scholarly journals Scrophularia koraiensis Nakai Attenuates Allergic Airway Inflammation via Suppression of NF-κB and Enhancement of Nrf2/HO-1 Signaling

Antioxidants ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 99 ◽  
Author(s):  
Tae-Yang Jung ◽  
A Yeong Lee ◽  
Jun-Ho Song ◽  
Min Young Lee ◽  
Je-Oh Lim ◽  
...  

Scrophularia koraiensis Nakai (Scrophulariaceae) is a medicinal herb that grows in Korea and which has been widely used to treat fever, edema, neuritis and laryngitis. Hence, we evaluated the anti-inflammatory and antioxidant effects of the ethanol extract (SKE) of S. koraiensis Nakai in an ovalbumin (OVA)-induced mouse model. We injected 20 μg of OVA with 2 mg of aluminum on day 0 and day 14 to induce allergic airway inflammation in six-week-old BALB/c mice, and mice were challenged with 1% OVA by nebulization for 1 h on days 21, 22, and 23. SKE was orally administered at 20 mg/kg and 40 mg/kg from day 18 to 23, and its effects were compared with those of montelukast treatment. SKE significantly reduced proinflammatory cytokines, inflammatory cell counts, immunoglobulin-E, and airway hyperresponsiveness during the OVA-induced allergic airway inflammation model; it also reduced airway inflammation and mucus production. In addition, SKE reduced the OVA-induced nuclear factor kappa B (NF-κB) phosphorylation in lung tissues while enhancing nuclear factor erythroid-derived 2-related factor (Nrf-2) and heme oxygenase-1 (HO-1) expression. In conclusion, SKE showed the protective effects on OVA-induced allergic airway inflammation via the suppression of NF-κB phosphorylation and the enhancement of the Nrf2/HO-1 signaling pathway. These results indicate that SKE is a potential therapeutic agent for allergic airway inflammation.

2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
Eun Sik Choi ◽  
Yun Jung Lee ◽  
Chang Seob Seo ◽  
Jung Joo Yoon ◽  
Byung Hyuk Han ◽  
...  

Samul-Tang (Si-Wu-Tang, SMT), composed of four medicinal herbs, is a well-known herbal formula treating hematological disorder or gynecologic disease. However, vascular protective effects of SMT and its molecular mechanisms on the vascular endothelium, known as the central spot of vascular inflammatory process, are not reported. The aim of this study was to investigate vascular protective effects of SMT water extract in human umbilical vein endothelial cells (HUVECs). Water extract of SMT was prepared and identified by HPLC-PDA analysis. Expression of cell adhesion molecules (CAMs) and heme oxygenase-1 (HO-1) and translocation of nuclear factor-kappa B (NF-κB) and nuclear factor-erythroid 2-related factor 2 (Nrf2) were determined by western blot. Nuclear localization of NF-κB and Nrf2 was visualized by immunofluorescence and DNA binding activity of NF-κB was measured. ROS production, HL-60 monocyte adhesion, and intracellular nitric oxide (NO) were also measured using a fluorescent indicator. SMT suppressed NF-κB translocation and activation as well as expression of CAMs, monocyte adhesion, and ROS production induced by TNF-αin HUVECs. SMT treated HUVECs showed upregulation of HO-1 and NO which are responsible for vascular protective action. Our study suggests that SMT, a traditionally used herbal formula, protects the vascular endothelium from inflammation and might be used as a promising vascular protective drug.


