α-B-Crystallin (CryAB, gene map locus: 11q22.3—q23.1) is a member of the small heat shock protein (HSP) family, a group of proteins that prevent protein aggregation upon exposure of a cell to heat and/or restore the biological activity of cell substrates. The missense mutation and the deletion mutation of CryAB can cause various forms of muscular disorder, including restrictive, hypertrophic, and dilated cardiomyopathies, heart failure, and skeletal muscle weakness. Collectively, these diseases constitute a rare autosomal-dominant inherited disorder called α-crystallinopathy (crystallinopathy), also known as desmin-related cardiomyopathy. The disease is a misfolded protein-related disease characterized by the formation of insoluble protein aggregates consisting of the CryAB protein in the patient's cardiomyocytes and skeletal myocytes. The details of crystallinopathy are unclear at the present time; what has been discovered concerning the disease mechanisms underlying crystallinopathy has been through experiments with genetically modified mice such as the CryAB knockout mouse and various mutant CryAB transgenic (TG) mice. Crystallinopathy can be recapitulated in TG mice by expressing the mutant CryAB Arg120Gly (R120G) protein, a causal mutation of crystallinopathy, specifically in the cardiomyocytes. CryAB R120G causes perinuclear formation of aggresomes containing preamyloid oligomer intermediates, which are wellknown as a primary toxic species in neurodegenerative disease. This suggests that crystallinopathy caused by the CryAB mutation could be considered one of the aggresomal and amyloid-related diseases. Moreover, recent findings have indicated that enhancement of HSP induction and inhibition of apoptotic cell death by mitochondrial protection may be a new therapeutic strategy for patients with crystallinopathy.

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Heat shock protein (HSP) 47 may play an important role in the pathogenesis of intestinal fibrosis. Daikenchuto (DKT), a traditional Japanese herbal (Kampo) medicine, has been reported to ameliorate intestinal inflammation. The aims of this study were to determine time–course profiles of several parameters of fibrosis in a rat model, to confirm the HSP47-expressing cells in the colon, and finally to evaluate DKT's effects on intestinal fibrosis. Colitis was induced in male Wistar rats weighing 200 g using an enema of trinitrobenzene sulfonic acid (TNBS). HSP47 localization was determined by immunohistochemistry. Colonic inflammation and fibrosis were assessed by macroscopic, histological, morphometric, and immunohistochemical analyses. Colonic mRNA expression of transforming growth factor β1 (TGF-β1), HSP47, and collagen type I were assessed by real time-polymerase chain reaction (PCR). DKT was administered orally once a day from 8 to 14 d after TNBS administration. The colon was removed on the 15th day. HSP47 immunoreactivity was coexpressed with α-smooth muscle actin-positive cells located in the subepithelial space. Intracolonic administration of TNBS resulted in grossly visible ulcers. Colonic inflammation persisted for 6 weeks, and fibrosis persisted for 4 weeks after cessation of TNBS treatment. The expression levels of mRNA and proteins for TGF-β1, HSP47, and collagen I were elevated in colonic mucosa treated with TNBS. These fibrosis markers indicated that DKT treatment significantly inhibited TNBS-induced fibrosis. These findings suggest that DKT reduces intestinal fibrosis associated with decreasing expression of HSP47 and collagen content in the intestine.

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The aim of this study was to investigate the protective effects of andrographolide (AP), a bioactive component isolated from Andrographis paniculata, on carbon tetrachloride (CCl₄)-induced liver injury as well as the possible mechanisms involved in this protection in mice. Acute liver injury was induced by CCl₄ intoxication in mice. Serum biological analysis, lipid peroxides and antioxidant estimation, histopathological studies, reverse transcription polymerase chain reaction (RT-PCR) and Western blot assay were carried out. CCl₄ treatment resulted in severe hepatic injury, as evidenced by significant elevation of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and typical histopathological changes, such as hepatocyte necrosis. Additionally, CCl₄ administration led to oxidative stress in mice, as indicated by a remarkable increase in the hepatic malondialdehyde (MDA) level, together with a significant decrease in liver reduced glutathione (GSH) content. However, CCl₄-induced hepatotoxicity was significantly attenuated by pretreatment with AP, as demonstrated by significant reduction of serum ALT, AST levels and hepatic MDA activity, along with a remarkable increase in hepatic GSH content. Histopathological changes induced by CCl₄ were also ameliorated by AP pretreatment. The marked increase of tumor necrosis factor-α (TNF-α) induced by CCl₄ was attenuated by AP, and the dramatic elevation of heme oxygenase-1 (HO-1) at transcriptional and protein levels was augmented following AP pretreatment. AP can effectively prevent liver injury induced by CCl₄, which may be due to inhibition of oxidative stress and inflammatory responses.

