Inhibition Of Inflammatory Mediators Research Articles

Inhibition of neutrophil migration and reduction of oxidative stress by ethyl p-coumarate in acute and chronic inflammatory models

BackgroundIt is well known that medicinal plants and their products are relevant candidates for the treatment of inflammatory conditions. Ethyl p-coumarate is a phenylpropanoid that has similar structure to others anti-inflammatory and antioxidant substances. However, these activities have never been tested. PurposeThe aim of this study was to investigate the effect of ethyl p-coumarate on inflammatory and oxidative stress parameters. Study designThis is an experimental study to evaluate the anti-inflammatory and antioxidant activities of ethyl p-coumarate in acute and chronic models of inflammation. MethodsThe anti-inflammatory effect of ethyl p-coumarate was evaluated in Swiss mice by carrageenan-induced paw edema model (1%, 50 μl), followed by histological analysis, and edema induced by compound 48/80 (12 µg/paw), histamine (100 µg/paw), serotonin (100 µg/paw) and prostaglandin E2 (3 nmol/paw) in comparison to indomethacin treatment (10 mg/kg, p.o.). In addition, peritonitis was induced by carrageenan (500 μg/cavity) to neutrophil and total leukocytes counting, myeloperoxidase (MPO), interleukin 6 (IL-6) and 8 (IL-8), nitrite (NO2−), glutathione (GSH) and malondialdehyde (MDA) measurements. The arthritis model was induced with Freund's complete adjuvant (id. 0.1 ml) in female Wistar rats, with measurement of joint diameter and X-ray. Changes in gastric tissue of Swiss mice were analyzed in comparison to indomethacin (20 mg/kg, p.o.). ResultsAfter treatment with ethyl p-coumarate, the animals had no apparent toxic effects, and significantly inhibited paw edema induced by edematogenic agents, neutrophil (p < 0.001) and total leukocyte (p < 0.001) migration, MPO (p < 0.01), IL-6 (p < 0.05) and IL-8 (p < 0.5), MDA (p < 0.5), GSH (p < 0.5), NO2− (p < 0.001), joint thickness and bones changes. Furthermore, were not observed significant formation of gastric lesions. ConclusionTaken together, these results suggest that ethyl p-coumarate exhibits anti-inflammatory activity through the inhibition of inflammatory mediators and leukocyte migration without causing gastric lesions.

Chondroprotective effect of curcumin and lecithin complex in human chondrocytes stimulated by IL-1β via an anti-inflammatory mechanism.

A complex of curcumin and lecithin developed to improve the solubility of curcumin, enhanced its chondroprotective effect via an anti-inflammatory mechanism. In macrophage, proinflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, prostaglandin E2 (PGE2), and nitric oxide (NO) were quantified. In addition, the activity of nuclear factor (NF)-κB was examined. With chondrocytes, inflammatory mediators were assessed by measuring the secretion levels of IL-6, IL-8, and PGE2, also the mRNA expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). Metalloproteinases (MMPs), tissue inhibitor of metalloprotease (TIMP)-1, type II collagen (COL2), proteoglycan (PG), and hyaluronic acid (HA) were measured with respect to the articulation surface. The complex promoted the anti-inflammatory effect by the inhibition of inflammatory mediators. In addition, mRNA expression levels ameliorated. Furthermore, it was effective in decreasing extracellular secretion of polypeptides, also corresponding intracellular MMPs and TIMP-1. In conclusion, the complex may be developed as a functional supplement to maintain articulation health.

Anti‑inflammatory and antitumor action of hydrogen via reactive oxygen species (Review)

Hydrogen (H2) has advantages that lead it to be used as a novel antioxidant in preventive and therapeutic applications. H2 can permeate into biomembranes, cytosol, mitochondria and nuclei, and can be dissolved in water or saline to produce H2 water or H2-rich saline. H2 selectively reduces oxidants of the detrimental reactive oxygen species (ROS), including hydroxyl radicals (·OH) and peroxynitrite (ONOO-), which serve a causative role in the promotion of tumor cell proliferation, invasion and metastasis, but do not disturb metabolic oxidation-reduction reactions in cell signaling. Compared with traditional antioxidants, H2 is a small molecule that can easily dissipate throughout the body and cells; thus, it may be a safe and effective antioxidant for inflammatory diseases and cancer, since ROS usually initiates tumor progression. Treatment with H2 may involve correction of the oxidative/anti-oxidative imbalance and suppression of inflammatory mediators. Therefore the present review will discuss the anti-inflammatory and anti-tumorigenic action of H2 via ROS.

