galangin and Inflammation

Numerous chronic diseases, such as cancer, diabetes, rheumatoid arthritis, cardiovascular disease, and gastrointestinal disorders, all have an inflammation-based etiology. In cellular and animal models of inflammation, flavonols were used to show potent anti-inflammatory activity. The flavonols enhanced the synthesis of the anti-inflammatory cytokines transforming growth factor and interleukin-10 (IL-10) and reduced the synthesis of the prostaglandins IL-6, tumor necrosis factor-alpha (TNF-α), and prostaglandin E2 (PGE2), IL-1. Galangin (GAL), a natural flavonol, has a strong ability to control apoptosis and inflammation. GAL was discovered to suppress extracellular signal-regulated kinase (ERK) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)p65 phosphorylation, which results in anti-inflammatory actions. Arthritis, inflammatory bronchitis, stroke, and cognitive dysfunction have all been treated with GAL. The current review aimed to demonstrate the anti-inflammatory properties of GAL and their protective effects in treating various chronic illnesses, including those of the heart, brain, skin, lungs, liver, and inflammatory bowel diseases.

Topics: Animals; Anti-Inflammatory Agents; Flavonols; Inflammation; Lipopolysaccharides; NF-kappa B

When used as an alternative source of drugs to treat inflammation-associated diseases, phytochemicals with anti-inflammatory properties provide beneficial impacts. Galangin is one of the most naturally occurring flavonoids. Galangin has many biological activities, such as anti-inflammatory, antioxidant, antiproliferative, antimicrobial, anti-obesity, antidiabetic, and anti-genotoxic activities. We observed that galangin was well tolerated and positively impacted disease underlying inflammation for the renal, hepatic, central nervous system, cardiovascular, gastrointestinal system, skin, and respiratory disorders, as well as ulcerative colitis, acute pancreatitis, retinopathy, osteoarthritis, osteoporosis, and rheumatoid arthritis. Galangin anti-inflammatory effects are mediated mainly by suppressing p38 mitogen-activated protein kinases, nuclear factor-kappa B, and nod-like receptor protein 3 signals. These effects are confirmed and supported by molecular docking. Clinical translational research is required to accelerate the bench-to-bedside transfer and determine whether galangin can be utilised as a safe, natural source of pharmaceutical anti-inflammatory medication for humans.

Topics: Acute Disease; Anti-Inflammatory Agents; Flavonoids; Humans; Inflammation; Molecular Docking Simulation; NF-kappa B; Pancreatitis

As one of the independent risk factors for atherosclerosis (AS), oxidized low-density lipoprotein (ox-LDL) can trigger damage to the vascular intima and induce the expression of various adhesion molecules. This study aimed to explore the effects of galangin, an extract of galangal, on ox-LDL-induced vascular endothelial cells.. The effects of different concentrations of galangin or ox-LDL on the metabolic activity of vascular endothelial cells were determined using the CCK8 assay. Afterward, the role of galangin in the expression levels of inflammatory factors was assessed using RT-qPCR and Western blotting. In addition, the influences of galangin on apoptosis and endothelial-mesenchymal transition (EndMT) were also evaluated. Through molecular docking, the Heme oxygenase-1 (HO-1) signaling pathway was proposed, and then the effects of the HO-1 signaling pathway on the regulatory roles of galangin were evaluated.. In this study, galangin was found to effectively increase the metabolic activity of ox-LDL-induced cells in a concentration-dependent manner. In addition, galangin was found to reduce ox-LDL-induced cell inflammation, apoptosis, and EndMT. Moreover, galangin could combine with HO-1 and regulate the HO-1 signaling pathway. The effects of galangin on cells were shown to be through the HO-1 signaling pathway.. To sum up, galangin reduced ox-LDL-induced inflammation, apoptosis, and EndMT of vascular endothelial cells via regulating the HO-1 signaling pathway.

