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Orientin Ameliorates LPS-Induced Inflammatory Responses through the Inhibitory of the NF- B Pathway and NLRP3 Inflammasome

Evidence-based Complementary and Alternative Medicine (2017) 2017
DOI: 10.1155/2017/2495496
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Abstract

Inflammation is a complex response to diverse pathological conditions, resulting in negative rather than protective effects when uncontrolled. Orientin (Ori), a flavonoid component isolated from natural plants, possesses abundant properties. Thus, we aimed to discover the potential therapeutic effects of orientin on lipopolysaccharide- (LPS-) induced inflammation in RAW 264.7 cells and the underlying mechanisms. In our studies, we evaluated the effects of Ori on proinflammatory mediator production stimulated by LPS, including tumor necrosis factor- (TNF-) Ξ±, interleukin- (IL-) 6, IL-18, and IL-1Ξ², along with prostaglandin E2 (PGE2) and NO. Our data indicated that orientin dramatically inhibited the levels of these mediators. Consistent with these results, the expression levels of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) were also reduced. Further study demonstrated that such inhibitory effects of Ori were due to suppression of the nuclear factor-kappa B (NF-B) pathway and nucleotide-binding domain- (NOD-) like receptor protein 3 (NLRP3) inflammasome activation, which may contribute to its anti-inflammatory effects. Together, these findings show that Ori may be an effective candidate for ameliorating LPS-induced inflammatory responses.

Figures

  • Figure 1: Effects of orientin on the cell viability in LPS-induced in RAW 264.7 cells. (a) The chemical structure of orientin (Ori). (b) Cells were treated with different dosages of Ori (10, 20, 40, 60, or 80πœ‡M) for 24 h and cell viability was evaluated by using an MTT assay.
  • Figure 2: Effects of orientin treatment on the secretion of TNF-𝛼, IL-6, IL-1𝛽, and IL-18 in LPS-inducedRAW264.7 cells. Cells were pretreated with or without orientin (10 or 40πœ‡M) for 1 h and were then exposed to LPS for another 24 h. (a–d). The effects of orientin on LPS-induced TNF-𝛼, IL-6, IL-1𝛽, and IL-18 generation were detected by ELISA, respectively. All data of three independent experiments are presented as means Β± SEM. ##𝑝 < 0.01 versus the control group; βˆ—π‘ < 0.05 and βˆ—βˆ—π‘ < 0.01 versus the LPS group.
  • Figure 3: Effects of orientin treatment on LPS-induced NO and PGE 2 generation, as well as iNOS and COX-2 expression in RAW 264.7 cells. Cells were pretreated with or without Ori (10 or 40πœ‡M) for 1 h and were then exposed to LPS for another 24 h. (a) The effect of Ori on NO production was analyzed by the Griess reaction; (b) PGE 2 production was measured by ELISA. (c-d) Effects of Ori on LPS-induced iNOS and COX-2 protein expression were analyzed byWestern blot. Total RNAwas extracted fromRAW264.7 cells and gene expression was quantified using real-time PCR. (g-h) Effects of Ori on LPS-induced iNOS and COX-2 mRNA expression. All data of three independent experiments are presented as means Β± SEM. ##𝑝 < 0.01 versus the control group; βˆ—π‘ < 0.05 and βˆ—βˆ—π‘ < 0.01 versus the LPS group.
  • Figure 4: Effects of orientin treatment on LPS-induced the NF-πœ…B activation in RAW264.7 cells. Cells were pretreated withOri (10 or 40 πœ‡M) for 6 h and then were exposed to LPS for 30min.The protein levels of Iπœ…B𝛼 and P-Iπœ…B𝛼 as well as the nuclear and cytoplasmic levels of NF-πœ…B (p65) were analyzed by Western blot. The relative densities of protein were performed by densitometric analysis; 𝛽-actin and Lamin B were used acted as an internal control, respectively. Similar data were repeated in three independent experiments, and one of three representative experiments is shown. All data from three independent experiments are presented as means Β± SEM. ##𝑝 < 0.01 versus the control group; βˆ—π‘ < 0.05 and βˆ—βˆ—π‘ < 0.01 versus the LPS group.
  • Figure 5: Effects of orientin on the activation of the NLRP3 inflammasome in RAW 264.7 Cells. Cells were pretreated with Ori (10 or 40 πœ‡M) for 1 h, followed by stimulation with LPS (1 πœ‡g/ml) for 6 h and ATP (5mM) for 40min.The protein levels were analyzed byWestern blot. The relative densities of protein were performed by densitometric analysis and 𝛽-actin was used acted as an internal control. Similar data were repeated in three independent experiments, and one of three representative experiments is shown. All data of three independent experiments are presented as means Β± SEM. ##𝑝 < 0.01 versus the control group; βˆ—π‘ < 0.05 and βˆ—βˆ—π‘ < 0.01 versus the LPS group.
  • Figure 6: Scheme summarizing the inhibitory of LPS-induced inflammation damage by Ori via suppressing activation of NF-πœ…B pathway and the NLRP3 inflammasome.

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APA

Xiao, Q., Qu, Z., Zhao, Y., Yang, L., & Gao, P. (2017). Orientin Ameliorates LPS-Induced Inflammatory Responses through the Inhibitory of the NF- B Pathway and NLRP3 Inflammasome. Evidence-Based Complementary and Alternative Medicine, 2017. https://doi.org/10.1155/2017/2495496

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