Potent Anti-inflammatory Compound Research Articles

Bioassay-guided isolation and UHPLC-DAD-ESI-MS/MS quantification of potential anti-inflammatory phenolic compounds from flowers of Inula montana L

Ethnopharmacological relevanceFlowers of Inula montana L. (Asteraceae), commonly known as “Arnica de Provence”, are used in the traditional medicine of Provence in France with the same indication as Arnica montana, for the relief of bruises, as an anti-inflammatory agent. Aims of the studyThe aim of our study is to evaluate its anti-inflammatory properties and to justify its traditional uses. Its potential valorization is evaluated in order to propose Inula montana as an alternative to Arnica montana. Materials and methodsBio-guided fractionation of ethanolic extract allowed the isolation of compounds responsible of the inhibition of NO production. The fractionation was realized using chromatographic techniques and structure elucidation was conducted by ESI-MS and NMR spectral data. Anti-inflammatory effect of ethanolic extract, different fractions and isolated pure compounds was studied in vitro on immortalized mouse macrophages RAW 264.7. An analytical UHPLC-DAD-ESI-MS/MS method was developed for the identification of these compounds in the herbal drug. This UHPLC-DAD method was validated and was used to compare the phenolic profile and content in plant material from the two collection sites: Bonnieux and Merindol. ResultsEleven compounds were identified by UHPLC-MS. Chlorogenic acid (1), Luteolin (2), Nepetin (3), 3,5-O-Dicaffeoylquinic acid (4), 1,5-O-Dicaffeoylquinic acid (5), Nepitrin (6), Hispiduloside (7) and Jaceosid (8) were isolated and identified by NMR. Compounds 9, 10 and 11 were confirmed to be 6-Hydroxykaempferol 3,7-dimethyl ether, Hispidulin and Chrysosplenol C, respectively by comparing retention times and MS/MS data with those of the authentic substances. Six compounds: 1 and 4–8 are reported for the first time in Inula montana L. Compounds 2–8 showed promising anti-inflammatory activity with the release of NO with IC50 value < 7 µM. The UHPLC-DAD method of quantification of three major bioactive compounds (1, 3 and 5) was validated. ConclusionFlowers extracts and isolated compounds present promising anti-inflammatory activity which provides a scientific basis for the traditional use of Inula montana and may be proposed in the same indications as Arnica montana. The developed and validated simple, accurate and rapid UHPLC method can be used for the quality control of the herbal drug.

Chlorogenic Acid Protects Against oxLDL-Induced Oxidative Damage and Mitochondrial Dysfunction by Modulating SIRT1 in Endothelial Cells.

Endothelial dysfunction is an important mechanism in the development of atherosclerosis and is thought to be critical for predicting cardiovascular diseases. Previous reports suggested that chlorogenic acid (CGA) is a potent antioxidant and anti-inflammatory compound. The molecular mechanisms underlying the inhibitory effects of CGA on oxLDL-induced oxidative injuries in human endothelial cells are still largely unknown. This study is aimed to test the hypothesis that CGA protects against oxLDL-facilitated oxidative stress by upregulating SIRT1 and to explore the role of AMPK/PGC-1 pathway and mitochondrial biogenesis. HUVECs were treated with oxLDL in the presence or absence of CGA pretreatment. Our data indicated that CGA pretreatment increased SIRT1 deacetylase activity levels. In addition, CGA reversed oxLDL-impaired SIRT1 and AMPK/PGC-1 activity and mitigated oxLDL-induced oxidative stress and dysfunction of mitochondrial biogenesis. However, silencing SIRT1, AMPK, and PGC-1 abated the ability of CGA to protect against oxidative stress. Results from the present study also suggested that CGA inhibits oxLDL-induced endothelial apoptosis through modulating SIRT1 and AMPK/PGC-1 function. These findings provide new insights into possible molecular mechanisms by which CGA mitigates oxLDL-induced endothelial oxidative stress and mitochondrial dysfunction by activating SIRT1 and modulating the AMPK/PGC-1 signaling pathway.

Triptolide, a HSP90 middle domain inhibitor, induces apoptosis in triple manner.

