Reduced scytonemin isolated from Nostoc commune suppresses LPS/IFNγ-induced NO production in murine macrophage RAW264 cells by inducing hemeoxygenase-1 expression via the Nrf2/ARE pathway

Reduced scytonemin (R-scy) and scytonemin (Scy) isolated from Nostoc commune exhibit anti-tumor and ultraviolet-absorbing properties. In this study, we examined the effects of R-scy and Scy on the induction of nitric oxide (NO) production by lipopolysaccharide (LPS) and interferon-γ (IFNγ) in murine macrophage RAW264 cells. While both R-scy and Scy suppressed LPS/IFNγ-induced NO production, R-scy exhibited a stronger inhibitory effect compared with Scy. To further elucidate the mechanisms underlying the anti-inflammatory effects of R-scy, we examined the changes in the intracellular signaling cascade after LPS/IFNγ stimulation in cells. In addition to the attenuation of LPS/IFNγ-induced upregulation of the inducible isoform of NO synthase, R-scy decreased the activity of nuclear factor-κB, phosphatidylinositol 3-kinase (PI3K)/Akt, and mitogen-activated protein kinases (MAPKs) after LPS/IFNγ stimulation. R-scy treatment increased heme oxygenase-1 (HO-1) expression by increasing the intracellular levels of reactive oxygen species and thereby activating nuclear factor erythroid 2-related factor 2 (Nrf2) and antioxidant response element signaling. The induction of HO-1 by R-scy was inhibited by pretreatment with an antioxidant, N-acetyl-cysteine (NAC), as well as SB203580 and LY294002, inhibitors for p38 MAPK and PI3K/Akt, respectively. Our findings suggest that the anti-inflammatory effects of R-scy could involve both the ROS/PI3K/Akt and the p38 MAPK/Nrf2 signaling pathways.     

Luteolin-7-O-glucoside suppresses leukotriene C(4) production and degranulation by inhibiting the phosphorylation of mitogen activated protein kinases and phospholipase Cγ1 in activated mouse bone marrow-derived mast cells

In this study, luteolin-7-O-glucoside (L7G), an herbal medicine isolated from Ailanthus altissima, inhibited 5-lipoxygenase (5-LOX)-dependent leukotriene C(4) (LTC(4)) production in bone marrow-derived mast cells (BMMCs) in a concentration-dependent manner with an IC(50) of 3.0 μM. To determine the action mechanism of L7G, we performed immunoblotting for cytosolic phospholipase A(2) (cPLA(2)) and mitogen-activated protein kinases (MAPKs) following c-kit ligand (KL)-induced activation of BMMCs with or without L7G. Inhibition of LTC(4) production by L7G was accompanied by a decrease in cPLA(2) phosphorylation, which occurred via the extracellular signal-regulated protein kinase-1/2 (ERK1/2) and p38 and c-Jun N-terminal kinase (JNK) pathways. In addition, L7G also attenuated mast cell degranulation in a dose-dependent manner (IC(50), 22.8 μM) through inhibition of phospholipase Cγ1 (PLCγ1) phosphorylation. Our results suggest that the anti-asthmatic activity of L7G may be mediated in part via the inhibition of LTC(4) generation and mast cell degranulation.     

Astilbin promotes the induction of regulatory NK1.1− CD4+ NKG2D+ T cells through the PI3K,STAT3, and MAPK signaling pathways

Astilbin is a potential agent for autoimmune and inflammatory diseases and has a protective effect in mice with DSS-induced colitis. NK1.1⁻ CD4⁺ NKG2D⁺ T cells are a subpopulation of regulatory T cells that produce TGF-β1 and IL-10. Whether astilbin directly promotes the induction of NK1.1⁻ CD4⁺ NKG2D⁺ T cells and whether these astilbin-stimulated T cells exert an immune-regulatory role remain unclear. Here, we show that astilbin efficiently induces the production of NK1.1⁻ CD4⁺ NKG2D⁺ T cells with high expressions of TGF-β1, IL-10, CCR6, and CCR9 in a dose-dependent manner ex vivo. These regulatory T cells also substantially inhibit the activities of CD8⁺ T cells and macrophages. Intraperitoneal injection of astilbin ameliorates the severity of colitis with an increase in the frequency of NK1.1⁻ CD4⁺ NKG2D⁺ T cells in the colon tissue of DSS-treated mice. Moreover, adoptive transfer of NK1.1⁻ CD4⁺ NKG2D⁺ T cells induced by astilbin remarkably protects against the onset of DSS-induced colitis. Finally, the PI3K, STAT3, and MAPK signaling pathways are involved in the induction of NK1.1⁻ CD4⁺ NKG2D⁺ T cells by astilbin. Taken together, our study elucidates a new immune-regulatory mechanism of astilbin by inducing the regulatory NK1.1⁻ CD4⁺ NKG2D⁺ T cells and indicates a potential clinical use of astilbin for patients with inflammatory bowel diseases.     

Syringol isolated from Eleusine coracana (L.) Gaertn bran suppresses inflammatory response through the down-regulation of cPLA2, COX-2, IκBα, p38 and MPO signaling in sPLA2 induced mice paw oedema

Inflammopharmacology - Eleusine coracana (L.) Gaertn (E. coracana) is one of the highest consuming food crops in Asia and Africa. E. coracana is a plant with several medicinal values including...