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Aim To investigate the mechanism by which formononetin (FN) inhibits mitochondrial dynamic-related protein 1 (DRP1) -NLRP3 axis via intervening the generation of ROS to reduce allergic airway inflammation. Methods In order to establish allergic asthma mouse model, 50 BALB/c mice aged 8 weeks were divided into the control group, model group, FN treatment group and dexamethasone group after ovalbumin (OVA) induction. Airway inflammation and collagen deposition were detected by HampE and Masson staining. Th2 cytokines and superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), and IgE levels in bronchoalveolar lavage fluid (BALF) were measured by ELISA, ROS in BEAS-2B cells was assessed by DCFH-DA staining, DRP1 expression in lung tissue and BEAS-2B cells was detected by immunohistochemistry and immunofluorescence, and the DRP1-NLRP3 pathway was analyzed by immunoblotting. Results FN treatment could effectively ameliorate the symptoms of asthmatic mouse model, including reducing eosinophil accumulation, airway collagen deposition, decreasing Th2 cytokine and IgE levels, reducing ROS and MDA production, increasing SOD and CAT activities, and regulating DRP1-NLRP3 pathway-related protein expression, thereby relieving inflammation. Conclusion FN ameliorates airway inflammation in asthma by regulating DRP1-NLRP3 pathway.
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Aim To discuss the mechanism of Lurong Dabu Decoction on cough variant asthma. Methods Guinea pigs were divided into normal group(CON), model group(OVA), Lurong Dabu Decoction high-dose group(HIGH),low-dose group(LOW), and dexamethasone group(DEX)at random. The CVA model was established by smoking plus injection of OVA, aluminum hydroxide solution and nebulized inhalation to stimulate cough. Gguinea pigs were dissected 24 hours after the last challenge to obtain alveolar lavage fluid(BALF)and lung tissues. Immunoadsorption(ELISA)method was applied to detect the types of inflammatory cells and the content of inflammatory cytokines in BALF; HE and Masson staining of the middle lobe of the left lung were used to observe the pathological changes in lung tissues; immunohistochemical staining was used to observe TLR4 and WNT-5A protein expression and distribution of lung tissues; the protein extracted from the upper lobe of the left lung was used to measure the level of TLR4 and WNT-5A protein in lung tissues by Western blot; immunofluorescence was employed to measure the fluorescence intensity of TLR4 and WNT-5A in lung tissues; flow cytometry was used to detect IL-4 and IFN-γ in guinea pig lung tissues. Results Lurong Dabu Decoction could improve guinea pig airway inflammation, inhibit collagen fiber deposition, reduce the content of IL-4, IL-5, and IL-13 in BALF, and inhibit the protein expression of TLR4 and WNT-5A in lung tissues and increase IFN-γ levels in lung tissues while decreasing IL-4 levels. Conclusion Lurong Dabu Decoction may inhibit the occurrence of CVA through TLR4/WNT-5A signaling pathway.
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Aim To investigate whether notoginsenoside Rl (PNS-R1) alleviates allergic rhinitis (AR) through AMP-activated protein kinase (AMPK)/mitochondrial fission critical protein (DRP1) -mediated mitochondrial fission. Methods Different doses of PNSRl were used to treat ovalbumin (OVA) -induced AR model mice,and the inhibitory effect of PNS-R1 on AR was investigated by observing allergic symptoms such as nasal rubbing and sneezing, as well as HE staining of nasal tissues. Serum IgE levels and nasal lavage fluid (NLF) inflammatory cytokine levels were detected by enzyme-linked immunosorbent assay (ELISA) and apoptosis-related proteins were detected by Western blot. In vitro human nasal epithelial cells (HNEpC) were stimulated with IL-13 to observe apoptosis, mitochondrial membrane potential, cellular ROS and mitochondrial ROS production, as well as the expression levels of AMPK/DRP1, expression levels of the TXNIP/NLRP3 inflammasomes and the translocation of DRP1. Results PNS-R1 attenuated allergic symptoms in AR mice, HE staining reduced inflammatory cells and reduced the levels of OVA-specific IgE in serum, and the levels of IL-4, IL-6, and IL-8 in NLF. PNS-R1 attenuated the apoptosis and ROS production of nasal epithelial cells in AR. In vitro PNS-R1 could up-regulate mitochondrial membrane potential after IL-13 stimulation, reduce ROS and mtROS production, the proportion of apoptotic positive cells, and reduce cleaved caspase-3, Bax, and up-regulate Bcl-2 expression, down-regulate DRP1 phosphorylation (Ser 616) and DRP1 translocation at the mitochondrial membrane in an AMPK-dependent manner, reducing TXNIP/NLRP3 expression. Conclusions PNS-R1 can protect mitochondrial integrity by inhibiting the AMPK/DRP1 signaling axis and its subsequent TXNIP/NLRP3 signaling axis,thereby alleviating rhinitis in AR mice.