Triptolide (TL) is a potent anti-tumor, anti-inflammatory and immunosuppressive natural compound. Mechanistic studies revealed that TL inhibits tumor growth and triggers programmed cell death. Studies further suggested that TL inhibits heat shock response in cancer cells to induce apoptosis. HSP90β is the major component of heat shock response and is overexpressed in different types of cancers. Given almost all identified HSP90β inhibitors are either N or C-terminal inhibitors, small molecules attacking cysteine(s) in the middle domain might represent a new class of inhibitors. In the current study, we showed that TL inhibits HSP90β in triple manner. Characterization suggests that TL inhibits ATPase activity by preventing ATP binding thus blunts the chaperone activity. TL disrupts HSP90β-CDC37 (co-chaperone) complex through middle domain Cys366 of HSP90β and causes kinase client protein degradation. At the cellular level, the TL-mediated decrease in CDK4 protein levels in HeLa cells causes reduced phosphorylation of Rb resulting in cell cycle arrest at the G1 phase. Furthermore, our results demonstrated that TL triggers programmed cell death in an HSP90β-dependent manner as knockdown of HSP90β further sensitized TL-mediated cell cycle arrest and apoptotic effect. Surprisingly, our data showed that TL is the first drug to be reported to induce site-specific phosphorylation of HSP90β to drive apoptosome formation in the early phase of the treatment.In summary, our study established that TL is a novel middle domain HSP90β inhibitor with bi-phasic multi-mechanistic inhibition. The unique regulatory mechanism of TL on HSP90β makes it an effective inhibitor.

17.4 POSSIBLE MECHANISMS INVOLVED IN THE ANTIPSYCHOTIC EFFECTS OF CANNABIDIOL (CBD)

BackgroundLaboratory rodents and human studies have demonstrated that cannabidiol (CBD) presents antipsychotic effects. Several mechanisms of action have been associated to CBD effects. Most of the studies that have investigated these mechanisms have been performed in vitro and their relevance for the in vivo effects of this drug is still uncertain.MethodsIn spite of its low affinity for CB1 receptor (CB1R), CBD is capable of antagonizing CB1R agonists at reasonable low concentrations. CBD can also inhibit anandamide uptake and metabolism, enhancing endocannabinoid tonus. It is also possible to attribute the antipsychotic action of CBD to an antagonism of CB1R. This suggestion was reinforced by the observation that patients in the initial prodromal states of psychosis and patients with schizophrenia had higher levels of anandamide in CSF than health controls. Moreover, there would be a decrease in glutamatergic inputs from this area to the prefrontal cortex, impairing locomotor activity and working memory and endocannabinoids could regulate this system. CBD could facilitate endocannabinoids “on demand” synthesis in post-synaptic neurons, acting pre-synaptic terminals and negatively regulating the release of neurotransmitters, particularly GABA and glutamate.ResultsAlso, an increase in anandamide levels induced by CBD could attenuate GABA release from ventral pallidum neurons, restoring the normal function of this system in psychotic patients. CBD can also increase adult neurogenesis in mice and that this effect has been shown to be dependent on the CB1 receptors. In addition to the mechanisms discussed above, CBD can produce several other effects that could also be involved to be responsible for its antipsychotic properties, including interaction with 5HT1A and TRPV1 receptors and anti-inflammatory/neuroprotective effects. CBD can act as a serotonin 1A receptor (5HT1A) agonist, although the role of 5-HT1A-mediated neurotransmission in schizophrenia is unclear, aripiprazole, an atypical antipsychotic, acts as a partial agonist at this receptor, an effect that could, together with its actions on D2 and 5-HT2A receptors, contribute to therapeutic effects of this drug. CBD can also activate Transient Receptor Vanilloid-1 (TRPV1) receptors that are expressed in several brain areas related to psychosis such as the prefrontal cortex, amygdala and hippocampus. Since CBD is also a potent anti-inflammatory, antioxidant and neuroprotective compound, it is possible that these effects are involved in its antipsychotic action.DiscussionSince CBD is also a potent anti-inflammatory, antioxidant and neuroprotective compound, it is possible that these effects are involved in its antipsychotic action.

Investigation of chronic efficacy and safety profile of two potential anti-inflammatory bipyrazole-based compounds in experimental animals.

