goniothalamin and Inflammation

Goniothalamin (GTN) is a natural compound isolated from Goniothalamus species. It is a potent anti-inflammatory agent. However, there is a paucity of scientific data about its toxicity. This study investigated GTN's anti-inflammatory mechanism and lipopolysaccharide (LPS)-induced lung injury in mice. Mice were distributed into four groups and injected with GTN intraperitoneally (Dosage-50 and 100 mg/kg). We analyzed the wet/dry weight ratio, infiltrated inflammatory cell count, myeloperoxidase (MPO) activity, and histopathological changes in the lung tissues of the mice. Results revealed GTN alleviated LPS-induced inflammation in mice. Western Blot and enzyme-linked immunosorbent assay techniques were used to investigate the effect of GTN on pro-inflammatory cytokines and proteins involved in the MAPK and nuclear factor-B (NF-κB) signaling pathways. Cytokines (macrophage migration inhibitory factor, interleukin [IL]-13, IL-6, TNF-α, and IL-1β) were inhibited by GTN. However, IL-10 was upregulated. Western blot analysis indicated that GTN suppressed the phosphorylation of jun N-terminal kinase, nuclear factor NF-kappa-B p65, I-kappa-B, extracellular signal-regulated kinases, NF-κB, and p38. GTN also suppressed the expression of TLR-4 protein, thereby, inhibiting MAPK and NF-κB signaling pathways. Thus, GTN can effectively prevent and cure acute lung injury.

Topics: Acute Lung Injury; Animals; Anti-Inflammatory Agents; Cytokines; Extracellular Signal-Regulated MAP Kinases; Inflammation; Lipopolysaccharides; Mice; NF-kappa B; Signal Transduction; Toll-Like Receptor 4

The tumor microenvironment offers multiple targets for cancer therapy, including pro-tumorigenic inflammation. Natural compounds represent an enormous source of new anti-inflammatory and anticancer agents. We previously showed that the styryl lactone goniothalamin (GTN) has promising antiproliferative and anti-inflammatory activities. Because inflammation is a major driver of colorectal cancer (CRC), we therefore evaluated the therapeutic and preventive potentials of GTN in colitis, colitis-associated cancer (CAC) and spontaneous CRC. First, in a simplistic model of inflammation in vitro, GTN was able to inhibit cytokine production in bone marrow-derived macrophages induced by lipopolysaccharide. Next, in dextran sulfate sodium (DSS) induced-colitis model, mice treated with GTN displayed restored tissue architecture, increased cell proliferation in the colonic crypts and reduced epithelial damage. Moreover, colon tissue from GTN-treated mice had significantly less expression of the inflammatory genes interleukin 1β (IL-1β), tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), S100A9, interleukin 23A (IL-23A), IL-22 and IL-17A In the azoxymethane/DSS model of CAC, GTN reduced tumor multiplicity, load and size. Additionally, GTN suppressed production of IL-6, IL-17 and TNF-α in tumor tissue, as well as abrogated stromal immune cell activation and nuclear translocation of NF-κB. Finally, in a tamoxifen inducible model of sporadic CRC, GTN-treated mice had significantly fewer tumors and decreased levels of IL-17A, IL-6, S100A9 and TNF-α protein within the tumors. These results suggest that GTN possesses anti-inflammatory and antitumor activities and represents a preventive and therapeutic agent modulating the inflammatory environment in the colon during colitis as well as CAC and CRC development.

Topics: Animals; Anti-Inflammatory Agents; Azoxymethane; Biological Products; Carcinogens; Cell Transformation, Neoplastic; Cells, Cultured; Colitis; Colorectal Neoplasms; Cytokines; Dextran Sulfate; Inflammation; Inflammation Mediators; Macrophages; Mice; Mice, Inbred C57BL; Pyrones

Prostate is highly affected by aging, which lead to inflammatory disorders that can predispose to cancer development. Chemoprevention has emerged as a new therapeutic approach, intensifying studies evaluating the biological properties of new compounds. The aim of this study was to characterize the inflammatory responses in the prostate ventral lobe from senile mice treated with Goniothalamin (GTN), a promising natural compound with anti-inflammatory and antiproliferative properties. Its activity was compared to Celecoxib, an established nonsteroidal anti-inflammatory drug (NSAID).. The animals were divided into: Control groups; Young (18-week-old FVB), Senile (52-week-old FVB). Treated groups: Senile-Goniothalamin (150 mg/kg orally), Senile-Celecoxib (10 mg/kg orally). The ventral lobe was collected after 4 weeks for light microscopy, immunohistochemistry, ELISA, and Western blotting analysis.. Both treatments were efficient in controlling the inflammatory process in the prostate from senile mice, maintaining the glandular morphology integrity. GTN reduced all inflammatory mediators evaluated (TNF-α, COX-2, iNOS) and different from Celecoxib, it also decreased the protein levels of NF-kB and p-NF-kB.. Finally, GTN and Celecoxib controlled inflammation in the prostate, and sensitized the senescent microenvironment to anti-inflammatory stimuli. Thus, both treatments are indicated as potential drugs in the prostatic diseases prevention during senescence. Prostate 77:838-848, 2017. © 2017 Wiley Periodicals, Inc.