2010 ◽  
Vol 33 (3) ◽  
pp. 196 ◽  
Author(s):  
Xia Ke ◽  
Jiangju Huang ◽  
Quan Chen ◽  
Suling Hong ◽  
Daoyin Zhu

Purpose. Allergic asthma is characterized by chronic airway inflammation and airway hyperresponsiveness driven by allergen-specific T helper (Th)2 cells. Mycobacterium bovis bacillus Calmette-Guérin (BCG) vaccination has been documented to suppress Th2 responses and allergic airway inflammation in animal models. Since interleukin (IL)-12 is capable of inhibiting Th2 responses, we sought to investigate whether IL-12 could function as an adjuvant to increase the efficacy of BCG vaccination against allergic asthma. Methods. BALB/c neonatal mice (24 mice, 48-72 h old) were randomly divided into 3 subgroups (n = 8 for each group) to be immunized with PBS (control) or BCG with or without DNA plasmid-expressing IL-12. All of the mice were then sensitized and provoked with ovalbumin (OVA) to establish a model of allergic asthma. Results. Mice vaccinated with BCG alone showed a significant reduction in airway inflammation, percentage of eosinophils in bronchoalveolar lavage (BAL) fluid, and serum OVA-specific immunoglobulin E (IgE) levels in comparison with control animals. The suppressive effects of BCG were substantially augmented by the combination with IL-12. Furthermore, a decreased IL-4 and increased interferon-gamma (IFN-γ) production in BAL fluid were observed in animals inoculated with BCG alone or with IL-12 relative to control animals. Conclusion. Our data indicate that the combined vaccination with BCG and IL-12 yields a favorable outcome in prevention of experimental allergic airway inflammation, which is likely mediated through triggering a shift from a Th2 response to a Th1 response.


Author(s):  
Zhidan Li ◽  
Wei Zhang ◽  
Fang Luo ◽  
Jian Li ◽  
Wenbin Yang ◽  
...  

Schistosoma japonicum infection showed protective effects against allergic airway inflammation (AAI). However, controversial findings exist especially regarding the timing of the helminth infection and the underlying mechanisms. Most previous studies focused on understanding the preventive effect of S. japonicum infection on asthma (infection before allergen sensitization), whereas the protective effects of S. japonicum infection (allergen sensitization before infection) on asthma were rarely investigated. In this study, we investigated the protective effects of S. japonicum infection on AAI using a mouse model of OVA-induced asthma. To explore how the timing of S. japonicum infection influences its protective effect, the mice were percutaneously infected with cercaria of S. japonicum at either 1 day (infection at lung-stage during AAI) or 14 days before ovalbumin (OVA) challenge (infection at post–lung-stage during AAI). We found that lung-stage S. japonicum infection significantly ameliorated OVA-induced AAI, whereas post–lung-stage infection did not. Mechanistically, lung-stage S. japonicum infection significantly upregulated the frequency of regulatory T cells (Treg cells), especially OVA-specific Treg cells, in lung tissue, which negatively correlated with the level of OVA-specific immunoglobulin E (IgE). Depletion of Treg cells in vivo partially counteracted the protective effect of lung-stage S. japonicum infection on asthma. Furthermore, transcriptomic analysis of lung tissue showed that lung-stage S. japonicum infection during AAI shaped the microenvironment to favor Treg induction. In conclusion, our data showed that lung-stage S. japonicum infection could relieve OVA-induced asthma in a mouse model. The protective effect was mediated by the upregulated OVA-specific Treg cells, which suppressed IgE production. Our results may facilitate the discovery of a novel therapy for AAI.


2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Se-Jin Lee ◽  
A. Yeong Lee ◽  
Je-Oh Lim ◽  
Ji Hye Lee ◽  
Tae-Yang Jung ◽  
...  

Yijin-tang is an oriental traditional herb used to treat inflammatory diseases. In the present study, we investigated the protective effects of Yijin-tang water extract (YTE) using an ovalbumin- (OVA-) induced asthma model, focusing on the antioxidant and anti-inflammatory properties of the herb. BALB/c mice were intraperitoneally injected with OVA on days 0 and 14 and then challenged with OVA on days 21, 22, and 23. The animals were orally administered YTE (200 and 400 mg/kg) from days 18 to 23, and this was found to significantly decrease airway hyperresponsiveness and release of inflammatory cells, cytokines, and OVA-specific immunoglobulin E in mice with asthma. In addition, YTE was associated with a marked reduction in airway inflammation and mucus production in lung tissue of mice with asthma. Furthermore, YTE suppressed the expression of matrix metalloproteinase-9 and phosphorylation of ERK in the lungs, which in turn led to a reduction in inducible nitric oxide synthases and an elevation in reduced glutathione and heme oxygenase-1. In conclusion, YTE effectively suppressed allergic responses in mice with asthma and the effect was closely related to antioxidant and anti-inflammatory properties of the herb. Our results indicate that YTE may be a potential agent for the treatment of allergic asthma.


