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Roots of Erigeron annuus Attenuate Acute Inflammation as Mediated with the Inhibition of NF- ? B-Associated Nitric Oxide and Prostaglandin E2 production.

ABSTRACT: Erigeron annuus is a naturalized plant belonging to Compositae (asteraceae) family, which is called the annual fleabane, and commonly found at meadows and roadside. This study investigated the anti-inflammatory effects of the extract of E. annuus roots (EER), as assessed by the paw edema formation and histological analysis in rat, and the productions of nitric oxide (NO), prostaglandin E2 (PGE2), and pro-inflammatory cytokines in Raw264.7 murine macrophages. Carrageenan treatment promoted infiltration of inflammatory cells and caused swelling in the hind paw. Oral administrations of EER (0.3?g/kg and 1?g/kg) attenuated acute inflammation similar to the result using dexamethasone (1?mg/kg). Treatment of macrophages with lipopolysaccharide (LPS) simulated inflammatory condition: LPS significantly increased the productions of NO, PGE2, and proinflammatory cytokines. EER suppressed activation of macrophages, preventing the induction of iNOS and COX-2 protein expressions. LPS treatment induced phosphorylation of I- ? B ? and increased the level of nuclear NF- ? B protein, both of which were suppressed by concomitant treatment of EER. In conclusion, EER ameliorated acute inflammation in rats, and the induction of NO, PGE2, and proinflammatory cytokines in Raw264.7 cells. EER's effects may be associated with its inhibition of NF- ? B activation, suggesting its effect on inflammatory diseases.

SUBMITTER: Jo MJ

PROVIDER: S-EPMC3595701 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Roots of Erigeron annuus Attenuate Acute Inflammation as Mediated with the Inhibition of NF- κ B-Associated Nitric Oxide and Prostaglandin E2 production.

Jo Mi Jeong MJ Lee Jong Rok JR Cho Il Je IJ Kim Young Woo YW Kim Sang Chan SC

Evidence-based complementary and alternative medicine : eCAM 20130224

Erigeron annuus is a naturalized plant belonging to Compositae (asteraceae) family, which is called the annual fleabane, and commonly found at meadows and roadside. This study investigated the anti-inflammatory effects of the extract of E. annuus roots (EER), as assessed by the paw edema formation and histological analysis in rat, and the productions of nitric oxide (NO), prostaglandin E2 (PGE2), and pro-inflammatory cytokines in Raw264.7 murine macrophages. Carrageenan treatment promoted infilt ...[more]

PMID: 23533473

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Project description:With increasing body weight, macrophages accumulate in adipose tissue. There, activated macrophages secrete numerous proinflammatory cytokines and chemokines, giving rise to chronic inflammation and insulin resistance. Prostaglandin E2 suppresses macrophage activation via EP4; however, the role of EP4 signaling in insulin resistance and type 2 diabetes mellitus remains unknown. In this study, we treated db/db mice with an EP4-selective agonist, ONO-AE1-329, for 4 weeks to explore the role of EP4 signaling in obesity-related inflammation in vivo. Administration of the EP4 agonist did not affect body weight gain or food intake; however, in the EP4 agonist-treated group, glucose tolerance and insulin resistance were significantly improved over that of the vehicle-treated group. Additionally, administration of the EP4 agonist inhibited the accumulation of F4/80-positive macrophages and the formation of crown-like structures in white adipose tissue, and the adipocytes were significantly smaller. The treatment of the EP4 agonist increased the number of anti-inflammatory M2 macrophages, and in the stromal vascular fraction of white adipose tissue, which includes macrophages, it markedly decreased the levels of proinflammatory cytokines and chemokines. Further, EP4 activation increased the expression of adiponectin and peroxidase proliferator-activated receptors in white adipose tissue. Next, we examined in vitro M1/M2 polarization assay to investigate the impact of EP4 signaling on determining the functional phenotypes of macrophages. Treatment with EP4 agonist enhanced M2 polarization in wild-type peritoneal macrophages, whereas EP4-deficient macrophages were less susceptible to M2 polarization. Notably, antagonizing peroxidase proliferator-activated receptor ? activity suppressed EP4 signaling-mediated shift toward M2 macrophage polarization. Thus, our results demonstrate that EP4 signaling plays a critical role in obesity-related adipose tissue inflammation and insulin resistance by regulating macrophage recruitment and polarization. The activation of EP4 signaling holds promise for treating obesity and type 2 diabetes mellitus.

Project description:BACKGROUND:Nutrition with ammonium (NH4+) can enhance the drought tolerance of rice seedlings in comparison to nutrition with nitrate (NO3-). However, there are still no detailed studies investigating the response of nitric oxide (NO) to the different nitrogen nutrition and water regimes. To study the intrinsic mechanism underpinning this relationship, the time-dependent production of NO and its protective role in the antioxidant defense system of NH4+- or NO3--supplied rice seedlings were studied under water stress. RESULTS:An early NO burst was induced by 3?h of water stress in the roots of seedlings subjected to NH4+ treatment, but this phenomenon was not observed under NO3- treatment. Root oxidative damage induced by water stress was significantly higher for treatment with NO3- than with NH4+ due to reactive oxygen species (ROS) accumulation in the former. Inducing NO production by applying the NO donor 3?h after NO3- treatment alleviated the oxidative damage, while inhibiting the early NO burst by applying the NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (c-PTIO) increased root oxidative damage in NH4+ treatment. Application of the nitric oxide synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl ester(L-NAME) completely suppressed NO synthesis in roots 3?h after NH4+ treatment and aggravated water stress-induced oxidative damage. Therefore, the aggravation of oxidative damage by L-NAME might have resulted from changes in the NOS-mediated early NO burst. Water stress also increased the activity of root antioxidant enzymes (catalase, superoxide dismutase, and ascorbate peroxidase). These were further induced by the NO donor but repressed by the NO scavenger and NOS inhibitor in NH4+-treated roots. CONCLUSION:These findings demonstrate that the NOS-mediated early NO burst plays an important role in alleviating oxidative damage induced by water stress by enhancing the antioxidant defenses in roots supplemented with NH4+.

Dataset Information

Roots of Erigeron annuus Attenuate Acute Inflammation as Mediated with the Inhibition of NF- ? B-Associated Nitric Oxide and Prostaglandin E2 production.

Publications

Roots of Erigeron annuus Attenuate Acute Inflammation as Mediated with the Inhibition of NF- κ B-Associated Nitric Oxide and Prostaglandin E2 production.

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