sauchinone and Inflammation

Inflammatory bowel disease (IBD) is characterized by chronic, unpredictable relapsing and inflammatory disease of the gastrointestinal tract. Daily diet patterns have long been one of the most important hotspots for IBD therapeutic strategies. Sauchinone (SAU), a key bioactive lignin isolated from the roots of the herb Saururus chinensis, has been known to play an anti-inflammatory role in several diseases. However, its effect on IBD has not yet been investigated. In the current study, we established 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice and treated them with SAU. Flow cytometric analysis was performed to determine the phenotype of T cells in the lamina propria. qRT-PCR and ELISA were performed to measure cytokine transcript and protein levels, respectively. We found that SAU ameliorated TNBS-induced mouse colitis and inflammatory responses in mucosal tissues and peripheral blood CD4

Topics: Animals; Benzopyrans; Colitis; Dioxoles; Humans; Inflammation; Inflammatory Bowel Diseases; Interleukin-10; Intestines; Mice; Positive Regulatory Domain I-Binding Factor 1; Signal Transduction; Th17 Cells; Trinitrobenzenesulfonic Acid

The pathogenesis of inflammation bowel disease (IBD) involves exaggerated effector T cell responses and impaired regulatory T cell functions. We previously found that sauchinone (SAU) ameliorated experimental colitis via facilitating Th17 cell production of IL-10, but how SAU regulated Th17 cell differentiation remains unknown. MicroRNAs (miR) have been recognized as a crucial regulator of T cell biology and play a considerable role in IBD. Here, we demonstrated that SAU significantly suppressed miR-340 expression in Th17 cells, and enforced miR-340 expression abrogated SAU inhibition of Th17 differentiation. miR-340 itself was found to facilitate Th17 differentiation, especially the pathogenic "Th1-like" subset. In human IBD, miR-340 was intimately correlated with the disease severity. SAU markedly decreased miR-340 in the inflamed mucosa tissues from IBD patients. Scaffold/matrix-associated region-binding protein 1 (SMAR1) was identified as a target gene of miR-340. We revealed that blockade of miR-340 significantly reduced mucosal damage and Th17 responses in the lamina propria in a mouse colitis model. Our findings suggest that miR-340 negatively affects SAU inhibition of Th17 differentiation and might play a crucial role in the regulation of pathogenic "Th1-like" Th17 cell generation, which might serve as a novel therapeutic target of IBD.

Topics: Base Sequence; Benzopyrans; Cell Cycle Proteins; Cell Differentiation; Colitis; Dioxoles; Disease Susceptibility; DNA-Binding Proteins; Down-Regulation; Forkhead Transcription Factors; Humans; Inflammation; Inflammatory Bowel Diseases; Intestines; MicroRNAs; Nuclear Proteins; Severity of Illness Index; T-Lymphocytes, Regulatory; Th1 Cells; Th17 Cells; Trinitrobenzenesulfonic Acid; Up-Regulation

Topics: Animals; Anti-Inflammatory Agents; Benzopyrans; Colitis; Dendritic Cells; Dextran Sulfate; Dioxoles; Inflammation; Male; Mice, Inbred C57BL; Positive Regulatory Domain I-Binding Factor 1; Th17 Cells

Sauchinone is one of the active lignan isolated from Saururus chinensis, which has been considered to possess various pharmacological activities, such as antitumor, hepatoprotective, antioxidant, and anti-inflammatory effects. However, the functional roles of sauchinone in interleukin-1 beta (IL-1β)-stimulated human osteoarthritis (OA) chondrocytes are still unknown. Thus, in this study, we investigated the anti-inflammatory effects of sauchinone in IL-1β-stimulated chondrocytes. Our results demonstrated that sauchinone significantly attenuated NO and PGE2 production, as well as inhibited iNOS and COX-2 expression in IL-1β-stimulated OA chondrocytes. In addition, sauchinone efficiently inhibited IL-1β-induced MMP-3 and MMP-13 release in human OA chondrocytes. Furthermore, sauchinone significantly attenuated the activation of NF-κB in human OA chondrocytes. In conclusion, we showed for the first time that sauchinone inhibited inflammatory response in IL-1β-stimulated human chondrocytes probably through inhibiting the activation of NF-κB signaling pathway. These data suggest that sauchinone may be a potential agent in the treatment of OA.