Topics: Apoptosis; Endothelial Cells; Heme Oxygenase-1; Humans; Inflammation; Lipoproteins, LDL; Molecular Docking Simulation; Signal Transduction

Methotrexate (MTX) is an efficient chemotherapeutic agent for treating various malignancies and autoimmune diseases. However, the long-term use of MTX can result in hepatotoxicity and this limits its use. Galangin (Gal) is a potent flavonoid with various biological activities; however, its protective effect against MTX hepatotoxicity has not been previously investigated. This study evaluated the hepatoprotective of Gal against MTX-induced liver injury. Rats received Gal for 10 days and a single dose of MTX (20 mg/kg) at day 7. The administration of MTX induced liver damage reflected by increased serum biomarkers of liver function and histopathological manifestations. MTX increased hepatic reactive oxygen species (ROS), nitric oxide (NO), malondialdehyde (MDA), and pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6), and diminished GSH and antioxidant enzymes. Gal relieved liver injury, ameliorated liver function, oxidative stress, and inflammation markers, and increased antioxidants in MTX-treated rats. In addition, Gal decreased the expression of inflammation and apoptosis markers in MTX-treated rats. In conclusion, Gal possesses a hepatoprotective effect mediated by attenuating oxidative damage, inflammation, and apoptosis in rats.

Topics: Animals; Antioxidants; Apoptosis; Chemical and Drug Induced Liver Injury; Flavonoids; Inflammation; Liver; Methotrexate; Oxidative Stress; Rats; Rats, Wistar

Alpinia calcarata (Haw.) Roscoe rhizomes are used to treat diabetes, rheumatism, gastrointestinal problems, inflammatory diseases, cough and respiratory problems in traditional practices. The primary objective of the study is to identify and isolate anti-inflammatory bioactive compounds from A.calcarata rhizomes and to assess its molecular mechanism.. The bioassay-guided fractionation of methanolic extract of A. calcarata rhizomes yielded chloroform fraction as the effective fraction and galangin as the bioactive compound identified by NMR studies. The anti-inflammatory action of galangin was evaluated by determining NO and cytokine production in LPS stimulated RAW264.7 cells. Further, its mechanism was studied on the expression levels of mRNA and protein targets by qPCR and Western blot analysis.. Based on the MTT assay, the concentration of 3.1-25 μM of galangin was selected for further studies. Galangin reduced the levels of NO and proinflammatory cytokines (TNF-α, IL-1β and IL-6) production in LPS induced RAW 264.7 cells in a dose-dependent manner. In addition, the qPCR analysis revealed a reduction in the mRNA expression levels of COX-2, IRAK 1 and JAK 1 in galangin treated LPS stimulated RAW 264.7 cells in a dose-dependent manner. Western blot analysis implicated that galangin has markedly reduced the protein expression levels of cell signaling regulators (JAK-1, IRAK-1, MyD88, MAPK (p38 and ERK) and NF-κB p65).. From the results, it is evident that the inhibition of these cell signaling regulators has contributed to the anti-inflammatory effects of galangin. To our knowledge, we are the first to report IRAK-1 and JAK-1 as therapeutic targets of galangin for its anti-inflammatory effect.

Topics: Alpinia; Animals; Anti-Inflammatory Agents; Dose-Response Relationship, Drug; Flavonoids; Inflammation; Interleukin-1 Receptor-Associated Kinases; Janus Kinase 1; Lipopolysaccharides; Mice; Mitogen-Activated Protein Kinases; Plant Extracts; RAW 264.7 Cells; Rhizome; Transcription Factor RelA

The objectives of this work were to assess the possibility of administration of omarigliptin and/or galangin to combat lipopolysaccharide (LPS)-induced neuroinflammation in rats and to explore the possible mechanisms that might contribute to their actions.. In a rat model of LPS-induced neuroinflammation, the changes in the behavioral tests, biochemical parameters, and the histopathological picture were assessed.. Administration of either omarigliptin or galangin to LPS-injected rats was able to significantly improve the behavioral changes with restoration of the oxidant/antioxidant balance, decrement of toll-like receptor-4 levels, and amelioration of the neuroinflammation associated with inhibition of apoptosis and restoration of glucagon-like peptide-1 levels in the cerebral tissues. In addition, omarigliptin and/or galangin significantly reduced the levels of phospho-Akt and glycogen synthase kinase 3 beta (GSK-3β) and significantly increased the expression of beclin-1 in the cerebral tissues compared versus the group treated with LPS alone. As a result, these changes were positively reflected on the histopathological and the electron microscopic picture of the cerebral tissues. These beneficial effects were maximally evidenced in rats treated with omarigliptin/galangin combination relative to the use of either omarigliptin or galangin alone.. Omarigliptin/galangin combination might be proposed as a promising therapeutic line for mitigation of the pathophysiologic events of LPS-induced neuroinflammation.