PurposeAlthough nonsteroidal anti-inflammatory drugs are widely used to treat a variety of disorders, their administration is associated with gastrointestinal side effects, acute kidney injury and liver enzymes’ elevation. Accordingly, researchers are encouraged to create novel agents with better safety profile. The aim of the current study was to evaluate the chronic efficacy and safety profile of two compounds previously proven to have acceptable acute anti-inflammatory and analgesic activities.Materials and methodsDoses were determined through formalin-induced mice paw edema-based dose–response curves. Granuloma weight was used to assess the chronic effect of the investigated compounds as compared to the vehicle and diclofenac representing the positive and the negative controls, respectively. Mice kidneys, livers and stomachs were histologically examined. Moreover, troponin I, alanine aminotransferase, aspartate aminotransferase, serum creatinine and blood urea nitrogen levels were measured.ResultsThe results highlight that the granulomas and exudates developed in mice after 7 days of treatment, with compound I and compound II were significantly lower than that of the negative control group. Moreover, compound I showed significantly better anti-inflammatory effect than diclofenac. Troponin level was undetected in all groups. Histopathological examination of the stomach revealed normal mucosa for both tested compounds and controls. Likewise, kidneys showed neither significant histologic alteration nor biomarkers increase as compared to the control over both 7- and 30-day treatment periods. Mice that received the tested compounds or diclofenac exhibited transient liver damage specifically; congestion, vacuolization, necrosis and inflammation after 7 days of treatment which decreased significantly after 30 days of treatment as emphasized by the Suzuki score and biomarker levels.ConclusionSince the tested compounds, specifically compound I, presented a satisfactory chronic safety profile as well as anti-inflammatory effect, it is worth conducting further molecular pharmacological, toxicological and bioavailability studies to elucidate the efficacy of these potential anti-inflammatory bipyrazole compounds.

Violacin A, a new chromanone produced by Streptomyces violaceoruber and its anti-inflammatory activity

A new chromanone derivative, named violacin A (1), was isolated from the fermentation broth of Streptomyces violaceoruber as a potential anti-inflammatory compound. The structure of violacin A was established using comprehensive NMR spectroscopic data analysis together with UV, IR, and MS data. The anti-inflammatory effects and action mechanisms of violacin A were investigated in vitro. The results demonstrated that violacin A attenuated the production of NO, IL-1β, IL-6, and TNF-α as well as inhibited the expression of iNOS in LPS-induced RAW 264.7 cells. Additionally, Western blot and qRT-PCR results revealed that 1 down-regulated pro-inflammatory cytokines expression correlated with the suppression of NF-κB signaling pathway.

Pharmacokinetics and Tissue Distribution Study of Pinosylvin in Rats by Ultra-High-Performance Liquid Chromatography Coupled with Linear Trap Quadrupole Orbitrap Mass Spectrometry.

Pinosylvin is a potential anti-inflammatory and antioxidant compound and the major effective medicinal ingredient in the root of Lindera reflexa Hemsl. However, few investigations have been conducted regarding the pharmacokinetics, excretion, characteristics of tissue distribution, and major metabolites of pinosylvin in rats after oral administration. To better understand the behavior and mechanisms of action underlying the activity of pinosylvin in vivo, we established a simple, sensitive, and reliable ultra-high-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for quantifying pinosylvin in rat plasma, urine, feces, and various tissues (including heart, liver, spleen, lung, kidneys, large intestine, small intestine, and stomach). Noncompartmental pharmacokinetic parameters indicated that pinosylvin is rapidly distributed and taken up by tissues. The time to peak (maximum) concentration (Tmax) was 0.137 h, and the apparent elimination half-life (t1/2) was 1.347±0.01 h. The results of the tissue distribution study suggest that pinosylvin is widely distributed to various tissues; the highest concentration was observed after 10 min in the stomach, followed by the heart, lung, spleen, and kidneys. Results of the excretion study suggest that a small amount of pinosylvin is excreted from the urine and feces in the parent form; the 73 h accumulative excretion ratios of urine and feces were 0.82% and 0.11%, respectively. It is likely that pinosylvin is mostly metabolized in vivo. Nine metabolites were found, and the main metabolic pathways of pinosylvin in rats included glucuronidation, hydroxylation, and methylation. Four metabolites had higher concentrations in the stomach, suggesting that the stomach is a potential target organ of pinosylvin. In conclusion, the present study may provide a material basis for studying the pharmacological action of pinosylvin and provides meaningful information for the clinical treatment of chronic gastritis and gastric ulcers using Radix Linderae Reflexae.

ANTI-INFLAMMATORY AND ANALGESIC ACTIVITIES OF AVOCADO SEED (Persea americana Mill.)

