Sinomenine Regulates Inflammatory Response and Oxidative Stress via Nuclear Factor kappa B (NF-κB) and NF-E2-Related Factor 2 (Nrf2) Signaling Pathways in Ankle Fractures in Children

Abstract

BackgrounThis study aimed to investigate the effects of SIN on ankle fracture and the underlying mechanisms in MG-63 cells.Mateeial/MethodsqRT-PCR and ELISA assay were used to detect the mRNA and protein levels of cytokines in peripheral blood of children with or without ankle fracture. The expression and activity of antioxidant and detoxifying enzymes were detected by ELISA assay. Pretreated MG-63 cells with/without SIN were stimulated with 1 μg/ml bradykinin (BK). A CCK-8 kit was used to detect the cell viability. The cytokines produced from MG-63 cells were detected by Western blotting and qRT-PCR. Moreover, Western blotting was used to detect the levels of p-p38 and p-NF-κB (p65), and the activation level of the Nrf2 signaling pathway was examined by qRT-PCR and Western blotting.ResultsIn this study, we found that compared with the healthy children, the mRNA and protein levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha (TNF-α) were significantly upregulated in children with ankle fracture. In addition, the expression and activity of antioxidant and detoxifying enzymes were imbalanced in children with ankle fracture. SIN treatment did not have a cytotoxic effect on MG-63 cells. SIN dose-dependently suppressed BK-induced upregulation of IL-1β, IL-6, TNF-α, p-p38, and p-NF-κB (p65). Furthermore, SIN dramatically inhibited oxidative stress induced by BK via balancing the expression and activity of antioxidant and detoxifying enzymes and inhibited the activation of Nrf2 signaling.ConclusionsSIN might be a potential agent for the treatment of ankle fracture through reducing inflammatory response and oxidative stress.

Inhibitory Effect of a Rosmarinic Acid-Enriched Fraction Prepared from Nga-Mon (Perilla frutescens) Seed Meal on Osteoclastogenesis through the RANK Signaling Pathway

“…The production of inflammatory cytokines is related to oxidative stress, and promotes osteoclastogenesis and bone resorption [ 37 , 38 , 39 , 40 ]. Moreover, several articles reported that LPS and IFN-γ are a crucial cytokine for the inflammation process via the activation of proinflammatory mediators such as NO, iNOS, and COX-2 [ 41 , 42 ].…”

Patients Undergoing Surgery for Hip Fractures Suffer from Severe Oxidative Stress as Compared to Patients with Hip Osteoarthritis Undergoing Total Hip Arthroplasty

“…Previous studies have reported induction of oxidative stress during fracture healing in animal models [ 33 , 34 , 45 ]. Oxidative stress is involved in ankle fractures in children [ 46 ], in burst spinal fractures [ 47 ], in osteoporotic spinal fractures treated with kyphoplasty [ 48 ], and mandible fractures internally fixed with titanium alloy plates [ 49 ]. Decreased levels of antioxidant defense enzymes in femoral head fracture patients as compared to a healthy population have been reported, and it has been suggested that oxidative stress and anti-inflammatory markers like interleukins might play an important role in bone fracture pathogenesis and in bone density changes [ 50 ].…”

Bioactivities and Mechanisms of Action of Sinomenine and Its Derivatives: A Comprehensive Review

“…et al demonstrated that SIN (100 mg/kg) notably reduced body weight and DAI score, ameliorated colon shortening in mice with DSS-induced colitis via activating the Nrf2/NQO-1 pathway [ 105 ]. J. Shen and team found that SIN (0.25–1 mM) mitigated BK-induced inflammation in MG-63 cells by downregulating IL-1β, IL-6, TNF-α, p-p38, and p-NF-κB-p65 in the P38 MAPK and NF-κB signaling pathways, reduced MDA, increased SOD and CAT, and upregulated Nrf2, HO-1, and NQO-1 via the inhibition of Nrf2 pathway activation ( Figure 8 ) [ 106 ]. S.P.…”

“…↓: NF-κB and MAPK, TNF-α, IL-6, IL-1β, IL-8, COX-2, iNOS, and MMP-2SOD, CAT, Nrf2, HO-1, NQO-1, and Nrf2. ↓: MAPKP38/NF-κB, IL-1β, IL-6, TNF-α, p-p38, p-NF-κB (P65), and MDA.NR[106]…”