Topics: Animals; Apoptosis; Drug Therapy, Combination; Flavonoids; Glucagon-Like Peptide 1; Glycogen Synthase Kinase 3 beta; Heterocyclic Compounds, 2-Ring; Inflammation; Lipopolysaccharides; Male; Microglia; Neuroinflammatory Diseases; Proto-Oncogene Proteins c-akt; Pyrans; Rats; Rats, Wistar; Signal Transduction; Toll-Like Receptor 4

Topics: Animals; Anti-Inflammatory Agents; Cell Line; Cell Survival; Cytokines; Dinoprostone; Epithelial Cells; Flavonoids; Hot Temperature; Inflammation; Intestinal Mucosa; Lipopolysaccharides; Molecular Docking Simulation; Molecular Structure; NF-kappa B; Quercetin; Rats; Signal Transduction; Toll-Like Receptor 4

Oxidative tissue injury and inflammatory response are the main regulators of diabetic nephropathy (DN). The potential protective effect of galangin (Gal), a powerful flavonoid with several promising bioactivities, on hyperglycemia-induced kidney injury in a rat model of DN has been investigated in this study. A rat model of diabetes was induced by intraperitoneal injection of 50 mg kg

Topics: Animals; Apoptosis; Caspase 3; Diabetes Mellitus, Experimental; Diabetic Nephropathies; Flavonoids; Inflammation; Male; Oxidative Stress; Rats; Rats, Wistar; Signal Transduction; Streptozocin; Transcription Factor RelA

Hepatotoxicity is a critical consequence of the iron overload conditions such as hemochromatosis and blood transfusion-requiring anemia. Iron induces hepatotoxicity largely through disruption of cellular redox homeostasis and induction of inflammatory responses. The present work explored the hepatoprotective activity of the bio-active flavone galangin against iron-evoked hepatotoxicity.. Iron overload model was established in male Wistar rats via intraperitoneal injection of 150 mg/kg iron-dextran subdivided over a ten-day experimental period. Galangin was administered in a daily oral dose of 15 mg/kg throughout the experimental period. Blood and liver tissue samples were collected on day eleven and subjected to biochemical and molecular investigations.. Galangin significantly reduced liver iron content and serum ferritin level, and alleviated the iron-evoked oxidative stress. It enhanced the liver cell integrity as reflected by decreased serum activity of the liver enzymes. Mechanistically, galangin up-regulated the redox-regulating transcription factor Nrf2 and its responsive proteins HO-1 and NQO1. Interestingly, galangin up-regulated the antioxidant and anti-inflammatory protein PPARγ and serum hepcidin levels under the iron overload conditions. Equally important, it diminished the nuclear shift of the inflammatory transcription factor NF-κB p65 and down-regulated the levels of the pro-inflammatory cytokines TNF-α and IL-1β.. The results of the present study highlight the mitigating activity of galangin against iron-induced hepatotoxicity. The study accentuated targeting of Nrf2, PPARγ, and NF-κB signaling as potential contributing mechanisms. While clinical studies are still required, the current study supports the possible implementation of galangin in controlling iron overload-associated hepatotoxicity.

Topics: Animals; Flavonoids; Inflammation; Iron Overload; Liver Diseases; Male; NF-E2-Related Factor 2; PPAR gamma; Rats; Rats, Wistar; Signal Transduction; Up-Regulation

Neuroinflammation resulting from microglial activation is involved in the pathogenesis of neurodegenerative diseases, including Parkinson's diseases. Microglial activation plays an important role in neuroinflammation and contributes to several neurological disorders. Hence, inhibition of both microglial activation and the generation of pro-inflammatory cytokines may lead to an effective treatment for neurodegenerative diseases. In the present study, the anti-neuroinflammatory effects of galangin were investigated in lipopolysaccharide (LPS)-stimulated BV-2 microglial cells. Galangin significantly decreased the generation of nitric oxide, interleukin-1β, and inducible nitric oxide synthase in LPS-stimulated BV-2 microglial cells. In addition, galangin inhibited the phosphorylation of p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase 1/2. Furthermore, it was observed that activation of both IκB-α and nuclear factor kappa B (NF-κB) was significantly increased following LPS stimulation, and this effect was suppressed by galangin treatment. In conclusion, galangin displayed an anti-neuroinflammatory activity in LPS-stimulated BV-2 microglial cells. Galangin inhibited LPS-induced neuroinflammation via the MAPK and NF-κB signaling pathways and might act as a natural therapeutic agent for the treatment of various neuroinflammatory conditions.