The purpose of this research is to evaluate the anti-inflammatory and analgesic activities of infusion and methanolic extract from avocado seeds. The anti-inflammatory activity was determined using carrageenan-induced paw edema in mice. The analgesic activity was assessed using acetic acid stimuli to induce peripheral pain in mice. Results of this research showed that both all level doses of infusion and methanolic extract of avocado seeds have a significant reduction on the mice paw edema. All level doses of methanolic extract of avocado seeds have a significant reduction on the number of abdominal writhes induced by acetic acid, but only the lowest dose of infusion showed a significant reduction. Our findings suggest that avocado seeds contains potential anti-inflammatory and analgesic compounds which support its traditional use. Further phytochemical studies are required to determine the active compounds are actually responsible for such properties.

Synthesis and Anti-Inflammatory Activity of 2-{[5-(2-Chlorophenyl)-4H-1,2,4-Triazol- 3-YL]Sulfanyl}-1-(Substituted Phenyl)Ethanones

With the aim of obtaining potential anti-inflammatory compounds, 2-{[5-(2-chlorophenyl)-4H-1,2,4-triazol-3-yl]sulfanyl}-1-(phenyl)ethanone and a series of its derivatives were synthesized, purified by flash chromatography, and characterised by spectral and elemental analysis. All the new synthesized compounds were evaluated for their anti-inflammatory activity using carrageenan-induced paw edema test on Wistar albino rats. The results suggest that 1-(4-fluorophenyl)-2-{[5-(2-chlorophenyl)-4H-1,2,4-triazol-3-yl]sulfanyl}ethanone 7l exhibit remarkable activity when compared with indomethacin even in the absence of carboxyl group in its structure, which reduces the possibility of gastric irritation.

Inhaled Simvastatin Nanoparticles for Inflammatory Lung Disease

Current inhaled treatments are not adequate to treat all lung diseases. In this study, a promising nanotechnology has been developed to deliver a potential anti-inflammatory and muco-inhibitory compound, simvastatin, for treatment of inflammatory lung diseases via inhalation. Simvastatin nanoparticles (SV-NPs) encapsulated with poly(lactic-co-glycolic) acid were fabricated using the solvent and anti-solvent precipitation method. SV-NPs were found to be stable up to 9months at 4°C in a freeze-dried form prior to reconstitution. The amount of mucus produced was significantly reduced after SV-NPs treatment on inflammation epithelial cell models and were effective in suppressing the proinflammatory marker expression. This study suggests that SV-NPs nebulization could potentially be used for the treatment of chronic pulmonary diseases.

Synthesis and PASS-assisted evaluation of coumarin–benzimidazole derivatives as potential anti-inflammatory and anthelmintic agents

Two series of novel derivatives have been designed by coupling medicinally important coumarin and benzimidazole nuclei through different linkers. These compounds have been predicted to be potent anti-inflammatory and anthelmintic by in silico studies using PASS (prediction of activity spectra for substances) software. The compounds are synthesized and evaluated for the predicted activities as well as for their in vitro antioxidant potential. Compounds of first series (4a–4f) are found good to moderate anti-inflammatory agents. Among these, compounds 4b and 4f exhibited maximum anti-inflammatory activity (45% inhibition), which is equivalent to the activity of indomethacin (48% inhibition) after 3 h (peak inflammatory response time). Compounds of second series (5a–5f) exhibit anthelmintic activity. Amongst these, compound 5f has mortality activity marginally higher than albendazole (10–11 s). Compound 5e is found to be the most potent antioxidant with remarkable EC50 value (0.08 µM/mL), which is though a little less than that of ascorbic acid (0.03 µM/mL). In addition, a comparative analysis of calculated Lipinski’s parameters reveals that all test compounds have the propensity to be orally bioavailable. Based on these findings, compounds 4b, 4f, 5e, and 5f are identified as new leads to develop potent anti-inflammatory, anthelmintic, and antioxidant compounds.