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Aim To investigate the protective effect and mechanism of JTE-013 on allergic rhinitis (AR) by regulating mitochondrial injury and apoptosis through RhoA/ROCKl/Drpl pathway. Methods AR model was established by ovalbumin (OVA) in mice. Nasal tissue sections were then stained with HE, TUNEL and DHE. Western blot assay. In vitro, human nasal epithelial cells (HNEpCs) were stimulated with human recombinant interleukin-13 (IL-13), and the effects of JTE-013 and Y27632-related protein expression were detected by Western blot. Immunofluorescence was used to observe the effects of JTE-013 and Y 27632 on total ROS, mitochondrial membrane potential and mitochondrial ROS generation, Drpl translocation and Cyt-c expression in cells. Results JTE-013 reduced the frequency of nose rubbing and sneezing, reduced nasal mucosal thickening and decreased eosinophil infiltration in AR mice. TUNEL and DHE staining results suggested that JTE-013 could inhibit apoptosis and reduce ROS expression in mouse nasal epithelial cells. Western blot showed that both JTE-013 and Y 27632 could significantly reduce RhoA, ROCK1, Drpl and p-Drpl(616), inhibit the expression of apoptotic proteins Bax, cleaved-caspase-3, Cyt-c, cleavedcaspase-9 and up-regulate the expression of p-Drpl (637) and Bcl-2. Immunofluorescence showed that inhibitors of JTE-013 or ROCK1 almost blocked IL-13mediated increase in ROS and mtROS production, inhibited decrease in mitochondrial membrane potential, and blocked Cyt-c expression and Drpl translocation in nasal mucosal epithelial cells. Conclusion JTE-013 can regulate the morphology and function of mitochondria by inhibiting RhoA/ROCKl/Drpl signaling axis, thereby alleviating nasal epithelial cell inflammation in mice with allergic rhinitis.
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Methods The model of heart failure after myocardial infarction was established by left coronary artery liga-tion in rats. Two weeks after modeling, all rats were randomly divided into model group, LGZGD group, and captopril group. Meanwhile sham operation group was set up. The rats were given continuous intragastric administration with drug or distilled water for 28 days, once a day. The behavioral signs of rats in each group were observed. The cardiac function of rats in each group was examined by echocardiography. Serum BNP and NT-ProBNP content were detected by enzyme-linked immunoassay; The changes of myocardial his-topathological and collagen fibers in rats were detected using sirius staining. The contents of oxidative stress index including ROS, SOD in myocardial tissue of rats in each group were observed by DCFH-DA fluorescent probe and Enzyme-linked immunoassay. The ultra-structure of mitochondria was observed by transmission electron microscopy. Expressions of apoptotic proteins ( mitochondrial CytC, cytoplasmic CytC) were detec- ted by Western blot. Expression of proteins related to the Nrf2/BNIP3 pathway were examined by immunoflu-orescence and Western blot. Results LGZGD could significantly improve the cardiac function of rats, reduce the contents of BNP and NT-ProBNP, inhibit the excessive deposition of collagen in myocardial interstiti-um, reduce ROS, increase the content of SOD, improve mitochondrial structure damage, up-regulate the expression of Nrf2 and nuclear translocation, and reduce the expression of BNIP3. Conclusions LGZGD can inhibit the ventricular remodeling and prevent the occurrence of heart failure after myocardial infarction. Its pharmacological effects are mainly related to regulating the Nrf2/BNIP3 pathway, activating Nrf2, promoting its nuclear transfer, and further down-regulating BNIP3 , protecting mitochondrial function, and reducing cardiomyocyte apoptosis.