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Electrolyzed reduced water (ERW), functional water, has various beneficial effects via antioxidant mechanism in vivo and in vitro. However there is no study about beneficial effects of ERW bathing. This study aimed to determine the effect of ERW bathing on the UVB-induced skin injury in hairless mice. For this purpose, mice were irradiated with UVB to cause skin injury, followed by individually taken a bath in ERW (ERW-bathing) and tap water (TW-bathing) for 21 d. We examined cytokines profile in acute period, and histological and ultrastructural observation of skin in chronic period. We found that UVB-mediated skin injury of ERW-bathing group was significantly low compared to TW control group in the early stage of experiment. Consistently, epidermal thickening as well as the number of dermal mast cell was significantly lowered in ERW-bathing group. Defection of corneocytes under the scanning electron microscope was less observed in ERW-bathing group than in TW-bathing group. Further, the level of interleukin (IL)-1β, tumor necrosis factor (TNF)-α and IL-12p70 in ERW group decreased whereas those of IL-10 increased. Collectively, our data indicate that ERW-bathing significantly reduces UVB-induced skin damage through influencing pro-/anti-inflammatory cytokine balance in hairless mice. This suggests that ERW-bathing has a positive effect on acute UVB-mediated skin disorders. This is the first report on bathing effects of ERW in UVB-induced skin injury.

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Inflammation and septic shock due to endotoxins from Gram-negative bacteria infection continue to pose significant challenges to human healthcare. It is, therefore, necessary to develop therapeutic strategies targeting endotoxins, such as lipopolysaccharide (LPS), to prevent their potentially systemic effects. Pathogenesis due to Gram-negative bacteria involves LPS binding to the host LPS-binding protein (LBP), causing detrimental downstream signaling cascades. Our previous study showed that CLP-19, a synthetic peptide derived from the Limulus anti-LPS factor (LALF), could effectively neutralize LPS toxicity; however, the detailed mechanisms underlying this anti-LPS effect remained unexplained. Thus, we carried out investigations to determine how the CLP-19 neutralizes LPS toxicity. CLP-19 was found to block LPS binding to LBP in a dose-dependent manner, as evidenced by competitive enzyme-linked immunosorbent assay (ELISA). In peripheral blood mononuclear cells, CLP-19 blocked LPS-induced phosphorylation of mitogen activated protein kinase (MAPK) signaling proteins p38, extracellular signal-regulating kinase (ERK)1/2 and c-Jun N-terminal kinase (JNK)1/2. Furthermore, CLP-19 potency in LPS antagonism in vitro and in vivo was directly associated with its ability to block the LPS-LBP interaction. Taken together, the results suggested that CLP-19's inhibitory effect on LPS-LBP binding and on the subsequent MAPK pathway signaling may be responsible for its anti-LPS mechanism. This peptide appears to represent a potential therapeutic agent for clinical treatment of sepsis.

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Inhibition of Rho kinase (ROCK) ameliorates many cardiovascular dysfunctions. The aim of the current study is to investigate the anti-inflammatory effects of fasudil, a selective ROCK inhibitor, on high cholesterol diet-induced hypercholesterolemic rats and its possible mechanisms. In hypercholesterolemic rats, we found the serum levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and several inflammatory markers including interleukin (IL)-8, IL-6, C-reaction protein (CRP) and soluble intercellular adhesion molecule (sICAM)-1 significantly elevated, while those of high-density lipoprotein cholesterol (HDL-C) and triglyceride (TG) decreased. Moreover, mRNA expressions of ROCK and nuclear factor-kappa B (NF-κB) and activity of ROCK in thoracic aorta were greatly up-regulated. Remarkably, administrating fasudil (10, 30 mg/kg per day) or simvastatin (10 mg/kg per day) to hypercholesterolemic rats for 2 weeks, activation of ROCK and NF-κB in thoracic aorta were suppressed, status of dyslipidemia were improved and inflammatory markers lowered. From the histopathological examination, fasudil treatment was found to lessen the thickening noted in the aortic intima and media of the hypercholesterolemic rats. These results suggested fasudil-induced inhibition of ROCK may improve lipid metabolism and has anti-inflammatory effect, which might expand the clinical application of fasudil as a new therapy for hypercholesterolemia and preventing the development of atherosclerosis.