Efek Ekstrak Kulit Mangga Arumanis terhadap Penurunan Edema Kaki Mencit Putih Jantan yang Diinduksi Karagenin

&#x0D; Mango is a plant contains many active compounds with health benefits. Total phenolic content of mango peel is higher than mango flesh, with its major component are mangiferin and quercetin. Quercetin has anti-inflammatory effects through the inhibition of inflammatory mediators are serotonin, bradykinin, histamine and prostaglandin, possibly could reduce oedema as a sign of inflammation. This study used carrageenin to induce inflammation by making paw oedema in mice. The aim of this research was to know the effect of arumanis mango peel extract to reduce paw oedema in white male mice. The was quasi experimental study with 7 study groups. Spearman analyses showed a correlation with significance of (p= 0.003) that mean it has a significant correlation (p &lt;0.01) at the 330th min. Spearman correlation coefficients was 0,632, indicated that the dose of extract and paw oedema have strong correlation. It can be concluded that mango peel extract has effect for reducing paw oedema in white male mice, with the smallest dose was 1,002mg / gBW.&#x0D; &#x0D; Keywords: mango, quercetin, paw oedema&#x0D;

Adiponectin inhibits inflammatory cytokines production by Beclin-1 phosphorylation and B-cell lymphoma 2 mRNA destabilization: role for autophagy induction.

Adiponectin potently suppresses inflammatory mediator production. Autophagy is known to play a critical role in the modulation of inflammatory responses by adiponectin. However, the underlying mechanisms are not clearly understood. Interaction between Beclin-1 and B-cell lymphoma 2 (Bcl-2) is a critical event in autophagy induction. We examined the effects of globular adiponectin (gAcrp) on the Beclin-1/Bcl-2 association and its underlying mechanisms. The effect of gAcrp on the interaction between Beclin-1 and Bcl-2 was examined by immunoprecipitation followed by Western blotting. To elucidate the underlying mechanisms, we determined the effects of gAcrp on Beclin-1 phosphorylation and Bcl-2 mRNA stability, and investigated their role in the suppression of inflammatory mediators using pharmacological inhibitors and transient target gene knockdown. Globular adiponectin disrupted the association between Beclin-1 and Bcl-2 and increased Beclin-1 phosphorylation at Thr119 , critical residue for binding with Bcl-2, via a death-associated protein kinase-1 (DAPK1)-dependent mechanism. Moreover, gAcrp reduced Bcl-2 expression via Bcl-2 mRNA destabilization, without significantly affecting Bcl-2 promoter activity and protein degradation, which was mediated by tristetraprolin (TTP) induction. Finally, DAPK1 and TTP were shown to play key roles in gAcrp-induced autophagosome formation and suppression of LPS-stimulated TNF-α and IL-1β expression. Beclin-1 phosphorylation and Bcl-2 mRNA destabilization mediated by DAPK1 and TTP are crucial events leading to autophagy and the suppression of inflammatory cytokine production by gAcrp. These results provide novel mechanisms underlying adiponectin's modulation of inflammatory responses. DAPK and TTP are potential therapeutic targets for the management of inflammation.

Disease modifying activity of Picrorhiza kurroa rhizome extract in experimental arthritis via inhibition of inflammatory mediators, MAPK phosphorylation and modulation of HO-1/Nrf-2 pathway

Disease modifying activity of Picrorhiza kurroa rhizome extract in experimental arthritis via inhibition of inflammatory mediators, MAPK phosphorylation and modulation of HO-1/Nrf-2 pathway

Anti-inflammatory activity of Echium amoenum extract on macrophages mediated by inhibition of inflammatory mediators and cytokines expression.