Nutrients ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 3380
Author(s):  
Hideaki Kadotani ◽  
Kazuhisa Asai ◽  
Atsushi Miyamoto ◽  
Kohei Iwasaki ◽  
Takahiro Kawai ◽  
...  

The fermented soy product ImmuBalance contains many active ingredients and its beneficial effects on some allergic diseases have been reported. We hypothesized that ImmuBalance could have potential effects on airway inflammation in a murine model of asthma. Mice sensitized and challenged with ovalbumin developed airway inflammation. Bronchoalveolar lavage fluid was assessed for inflammatory cell counts and levels of cytokines. Lung tissues were examined for cell infiltration and mucus hypersecretion. Oral administration of ImmuBalance significantly inhibited ovalbumin-induced eosinophilic inflammation and decreased Th2 cytokine levels in bronchoalveolar lavage fluid (p < 0.05). In addition, lung histological analysis showed that ImmuBalance inhibited inflammatory cell infiltration and airway mucus production. Our findings suggest that supplementation with ImmuBalance may provide a novel strategy for the prevention or treatment of allergic airway inflammation.


2021 ◽  
Vol 12 ◽  
Author(s):  
Ba-Wool Lee ◽  
Ji-Hye Ha ◽  
Yeongseon Ji ◽  
Seong-Hun Jeong ◽  
Ju-Hong Kim ◽  
...  

Alnus hirsuta (Spach) Rupr. (AH), a member of the Betulaceae family, is widely used in Eastern Asia of as a source of medicinal compounds for the treatment of hemorrhage, diarrhea, and alcoholism. In this study, we investigated the protective effects of a methanolic extract of AH branches against airway inflammation and mucus production in tumor necrosis factor (TNF)-α-stimulated NCI-H292 cells and in an ovalbumin (OVA)-challenged allergic asthma mouse model. Female BALB/c mice were injected with OVA (40 μg) and aluminum hydroxide (2 mg) on days 0 and 14 to induce allergic airway inflammation. The mice were then challenged with 1% OVA from days 21–23. Mice were treated with AH (50 and 100 mg/kg/day; 2% DMSO) or dexamethasone (positive control; 3 mg/kg/day) from days 18–23. AH treatment effectively attenuated airway resistance/hyperresponsiveness and reduced levels of T helper type 2 (Th2) cytokines, eotaxins, and number of inflammatory cells in bronchoalveolar lavage fluid, and immunoglobulin E in serums of OVA-challenged mice. In histological analysis, AH treatment significantly inhibited airway inflammation and mucus production in OVA-challenged mice. AH treatment downregulated the phosphorylation of I kappa B-alpha, p65 nuclear factor-kappa B (p65NF-κB), and mitogen-activated protein kinases with suppression of mucin 5AC (MUC5AC) in lung tissue. Moreover, AH treatment decreased the levels of pro-inflammatory cytokines and Th2 cytokines, as well as MUC5AC expression, and inhibited the phosphorylation of p65NF-κB in TNF-α-stimulated NCI-H292 cells. These results indicate that AH might represent a useful therapeutic agent for the treatment of allergic asthma.


Antioxidants ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 563
Author(s):  
Ba-Wool Lee ◽  
Ji-Hye Ha ◽  
Han-Gyo Shin ◽  
Seong-Hun Jeong ◽  
Ju-Hong Kim ◽  
...  