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Following sinoaortic denervation (SAD) rats present intense arterial pressure lability without sustained hypertension. This study aimed to verify the effects of heptanol (a putative gap-junction blocker) and tetraethylammonium (TEA, a putative gap-junction activator) on rhythmic contractions (RCs) and vascular reactivity in the aortas isolated from SAD and Sham-operated (SO) rats. Rhythmic contractions were observed with phenylephrine in endothelium-removed aortic rings from SAD rats. We evaluated the effects of the gap-junction modulators heptanol or TEA on the frequency and amplitude of these oscillations. Additionally, concentration–response curves were constructed to TEA and KCl and in pre-contracted arteries (with phenylephrine or KCl) to heptanol in order to verify the effects of those gap-junction modulators. Comparatively, rhythmic contractions were observed in 10/10 SAD rat aortas vs. 2/10 controls. Heptanol decreased the frequency of oscillations in a concentration-dependent manner. TEA increased the amplitude and frequency of RCs. In the experiments of concentration–response curves to TEA, the maximal contractile effect was similar in both groups, although the potency was lower in SAD than in SO rat aortas. The relaxation to heptanol was different between the groups only after pre-contraction induced by phenylephrine. Heptanol showed higher potency in SAD as compared to SO rat aortas. In conclusion, arterial pressure lability occurs only in SAD rats, and their isolated aortas exhibit intense RCs. These RCs seem to be dependent of the gap-junction communication, since these oscillations are intensified by TEA and inhibited by heptanol. After SAD, aortas are more sensitive to heptanol and less sensitive to TEA.

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To determine whether the antihypertensive effect of nattokinase is associated with the protease activity of this enzyme, we compared nattokinase with the fragments derived from nattokinase, which possessed no protease activity, in terms of the effect on hypertension in spontaneously hypertensive rats (SHR). In the continuous oral administration test, the groups were given a basic diet alone (control), the basic diet containing nattokinase (0.2, 2.6 mg/g diet) or the basic diet containing the fragments derived from nattokinase (0.2, 0.6 mg/g diet). The group fed the basic diet containing high-dosage nattokinase (2.6 mg/g diet) showed significant reductions in systolic blood pressure (SBP), diastolic blood pressure (DBP) and plasma fibrinogen level, compared with control group and no influence on activities of renin and angiotensin-converting enzyme (ACE, EC 3.4.15.1), and plasma angiotensin II level in the renin-angiotensin system. The treatment of the basic diet containing high-dosage fragments (0.6 mg/g diet) significantly decreased SBP, DBP and plasma angiotensin II level in plasma but the treatment did not influence on plasma fibrinogen level. These results suggest that nattokinase and its fragments are different from each other in the mechanism to reduce hypertension. Nattokinase, retained its protease activity after absorbance across the intestines, may decrease blood pressure through cleavage of fibrinogen in plasma. The fragments, which absorbed as nattokinase-degradation products, prevents the elevation of plasma angiotensin II level to suppress hypertension.

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Terminalia chebula has been widely used in India as a folk medicine. This study investigated the in vivo anti-hyperglycemia and anti-diabetic complication effects of the EtOAc-soluble portion of ethanolic extract of T. chebula fruit (EETC) containing 29.4% chebulic acid. Rats were divided into non-diabetic, untreated diabetic and diabetic groups. Streptozotocin (40 mg/kg body weight (BW))-induced diabetic rats were orally administered the aminoguanidine (100 mg/kg BW), high dose (500 mg/kg BW; HEETC) and low dose (100 mg/kg BW; LEETC) for 13 weeks. HEETC administration reduced the levels of blood glucose and serum lipids, decreased malondialdehyde concentrations of serum and thoracic aorta in diabetic rats, and significantly improved serum biochemical values and the pathomorphological changes of the liver and kidney in diabetic rats. Also, HEETC decreased the advanced glycation end products (AGEs) distribution in testis seminiferous tubules. Therefore, HEETC has a merit to be a potent candidate to control glycemic and diabetic complications.

