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Novel anti-inflammatory activity of chlorojanerin isolated from Sausurrea heteromalla (D. Don) Hand.-Mazz.

ABSTRACT: Medicinal plants have shown great promise as a source of novel drug compounds for the treatment of inflammatory disorders. In our search for new entities with anti-inflammatory potential, the extracts of the whole plant of Saussurea heteromalla (family-Asteraceae), collected from Himalayas, were evaluated in the high throughput screen for TNF-α and IL-6 inhibitors. The plant has been found as a new source of chlorojanerin, a guaianolide type of sesquiterpene lactone. This is the first report on the potent anti-inflammatory activity of the compound. Chlorojanerin was shown to be significantly effective in inhibiting TNF-α and IL-6 production in LPS induced THP-1 cells (TNF-α, IC50 = 3µM and IL-6, IC50 = 0.8µM). The compound also blocked TNF-α and IL-6 production from LPS induced human monocytes and synovial cells from RA patients. Chlorojanerin also inhibited the binding of NF-κB in a GFP reporter assay system. Transcriptional profiling of the LPS stimulated THP-1 cells revealed that chlorojanerin exerted its anti-inflammatory effect by inhibiting the expression of genes involved in activating the transcription factor – NF-κB. Real time analysis of these genes validated the effect of chlorojanerin on the classical downstream targets of NF-κB. Thus, this study clearly delineated 8 targets specific for the effect of chlorojanerin on NF-κB induced signaling at the mRNA level. This work is a step towards the isolation and characterization of lead anti-inflammatory agents from the extract of Saussurea heteromalla, which can be developed into better therapeutic molecules targeted towards some specific inflammatory diseases.

ORGANISM(S): Homo sapiens

PROVIDER: GSE34180 | GEO | 2011/12/14

SECONDARY ACCESSION(S): PRJNA149693

REPOSITORIES: GEO

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Novel anti-inflammatory activity of chlorojanerin isolated from Sausurrea heteromalla (D. Don) Hand.-Mazz.

Project description:Medicinal plants have shown great promise as a source of novel drug compounds for the treatment of inflammatory disorders. In our search for new entities with anti-inflammatory potential, the extracts of the whole plant of Saussurea heteromalla (family-Asteraceae), collected from Himalayas, were evaluated in the high throughput screen for TNF-α and IL-6 inhibitors. The plant has been found as a new source of chlorojanerin, a guaianolide type of sesquiterpene lactone. This is the first report on the potent anti-inflammatory activity of the compound. Chlorojanerin was shown to be significantly effective in inhibiting TNF-α and IL-6 production in LPS induced THP-1 cells (TNF-α, IC50 = 3µM and IL-6, IC50 = 0.8µM). The compound also blocked TNF-α and IL-6 production from LPS induced human monocytes and synovial cells from RA patients. Chlorojanerin also inhibited the binding of NF-κB in a GFP reporter assay system. Transcriptional profiling of the LPS stimulated THP-1 cells revealed that chlorojanerin exerted its anti-inflammatory effect by inhibiting the expression of genes involved in activating the transcription factor – NF-κB. Real time analysis of these genes validated the effect of chlorojanerin on the classical downstream targets of NF-κB. Thus, this study clearly delineated 8 targets specific for the effect of chlorojanerin on NF-κB induced signaling at the mRNA level. This work is a step towards the isolation and characterization of lead anti-inflammatory agents from the extract of Saussurea heteromalla, which can be developed into better therapeutic molecules targeted towards some specific inflammatory diseases. Single dye labelling with Cy3 for all treatment RNA samples. Treatments included unstimulated, LPS stimulated, Chlorjanerin treatment and dexamethasone treatment.