Betulinic acid, isolated from the leaves of Syzygium cumini (L.) Skeels, ameliorates the proteinuria in experimental membranous nephropathy through regulating Nrf2/NF-κB pathways

Membranous nephropathy (MN) is associated with increased oxidative stress and inflammatory markers in the kidney. Betulinic acid (BA) is a potent antioxidant and anti-inflammatory compound isolated from the leaves of Syzygium cumini (L.) Skeels. In the present study, we investigated the effects of BA on experimental MN in rats and explored the mechanisms by which it enhances antioxidant activities and resolves inflammatory condition in experimental MN. Passive Heymann nephritis (PHN) was induced in Sprague-Dawley rats by a single tail vein injection of anti- Fx1A antiserum. The rats were orally administered BA (25 and 50 mg kg −1 d −1) or dexamethasone (DEX; 0.07 mg kg-1, reference compound) for 4 weeks after the induction of PHN. Blood, urine, and kidney tissue were collected for analysis at the end of the study. Treatment of PHN rats with BA or DEX significantly attenuated renal dysfunction, histopathological alterations and reduced immune complex deposition in the kidneys. Furthermore, BA ameliorated mRNA and protein expression of NF-κB, iNOS, TNF-α, Nrf2, HO-1 and NQO1 in the kidney. BA also restored malondialdehyde level and antioxidant enzyme activities in the kidney. In a nutshell, the protective effect of BA can be explained by its anti-inflammatory and anti-oxidant activities, which in turn is due to downregulation of NF-κB pathway and activation of Nrf2. The results indicated that BA can effectively suppress experimental PHN in rats by regulating Nrf2/NF-κB pathways.

In vivo analgesic, anti-inflammatory and antioxidant potentials of Achillea odorata from north Algeria

ObjectiveThe current study aimed at evaluating in Albino mice the analgesic, anti-inflammatory, and antioxidant effects of Achillea odorata; a medicinal plant commonly used in Algerian folk medicine to provide scientific basis for its use. MethodsThe biological tests were performed on aqueous extracts. Antinociceptive activity was estimated using acetic acid that induces algesia in mice. Anti-inflammatory activity was investigated using carrageenan-induced paw edema method and the antioxidant effect was performed using MDA, GSH, CAT and SOD estimations. ResultsThe study of the analgesic activity of the A. odorata polyphenolic extract showed a very potent analgesic activity with an ability to inhibit abdominal cramps similar to that of positive control. In addition, evaluation of edema inhibition percentage showed that plant extract has a significant anti-inflammatory activity. In addition, the extract has the ability to modulate the redox potential in vivo, induced by inflammation, which has been demonstrated by the determination of GSH, MDA, CAT and SOD. ConclusionsOur results suggest that A. odorata possesses potential antinociceptive, anti-inflammatory and antioxidant compounds which could be tested as drug candidates against oxidative and inflammation-related pathological processes.

β -Caryophyllene ameliorates the development of experimental autoimmune encephalomyelitis in C57BL/6 mice

Multiple sclerosis is the most common autoimmune inflammatory and demyelinating disease of the central nervous system. The experimental autoimmune encephalomyelitis (EAE) is an appropriate and a well-establish model for studying the pathogenesis of MS. β-caryophyllene (BCP), a natural sesquiterpene found in many plant species, is a potent anti-inflammatory compound. Herein we investigated the in vitro and in vivo immunomodulatory effects of BCP on C57BL/6 mice induced with EAE. BCP was in vitro evaluated (4, 20, and 40μM) on splenocytes obtained from EAE-induced C57BL/6 mice, and in vivo (25 or 50mg/kg/day) orally administered on EAE-mice. The clinical course, body weight, cytokines and oxygen radicals production were investigated in C57BL/6 EAE-mice. In vitro and in vivo immunological responses were evaluated by ELISA, and CNS sections were stained by hematoxylin and eosin methods The in vitro production of H2O2, NO, IFN-γ, and TNF- α was inhibited by BCP (20 and 40μM) in cultured cells from EAE-mice. BCP (25 and 50mg/kg/day) reduced clinical score and severity of EAE and inhibited H2O2, NO, TNF-α, IFN-γ and, IL-17 production. EAE-mice, orally treated with BCP (mainly at 50mg/kg/day), displayed levels of cytokines and clinical signs similar to animals with no EAE disease, demonstrating the therapeutic action of BCP on EAE animals. Histopathological and histomorphometric analysis confirmed that BCP treatment significantly reduced the numbers of inflammatory infiltrates and attenuated neurological damages in the CNS of EAE-mice.

An Active Drimane-Type Lactone from Polygonum jucundum Attenuates Lipopolysaccharide-Induced Acute Lung Injury in Mice Through TLR4-MAPKs Signaling Pathway.