Topics: Aged; Benzopyrans; Cells, Cultured; Chondrocytes; Cyclooxygenase 2; Dinoprostone; Dioxoles; Female; Humans; Inflammation; Interleukin-1beta; Matrix Metalloproteinase 13; Matrix Metalloproteinase 3; Middle Aged; Nitric Oxide; Nitric Oxide Synthase Type II; Osteoarthritis

Sauchinone, a diastereomeric lignan isolated from the roots of Saururus chinensis (LOUR.) BAILL. (Saururaceae), is reported to exert a variety of biological activities such as hepatoprotective, anti-inflammatory actions and inhibitory effects on bone resorption. In this study, we investigated the effect of sauchinone in suppressing cell adhesion molecules such as vascular cell adhesion molecule-1 (VCAM-1) and intracellular adhesion molecule-1 (ICAM-1) expression in high glucose stimulated human umbilical vein endothelial cells (HUVEC). Sauchinone inhibited the phosphorylation and degradation of IκB-α, as well as the nuclear translocation of nuclear factor kappa B (NF-κB) p65 caused by the stimulation of high glucose. In addition, sauchinone induced heme oxygenase (HO)-1 expression through nuclear translocation of nuclear factor E2-related factor 2 in HUVEC. The effects of sauchinone on the high glucose-induced expression of VCAM-1 and ICAM-1 and nuclear translocation of NF-κB p65 were partially reversed by transfection of the cells with HO-1 siRNA. These findings suggest that sauchinone-induced HO-1 expression plays a key role in the vascular protective effects of sauchinone in HUVEC.

Topics: Anti-Inflammatory Agents; Benzopyrans; Dioxoles; Heme Oxygenase-1; Human Umbilical Vein Endothelial Cells; Humans; I-kappa B Kinase; I-kappa B Proteins; Inflammation; Intercellular Adhesion Molecule-1; NF-E2-Related Factor 2; NF-kappa B; NF-KappaB Inhibitor alpha; Phosphorylation; Phytotherapy; Plant Extracts; Saururaceae; Transfection; Tumor Necrosis Factor-alpha; Umbilical Veins; Vascular Cell Adhesion Molecule-1; Vascular Diseases

Activated microglial cells play an important role in inflammatory responses in the central nervous system (CNS) that are involved in neurodegenerative diseases. Sauchinone has been shown to modulate the expression of inflammatory factors through nuclear factor-kappa B (NF-κB) signaling pathway. Here, we examined the effect of sauchinone on the inflammatory responses of microglia cells induced by lipopolysaccharide (LPS) and explored the mechanism underlying action of sauchinone. BV2 cells treated with LPS showed an up-regulation of nitric oxide (NO) and prostaglandin (PGE(2)) release, whereas sauchinone suppressed this up-regulation. Sauchinone inhibited both mRNA and protein expression of COX-2, iNOS, TNF-α and IL-1β. In addition, sauchinone blocked the activation of NF-κB through its inhibition of I-κB phosphorylation. Interestingly, sauchinone had no effect on the LPS-induced phosphorylation of mitogen activated protein kinases (MAP kinases; ERK1/2, p38, JNK), but it did inhibit Akt phosphorylation. These results suggest that the inhibitory effect of sauchinone on the LPS-induced production of inflammatory mediator in BV2 cells is associated with the suppression of the NF-κB and Akt signaling pathways. Therefore, sauchinone may be a useful treatment for neurodegenerative disease by inhibiting inflammatory responses in activated microglia.

Topics: Animals; Benzopyrans; Cell Line; Dinoprostone; Dioxoles; Humans; Immunosuppression Therapy; Inflammation; Inflammation Mediators; Lipopolysaccharides; Mice; Microglia; Neurodegenerative Diseases; NF-kappa B; Nitric Oxide; Oncogene Protein v-akt; Signal Transduction

Sauchinone, a biologically active lignan isolated from the roots of Saururus chinensis (LOUR.) BAILL. (Saururaceae), is reported to exert a variety of biological activities, such as hepatoprotective, anti-inflammatory actions and inhibitory effects on bone resorption. In this study, we investigated the effect of sauchinone in suppressing cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression, leading to a reduction in COX-2-derived prostaglandin E(2) (PGE(2)) and iNOS-derived nitric oxide (NO) production in lipopolysaccharide (LPS) stimulated RAW264.7 macrophages. Present study also demonstrates the effects of sauchinone in inducing heme oxygenase-1 (HO-1) expression and an increase in heme oxygenase (HO) activity in RAW264.7 macrophages. The effects of sauchinone on LPS-induced PGE(2), NO, tumor necrosis factor-α (TNF-α) and interlukine-1β (IL-1β) production were partially reversed by the HO-1 inhibitor Tin protoporphyrin was also seen in this study. In addition, we found that treatment with extracellular signal-regulated kinase (ERK) inhibitor (PD98059) reduced sauchinone-induced HO-1 expression. Sauchinone also increased ERK phosphorylation. These results suggest that sauchinone inhibits pro-inflammatory mediators through expression of anti-inflammatory HO-1 via ERK pathway.

Topics: Animals; Anti-Inflammatory Agents; Benzopyrans; Cell Line; Cyclooxygenase 2; Dioxoles; Drug Evaluation, Preclinical; Enzyme Inhibitors; Extracellular Signal-Regulated MAP Kinases; Flavonoids; Heme Oxygenase-1; Inflammation; Inflammation Mediators; Lipopolysaccharides; Macrophages; Metalloporphyrins; Mice; Molecular Targeted Therapy; Nitric Oxide; Nitric Oxide Synthase Type II; Phosphorylation; Phytotherapy; Plant Preparations; Plant Roots; Protoporphyrins; Saururaceae; Signal Transduction; Tumor Necrosis Factor-alpha