Echium amoenum (Boraginaceae) is an important remedy used for various illnesses. In this study, we investigated the anti-inflammatory effects of E. amoenum in the J774.1A macrophage cell line. We prepared ethyl acetate, dichloromethane and hexane extracts from E. amoenum flowers and examined their possible cytotoxic effects using MTT assay. Lipopolysaccharide (LPS)-stimulated macrophages were treated with the extracts after which we measured nitric oxide (NO) production by Griess method. Inducible NO synthase (iNOS), cyclooxygenase-2 (COX2), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 gene expressions were examined by real time-PCR. IL-1β and IL-6 cytokine levels were measured by enzyme-linked immunosorbent assay (ELISA). The hexane extract with a half maximal inhibitory concentration (IC50) of 39.8 μg/mL most effectively reduced NO production. Real time-PCR analysis indicated reduced levels of iNOS ((0.05 ± 0.006 relative fold change (RFC)) and COX2 (0.06 ± 0.002 RFC) gene expressions with the 100 μg/mL hexane extract (P < 0.001). IL1-β, TNF-α, and IL-6 gene expression levels decreased at all concentrations of the extract (less than ≈ 0.28 RFC). Treatment of LPS-stimulated cells with 100 μg/mL of the extract reduced IL-1β secretion to 27.9 ± 0.21 pg/mL and IL-6 to 555 ± 166 pg/mL. In conclusion, E. amoenum hexane extract showed the greatest reduction in macrophage NO secretion compared to other extracts. This extract could modulate the inflammatory mode of the macrophages by causing reductions in iNOS and COX2 enzymes as well as IL-1β, IL-6, and TNF-α cytokine levels. The results of this study have shown the anti-inflammatory effects of this plant. Further studies regarding its therapeutic potential in inflammatory disorders are recommended.

Antidiabetic and antioxidant activity of ethyl acetate extract fraction of Moringa oleifera leaves in streptozotocin-induced diabetes rats via inhibition of inflammatory mediators

Objective: To evaluate the antioxidant and antidiabetic mechanism(s) of ethyl acetate extract fraction of Moringa oleifera (M. oleifera) leaves on streptozotocin-induced diabetes in male Sprague-Dawley rats. Methods: A total of 24 adult male rats were segregated randomly into four groups (6 rats each group). Streptozotocin-induced diabetes rats were given (oral gavage) ethyl acetate extract fraction of M. oleifera (200 mg/kg b.w.) for 30 d. The rats of control and experimental groups were sacrificed after 24 hours of final dose of treatment, to extract blood and pancreatic tissue for biochemical and histopathological analysis. Results: The ethyl acetate extract fraction of M. oleifera significantly reversed (P

Antiallodynic and antihyperalgesic activities of zerumbone via the suppression of IL-1β, IL-6, and TNF-α in a mouse model of neuropathic pain.

BackgroundNeuropathic pain is a debilitating condition that severely affects the quality of life for those with this pain condition, and treatment for pain relief is greatly sought-after. Zerumbone (Zer), a sesquiterpene compound isolated from the rhizomes of a Southeast Asian ginger plant, Zingiber zerumbet (L.) Roscoe ex Smith. (Zingiberaceae), showed antinociceptive and antiinflammatory properties when previously tested on models of nociception and inflammation.ObjectiveThis study investigated the effects of prophylactic administration of zerumbone on allodynia and hyperalgesia in a mouse model of chronic constriction injury (CCI)-induced neuropathic pain.MethodsIntraperitoneal administration of Zer (5–50 mg/kg) from day 1 post-surgery was carried out to identify the onset and progression of the pain condition. Responses toward mechanical and cold allodynia, and mechanical and thermal hyperalgesia were assessed on days 3, 5, 7, 9, 11, and 14 post-surgery. Blood plasma and spinal cord levels of interleukin (IL)-1β, IL-6, tumor necrosis factor-α, and IL-10 were screened using enzyme-linked immunosorbent assay on day 15.ResultsZer (10 and 50 mg/kg) attenuated pain symptoms on all days of behavioral testing without any signs of sedation in the rotarod test. ED50 values for mechanical allodynia, cold allodynia, thermal hyperalgesia, and mechanical hyperalgesia were 9.25, 9.507, 8.289, and 9.801 mg/kg, respectively. Blood plasma and spinal levels of IL-1β, IL-6, and tumor necrosis factor-α but not IL-10 were significantly (p<0.05) suppressed by zer treatment.Discussion and conclusionZer exhibits its antiallodynic and antihyperalgesic properties via reduced sensitization at nociceptor neurons possibly through the suppression of inflammatory mediators. Zer may prove to be a novel and beneficial alternative for the management of neuropathic pain.

Clinical efficacy of recombinant human latrophilin 3 antibody in the treatment of pediatric asthma.

