Embelin reduces cutaneous TNF-α level and ameliorates skin edema in acute and chronic model of skin inflammation in mice

Kumar, Girijesh; Dhamotharan, R.; Kulkarni, Nagaraj M.; Mahat, Mahamad Yunnus A.; Gunasekaran, J.; Ashfaque, Mohammad

doi:10.1016/j.ejphar.2011.04.037

Cited by 67 publications

(25 citation statements)

References 15 publications

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“…Previously, TPA-induced skin inflammation in mice has been shown to involve potent upregulation of TNF-α [30,31]. Here we report that TNF-α expression levels were the most severely affected cytokine level by peptide treatment.…”

Section: Discussionsupporting

confidence: 48%

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Anti-inflammatory effect of a retrovirus-derived immunosuppressive peptide in mouse models

et al. 2013

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BackgroundShort dimeric or mulitmeric peptides derived from a highly conserved stretch of amino acids from gammaretroviral envelope proteins has been found to have immunosuppressive properties in vitro. Here we test the hypothesis that such immunosuppressive peptides may serve as immunomodulatory reagents for treatment of inflammatory disorders.ResultsThe anti-inflammatory effect of a synthetic retrovirus-derived immunosuppressive peptide of 17 amino acids was tested in two murine skin inflammation models, a TPA-induced acute toxic contact eczema model and an oxazolone-induced allergic contact dermatitis. Overall, mice (n = 24) treated with a topically applied cream containing the dimeric immunosuppressive peptide exhibited a reduction of 28.8% in ear thickness (range 20.1-42.5), whereas the application of a scrambled peptide dimer or a monomer of the immunosuppressive peptide remained without effect (p = 0.028). Furthermore, ear biopsies from mice treated with the dimeric immunosuppressive peptide showed a significant reduction in mRNA of the pro-inflammatory cytokines TNF-α, IL-17C, and IL-6 as well as the chemokine CXCL2 compared to mice treated with control peptides.ConclusionUsing two murine skin inflammation models, we show that an immunosuppressive retroviral peptide is capable of reducing inflammatory disorders. The results indicate that virus-derived immunosuppressive peptides capable of down-regulating several proinflammatory cytokines may represent a novel class of drugs for the treatment of excess inflammation.

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Section: Discussionsupporting

confidence: 48%

“…In addition, levels of another important regulator in autoimmune diseases, IL-17C was significantly reduced upon treatment of inflamed ears with cream containing retroviral peptide. Recently, anti-IL-17A receptor antibodies have proven successful in early clinical trials [2,30]. …”

Section: Discussionmentioning

confidence: 99%

Anti-inflammatory effect of a retrovirus-derived immunosuppressive peptide in mouse models

et al. 2013

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“…Topical TPA application to the skin induces cutaneous inflammation characterized by increased vascular permeability, swelling and edema, inducing a significant inflammatory cell infiltration within the dermis [35–37]. We have previously reported that transgenic expression of VEGF-C in the skin, resulting in an expanded dermal lymphatic network, limits acute skin inflammation and reduces dermal edema formation in response to challenge by oxazolone and UV-B [5].…”

Section: Discussionmentioning

confidence: 99%

Lymphatic endothelial cells attenuate inflammation via suppression of dendritic cell maturation

et al. 2016

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Vascular endothelial growth factor-C (VEGF-C)-induced lymphangiogenesis and increased tissue drainage have been reported to inhibit acute and chronic inflammation, and an activated lymphatic endothelium might mediate peripheral tolerance. Using transgenic mice overexpressing VEGF-C in the skin, we found that under inflammatory conditions, VEGF-C-mediated expansion of the cutaneous lymphatic network establishes an immune-inhibitory microenvironment characterised by increased regulatory T (Treg) cells, immature CD11c+CD11b+ dendritic cells (DCs) and CD8+ cells exhibiting decreased effector function. Strikingly, lymphatic endothelial cell (LEC)-conditioned media (CM) potently suppress DC maturation with reduced expression of MHCII, CD40, and IL-6, and increased IL-10 and CCL2 expression. We identify an imbalance in prostaglandin synthase expression after LEC activation, favoring anti-inflammatory prostacyclin synthesis. Importantly, blockade of LEC prostaglandin synthesis partially restores DC maturity. LECs also produce TGF-β1, contributing to the immune-inhibitory microenvironment. This study identifies novel mechanisms by which the lymphatic endothelium modulates cellular immune responses to limit inflammation.

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“…In our present investigation, we evaluated the lung wet-to-dry weight ratio to quantify the magnitude of pulmonary edema, which is a typical symptom of inflammation and a major characteristic of ALI [1, 25, 26]. Here, RJFs decreased the lung W/D ratio, which indicated that RJFs could inhibit the leakage of serous fluid into lung tissue and attenuate the development of pulmonary edema.…”

Section: Discussionmentioning

confidence: 99%

Rabdosia japonicavar.glaucocalyxFlavonoids Fraction Attenuates Lipopolysaccharide-Induced Acute Lung Injury in Mice

Chu

et al. 2014

Evidence-Based Complementary and Alternative Medicine

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Rabdosia japonica var. glaucocalyx (Maxim.) Hara, belonging to the Labiatae family, is widely used as an anti-inflammatory and antitumor drug for the treatment of different inflammations and cancers. Aim of the Study. To investigate therapeutic effects and possible mechanism of the flavonoids fraction of Rabdosia japonica var. glaucocalyx (Maxim.) Hara (RJFs) in acute lung injury (ALI) mice induced by lipopolysaccharide (LPS). Materials and Methods. Mice were orally administrated with RJFs (6.4, 12.8, and 25.6 mg/kg) per day for 7 days, consecutively, before LPS challenge. Lung specimens and the bronchoalveolar lavage fluid (BALF) were isolated for histopathological examinations and biochemical analysis. The level of complement 3 (C3) in serum was quantified by a sandwich ELISA kit. Results. RJFs significantly attenuated LPS-induced ALI via reducing productions of the level of inflammatory mediators (TNF-α, IL-6, and IL-1β), and significantly reduced complement deposition with decreasing the level of C3 in serum, which was exhibited together with the lowered myeloperoxidase (MPO) activity and nitric oxide (NO) and protein concentration in BALF. Conclusions. RJFs significantly attenuate LPS-induced ALI via reducing productions of proinflammatory mediators, decreasing the level of complement, and reducing radicals.

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Embelin reduces cutaneous TNF-α level and ameliorates skin edema in acute and chronic model of skin inflammation in mice

Cited by 67 publications

References 15 publications

Anti-inflammatory effect of a retrovirus-derived immunosuppressive peptide in mouse models

Anti-inflammatory effect of a retrovirus-derived immunosuppressive peptide in mouse models

Lymphatic endothelial cells attenuate inflammation via suppression of dendritic cell maturation

Rabdosia japonicavar.glaucocalyxFlavonoids Fraction Attenuates Lipopolysaccharide-Induced Acute Lung Injury in Mice

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