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Objective To investigate the protective effect and mechanism of polydatin ( PD) on allergic rhinitis (AH) by regulating mitophagy through PINK1- Parkin signaling pathway, and to provide a new target for clinical treatment of AH.Methods Thirty-two BALB/c murine were randomly divided into 4 groups: control group, OVA group, PD low-dose (30 mg • kg 1 ) and high-dose ( 45 mg • kg 1 ) treatment groups.At the end of modeling, the total number of sneezing and nasal nibbing of murine was recorded.HE staining was used to observe the morphology of na- sal mucosal epithelium and eosinophil infiltration.Western blot was used to detect the expression of P1NK1 , Parkin, TOM20 and mitochondrial apoptosis- related proteins Bax, Bcl-2, caspase-3, cleaved- caspase-3 and Cytochrome C.Hie expression of P1NK1 and cleaved-caspase-3 in nasal epithelial cells (HNEpC) was observed by immunofluorescence.Re¬sults The frequency of sneezing and nasal rubbing movements was significantly increased, the nasal mu¬cosa epithelium was thickened, and eosinophils were accumulated in AH murine , these results were reversed after PD treatment.Western blot results shower] that signaling proteins PINK1/Parkin anrl pro-apoptotie pro¬teins, including Bax, caspase-3, cleaved-caspase-3 and Cytochrome C were significantly overexpressed, the expression of TOM20 and Bcl-2 was decreased in OVA group, and PD up-regulated the levels of P1NK1 , Parkin, as well as Bcl-2 and inhibited the expression of TDM20 and pro-apoptotic proteins, while after pre- treatment with mitochondrial division inhibitor 1 ( Mdi- vi-1 ) , the expression of P1NK1 and Parkin was re¬duced , the expression of TOM20 was increased, while PD treatment did not significantly affect this effect.From the immunofluorescence results, it can be seen that the level of P1NK1 was increased after IL-13 stim¬ulation of HNEpCs compared with the control group, and PD further up-regulated the expression of P1NK1 , which was suppressed after pretreatment with Mdivi-1 , while PD did not change this phenomenon.Western blot results for P1NK1 and cleaved-caspase-3 were con¬firmed by immunofluorescence.Conclusion PD may activate mitophagy through the P1NK1 -Parkin signaling pathway, thereby protecting against AR.
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Sphingosine-1-phosphate (SIP) is an important bio- active phospholipid molecule, which is involved in the occurrence and development of cardiovascular diseases such as atherosclerosis, myocardial ischemia and reperfusion injury, myocardial infarction, myocardial fibrosis and myocardial remodeling, and it plays a wide range of biological effects in human cardiovascular system.SIP acts mainly in the form of binding of sphingosine-1-phosphate receptor (SI Pits), selectively binding vascular endothelial cells and smooth muscle cells, which plays a role in the fight against cardiovascular diseases.This paper reviews the biological effects of SIP in cardiovascular system, i- dentifies effective targets in cardiovascular diseases, and alleviates the damage caused by SI P.aiming to provide new ideas for the study of SIP in cardiovascular direction.
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Aim To investigate the effect of astragalin (AG) on airway inflammation in asthmatic mice and its mechanism. Methods Fifty SPF male mice were randomly divided into normal group, asthma model group, and astragalin low (AG25), medium (AG50), and high (AG100) dose groups. A mouse model of asthma was prepared by egg albumin inhalation, the number of cells was counted by Diff-Quik staining after collecting bronchoalveolar lavage fluid (BALF), and IL4, 5, and 13 levels in BALF were measured by ELISA. The inflammatory changes in mouse lung tissues were observed using HE staining. Reactive oxygen species (ROS) levels were measured using a DCFH-DA probe, and superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were measured by colorimetry. IL-4, IL-5, IL-13, NOX2, p47phox, p-NF-κBp65, NF-κBp65, IκBα, p-IκBα and β-actin expressions in lung tissues were detected by Western blot. Results AG significantly reduced the number of inflammatory cells and total cells in BALF, decreased IL-4, IL-5, and IL-13 contents in BALF and lung tissues, and reduced inflammatory cell infiltration in lung tissues. AG inhibited nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) and p47phox expression, decreased ROS levels and MDA levels, increased SOD activity, and inhibited IκBα and NF-κBp65 phosphorylation. Conclusion AG attenuates airway inflammation in asthma by modulating the oxidative stress response through the NOX2/ROS/NF-κB signaling pathway.