Pediatric asthma is a chronic pulmonary inflammatory disease featuring hypersecretion of mucus and inflammation in the airway, resulting in dysfunction of the airway smooth muscle. Previous evidence demonstrated that latrophilins, a novel family of receptors, present a beneficial effect on airway smooth muscle cells. In the present study, the therapeutic effects of recombinant human latrophilin 3 (rhLPHN3) antibody (Ab) in patients with pediatric asthma were investigated, and the molecular mechanism underlying the function of LPHN3 in the treatment of asthma in clinical practice was examined. A total of 342 pediatric asthma cases were recruited and randomly divided into three groups, receiving treatment with rhLPHN3 Ab (n=134), salbutamol (n=108) or montelukast (n=100) by nasal aerosolization. Each group received the respective clinically tested dose for 16 weeks. Inflammatory factors interleukin (IL)-10, IL-17, IL-4, matrix metallopeptidase-9 (MMP-9), interferon-γ (IFN-γ) and transforming growth factor-β (TGF-β) levels in peripheral blood mononuclear cells were analyzed prior to and post treatment. The clinical outcomes revealed that pathological alterations were significantly improved following treatment with rhLPHN3 Ab for patients with pediatric asthma when compared with those receiving salbutamol and montelukast. It was also observed that rhLPHN3 Ab downregulated the plasma concentration levels of IL-10, IL-17, IL-4 and MMP-9, and upregulated IFN-γ and TGF-β levels in the three groups. In addition, clinical data demonstrated that rhLPHN3 Ab significantly promoted E-selectin and mucin 5AC expression, as well as improved the activation of nuclear factor (NF)-κB p65 DNA binding activity and the phosphorylation levels of protein kinase A. Furthermore, rhLPHN3 Ab markedly improved adhesion and proliferation of airway smooth muscle cells, which led to promotion of the contraction of these cells. In conclusion, these clinical data suggest that rhLPHN3 Ab serves an important role in the inhibition of inflammatory mediators through downregulation of NF-κB signaling pathway, which contributes to airway remodeling and bronchodilation in patients with pediatric asthma.

Abstract SY06-01: Tumor-associated myelomonocytic cells as therapeutic targets

Abstract SY06-01: Tumor-associated myelomonocytic cells as therapeutic targets

Anti-inflammatory effect of Naravelia zeylanica DC via suppression of inflammatory mediators in carrageenan-induced abdominal oedema in zebrafish model.

The traditional herbal medicines are receiving great importance in the health care sector, especially in Indian system of medicine, i.e, Ayurveda. The present study focused on the standardization of Naravelia zeylanica (L.) DC in terms of its active phytochemicals and to evaluate the anti-inflammatory activity of ethanol extract of N. zeylanica (ENZ). An analytical method was developed by high-performance liquid chromatography for simultaneous determination of β-sitosterol, lupeol and oleanolic acid in ENZ. The cell viability of ENZ was investigated using MTT assay. IC50 value of ENZ on cell viability was found to be 653.01µg/mL. To determine the anti-inflammatory activity of ENZ by in vitro method, LPS was added to the macrophage cells to induce activation and ENZ was further added to observe the recovery of inflamed cells. These cells when treated with ENZ, the percentage of viable cells were considerably increased to 74.68%. Loss of mitochondrial membrane potential on treatment with LPS and its recovery by ENZ was studied and found that the number of cells that were damaged on treatment with ENZ+LPS was comparatively lesser than treatment with LPS only. An in vivo anti-inflammatory study was carried out in carrageenan-induced abdominal oedema method in adult zebrafish which revealed the percentage inhibition of inflammation at graded dose levels of ENZ as 23.5% at 100mg/kg, 62.4% at 200mg/kg and 87.05% at 350mg/kg when compared with standard of diclofenac which showed 85% inhibition at 100mg/kg. The PCR amplification of DNA extracted from adult zebrafish showed that increased concentration of ENZ considerably downregulates the expression of TNF-α and iNOS, the mediators of inflammation.

Aloe Metabolites Prevent LPS-Induced Sepsis and Inflammatory Response by Inhibiting Mitogen-Activated Protein Kinase Activation.