2011-12-14 | E-GEOD-34180 | biostudies-arrayexpress

THP1 Human Monocyte cells Project A (part I)

Project description:Citrate, a central component of cellular metabolism, is a widely used anti-coagulant due to its ability to chelate calcium. Adenosine triphosphate (ATP)-citrate lyase, which metabolizes citrate, has been shown to be essential for inflammation, but the ability of exogenous citrate to impact inflammatory signalling cascades remains largely unknown. We hypothesized that citrate would modulate inflammatory responses as both a cellular metabolite and calcium chelator, and tested this hypothesis by determining how clinically relevant levels of citrate modulate monocyte proinflammatory responses to lipopolysaccharide (LPS) in a human acute monocytic leukaemia cell line (THP-1). In normal medium (0•4 mM calcium), citrate inhibited LPS-induced tumour necrosis factor (TNF)-α and interleukin (IL)-8 transcripts, whereas in medium supplemented with calcium (1•4 mM), TNF-α and IL-8 levels increased and appeared independent of calcium chelation. Using an IL-8–luciferase plasmid construct, the same increased response was observed in the activation of the IL-8 promoter region, suggesting transcriptional regulation. Tricarballylic acid, an inhibitor of ATP-citrate lyase, blocked the ability of citrate to augment TNF-α, linking citrate's augmentation effect with its metabolism by ATP-citrate lyase. In the presence of citrate, increased histone acetylation was observed in the TNF-α and IL-8 promoter regions of THP-1 cells. We observed that citrate can both augment and inhibit proinflammatory cytokine production via modulation of inflammatory gene transactivation. These findings suggest that citrate anti-coagulation may alter immune function through complex interactions with the inflammatory response. Research is published, core data not used but project description is relevant: http://onlinelibrary.wiley.com/doi/10.1111/cei.12591/full

2015-06-04 | ST000172 | MetabolomicsWorkbench

THP1 Human Monocyte cells Project A (part II)

2015-06-11 | ST000202 | MetabolomicsWorkbench

Theissenolactone C inhibits lipopolysaccharide-induced TAK-1/IKK signaling and improves septic injuries in vivo

Project description:Sepsis is a common leading cause of death and evolves to multi-organ injury. Clinical studies show that endotoxin lipopolysaccharide (LPS) acts as an exogenous pyrogen and produces many types of mediators involved in septic shock. In vivo and in vitro, LPS can induce the expression of pro-inflammatory mediators in human monocytes, such as proteinases, cytokines and inducible nitric oxide synthase (NOS). The released cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1β, play important roles in sepsis or chronic infection. These cytokines could also enhance the matrix metalloproteinases (MMP) production in monocytes, which leads to serious tissue structure destruction. Theissenolactone C (LC53) is derived from the Taiwan strains Xylariaceae (Xylariaceae) Theissenia cinerea. In this study, microarray technology was first applied to detect the possible regulated genes in LPS-activated human monocytic cells (THP-1) under pretreatment of LC53. We also found LC53 obviously decreased LPS-induced extracellular MMP-9, TNF-α and IL-6 levels in THP-1 cells within 24 hours. It inhibited LPS-induced intracellular MMP-9 protein and mRNA expression. In signaling studies, LC53 could block the LPS-induced degradation of IκBα, p65 translocation, and NF-κB regulated gene reporter activity. It also decreased the phosphorylation of IKKα/β while not affected the TAK1 and p38 phosphorylation. In vivo studies showed LC53 could improve the cecum shrinkage, decrease plasma TNF-α/IL-6 levels, and lower the hepatic iNOS/MMP-9 expression in LPS-induced mice endotoxemia model. Theissenolactone C may be a promising potential therapeutic agent which might be through its inhibition on TAK1/TAB2/3/IKK pathway for endotoxemia injuries.