Lindera obtusiloba is widespread in northeast Asia and used for treatment of improvement of blood circulation and anti-inflammation. In this study, we investigated anti-inflammatory and anti-oxidant effects of the methanolic extract of L. obtusiloba leaves (LOL) in an ovalbumin (OVA)-challenged allergic asthma model and tumor necrosis factor (TNF)-α-stimulated NCI-H292 cell. Female BALB/c mice were sensitized with OVA by intraperitoneal injection on days 0 and 14, and airway-challenged with OVA from days 21 to 23. Mice were administered 50 and 100 mg/kg of LOL by oral gavage 1 h before the challenge. LOL treatment effectively decreased airway hyper-responsiveness and inhibited inflammatory cell recruitment, Th2 cytokines, mucin 5AC (MUC5AC) in bronchoalveolar lavage fluid in OVA-challenged mice, which were accompanied by marked suppression of airway inflammation and mucus production in the lung tissue. LOL pretreatment inhibited the phosphorylation of mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-κB) with suppression of activator protein (AP)-1 and MUC5AC in the lung tissue. LOL also down-regulated expression of inflammatory cytokines, and inhibited the activation of NF-κB in TNF-α-stimulated NCI-H292 cells. LOL elevated the translocation of nuclear factor-erythroid 2-related factor (Nrf-2) into nucleus concurrent with increase of heme oxyngenase-1 (HO-1) and NAD(P)H quinine oxidoreductase 1 (NQO1). Moreover, LOL treatment exhibited a marked increase in the anti-oxidant enzymes activities, whereas effectively suppressed the production of reactive oxygen species and nitric oxide, as well as lipid peroxidation in lung tissue of OVA-challenged mice and TNF-α-stimulated NCI-H292 cells. These findings suggest that LOL might serve as a therapeutic agent for the treatment of allergic asthma.


2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Lu Xu ◽  
Yifan Yu ◽  
Rui Sang ◽  
Jinxia Li ◽  
Bingjie Ge ◽  
...  

Taraxasterol, a pentacyclic-triterpene compound, is one of the main active components isolated from the traditional Chinese medicinal herb Taraxacum. The objective of this study is to evaluate the protective effects of taraxasterol and its possible underlying mechanisms against ethanol-induced liver injury in mice. ICR mice were fed with Lieber-DeCarli diet containing 5% ethanol for 10 d and then challenged with a single dose of 20% ethanol (5 g/kg BW) by intragastric administration. The mice were intragastrically treated daily with taraxasterol (2.5, 5, and 10 mg/kg). Tiopronin was used as a positive control. The liver index was calculated, and the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in sera were detected. The contents of reactive oxygen species (ROS), malondialdehyde (MDA), and glutathione (GSH) and the activity of superoxide dismutase (SOD) in the livers were measured. The histopathological changes of liver tissues were observed by hematoxylin and eosin (H&E) staining. The protein expression levels of hepatic cytochrome P450 2E1 (CYP2E1), nuclear factor erythroid 2-related factor 2 (Nrf2), antioxidant protein heme oxygenase-1 (HO-1), and nuclear factor-kappa B (NF-κB) signaling pathway in liver tissues were detected by immunohistochemistry and Western blot methods. Taraxasterol significantly reduced the ethanol-induced increases of liver index, ALT, AST, and TG levels in sera and TG and MDA contents in the livers and hepatic ROS production and suppressed the ethanol-induced decreases of hepatic GSH level and SOD activity. Taraxasterol also significantly inhibited the secretion of proinflammatory cytokines TNF-α and IL-6 induced by ethanol. In addition, taraxasterol improved the liver histopathological changes in mice with ethanol-induced liver injury. Further studies revealed that taraxasterol significantly inhibited the ethanol-induced upregulation of CYP2E1, increased the ethanol-induced downregulation of Nrf2 and HO-1, and inhibited the degradation of inhibitory kappa Bα (IκBα) and the expression level of NF-κB p65 in liver tissues of ethanol-induced mice. These findings suggest that taraxasterol possesses the potential protective effects against ethanol-induced liver injury in mice by exerting antioxidative stress and anti-inflammatory response via CYP2E1/Nrf2/HO-1 and NF-κB signaling pathways.