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Recent studies indicate that several transcription units assemble to form a ‘transcription factory’ where active transcription occurs in the nuclei. Previously, we generated chicken B-lymphocyte-derived DT40 cells lacking six transcriptional regulatory regions scattered in and around the immunoglobulin (Ig)-β gene. The deletions caused a complete shut down of transcription and epigenetic regulation of the Ig-β gene, demonstrating that the scattered regulatory regions cooperated in the transcriptional and epigenetic regulation of the gene. However, the in vivo 3-dimensional spatial relationships between the Ig-β promoter and these six regulatory regions were not investigated. In this study, we used chromosome conformation capture (3C) technology and demonstrated that the Ig-β promoter physically interacted with the scattered regulatory regions. We found that the Ig-β promoter also interacted with two downstream promoters of ubiquitously expressed genes, rad motif 1 (RDM1) and Plekhm1, to form a transcription factory, but not with three ubiquitously expressed genes, BAF60b, p45/SUG, and RRMJ3, located upstream of the Ig-β gene. In this factory, the chromatin from the three promoters and the scattered regulatory regions of the Ig-β gene formed a complex structure with many chromatin loops.

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Vascular smooth muscle cell (SMC) migration and proliferation contribute to arterial wound repair and thickening of the intimal layer in atherosclerosis. SMC can physically interact with monocytes and macrophages within the intima. This study evaluated whether macrophages modulated proliferation and migration of SMC in close proximity, which was suppressed by 1—25 μg/ml sensitive fern (Onoclea sensibilis) extract (SFE) inhibiting protein-tyrosine phosphatase-1B activity. The addition of conditioned media of THP-1-derived macrophages substantially promoted human aortic smooth muscle cell (HAoSMC) proliferation by ≈30%. HAoSMC proliferation was significantly attenuated by ≥10 μg/ml SFE most likely due to its diminution of platelet derived growth factor (PDGF)-BB secreted by neighbor macrophages. HAoSMC migration was also enhanced by culturing in THP-1 macrophage conditioned media, as evidenced by a scratch wound assay. However, the presence of ≥10 μg/ml SFE did not allow such migaration. When SFE was treated to THP-1 macrophages, the secretion of the adipokines, visfatin and resistin, was abrogated. SFE at 1—25 μg/ml dose-dependently diminished resistin-stimulated secretion of collagen IV and connective tissue growth factor (CTGF) in HAoSMC, indicating that macrophage resistin plays a role in the extracellular matrix (ECM) production of vascular SMC. These results demonstrate that SFE disturbed proliferation and migration of SMC instigated by inflammatory macrophages in close proximity. Therefore, this study provides novel information that SFE has the potential capability to prevent atherosclerosis involving SMC proliferation, migration and fibrogenic activation within the vessels.

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Rheumatoid arthritis (RA) is a disease with significant gender differences in its prevalence and clinical features. Interleukin (IL)-1 and tumor necrosis factor (TNF) α produced by synoviocytes are principle inflammatory and destructive mediators of RA. We found that a potent androgen, 5α-dihydrotestosterone (DHT) inhibits IL-1α-induced production and mRNA expression of IL-8, IL-6 and IL-1β from RA patient-derived fibroblast-like synovial cell line MH7A. Promoter analysis of the IL-8 gene revealed that nuclear factor (NF)-κB activation is critical for its transcriptional activation by IL-1α, and DHT inhibited the IL-1α-induced NF-κB activation in a manner dependent on the androgen receptor (AR). DHT also inhibited the effects of TNFα on the cells overexpressed with AR, indicating that sufficient expression level of functional AR was necessary for the inhibitory effect of DHT on TNFα. These results suggest that androgen contributes to the prevention against RA and its gender difference by inhibiting IL-1α or TNFα-induced proinflammatory cytokine production from synovial fibroblast-like cells by inhibiting NF-κB activation in a manner depending on AR.