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Aim To investigate the efficacy of arctigenin on airway inflammation in a mouse model of asthma and the mechanism related to the SIRT1/NLRP3 signaling pathway. Methods Forty female BALB/c mice of clean grade were selected and divided into control group, OVA model group and ATG group (5, 10 and 20 mg · kg
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The study is to investigate the effect of glaucocalyxin A (GLA) on mast cell-mediated anaphylaxis. The animal welfare and experimental process of this experiment followed the regulations of the Animal Ethics Committee of Yanbian University. BALB/c mice were used in the animal experiment and randomly divided into five groups, control group, model group, and GLA low, medium, and high dose groups (10, 20, and 40 mg·kg-1). Mice were sensitized by intradermal injection of anti-dinitrophenyl-immunoglobulin E (DNP-IgE) into the ears and challenged with a mixture of DNP-human serum albumin (HSA) and 4% evans blue into the tail veins to prepare an animal skin passive cutaneous anaphylaxis (PCA) model, which was collected from both ears for measurement of dye staining and histology. Rat peritoneal mast cells (RPMCs) were used in the cell experiment and divided into control, IgE + antigen (Ag), and IgE + Ag + GLA groups to determine histamine release as well as calcium influx levels. High-affinity IgE receptor (FcεRI)-mediated signaling pathway proteins and HMGB1/TLR4/NF-κB (high mobility group box 1/toll like receptor 4/nuclear transcription factor kappa B) signaling proteins were detected by Western blot. The results of animal experiments suggest that GLA inhibits PCA, reduces evans blue dye exudation, and reduces ear inflammation and ear thickness in mice. The results of cellular experiments suggested that GLA could reduce histamine release and calcium influx, and inhibit tumor necrosis factor-α (TNF-α), interleukin (IL)-4, IL-13, and IL-1β production; Western blot results showed that GLA inhibited FcεRI-mediated phosphorylation levels of spleen tyrosine kinase (Syk), Lck/Yes novel tyrosine kinase (Lyn), tyrosine kinase Fyn (Fyn), growth-factor receptor-bound protein 2 (Gab2), and phospholipase C (PLC) γ1, while GLA inhibited HMGB1/TLR4 signaling pathway to limit NF-κB p65 nuclear metastasis. The results indicate that GLA inhibits mast cell degranulation and attenuates allergic inflammation through the HMGB1/TLR4/NF-κB signaling pathway.
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Aim To investigate whether polydatin re-duces airway inflammation in asthmatic mouse model and explore whether this pathway is related to p38 MAPK/Nrf2/HO-1 . Methods After the establish-ment of the OVA-induced asthmatic mouse model, the animals were injected with 30 mg·kg-1 and 45 mg· kg-1 of polydatin diluted in 0. 2 mL normal saline, while the control group was replaced by normal saline. HE, PAS and Masson staining were used to observe the pathological changes of lung tissue. Diff-Quick staining was used to classify and count the number of inflamma-tory cells in BALF. ELISA was used to detect IgE ex-pressions in BALF. The content of ROS in BALF cells was detected by DHR-123 . The activities of antioxidant enzymes SOD, CAT and MDA in BALF were detected by the enzyme-linked immunosorbent assay kit. The expression of HO-1 in lung tissue was detected by im-munohistochemistry. The protein and mRNA expres-sions of Nrf2 and HO-1 in lung tissue of mice were de-tected by Western blot and RT-PCR. Results Poly-datin treatment significantly reduced inflammatory cell infiltration mucosal secretion, goblet cell proliferation and collagen deposition in the lung tissue of mice, and decreased the number of inflammatory cells and the ex-pression of total IgE and ROS in BALF. It also in-creased the levels of antioxidant enzymes such as SOD and CAT, and lowered the level of MDA. Polydatin re-duced the phosphorylation of p38 MAPK in the lung tissue of mice, enhanced the levels of mRNA and pro-tein expressions of Nrf2 and HO-1 and promoted the nuclear transfer of Nrf2 . The above effects of polydatin were dose-dependent. Conclusions Polydatin exerts anti-oxidative effects in OVA-induced asthmatic mouse model via anti-oxidant pathway. The mechanism may be achieved through the p38 MAPK/Nrf2/HO-1 path-way.
