction. AuNGs inhibit the activation of NF-kB and other inflammatory mediators and attenuate inflammation and cartilage destruction. COX-2: cyclooxygenase-2; IKK: IkB kinases; IKB: I Kappa B; IL-1β: interleukin-6; IL-6: interleukin-6; iNOS: inducible nitric oxide synthase; NF-kB: nuclear transcription factor kappa B; ROS: reactive oxygen species; TNF-α: tumour necrosis factor-alpha.

Effects of treatment with gold nanoparticles in a model of acute pulmonary inflammation induced by lipopolysaccharide

“…GNPs have been studied for their anti‐inflammatory and antioxidative properties (Fraga et al, ; Jeong, Kim, Seok, & Cho, ; Muller, Ferreira, da Silva, et al, ; Silveira et al, ). In our study, administration of GNPs resulted in reduced production of inflammatory cytokines (INF‐γ, IL‐1β, and IL6) due to the suppression of NF‐κB (through the probable inhibition of translocation of NF‐κB to the nucleus due to reduction in the phosphorylation of IKK‐β), the major transcription factor responsible for cytokine production under pathological conditions (Khan & Khan, ; Norton, ). In addition to this mechanism of action, studies have shown that GNPs also block the activation of NF‐κB via interaction with cys‐179 component of IKK‐β residue, and thereby, reduce the production of pro‐inflammatory cytokines (Gul et al, ; Jeon, Byun, & Jue, ; Lai, Shieh, Tsou, & Wu, ).…”

“…Several alternatives are being created with the aim of alleviating oxidative stress. The use of non‐enzymatic antioxidants, such as vitamin C, vitamin A, vitamin E, and n ‐acetilcysteine (NAC), among others, and gold nanoparticles (GNPs), have been demonstrated to be effective in decreasing ROS effects (Khan & Khan, ; Moser & Chun, ). Nanotechnology has been showing a wide range of applications in the area of medical research.…”

The Inhibitory Effect of Curcumin on Virus-Induced Cytokine Storm and Its Potential Use in the Associated Severe Pneumonia

“…On the other hand, ROS acts as a second messenger to regulate intracellular signaling events. For example, it activates the nuclear factor-κB (NF-κB) to promote further production of pro-inflammatory cytokines such as TNF-α, IL-6, IL-8, and other inflammatory factors (Baldwin, 1996;Cohen et al, 2009;Zhang et al, 2016;Hellebrekers et al, 2018;Khan and Khan, 2018). Therefore, pro-inflammatory cytokines and ROS exert forward feedback regulation of their production.…”

“…Other inflammatory mediators have been reported to be regulated by curcumin. One of them is cyclooxygenase 2 (COX-2), a key enzyme for the synthesis of prostaglandin (Khan and Khan, 2018). In an animal model of chronic obstructive pulmonary disease, it has been shown that curcumin treatment effectively inhibits the degradation of IκBα and disturbs the production of COX-2 (Yuan et al, 2018).…”

Advanced nanomedicines for the treatment of inflammatory diseases

“…The use of gold for therapeutic purposes dates back to Antiquity in China and Egypt, but only recently the scientific community developed a strong interest in gold nanoparticles for biomedical applications, especially because they can be easily functionalised and possess imaging and therapeutic capabilities [130]. The anti-inflammatory property of nanogold was recently explained by the down regulation of inflammatory mediators like TNF-α, IL-1β, COX-2 and transcription factor NF-kB (Nuclear factor-kB) [131]. Although systemic administration of these nanoparticles produced a significant anti-inflammatory activity in vivo, on different mouse models [132,133], it has to be noted that gold, even if well tolerated by the body, is not a biodegradable material and may remain for a long time into the body, as previously demonstrated in a mouse model [134].…”