2018-08-31 | GSE65630 | GEO

Transcription profiling of endotoxin-stimulated human monocytic cells in presence and absence of host defense peptide LL-37

Project description:The objective of the study was to evaluate transcriptional response of endotoxin-stimulated human monocytic cells in presence and absence of host defense peptide LL-37. A functional genomics approach was used to establish a temporal transcriptional profile and identify differentially expressed genes in LPS (100ng/ml)-stimulated human monocytic THP-1 cells, in the presence or absence of LL-37 (20ug/ml) after 1, 2, 4 and 24 hrs of stimulation. The peptide significantly inhibited the expression of LPS-induced pro-inflammatory genes regulated by NF-kappa B, such as NF-kappa B1 (p105/p50) and TNF-alpha-induced protein 2 (TNFAIP2). In contrast, LL-37 did not significantly inhibit LPS-induced genes that antagonize inflammation, such as TNF-alpha-induced protein 3 (TNFAIP3) and the NF-kappa B inhibitor, NF-kappa BIA, or genes involved in cell movement and recruitment (chemokines). The trends of gene expression were further validated by quantitative real-time PCR. This study implicates that LL-37 plays a role in the delicate balancing act of inflammatory responses.

2006-08-01 | E-FPMI-4 | biostudies-arrayexpress

Effect of Ginsenoside Rb1 on inflammatory reaction and odontogenic differentiation of human dental pulp cell

Project description:Ginsenoside Rb1 (G-Rb1) has been reported to diminish inflammation associated with diseases. We investigated the effect of G-Rb1 on the inflammatory reactions and the odontogenic differentiation of human dental pulp cells (hDPCs). G-Rb1 affected the levels of TNF-α, IL-6, and IL-8, as these showed reduced levels with exposure to lipopolysaccharide (LPS). Additionally, less mRNA and protein expressions of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) were shown. G-Rb1 suppressed the LPS-induced increase of cell adhesion molecules and inflammatory cytokines, while also inhibiting PI3K/Akt, phosphorylation of NF-κB transcription factors, ERK and JNK of MAPK signaling in hDPCs.

2024-02-18 | GSE255672 | GEO

Moringa isothiocyanate-1 inhibits inflammation via NF-κB pathway in skeletal muscle cells

Project description:This study aims to investigate the effect of Moringa isothiocyanate-1 (MIC-1) derived from seeds of Moringa oleifera Lam in lipopolysaccharide (LPS)-induced muscle inflammation models. MIC-1 decreased nitric oxide production, and reduced the expression of pro-inflammatory markers, in C2C12 myoblasts. The daily oral treatment of MIC-1 (80 mg/kg) for three days significantly reduced the expression of pro-inflammatory markers (TNF-α, Ifn-α, IL-1β, IL-6) in gastrocnemius tissue of mice. Transcriptomic analysis provided insight into the inhibitory effects of MIC-1 on the LPS-induced inflammation, which suggests that MIC-1 acts via inflammation, and immunity pathways in myoblasts and skeletal muscle tissue. MIC-1 inhibited the nuclear accumulation of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in the LPS-treated murine, which supports that MIC-1 decreases inflammation and regulates immune responses at a gene expression level in LPS-induced inflammation murine model.

2022-07-28 | GSE209706 | GEO

Genipin inhibits LPS-induced acute systemic inflammation in mice

Project description:Genipin is a natural blue colorant in food industry. Inflammation is correlated with human disorders, and nuclear factor-κB (NF-κB) is the critical molecule involved in inflammation. In this study, the anti-inflammatory effect of genipin on the lipopolysaccharide (LPS)-induced acute systemic inflammation in mice was evaluated by NF-κB bioluminescence-guided transcriptomic analysis. Transgenic mice carrying the NF-κB-driven luciferase genes were administered intraperitoneally with LPS and various amounts of genipin. Bioluminescent imaging showed that genipin significantly suppressed LPS-induced NF-κB-dependent luminescence in vivo. The suppression of LPS-induced acute inflammation by genipin was further evidenced by the reductions of cytokine levels in sera and organs. Microarray analysis of these organs showed that the transcripts of 79 genes were differentially expressed in both LPS and LPS/genipin groups, and one third of these genes belonged to chemokine ligand, chemokine receptor, and interferon (IFN)-induced protein genes. Moreover, network analysis showed that NF-κB played a critical role in the regulation of genipin-affected gene expression. In conclusion, we newly identified that genipin exhibited anti-inflammatory effects in a model of LPSinduced acute systemic inflammation via downregulation of chemokine ligand, chemokine receptor, and IFN-induced protein productions. A total of 25 transgenic mice (female, 6 to 8 weeks old) were randomly divided into five groups of five mice: (1) mock, no treatment; (2) LPS (4 mg/kg), (3) LPS plus genipin (1 mg/kg), (4) LPS plus genipin (10 mg/kg), and (5) LPS plus genipin (100 mg/kg). Mice were challenged intraperitoneally with LPS and then with genipin 10 min later. Four hours later, mice were imaged for the luciferase activity, and subsequently sacrificed for ex vivo imaging, RNA extraction, and immunohistochemical staining.