Topics: Animals; Anti-Inflammatory Agents; Cytokines; Flavonoids; Gene Expression Regulation; Inflammation; Interleukin-1beta; Lipopolysaccharides; Mice; Microglia; Mutagens; NF-KappaB Inhibitor alpha; Nitric Oxide; Phosphorylation; Signal Transduction

Cyclophosphamide (CP) is a widely used chemotherapeutic agent; however, its clinical application is limited because of its multi-organ toxicity. Galangin (Gal) is a bioactive flavonoid with promising biological activities. This study investigated the hepatoprotective effect of Gal in CP-induced rats. Rats received Gal (15, 30 and 60 mg/kg/day) for 15 days followed by a single dose of CP at day 16. Cyclophosphamide triggered liver injury characterized by elevated serum transaminases, alkaline phosphatase (ALP) and lactate dehydrogenase (LDH), and histopathological manifestations. Increased hepatic reactive oxygen species, malondialdehyde, nitric oxide, and oxidative DNA damage along with declined glutathione and antioxidant enzymes were demonstrated in CP-administered rats. CP provoked hepatic nuclear factor-kappaB (NF-κB) phosphorylation and increased mRNA abundance of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) both expression and serum levels. Gal prevented CP-induced liver injury, boosted antioxidants and suppressed oxidative stress, DNA damage, NF-κB phosphorylation and pro-inflammatory mediators. Gal diminished Bax and caspase-3, and increased B-cell lymphoma-2 (Bcl-2) in liver of CP-administered rats. In addition, Gal increased peroxisome proliferator-activated receptor gamma (PPARγ) expression and activated hepatic nuclear factor erythroid 2-related factor 2 (Nrf2) signaling showed by the increase in Nrf2, NAD(P)H: quinone acceptor oxidoreductase-1 (NQO-1) and heme oxygenase 1 (HO-1) in CP-administered rats. These findings suggest that Gal prevents CP hepatotoxicity through activation of Nrf2/HO-1 signaling and attenuation of oxidative damage, inflammation and cell death. Therefore, Gal might represent a promising adjuvant therapy to prevent hepatotoxicity in patients on CP treatment.

Topics: Animals; Apoptosis; Chemical and Drug Induced Liver Injury; Cyclophosphamide; Disease Models, Animal; Flavonoids; Hepatocytes; Inflammation; Male; NF-E2-Related Factor 2; Oxidative Stress; Rats; Rats, Wistar; Signal Transduction

Flavonols are compounds that have been shown to possess potent anti‑inflammatory effects in cellular and animal models of inflammation. In the present study, the anti‑inflammatory effects and mechanisms of two natural flavonols, quercetin and galangin, in lipopolysaccharide (LPS)‑stimulated RAW264.7 macrophages were investigated. It was identified that quercetin and galangin markedly reduced the production of nitric oxide (NO), inducible NO synthase and interleukin‑6, and the nuclear translocation of nuclear factor‑κB (NF‑κB). In addition, LPS‑induced activation of extracellular signal‑regulated kinase 1/2 (Erk1/2) and c‑Jun N‑terminal kinase (JNK) was suppressed by quercetin and galangin. Taken together, these data implied that NF‑κB, Erk1/2 and JNK may be potential molecular targets of quercetin and galangin in an LPS‑induced inflammatory response. Subsequently, the effects of oral administration of quercetin or galangin, either alone or in combination, in a 2,4‑dinitrochlorobenzene‑induced atopic dermatitis (AD) mouse model were investigated. As a result, measurements of ear thickness and the levels of serum immunoglobulin E, and histological analysis revealed that the two flavonols led to a decrease in inflammation, whereas, in combination, they were even more effective. These results suggested that quercetin and galangin may be promising therapeutic agents for AD. Additionally, their combination may be a novel therapeutic strategy for the prevention of AD.

Topics: Animals; Dermatitis, Atopic; Dinitrochlorobenzene; Disease Models, Animal; Flavonoids; Flavonols; Humans; Immunoglobulin E; Inflammation; Interleukin-6; Lipopolysaccharides; MAP Kinase Kinase 4; MAP Kinase Signaling System; Mice; NF-kappa B; Nitric Oxide; Quercetin; RAW 264.7 Cells