The herbs of Polygonum jucundum Lindex. (Polygonaceae) is a traditional Chinese medicine for inflammatory diseases. 2α-Hydroxyl-3β-angeloylcinnamolide (HAC), a drimane-type sesquiterpenoid, was the major active compound of the ethanol extract of P. jucundum which inhibited the production of inflammatory mediators. However, the biological mechanism of HAC for anti-inflammatory activity has not been reported. In the current study, we investigated whether HAC could suppress the production of inflammatory mediators in lipopolysaccharide (LPS)-induced acute lung injury in mice (ALI) through downregulation of Toll-like receptor 4 (TLR4) and activations of mitogen-activated protein kinases (MAPKs) and inducible protein nitric oxide synthase (iNOS). Moreover, our data indicated that HAC inhibits the overexpression of iNOS and TLR4 in LPS-treated RAW264.7, and also inhibits MAPK signal. These findings suggest that HAC shows anti-inflammatory effects in ALI mice through suppressing TLR4-mediated MAPK pathway in activated macrophages. In addition, six derivatives of HAC obtained by structure modification were investigated for their inhibitory effects on the production of nitric oxide (NO) and tumor necrosis factor-α (TNF-α), suggesting that the acetylation could increase the inhibition of HAC on TNF-α release in LPS-treated RAW264.7 cells. In summary, all these results showed that HAC may be a potential anti-inflammatory lead compound for the treatment of acute lung injury.

Identification of new anti-inflammatory agents based on nitrosporeusine natural products of marine origin

Nitrosporeusines A and B are two recently isolated marine natural products with novel skeleton and exceptional biological profile. Interesting antiviral activity of nitrosporeusines and promising potential in curing various diseases, evident from positive data from various animal models, led us to investigate their anti-inflammatory potential. Accordingly, we planned and synthesized nitrosporeusines A and B in racemic as well as enantiopure forms. The natural product synthesis was followed by preparation of several analogues, and all the synthesized compounds were evaluated for in vitro and in vivo anti-inflammatory potential. Among them, compounds 25, 29 and 40 significantly reduced levels of nitric oxide (NO), reactive oxygen species (ROS) and pro-inflammatory cytokines. In addition, these compounds suppressed several pro-inflammatory mediators including inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), nuclear factor-κB (NF-κB), and thereby can be emerged as potent anti-inflammatory compounds. Furthermore, all possible isomers of lead compound 25 were synthesized, characterized and profiled in same set of assays and found that one of the enantiomer (−)-25a was superior among them.

CYCLOSPORIN H: A NOVEL ANTI-INFLAMMATORY THERAPY FOR INFLUENZA FLU PATIENTS

Relatively little is known about the inflammatory mediators and mechanisms that drive the progression of influenza flu infection to cytokine storm, lung dysfunction, organ failure, and ultimately death. Vaccines and antiviral medications cannot control the excessive host inflammatory response associated with severe influenza flu infection. Studies by Elgebaly et al demonstrated the rapid release of a potent inflammatory mediator, recently named Nourin, by local mammalian tissues in response to injury and infection. Nourin is a formyl peptide that acts through the formyl peptide receptor (FPR) on phagocytic leukocytes. As an initial signal in the innate immunity, Nourin stimulates leukocyte chemotaxis, induces acute and chronic inflammation, and stimulates the release of a number of the cytokine storm mediators from monocytes, neutrophils and endothelial cells. Furthermore, Nourin detected in plasma samples from patients with severe influenza infection was much higher compared to moderate influenza. The Nourin antagonist, Cyclosporin H, is a potent anti-inflammatory compound, which acts as a specific competitive antagonist of formyl peptides on the formyl peptide receptor (FPR) on phagocytic: leukocytes. Cyclosporin H completely blocked neutrophil chemotaxis induced by: (a) the standard formyl peptide, f-MLF, (b) the Staphylococcus aureus bacteria-derived formyl peptide Phenol-soluble modulins, such as PSM3a, plus(c) the host-derived Nourin released by: (1) cultured epithelial cells infected with the PR8 HINI influenza virus for 6.to 24 hours, (2),Nourin detected in the serum of mouse model of HINI Swine flu influenza infection for 6 hours , along with (3) Nourin detected in plasma samples collected from severe and moderate influenza pa- tients. Furthermore, in-vivo treatment by Cyclosporin H in the mouse model of HINI Swine flu influenza infection for 5 days markedly reduced lung inflammation and endothelial cell damage. Thus, two clinical applications for Nourin and its antagonist Cyclosporin H are proposed: Diagnostic Application: The blood Nourin test can be used as a key inflammatory biomarker for "early" detection and monitoring of influenza flu patients proceeding to hyperactive inflammation and, thus, permitting early crucial anti-inflammatory therapy. Therapeutic Application: Cyclosporin H will specifically block Nourin as an important initial stimulant of cytokine mediators, and thus can control the development and progression of cytokine storm plus organ inflammation, which usually initiates 3 to 8 days post influenza. Since Cyclosporin H does not target the virus,, it will not develop drug resistance,and will reduce the host uncontrpolled inflammatory response, induced by both new strains of flu viruses and existing viruses with mutations.