Topics: Aging; Animals; Anti-Inflammatory Agents; Antineoplastic Agents; Celecoxib; Chemoprevention; Drug Monitoring; Immunohistochemistry; Inflammation; Inflammation Mediators; Male; Mice; Prostate; Prostatic Neoplasms; Pyrones; Treatment Outcome

The present study aimed to further investigate the anti-inflammatory activity of goniothalamin (GTN), a styryl lactone, as well as its antinociceptive effects.. The anti-inflammatory activity was evaluated in models of paw edema induced by different mediators in mice and carrageenan-induced peritonitis. Evaluation of the antinociceptive effect was performed through acetic acid-induced writhing test and formalin test. Activity of GTN on gene expression levels of interleukin-1beta (IL-1β), induced nitric oxidase synthase (iNOS) and cyclooxygenase-2 (COX-2) were evaluated in vitro in lipopolysaccharide (LPS)-stimulated macrophage (RAW 264.7), as well as gene expression and protein levels of tumor necrosis factor-alpha (TNF-α).. Pretreatment with GTN (300 mg/kg) significantly reduced paw edema induced by compound 48/80, prostaglandin E2, phospholipase A2 and bradykinin. GTN (10, 30 and 100mg/kg) inhibited leukocyte migration in the peritonitis model and gene expression levels of IL-1β, iNOS and TNF-α, as well as TNF-α protein levels, in LPS-stimulated macrophages, without affecting COX-2 gene expression levels. GTN inhibited nociception induced by acetic acid in the writhing model and in the formalin test, when both neurogenic and inflammatory phases were inhibited.. For the first time the acute anti-inflammatory profile of GTN is characterized and its antinociceptive activity reported. The current study shows that GTN inhibits both vascular and cellular phases of inflammation, with bradykinin and PLA2 induced inflammation being the most affected by GTN. Its anti-inflammatory effects also involved the in vitro inhibition of gene expression of alarm cytokines and mediators as IL-1β, iNOS and TNF-α.

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Cell Migration Assays, Leukocyte; Cyclooxygenase 2; Edema; Gene Expression Regulation; Inflammation; Interleukin-1beta; Macrophages; Mice; Mice, Inbred BALB C; Nitric Oxide Synthase Type II; Pain; Peritonitis; Pyrones; Tumor Necrosis Factor-alpha

An evaluation of Indonesian plants to identify compounds with immune modulating activity revealed that the methanolic extract of an Alphonsea javanica Scheff specimen possessed selective anti-inflammatory activity in a nuclear factor-kappa B (NF-κB) luciferase and MTT assay using transfected macrophage immune (Raw264.7) cells. A high-throughput LC/MS-ELSD based library approach of the extract in combination with the NF-κB and MTT assays revealed the styryl lactone (+)-altholactone (2) was responsible for the activity. Compound 2, its acetylated derivate (+)-3-O-acetylaltholactone (3), and the major compound of this class, (+)-goniothalmin (1), were further evaluated to determine their anti-inflammatory potential in the NF-κB assay. Concentration-response studies of 1-3 indicated that only 2 possessed NF-κB based anti-inflammatory activity. Compound 2 reduced the LPS-induced NO production, phosphorylation of IκBα, and the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) using Western blot analysis. Further studies using qPCR indicated 2 reduced the expression of eight pro-inflammatory cytokines/enzymes (0.8-5.0μM) which included: COX-2, iNOS, IP-10, IL-1β, MCP-1, GCS-F, IL-6 and IFN-β. These results indicated that 2 displays broad spectrum immune modulating activity by functioning as an anti-inflammatory agent against LPS-induced NF-κB signaling. Conversely the selective cytotoxicity and in vivo anti-tumor and anti-inflammatory activity previously reported for 1 do not appear to arise from a mechanism that is linked to the NF-κB immune mediated pathway.

Topics: Animals; Anti-Inflammatory Agents; Blotting, Western; Cell Line; Cytokines; Furans; Humans; Immunomodulation; Inflammation; Inhibitory Concentration 50; Mice; Models, Molecular; Molecular Structure; Polymerase Chain Reaction; Pyrones; RNA, Messenger