Aloe, a polyphenolic anthranoid-containing Aloe vera leaves, is a Chinese medicine and a popular dietary supplement worldwide. In in vivo situations, polyphenolic anthranoids are extensively broken down into glucuronides and sulfate metabolites by the gut and the liver. The anti-inflammatory potential of aloe metabolites has not been examined. The aim of this study was to investigate the anti-inflammatory effects of aloe metabolites from in vitro (lipopolysaccharides (LPS)-activated RAW264.7 macrophages) and ex vivo (LPS-activated peritoneal macrophages) to in vivo (LPS-induced septic mice). The production of proinflammatory cytokines (TNF-[Formula: see text] and IL-12) and NO was determined by ELISA and Griess reagents, respectively. The expression levels of iNOS and MAPKs were analyzed by Western blot. Our results showed that aloe metabolites inhibited the expression of iNOS, decreased the production of TNF-[Formula: see text], IL-12, and NO, and suppressed the phosphorylation of MAPKs by LPS-activated RAW264.7 macrophages. In addition, aloe metabolites reduced the production of NO, TNF-[Formula: see text] and IL-12 by murine peritoneal macrophages. Furthermore, aloe administration significantly reduced the NO level and exhibited protective effects against sepsis-related death in LPS-induced septic mice. These results suggest that aloe metabolites exerted anti-inflammatory effects in vivo, and that these effects were associated with the inhibition of inflammatory mediators. Therefore, aloe could be considered an effective therapeutic agent for the treatment of sepsis.

Acupuncture ameliorates inflammatory response in a chronic unpredictable stress rat model of depression.

Depression is one of the most common psychiatric disorders. Chronic inflammatory response has been viewed as a key factor in depression. Acupuncture in Chinese medicine has been shown to be an effective treatment for depression. In the present study, we investigated the mechanism underlying antidepressant effect of acupuncture. The rats were subjected to chronic unpredictable mild stress (CUMS) for 28days to induce depressive-like behaviors. Acupuncture treatment was applied once every other day during the 28-day stress period. The behavioral tests (body weight, sucrose consumption and locomotor activity) were performed. The expressions of nitric oxide (NO), prostaglandin E2 (PGE2), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and nuclear factor kappa B (NF-κB) were determined in the rat hippocampus and prefrontal cortex. CUMS induced depressive-like behavior in rats, which was alleviated by acupuncture treatment. The increased levels of NO, PGE2, iNOS and COX-2 induced by CUMS, were all significantly decreased in the hippocampus and prefrontal cortex by acupuncture. Moreover, acupuncture markedly inhibited the activation of NF-κB in rats. These findings showed that the antidepressant-like effect of acupuncture might be mediated by inhibition of inflammatory mediators via modulation of NF-κB in the brain regions.

Protective effects of active hexose correlated compound in a rat model of liver injury after hepatectomy

Background: Recent evidence has indicated that a functional food, active hexose correlated compound (AHCC), has liver-protective effects via suppression of inflammatory mediators, such as inducible nitric oxide synthase (iNOS) and tumor necrosis factor (TNF)-α.Objective: This study aimed to investigate whether AHCC has beneficial effects in a rat model of endotoxin-induced liver injury after partial hepatectomy, in addition to clarifying the mechanisms of action of AHCC.Methods: Rats were treated with 70% of partial hepatectomy and lipopolysaccharide (PH/LPS) to induce acute liver injury. A normal diet with or without 2% AHCC was administered orally 10 days before 70% hepatectomy. Inflammatory mediators were analyzed.Results: AHCC improved the survival rate by 70% in PH/LPS rats. AHCC prevented an increase in serum transaminase levels, and histopathological changes and apoptosis in the liver. AHCC reduced iNOS mRNA and protein expression in the liver, resulting in inhibition of nitric oxide production. AHCC also reduced TNF-α, cytokine-induced neutrophil chemoattractant-1, and interleukin-6 mRNA expression, but enhanced expression of interleukin-10. An electrophoretic mobility shift assay with hepatic nuclear extracts demonstrated that AHCC reduced the activation of nuclear factor (NF)-κB induced by PH/LPS treatment.Conclusion: AHCC inhibits induction of inflammatory mediators, including iNOS and TNF-α, in part through inhibition of NF-κB activation in a rat model of liver injury. Our findings suggest that AHCC prevents postoperative liver failure after liver resection.Keywords: active hexose correlated compound, inducible nitric oxide synthase, liver injury, nuclear factor-κB, tumor necrosis factor-α