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Medicinal mushrooms have been shown to have profound health promoting benefits. Among them, Lentinus edodes is well-known to have anti-tumor, anti-inflammatory, and immunomodulatory effects. The aim of the present study is to evaluate whether Lentinus edodes ethanol extract (LE) inhibit airway inflammatory response in a murine asthma model induced by exposure to ovalbumin (OVA). The pretreatment of LE substantially attenuated airway hyperresponsiveness and eosinophilic inflammation in OVA-challenged mice. In addition, the increased levels of Th2 cytokines (IL-4, IL-5, and IL-13), eotaxin, and adhesion molecules in bronchoalveolar lavage fluids at 48 h after OVA inhalation was significantly reduced by the administration of LE. Furthermore, LE suppressed OVA-induced activation of nuclear factor-kappa B and p38 mitogen-activated protein kinase in lung tissues. Taken together, it is proposed that LE may serve as an effective therapeutic agent for allergic airway disease.
Subject(s)
Animals , Mice , Agaricales , Asthma , Bronchoalveolar Lavage Fluid , Cytokines , Eosinophils , Ethanol , Inflammation , Inhalation , Interleukin-5 , Lung , NF-kappa B , Ovalbumin , Ovum , Protein Kinases , Shiitake MushroomsABSTRACT
Phellinus linteus has been used as a traditional herbal medicine in Asian countries and is known to have anti-tumor, immunomodulatory, anti-inflammatory, and anti-allergic activities. However, the protective effects of P. linteus against experimental asthma have not been fully investigated. The objective of this study was to determine whether P. linteus ethanol extract (PLE) suppresses inflammatory response in an OVA-induced asthma model. As expected, the oral administration of PLE significantly inhibited eosinophilic airway inflammation and airway hyperresponsiveness in OVA-challenged BALB/c mice. Supporting these data, the augmentation of Th2 cytokines (IL-4, IL-5, and IL-13), eotaxin, and adhesion molecules in lung tissues and bronchoalveolar lavage fluid after OVA inhalation was markedly attenuated by PLE. Furthermore, PLE reduced OVA-induced activation of NF-kappaB and p38 MAPK in lung tissues. Therefore, our results suggest the potential of P. linteus as a therapeutic agent for asthma.
Subject(s)
Animals , Humans , Mice , Administration, Oral , Asian People , Asthma , Bronchoalveolar Lavage Fluid , Cytokines , Eosinophils , Ethanol , Herbal Medicine , Inflammation , Inhalation , Interleukin-5 , Lung , NF-kappa B , Ovum , p38 Mitogen-Activated Protein KinasesABSTRACT
Sparassis crispa is an edible mushroom with various medicinal properties. Here we demonstrate the effect of Sparassis crispa on carbon tetrachloride (CCl4)-induced hepatotoxicity and the underlying mechanism. To evaluate the hepatoprotective effects of Sparassis crispa ethanol extract (SCE), 50 male Sprague-Dawley rats were equally divided into 5 groups. Group I is the normal control rats with an intraperitoneal (i.p.) 0.5% carboxy methyl cellulose (CMC) pretreatment and olive oil treatment. Group II is the model group with an i.p. 0.5% CMC and 0.5 mL/kg CCl4 treatment. Group III and IV is the CCl4-administered rats pretreated with an i.p. 100 and 200 mg/kg SCE, respectively. Group V includes the silymarin group with an i.p. 50 mg/kg silymarin and CCl4 treatment. At 16 h after the CCl4 treatment, the levels of serum aminotransferases, TNF-alpha, and lipid peroxidation were substantially increased, whereas the activity of hepatic antioxidative enzymes, such as superoxide dismutase and catalase, was decreased. These changes were attenuated by SCE. The histological studies also showed that SCE inhibited the CCl4-induced liver injury. Furthermore, the contents of hepatic nitrite, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) were elevated after CCl4 treatment, while the cytochrome P450 2E1 (CYP2E1) expression was suppressed. SCE treatment inhibited the formation of liver nitrite, reduced the over-expression of iNOS and COX-2 proteins, but restored the liver CYP2E1 content compared with the CCl4-treated model group. The present data elucidate that SCE protects the liver against CCl4-induced acute hepatotoxicity, which might be due to its ability to restore the CYP2E1 function and suppress the inflammatory responses, in combination with its capacity to reduce oxidative stress.