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The purpose of this study was to investigate the pharmacokinetics of nilvadipine (NiD) from disintegration-controlled matrix tablets (DCMT). A further purpose was to clarify biological factors that affect the absorption of NiD from DCMT. Two DCMT formulations, which released approximately 80% of NiD in 6 h (DCMT-M) and 10 h (DCMT-S) in vitro, were prepared and compared with immediate-release (IR) tablets. The T_max and mean residence time from DCMT-M and DCMT-S were significantly longer than those from IR tablets in fasted dogs. The area under the plasma concentration–time curve (AUC) (0—infinity) from DCMT-M in both fed and fasted dogs and IR tablets were comparable in both fed and fasted dogs, indicating complete drug release and absorption without food effect. In contrast, the AUC from DCMT-S was significantly lower than the AUC from IR tablets in fasted dogs. The AUC from DCMT-S increased in fed dogs, but it was still lower than the AUC from IR tablets. In vivo absorption profiles calculated by deconvolution method suggested that the duration of drug absorption from DCMT-S was prolonged from 6 h in fasted condition to 8 h in fed condition, suggesting longer gastro-intestinal (GI) transit time in fed condition allowed longer drug release duration from DCMT-S. Regional drug absorption was also evaluated using NiD solution. The results indicated NiD was almost completely absorbed from canine jejunum, ileum and colon, indicating drug permeation is not a rate-limiting factor of NiD absorption. Therefore, limited GI transit time is the primary factor that affects the drug release from DCMT and subsequent NiD absorption.

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Ischemia/reperfusion (I/R) injury is induced by reactive oxygen species (ROS). During intestinal I/R, the amount of nitric oxide (NO), which is a ROS, is increased. In this study, we examined the protection against I/R injury by inhibition of NO generation. Wistar/ST rats were exposed to 1 h of ischemia, followed by reperfusion for 4 h. The rats were intravenously injected with 100 mg/kg aminoguanidine (AG), which is a selective inducible NO synthase (iNOS) inhibitor, for 5 min before ischemia. The increase in NO₂⁻ by intestinal I/R was significantly inhibited by AG 1 h after reperfusion. Moreover, the increase in area under curve of 0 to 1 h after reperfusion (AUC_0—1) of paracellular marker was inhibited. However, 3 h after reperfusion, the survival ratio of rats was significantly decreased in the intestinal I/R condition with AG. The amount of NO₂⁻ and AUC of 3 to 4 h after reperfusion (AUC_3—4) of paracellular marker in intestinal I/R groups were increased by AG compared with those in the I/R condition without AG 3 h after reperfusion. These data indicated that AG, which was given by single pre-administration, can clearly inhibit intestinal I/R injury 1 h after reperfusion. However, the injury occurs again 3 h after reperfusion and grows worse.

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It has been suggested that some food components, such as bioflavonoids, affect the bioavailability of ascorbic acid in humans. Since little is known in Japan about the effective intake of this dietary requirement, we tested young Japanese males after the ingestion of commercial ascorbic acid or acerola (Malpighia emarginata DC.) juice to compare the quantities absorbed and excreted. Healthy Japanese subjects received a single oral dose of ascorbic acid solution (50, 100, 200 or 500 mg) and received distilled water as a reference at intervals of 14 d or longer. All subjects were collected blood and urine until 6 h after ingestion and evaluated for time-dependent changes in plasma and urinary ascorbic acid levels. Predictably, the area under the curve (AUC) values in plasma and urine after ingestion increased dose-dependently. Next, each subject received diluted acerola juice containing 50 mg ascorbic acid. Likewise, their plasma and urinary ascorbic acid concentrations were measured. In plasma, the AUC value of ascorbic acid after ingestion of acerola juice tended to be higher than that from ascorbic acid alone. In contrast, the urinary excretion of ascorbic acid at 1, 2 and 5 h after ingestion of acerola juice were significantly less than that of ascorbic acid. These results indicate that some component of acerola juice favorably affected the absorption and excretion of ascorbic acid.

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Catalase protects cells from reactive oxygen species-induced damage by catalyzing the breakdown of hydrogen peroxide to oxygen and water. Arsenite decreases catalase activity; it activates phosphatidylinositol 3-kinase (PI3K) and its key downstream effector Akt in a variety of cells. The PI3K pathway is known to inhibit catalase expression. c-Met, an upstream regulator of PI3K and Akt, is also involved in the regulation of catalase expression. To examine the involvement of c-Met and PI3K pathways in the arsenite-induced downregulation of catalase, catalase mRNA and protein expression were analyzed in the human hepatoma cell line HepG2 treated with arsenite and either an inhibitor of c-Met (PHA665752 (PHA)) or of PI3K (LY294002 (LY)). Arsenite treatment markedly activated Akt and decreased the levels of both catalase mRNA and protein. Both PHA and LY attenuated arsenite-induced activation of Akt. PHA and LY treatment also prevented the inhibitory effect of arsenite on catalase protein expression but did not affect the level of catalase mRNA. These findings suggest that arsenite-induced inhibition of catalase expression is regulated at the mRNA and post-transcriptional levels in HepG2 cells, and that the post-transcriptional regulation is mediated via c-Met- and PI3K-dependent mechanisms.