A Review of Pharmacognostical Studies on Moringa oleifera Lam. flowers

Moringa oleifera Lam. of the family Moringaceae, popularly called ‘miracle tree’ is a native of sub Himalayan tracts of Northern India and is widely cultivated in tropical and subtropical regions. Research on Moringa mainly pivoted around its leaves and seeds because of their immense nutraceutical potential but recently there is a greater interest in flowers too, mostly inspired by the positive outcomes of several pharmacognostical studies on flowers. Moringa flower is a rich reservoir of bioactive phytochemicals and crude flower extracts showed promising antibacterial, antifungal, anti larval, antioxidant, anti inflammatory and anticancer properties. This review concisely presents the various phytochemicals identified and isolated as well as the various bioassays employed to validate the therapeutic potential of flower. It is prepared after a detailed search on Google scholar. Reports on Moringa oleifera flower were sorted and tabulated based on the bioassays performed and solvents used for extraction. A grading pattern is adopted for comparing efficiency of different extracts in eliciting bioactivities. Many of these studies are at the preliminary stage but two of them present advanced mechanisms. First is the presence of a proteinaceous larvicidal compound ‘MoFTI’ in the flower capable of inhibiting larval trypsin of Aedes aegypti. The second describes flower extract’s anti inflammatory mechanism effecting via NF-KB pathway and consequent suppression of inflammatory mediators’ activation, but short of identifying lead compound/compounds behind this effect. Thus authors suggest further studies to elucidate the detailed mechanisms, identify and isolate the active compound or compounds of synergism behind the many therapeutic potential of the Moringa flower extracts.

Piperine attenuates lipopolysaccharide (LPS)-induced inflammatory responses in BV2 microglia

Piperine, the chief alkaloid isolated from Piper nigrum, has been known to have anti-inflammatory effect. However, the effects of piperine on neuroinflammation have not been reported. In the present study, we evaluated the effects of piperine on neuroinflammation in BV2 microglia and investigated the molecular mechanism. The results showed that piperine significantly inhibited LPS-induced TNF-α, IL-6, IL-1β, and PGE2 production in BV2 cells. Western blot analysis showed that piperine dose-dependently inhibited LPS-induced NF-κB activation. Furthermore, piperine was found to amplify the expression of Nrf2 and HO-1 up-regulated by LPS. In addition, the inhibition of inflammatory mediators by piperine can be reversed by transfection with Nrf2 siRNA. In conclusion, piperine inhibited LPS-induced inflammatory response by activating Nrf2 signaling pathway. These results indicated that piperine may be a promising agent for the treatment of neurodegenerative diseases.

428 - The Fruit of Acanthopanax Senticosus (Rupr. Et Maxim) Harms, or Goka, Improves Insulin Resistance in High-Fat Diet Fed Obese Mice

Insulin resistance is a risk factor for metabolic disease including type 2 diabetes and dyslipidemia that is induced by obesity associated chronic inflammation and oxidative stress. Therefore, the treatments of the inflammation and/or oxidative stress are important to improve the insulin resistance. Acanthopanax Senticosus (Rupr. et Maxim) Harms (Goka) has been applied to traditional Chinese medicine, due to its anti-inflammatory and anti-oxidative effects (though detailed information are not available to date). Thus, Goka might lead to the improvement in the status of insulin resistance. The aim of the present study was to investigate whether Goka fruit (GF) improves insulin resistance via the suppression of inflammatory mediators and oxidative stress. After eight weeks induction of high-fat diet, mice were divided into four groups; vehicle (HFD), HFD-GF (500 mg/kg and 1000 mg/kg), and HFD-metformin (MET) (300 mg/kg) for 12 weeks of oral administration, respectively. Insulin tolerance test revealed that HFD-GF groups significantly decreased plasma glucose level than HFD. HFD-GF group exhibited significant reduction of hepatic lipid accumulation rather than HFD. In the adipose tissues, expression of cyclooxygenase-2 (COX-2) and tumor necrosis factor-alpha (TNF-α) were tend to decreased by HFD-GF administration rather than HFD. Thiobarbituric acid reactive substance (TBARS) in HFD-GF were tend to lower than that of the HFD group. These results suggest that GF improved the HFD induced insulin resistance through the alleviate obesity associated inflammation and oxidative stress in the peripheral tissue.