Subject(s)
Animals , Humans , Male , Rats , Agaricales , Carbon Tetrachloride , Carbon , Catalase , Cyclooxygenase 2 , Cytochrome P-450 CYP2E1 , Ethanol , Lipid Peroxidation , Liver , Methylcellulose , Nitric Oxide Synthase Type II , Olea , Oxidative Stress , Rats, Sprague-Dawley , Silymarin , Superoxide Dismutase , Transaminases , Tumor Necrosis Factor-alpha , Olive OilABSTRACT
This study is to investigate the anti-allergic effect of anthocyanidin and to explore its possible mechanism. The experiments of passive cutaneous anaphylaxis reaction (PCA) and colorimetry were used to determine the effect of anthocyanidin on degranulation of mast cells in vivo. For in vitro study, various concentrations of anthocyanidin (100, 50 and 25 micromol x L(-1)) were added to the culture medium of mast cells cultured with 100 microg x L(-1) of dinitrophenyl (DNP) specific IgE overnight. The azelastine (100 micromol x L(-1)) was selected as the positive control. The antigen (DNP-human serum albumin, DNP-HAS)-induced release of degranulation was measured by enzymatic assay, histamine was determined by EIA, and interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) were measured by Western blotting, separately. In addition, the effects of anthocyanidin on phosphorylation of NF-kappaB, p38MAPK and Akt were observed by Western blotting. The results showed that treatments with anthocyanidin (100 and 50 mg x kg(-1)) were followed by a decrease in PCA of rats. Anthocyanidin (100 and 50 micromol x L(-1)) obviously suppressed the degranulation from mast cells, whereas results from anthocyanidin (100 and 50 micromol x L(-1)) group indicated significant inhibitory effect on histamine, the calcium uptake, TNF-alpha, IL-6, phosphorylation of NF-kappaB, p38MAPK and Akt of mast cells induced by antigen. Anthocyanidin may suppress the anaphylactic reaction by inhibiting the action of mast cells. NF-kappaB, p38MAPK and Akt at least in part contribute to this event.
Subject(s)
Animals , Male , Rats , Anthocyanins , Pharmacology , Anti-Allergic Agents , Pharmacology , Calcium , Metabolism , Cell Degranulation , Histamine Release , Immunoglobulin E , Allergy and Immunology , Interleukin-6 , Metabolism , Mast Cells , Allergy and Immunology , Metabolism , Physiology , Passive Cutaneous Anaphylaxis , Proto-Oncogene Proteins c-akt , Metabolism , Random Allocation , Rats, Sprague-Dawley , Signal Transduction , Transcription Factor RelA , Metabolism , Tumor Necrosis Factor-alpha , Metabolism , p38 Mitogen-Activated Protein Kinases , MetabolismABSTRACT
Mast cells participate in allergies and inflammation by secreting a variety of pro-inflammatory mediators. Curcumin, the active component of turmeric, is a polyphenolic phytochemical with anti-tumor, anti-inflammatory, anti-oxidative, and anti-allergic properties. The effects of curcumin on compound 48/80-induced mast cell activation and passive cutaneous anaphylactoid reactions are unknown. In this report, we investigated the influences of curcumin on the passive cutaneous anaphylactoid response in vivo and compound 48/80-induced mast cell activation in vitro. The mechanism of action was examined by calcium uptake measurements and cAMP assays in mast cells. Curcumin significantly attenuated the mast cell-mediated passive cutaneous anaphylactoid reaction in an animal model. In agreement with this in vivo activity, curcumin suppressed compound 48/80-induced rat peritoneal mast cell (RPMC) degranulation and histamine release from RPMCs. Moreover, compound 48/80-elicited calcium uptake into RPMCs was reduced in a dose-dependent manner by curcumin. Furthermore, curcumin increased the level of intracellular cAMP and significantly inhibited the compound 48/80-induced reduction of cAMP in RPMCs. These results corroborate the finding that curcumin may have anti-allergic activity.