2020 ◽  
Vol 21 (6) ◽  
pp. 2048 ◽  
Author(s):  
Suvesh Munakarmi ◽  
Lokendra Chand ◽  
Hyun Beak Shin ◽  
Kyu Yun Jang ◽  
Yeon Jun Jeong

3,3′-Diindolylmethane (DIM), a metabolic product of indole-3-carbinol extracted from cruciferous vegetables exhibits anti-inflammatory and anti-cancer properties. Earlier, the product has been demonstrated to possess anti-fibrotic properties; however, its protective effects on liver injury have not been clearly elucidated. In this study, we postulated the effects and molecular mechanisms of action of DIM on carbon tetrachloride (CCl4)-induced liver injury in mice. Acute liver injury was induced by a single intraperitoneal administration of CCl4 (1 ml/kg) into mice. DIM was injected via subcutaneous route for three days at various doses (2.5, 5 and 10 mg/kg) before CCl4 injection. Mice were sacrificed and serum was collected for quantification of serum transaminases. The liver was collected and weighed. Treatment with DIM significantly reduced serum transaminases levels (AST and ALT), tumor necrosis factor-α (TNF-α) and reactive oxygen species (ROS). CCl4- induced apoptosis was inhibited by DIM treatment by the reduction in the levels of cleaved caspase-3 and Bcl2 associated X protein (Bax). DIM treated mice significantly restored Cytochrome P450 2E1, nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expression in CCl4 treated mice. In addition, DIM downregulated overexpression of hepatic nuclear factor kappa B (NF-κB) and inhibited CCl4 mediated apoptosis. Our results suggest that the protective effects of DIM against CCl4- induced liver injury are due to the inhibition of ROS, reduction of pro-inflammatory mediators and apoptosis.


Marine Drugs ◽  
2019 ◽  
Vol 17 (7) ◽  
pp. 431 ◽  
Author(s):  
Jiali Chen ◽  
Fang Gong ◽  
Mei-Fang Chen ◽  
Chengyong Li ◽  
Pengzhi Hong ◽  
...  

Angiotensin II (Ang II) is closely involved in endothelial injury during the development of hypertension. In this study, the protective effects of the tilapia by-product oligopeptide Leu-Ser-Gly-Tyr-Gly-Pro (LSGYGP) on oxidative stress and endothelial injury in Angiotensin II (Ang II)-stimulated human umbilical vein endothelial cells (HUVEC) were evaluated. LSGYGP dose-dependently suppressed the fluorescence intensities of nitric oxide (NO) and reactive oxygen species (ROS), inhibited the nuclear factor-kappa B (NF-κB) pathway, and reduced inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and endothelin-1 (ET-1) expression, as shown by western blot. In addition, it attenuated the expression of gamma-glutamyltransferase (GGT) and heme oxygenase 1 (HO-1), as well as increasing superoxide dismutase (SOD) and glutathione (GSH) expression through the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. Other experiments revealed that LSGYGP increased the apoptotic inhibition ratio between cleaved-caspase-3/procaspase-3, reduced expressions of pro-apoptotic ratio between Bcl-2/Bax, inhibited phosphorylation of mitogen-activated protein kinases (MAPK), and increased phosphorylation of the serine/threonine kinase (Akt) pathway. Furthermore, LSGYGP significantly decreased Ang II-induced DNA damage in a comet assay, and molecular docking results showed that the steady interaction between LSGYGP with NF-κB may be attributed to hydrogen bonds. These results suggest that this oligopeptide is effective in protecting against Ang II-induced HUVEC injury through the reduction of oxidative stress and alleviating endothelial damage. Thus, it has the potential for the therapeutic treatment of hypertension-associated diseases.


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