Asiatic acid inhibits pulmonary inflammation induced by cigarette smoke

Asiatic acid (AA) is one of the major components of Titrated extract of Centella asiatica (TECA), which has been reported to possess antioxidant and anti-inflammatory activities. The purpose of this study was to investigate the protective effect of AA on pulmonary inflammation induced by cigarette smoke (CS). AA significantly attenuated the infiltration of inflammatory cells in bronchoalveolar lavage fluid (BALF) of CS exposure mice. AA also decreased ROS production and NE activity, and inhibited the release of proinflammatory cytokines in BALF. AA reduced the recruitment of inflammatory cells and MCP-1 expression in lung tissue of CS exposure mice. AA also attenuated mucus overproduction, and decreased the activation of MAPKs and NF-kB in lung tissue. Furthermore, AA increased HO-1 expression and inhibited the reduced expression of SOD3 in lung tissue. These findings indicate that AA effectively inhibits pulmonary inflammatory response, which is an important process in the development of chronic obstructive pulmonary disease (COPD) via suppression of inflammatory mediators and induction of HO-1. Therefore, we suggest that AA has the potential to treat inflammatory disease such as COPD.

Abstract 2607: Honokiol, a phytochemical from magnolia plant, prevents UV radiation-induced immune suppression in mice through inhibition of PGE2 and DNA methylation

Abstract The exposure of ultraviolet radiation (UVR) to murine skin suppresses the development of allergic contact hypersensitivity (CHS) response which is considered to be a prototypic T-cell mediated immune response. UVR-induced suppression of immune system has been implicated in skin cancer risk. Honokiol has been shown to have anti-skin carcinogenic activity, and here we have assessed the effect of honokiol on UVR-induced immunosuppression and its possible mechanism of action. Our CHS experiments revealed that exposure of C3H/HeN mouse skin with UVB radiation (150 mJ/cm2) for 4 consecutive days resulted in significant suppression of CHS response (75%, P&amp;lt;0.001) to the skin contact sensitizer, 2,4-dinitrofluorobenzene (DNFB), which was associated with the enhancement in the levels of cyclooxygenase-2 (COX-2) expression and prostaglandin E2 (PGE2) production. Topical treatment of mice with honokiol (0.5 and 1.0 mg/cm2 skin area) in hydrophilic-cream based topical formulation or indomethacin (50 μg/mouse), a COX-2 inhibitor, significantly inhibits UV radiation-induced suppression of CHS response (P&amp;lt;0.01-0.005). The exposure of mice with UVB resulted in DNA hypermethylation, increase in DNA methyltransferase (Dnmt) activity, and elevated levels of Dnmt proteins in mouse skin, while treatment of mice with honokiol before each UVB exposure reduced the levels of DNA methylation as well as Dnmt activity compared with non-honokiol-treated control mice. The COX-2 deficient mice are resistant to UV-induced suppression of CHS response. Treatment of UVB exposed COX-2-deficient mice with PGE2 (50 μg/mouse/day) results in UV-induced suppression of CHS, increase in DNA methylation and Dnmt activity in the skin. Further, treatment of honokiol reversed the effect of PGE2 on UV-induced suppression of CHS response in COX-2-deficient mice. Treatment of C3H/HeN mice with 5-aza-2’-deoxycytidine (5-Aza-dc, 1.0 mg/kg body weight, i.p.), a DNA demethylating agent, after each UVB exposure restored the CHS response which was associated with a reduction in Dnmt activity and global DNA methylation levels compared to the UV-exposed mice which were not treated with 5-Aza-dc. We also compared the effect of honokiol with commercially available anti-cancer drugs, such as imiquimod and 5-fluorouracil, on CHS response in UV-exposed mice. Topical treatment of mice with equi-molar concentrations of honokiol and cancer drugs did not show significant difference in terms of inhibition of UVB induced immune suppression and thus suggests honokiol as a substitute for these drugs. These findings provide evidence that honokiol acts through inhibition of inflammatory mediators and subsequently DNA demethylation in UVR-exposed mouse skin. Citation Format: Santosh K. Katiyar, Tripti Singh, Ram Prasad. Honokiol, a phytochemical from magnolia plant, prevents UV radiation-induced immune suppression in mice through inhibition of PGE2 and DNA methylation. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2607.