In an attempt to connect the legacy of centuries of invaluable knowledge from traditional medicine and the current understanding to the molecular mechanism of diseases, we took the advantage of the emergence of in silico screening as a promising tool for identification of potential leads from libraries of natural products. Traditional Chinese Medicine database was subjected to structure based virtual screening for identification of anti-inflammatory compounds using the 3D crystal structure of p38 alpha mitogen activated protein kinase. The molecular docking studies revealed the potential activity of several classes of compounds known to be the constituents of the rhizomes of Alpinia officinarum Hance (Lesser galangal). Five compounds, galangin, kaempferide, isorhamnetin, and two diarylheptanoids, were isolated from the rhizomes of the plant using vacuum liquid chromatography and flash chromatography techniques. The anti-inflammatory activity of these compounds was investigated on HepG2 cells stimulated by lipopolysaccharide. The latter induced the gene expression of proinflammatory cytokines; interleukin-1β, interleukin-6, tumor necrosis factor alpha. Addition of the 5 isolated compounds downregulated this increased gene expression in a dose dependent manner. Thus, these results indicate that the isolated compounds from A. officinarum could be used as a beneficial source for preventing and treating inflammatory diseases.

Topics: Alpinia; Anti-Inflammatory Agents; Crystallography, X-Ray; Cytokines; Diarylheptanoids; Drugs, Chinese Herbal; Flavonoids; Hep G2 Cells; Humans; Inflammation; Lipopolysaccharides; Molecular Docking Simulation; Plant Extracts; Rhizome

Rheumatoid arthritis (RA) is a chronic autoimmune disease that significantly affects patient quality of life. Galangin is an extract with multiple health benefits, including anti‑oxidative, anti‑proliferative, immunoprotective and cardioprotective effects. However, to the best of the authors' knowledge, no detailed studies have investigated its regulatory effects on the nuclear factor (NF)‑κB/NLR family pyrin domain containing 3 (NLRP3) signaling pathway. The present study aimed to investigate the protective mechanism of galangin in RA fibroblast‑like synoviocytes with regards to the NF‑κB/NLRP3 signaling pathway. Human RA fibroblast‑like synovium cells (RAFSCs) were treated with lipopolysaccharide (LPS) to induce inflammation. The levels of interleukin (IL)‑1β, tumor necrosis factor (TNF)‑α, IL‑18, inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)‑2, prostaglandin E2 (PGE2), and nitric oxide (NO) were measured by enzyme‑linked immunosorbent assay or western blotting in the absence or presence of different concentrations of galangin. Superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were additionally evaluated. Furthermore, factors involved in the NF‑κB/NLRP3 pathway, including NLRP3, apoptosis‑associated speck‑like protein containing A, IL‑1β, pro‑caspase‑1, caspase‑1, phosphorylated (p)‑NF‑κB inhibitor α and p‑NF‑κB, were assessed by western blotting. The results revealed that LPS significantly stimulated IL‑1β, TNF‑α, IL‑18, PGE2, NO, iNOS, COX‑2 and NF‑κB/NLRP3 factor expression, compared with the control. SOD activity was reduced. Pre‑treatment with galangin significantly attenuated the effects of LPS, and galangin was demonstrated to have effective anti‑oxidative properties. In conclusion, galangin protected RAFSCs through downregulation of the NF‑κB/NLRP3 signaling pathway. These findings suggested that galangin may provide a novel direction for the development of RA therapies in the future.

Topics: Anti-Inflammatory Agents; Arthritis, Rheumatoid; Cells, Cultured; Fibroblasts; Flavonoids; Humans; Inflammation; NF-kappa B; NLR Family, Pyrin Domain-Containing 3 Protein; Protective Agents; Signal Transduction; Synoviocytes

Cisplatin is a widely used chemotherapeutic agent but now-a-days its usage is limited in clinical chemotherapy because of its severe nephrotoxic effect on renal tissues. Galangin, a flavonoid obtained from ginger family has been demonstrated to have antioxidant, anti-apoptotic and anti-inflammatory properties. This study is aimed to investigate the possible ameliorative effect of galangin in a rodent model of cisplatin-induced nephrotoxicity.. Adult male albino wistar rats were divided into six groups (n=6) viz normal, cisplatin-control, galangin (25, 50 and 100mg/kg p.o.) and per se (100mg/kg galangin, p.o.). Galangin was administrated orally to the rats for a period of 10 days. On the 7th day of the treatment, nephrotoxicity was induced in all the groups by a single dose of cisplatin (8mg/kg, i.p.) (except normal and per se group). On the 11th day, the rats were anaesthetized and blood was withdrawn via direct heart puncture for biochemical estimation. Rats were sacrificed and kidneys were isolated and preserved for evaluation of histopathological, ultra structural immunohistochemical studies and western blot analysis.. Cisplatin significantly impaired renal function and increased oxidative stress and inflammation. It also increased expression of pro-apoptotic proteins Bax and caspase-3 and decreased the expression of the anti-apoptotic protein Bcl-2. Histological and ultrastructural findings were also supportive of renal tubular damage. Pretreatment with galangin (100mg/kg p.o.) preserved renal function, morphology, suppressed oxidative stress, inflammation and the activation of apoptotic pathways. TUNEL assay showed decreased DNA fragmentation on galangin pre-treatment. Furthermore, galangin (100mg/kg) pre-treatment also reduced the expression of NFκB along with proteins MAPK pathway i.e. p38, JNK and ERK1/2.. In conclusion, Galangin (100mg/kg, p.o.) significantly ameliorated cisplatin induced nephrotoxicity by suppressing MAPK induced inflammation and apoptosis.