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Accumulating evidence in humans demonstrates that visuo-spatial deficits are the most consistently reported cognitive abnormalities in Parkinson's disease (PD). Ezrin, radixin, and moesin are collectively known as ERM proteins. Although ERM proteins have important implications in cell-shape determination and relevant signaling pathway, they have not been studied in the hippocampus in association with visuo-spatial memory impairments. The purpose of the present study is to examine whether the expression level of ERM proteins in the hippocampus is changed by an intrastriatal injection of 6-hydroxydopamine (6-OHDA) in mice. The intrastriatal injection of 6-OHDA induced partial dopaminergic deficits and spatial memory impairments. We also found that ezrin was increased in the hippocampus by the microinjection of 6-OHDA. On the other hand, protein levels of radixin and moesin were not influenced by 6-OHDA lesions. These results suggest that excessive ezrin may be related to visuo-spatial memory impairments.

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Hippocampus is one of the earliest brain regions that gets affected by ischemia, however, no pharmacological therapy exists yet that can fully counteract the ischemic damage. Here we study the effect of sulbutiamine, a synthetic thiamine analogue that can cross the blood–brain barrier easily, on hippocampal neurons under an in vitro model of ischemia, oxygen–glucose deprivation (OGD). We find that exposure to OGD in the presence of sulbutiamine significantly increases neuronal viability and enhances electrophysiological properties such as excitatory synaptic transmissions and intrinsic neuronal membrane input resistance in a concentration-dependent manner. Overall, here we report, for the first time, the neuroprotective evidence of sulbutiamine on hippocampal CA1 pyramidal neurons under OGD, which may have beneficial implications as a possible therapeutic agent/substance against ischemic insult.

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Although gemcitabine is frequently used in the treatment of cancer, it is associated with myelosuppression. An animal study showed that the tolerability of gemcitabine varied with changes in treatment time; however, no clinical data have verified this finding. The purpose of this study was to determine the relationship between treatment time and development of hematologic toxicity in patients treated with gemcitabine. Gemcitabine-induced hematologic toxicity was retrospectively investigated in 77 patients. Patients were divided into two treatment-time groups: 9:00 and 15:00. Hematologic toxicity was evaluated on day 8 and 15 after treatment. On day 8 and 15, the changing count of white blood cells was significantly reduced in patients treated at 15:00 compared with those treated at 9:00 (p<0.01 and p<0.05, respectively). On days 8 and 15, the changing count of platelet was significantly reduced in patients treated at 15:00 compared with those treated at 9:00 (p<0.05). The incident of over common terminology criteria for adverse events (CTCAE) grade 2 white blood cell decreased was significantly reduced in patients treated at 15:00 compared with those treated at 9:00 (p=0.048, odds ratio=2.92). In conclusion, this cohort study demonstrated that gemcitabine-induced hematologic toxicity could be alleviated by treating patients at 9:00.

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In this study, manassantin A (Man A), an herbal medicine isolated from Saururus chinensis (S. chinensis), markedly inhibited 5-lipoxygenase (5-LO)-dependent leukotriene C₄ (LTC₄) generation in bone marrow-derived mast cells (BMMCs) in a concentration-dependent manner. To investigate the molecular mechanisms underlying the inhibition of LTC₄ generation by Man A, we assessed the effects of Man A on phosphorylation of cytosolic phospholipase A₂ (cPLA₂) and mitogen-activated protein kinases (MAPKs). Inhibition of LTC₄ generation by Man A was accompanied by a decrease in cPLA₂ phosphorylation, which occurred via the MAPKs including extracellular signal-regulated protein kinase-1/2 (ERK1/2) as well as p38 and c-Jun N-terminal kinase (JNK) pathways. Taken together, the present study suggests the Man A represents a potential therapeutic approach for the treatment of airway allergic-inflammatory diseases.

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