quercetin-3-o-methyl-ether and Inflammation

Inflammation is a biological function which triggered after the mechanical tissue disruption or from the responses by the incidence of physical, chemical or biological negotiator in body. These responses are essential act provided by the immune system during infection and tissue injury to maintain normal tissue homeostasis. Inflammation is a quite complicated process at molecular level with the involvement of several proinflammatory expressions. Several health problems are associated with prolonged inflammation, which effects nearly all major to minor diseases. The molecular and epidemiological studies jagged that the inflammation is closely associated with several disorders with their specific targets. It would be great achievement for human health around the world to overcome on inflammation. Mostly used anti-inflammatory drugs are at high risk of side effects and also expensive. Hence, the plant-based formulations gained a wide acceptance by the public and medical experts to treat it. Due to extensive dispersal, chemical diversity and systematically established biological potentials of natural products have induced renewed awareness as a gifted source for medications. However, today's urgent need to search for cheaper, more potent and safe anti-inflammatory medications to overcome on current situation. The goal of this review to compile an update on inflammation, associated diseases, molecular targets, inflammatory mediators and role of natural products. The entire text concise the involvement of various cytokines in pathogenesis of various human disorders. This assignment discussed about 321 natural products with their promising anti-inflammatory potential discovered during January 2009 to December 2018 with 262 citations.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Biological Products; Cardiovascular Diseases; Humans; Inflammation; Neoplasms; Skin Diseases

Esophageal squamous cell carcinoma (ESCC) is highly prevalent in Asia, especially in China. Research findings indicate that nitrosamines, malnutrition, unhealthy living habits, and genetics contribute to esophageal carcinogenesis. Currently, the 5-year survival rate for ESCC patients remains low, owing in part to a lack of a clear understanding of mechanisms involved. Chemoprevention using natural or synthesized compounds might be a promising strategy to reduce esophageal cancer incidence. The epidermal growth factor receptor (EGFR) can activate downstream pathways including the phosphatidylinositol 3-kinase (PI3K) pathway and the Ras/mitogen-activated protein kinase (MAPK) pathways. Among the important players, AKT and ERKs have an important relationship with cancer initiation and progression. Here, we found that phosphorylated (p)-AKT and p-ERKs were highly expressed in esophageal cancer cell lines and in esophageal cancer patients. Human phospho-kinase array and pull-down assay results showed that quercetin-3-methyl ether (Q3ME) is a natural flavonoid compound that interacted with AKT and ERKs and inhibited their kinase activities. At the cellular level, Q3ME attenuated esophageal cancer cell proliferation and anchorage-independent growth. Western blot analysis showed that this compound suppressed the activation of AKT and ERKs downstream signaling pathways, subsequently inhibiting activating protein-1 (AP-1) activity. Importantly, Q3ME inhibited the formation of esophageal preneoplastic lesions induced by N-nitrosomethylbenzylamine (NMBA). The inhibition by Q3ME was associated with decreased inflammation and esophageal cancer cell proliferation in vivo. Collectively, our data suggest that Q3ME is a promising chemopreventive agent against esophageal carcinogenesis by targeting AKT and ERKs.

Topics: Animals; Biomarkers; Cell Line, Tumor; Cell Transformation, Neoplastic; Esophageal Mucosa; Esophageal Neoplasms; Humans; Inflammation; Mitogen-Activated Protein Kinases; Molecular Structure; Proto-Oncogene Proteins c-akt; Quercetin; Rats; Ribosomal Protein S6 Kinases, 70-kDa; Signal Transduction; Structure-Activity Relationship; TOR Serine-Threonine Kinases

This protocol describes microsphere-based protease assays for use in flow cytometry and high-throughput screening. This platform measures a loss of fluorescence from the surface of a microsphere due to the cleavage of an attached fluorescent protease substrate by a suitable protease enzyme. The assay format can be adapted to any site or protein-specific protease of interest and results can be measured in both real time and as endpoint fluorescence assays on a flow cytometer. Endpoint assays are easily adapted to microplate format for flow cytometry high-throughput analysis and inhibitor screening.

Topics: Animals; Biotinylation; Flow Cytometry; Fluorescence Resonance Energy Transfer; Green Fluorescent Proteins; High-Throughput Screening Assays; Humans; Inflammation; Kinetics; Microspheres; Peptide Hydrolases; Peptides; Reproducibility of Results; Temperature

The anti-inflammatory activities of the isolated flavonoids, quercetin 3-O-methyl ether (1), kaempferol (2), and quercetin (3), of Rhamnus nakaharai, and anthraquinone, frangulin B (4), of Rhamnus formosana, were assessed in vitro by determining their inhibitory effects on the chemical mediators released from mast cells, neutrophils, macrophages, and microglial cells. Compounds 1 - 3 strongly inhibited the release of beta-glucuronidase and lysozyme from rat neutrophils stimulated with formyl-Met-Leu-Phe/cytochalasin B (fMLP/CB). Compound 1 strongly inhibited superoxide anion formation in fMLP/CB or phorbol 12-myristate 13-acetate (PMA)-stimulated rat neutrophils. Compound 1 exhibited potent inhibitory effect on tumor-necrosis factor-alpha ( TNF-alpha) formation in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells while 1 and 4 showed potent inhibitory effects on TNF-alpha formation in LPS/IFN-gamma (interferon-gamma)-stimulated murine microglial cell lines N9.

Topics: Animals; Anthraquinones; Anti-Inflammatory Agents, Non-Steroidal; Cell Degranulation; Flavonoids; Glucuronidase; Inflammation; Kaempferols; Macrophages; Male; Microglia; Molecular Structure; Muramidase; Neutrophils; Phytotherapy; Plant Bark; Plant Preparations; Quercetin; Rats; Rhamnus; Structure-Activity Relationship