2012-02-25 | E-GEOD-35934 | biostudies-arrayexpress

Exploring the effect and mechanism of roselle drink on the urinary tract infection in clinics and the lipopolysaccharide-induced renal inflammation in mice

Project description:Urinary tract infection (UTI) is a common problem in long-term care facilities. Roselle (Hibiscus sabdariffa Linn.) has been used in fold medicine as an anti-inflammatory agent. In this study, we surveyed the effect of roselle drink on the prevention of UTI in long-term care facilities and analyzed the anti-inflammatory potential of roselle on lipopolysaccharide (LPS)-induced renal inflammation. By survey questionnaires, we found that roselle drink was the most commonly used treatment for the routine care of residents. In addition, taking roselle drink in residents with urinary catheters reduced the incidence of UTI by 36%. Roselle suppressed LPS-induced nuclear factor-κB (NF-κB) activation in cells in a dose-dependent manner, and the maximal inhibition (73.75±4.11%) was observed at 100 μg/ml roselle drink. Roselle also suppressed LPS-induced interleukin-1β (IL-1β) production in mice. Gene expression profile of roselle in kidney showed that roselle downregulated the expression of inflammatory genes, and NF-κB was the main transcription factor involved in the regulation of roselle-regulated gene expression. Immunohistochemical staining further showed that roselle inhibited LPS-induced NF-κB activation and inflammatory cell infiltration in kidney. In conclusion, our findings suggested that roselle drink might be a potent benefit herbal supplement for UTI. Moreover, roselle ameliorated LPS-induced renal inflammation via regulating inflammatory gene expression and NF-κB pathway.

2017-08-21 | GSE73939 | GEO

The protection of Evodiamine against Ulcerative Colitis and Colorectal Cancer via anti-inflammation

Project description:Evodiamine (Evo), a kind of alkaloid mostly extracted from Tetradium ruticarpum, which has many pharmacological functions, such as antidiarrheal, antiemetic, and antiulcer effects. In this study, the effects of Evo were investigated in DSS-induced ulcerative colitis (UC) mice and C57BL/6-ApcMinC/Gpt mice with colorectal cancer (CRC). The results showed Evo not only sup-pressed the weight loss and the shorthen of colon, decreased disease activity index (DAI) and ameliorated the pathological alteration of colon in UC mice, but also inhibited the numbers and sizes of colonic tumor of ApcMinC/Gpt mice. Meanwhiles, Evo regulated nuclear factor-kappa B (NF-κB) related signal pathways to mediate various cytokines such as interleukins (Ils), tumor necrosis factor-α (TNF-α) to achieve anti-inflammatory and anti-tumor effects. In SW480 and Caco cells, Evo reduced the cell viabilities, promoted the mitochondrial membrane potential (MMP) and caused the over-accumulation of intracellular reactive oxygen species (ROS). Theoretical evi-dences indicated Evo binding NF-κB may be useful to contain ordered domain (α helix) in NF-κB, which can induce NF-κB to perform its function. Our results provide experimental and theoretical evidence that Evo might be promising and effective treatments in clinics for UC and CRC.

2022-05-20 | PXD027745 | Pride

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