Synthesis of 1-indanones with a broad range of biological activity.

This comprehensive review describes methods for the preparation of 1-indanones published in original and patent literature from 1926 to 2017. More than 100 synthetic methods utilizing carboxylic acids, esters, diesters, acid chlorides, ketones, alkynes, alcohols etc. as starting materials, have been performed. This review also covers the most important studies on the biological activity of 1-indanones and their derivatives which are potent antiviral, anti-inflammatory, analgesic, antimalarial, antibacterial and anticancer compounds. Moreover, they can be used in the treatment of neurodegenerative diseases and as effective insecticides, fungicides and herbicides.

Mangiferin from Pueraria tuberosa reduces inflammation via inactivation of NLRP3 inflammasome

Recent reports have demonstrated the role of phyto-constituents in modulating inflammatory responses. Mangiferin isolated from Mangifera indica is known to induce potent anti-oxidative, anti-diabetic and anti-inflammatory activity. However, the molecular mechanism of its anti-inflammatory activity is not properly understood. In this study we have isolated Mangiferin from the tubers of Pueraria tuberosa (PT-Mangiferin) and analysed the mechanism of its potent anti-inflammatory effects in LPS stimulated RAW 264.7 mouse macrophage cell line and in a carrageenan induced air pouch model. PT-Mangiferin was non-toxic to primary cells but showed significant toxicity and apoptotic effect on cancerous cells. It significantly reduced the production of pro-inflammatory mediators (COX-2, iNOS and TNF-α) in LPS stimulated RAW 264.7 cells. Further, it has also reduced the generation of ROS and inhibited LPS induced NF-kB translocation in these cells. Additionally, PT-Mangiferin significantly reduced inflammation in a mouse air pouch model by inhibiting the infiltration of monocytes and neutrophils and reducing the production of cytokines. These effects were mediated via inactivation of NLRP3 inflammasome complex and its downstream signalling molecules. Taken together these results suggest that PT-Mangiferin is potent anti-inflammatory compound that reduces inflammation and holds promise in development of herbal based anti-inflammatory therapeutics in future.

Novel benzoxazole derivatives DCPAB and HPAB attenuate Th1 cell-mediated inflammation through T-bet suppression

Interferon-γ (IFN-γ), a critical inflammatory cytokine, is primarily produced by T helper 1 (Th1) cells and accelerates the pathogenesis of inflammatory colitis. Pharmacological suppression of IFN-γ production attenuates dysregulated inflammatory responses and may be beneficial for treating inflammatory disease. In this study, we aimed to discover potent anti-inflammatory compounds that suppress IFN-γ production and found that the novel benzoxazole derivatives, 2-((3,4-dichlorophenyl) amino) benzo[d]xazol-5-ol (DCPAB) and 2-((3,4-hydroxyphenyl) amino) benzo[d]xazol-5-ol (HPAB), suppressed IFN-γ production by T cells. Treatment of CD4+ T cells with DCPAB and HPAB selectively inhibited Th1 cell development, and DCPAB more potently suppressed IFN-γ than HPAB did. Interestingly, DCPAB and HPAB significantly suppressed the expression of T-box containing protein expressed in T cells (T-bet) that activates IFN-γ gene transcription. DCPAB additionally suppressed transcriptional activity of T-bet on IFN-γ gene promoter, whereas HPAB had no effect on T-bet activity. IFN-γ suppressive activity of DCPAB and HPAB was impaired in the absence of T-bet but was retrieved by the restoration of T-bet in T-bet-deficient T cells. Furthermore, DCPAB and HPAB attenuated inflammatory colitis development that was induced by CD4+ T cells in vivo. We suggest that the novel benzoxazole derivatives, DCPAB and HPAB, may have therapeutic effects on inflammatory colitis.