Subject(s)
Animals , Rats , Calcium , Curcuma , Curcumin , Histamine , Histamine Release , Hypersensitivity , Inflammation , Mast Cells , Models, AnimalABSTRACT
The bear bile has been used as a traditional drug medicine and has been known to have anti-tumor, anti-inflammatory and anti-oxidant effects. The purpose of this study is to investigate the inhibitory effect of bear bile on compound 48/80-induced mast cell activation in vitro and anti-dinitrophenyl (DNP) IgE-mediated vascular permeability in vivo. For this, the effects of bear bile on the degranulation, histamine release, calcium influx and the change of the intracellular cAMP levels of rat peritoneal mast cells (RPMCs) and the influences of the oral treatment of bear bile on IgE-mediated cutaneous vascular permeability were studied. the results were as follows; the compound 48/80-induced degranulation, histamine release and calcium influx of RPMCs were inhibited by pretreatment with bear bile, the cAMP levels of RPMCs were increased by pretreatment with bear bile, and bear bile inhibited anti-DNP IgE-mediated cutaneous vascular permeability. From the above results, it is suggested that bear bile contains some substances which inhibit anti-DNP IgE-mediated vascular permeability and mast cell activation. Bear bile potentially may serve as an effective therapeutic agent for allergic diseases.
Subject(s)
Animals , Rats , Antioxidants , Bile , Calcium , Capillary Permeability , Histamine Release , Immunoglobulin E , Mast Cells , UrsidaeABSTRACT
<p><b>OBJECTIVE</b>To study the effects of immunoglobulin on the neuronal expression of IL-1beta and IL-1ra and the neuronal death at hippocampus in rats with convulsion induced by pentylenetetrazol.</p><p><b>METHODS</b>The epilepsy model was established by injecting intraperitoneally pentylenetetrazol (PTZ) into Wistar rats. Forty-five rats were randomly divided into three groups, normal control group, PTZ plus intravenous immunoglobulin (PTZ-IVIG); PTZ plus normal saline (PTZ-NS). Neuronal death was assessed by light microscopy with the hematoxylin-eosin (HE) staining and with in situ terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL). IL-1beta and IL-1ra expressions were examined by histochemistry.</p><p><b>RESULTS</b>The ratio of IL-1beta/IL-1ra at hippocampal CA(1) region in PTZ-IVIG group (0.5 +/- 0.1) was significantly lower than that in PTZ-NS group (1.9 +/- 0.5, t = 12.9, P < 0.05). Apoptotic cell numbers at the hippocampal CA(1) region were significantly decreased in the PTZ-IVIG group, compared to PTZ-NS group (t = 27.1, P < 0.05). The numbers of positive cells were 16.4 +/- 3.3/1000 microm(2) in the former and 41.7 +/- 3.5/1000 microm(2) in the latter. Necrotic cell numbers at the hippocampal CA(1) region were significantly decreased in the PTZ-IVIG group (19.0 +/- 2.6/1000 microm(2)), compared to PTZ-NS group (42.3 +/- 4.9/1000 microm(2), t = 20.9, P < 0.05).</p><p><b>CONCLUSION</b>Immunoglobulin could inhibit neuronal death induced by convulsion and its possible mechanism might be the regulation of IL-1 system in neurons.</p>