Topics: Acute Kidney Injury; Animals; Anti-Inflammatory Agents; Antineoplastic Agents; Antioxidants; Apoptosis; bcl-2-Associated X Protein; Caspase 3; Cisplatin; DNA Fragmentation; Flavonoids; Inflammation; Kidney; Male; MAP Kinase Signaling System; NF-kappa B; Oxidative Stress; Rats; Rats, Wistar

Parkinson's disease (PD) is caused by the loss of dopaminergic (DA) neurons in the midbrain substantia nigra (SN). Neuroinflammation, which is marked by microglial activation, plays a very important role in the pathogenesis of PD. Pro-inflammatory mediators produced by activated microglia could damage DA neurons. Hence, the inhibition of microglial activation may provide a new approach for treating PD. Galangin has been shown to inhibit inflammation in a variety of diseases, but not PD. In this study, we aimed to investigate the anti-inflammatory effect of galangin and the underlying mechanisms in Lipopolysaccharide (LPS) induced PD models. We first examined the protective effect of galangin in the LPS-induced PD rat model. Specifically, we investigated the effects on motor dysfunction, microglial activation, and the loss of DA neurons. Then, galangin was used to detect the impact on the inflammatory responses and inflammatory signaling pathways in LPS-induced BV-2 cells. The in vivo results showed that galangin dose-dependently attenuates the activation of microglia, the loss of DA neurons, and motor dysfunction. In vitro, galangin markedly inhibited LPS-induced expression of tumor necrosis factor α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β), cyclooxygenase 2 (COX-2), and induced nitric oxide synthase (iNOS) via associating with the phosphorylation of c-JUN N-terminal Kinase (JNK), p38, protein kinase B (AKT), and nuclear factor κB (NF-κB) p65. Collectively, the results indicated that galangin has a role in protecting DA neurons by inhibiting microglial activation.

Topics: Animals; Anti-Inflammatory Agents; Biomarkers; Cell Line; Cell Survival; Disease Models, Animal; Dopaminergic Neurons; Dose-Response Relationship, Drug; Flavonoids; Inflammation; Lipopolysaccharides; Mice; Microglia; Neuroprotective Agents; Parkinson Disease; Rats; Rats, Wistar

A great number of people are suffering from allergic inflammatory disease such as asthma, atopic dermatitis, and sinusitis. Therefore discovery of drugs for the treatment of these diseases is an important subject in human health. In this study, we investigated anti-allergic inflammatory effect of galangin and underlying mechanisms of action using in vitro and in vivo models. Galangin inhibited histamine release by the reduction of intracellular calcium in phorbol 12-mystate 13-acetate plus calcium ionophore A23187-stimulated human mast cells (HMC-1). Galangin decreased expression of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β, and IL-8. The inhibitory effect of galangin on theses pro-inflammatory cytokines was related with c-Jun N-terminal kinases, and p38 mitogen-activated protein kinase, nuclear factor-κB, and caspase-1. Furthermore, galangin attenuated IgE-mediated passive cutaneous anaphylaxis and the expression of histamine receptor 1 at the inflamed tissue. The inhibitory effects of galangin were more potent than cromolyn, a known anti-allergic drug. Our results showed that galangin down-regulates mast cell-derived allergic inflammatory reactions by blocking histamine release and expression of pro-inflammatory cytokines. In light of in vitro and in vivo anti-allergic inflammatory effects, galangin could be a beneficial anti-allergic inflammatory agent.

Topics: Anaphylaxis; Animals; Anti-Allergic Agents; Anti-Inflammatory Agents, Non-Steroidal; Calcium; Caspase 1; Cells, Cultured; Cytokines; Flavonoids; Histamine Release; Humans; Hypersensitivity; Inflammation; Male; Mast Cells; Mice, Inbred ICR; NF-kappa B; p38 Mitogen-Activated Protein 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