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Inhibitory effects of L-theanine on airway inflammation in ovalbumin-induced allergic asthma
Abstract
L-theanine, a water-soluble amino acid isolated from green tea (Camellia sinensis), has anti-inflammatory activity, antioxidative properties, and hepatoprotective effects. However, the anti-allergic effect of L-theanine and its underlying molecular mechanisms have not been elucidated. In this study, we investigated the protective effects of L-theanine on asthmatic responses, particularly airway inflammation and oxidative stress modulation in an ovalbumin (OVA)-induced murine model of asthma. Treatment with L-theanine dramatically attenuated the extensive trafficking of inflammatory cells into bronchoalveolar lavage fluid (BALF). Histological studies revealed that L-theanine significantly inhibited OVA-induced mucus production and inflammatory cell infiltration in the respiratory tract and blood vessels. L-theanine administration also significantly decreased the production of IgE, monocyte chemoattractant protein-1 (MCP-1), interleukin (IL)-4, IL-5, IL-13, tumor necrosis factor-alpha (TNF-α), and interferon-gamma (INF-γ) in BALF. The lung weight decreased with L-theanine administration. L-theanine also markedly attenuated the OVA-induced generation of reactive oxygen species and the activation of nuclear factor kappa B (NF-κB) and matrix metalloprotease-9 in BALF. Moreover, L-theanine reduced the TNF-α-induced NF-κB activation in A549 cells. Together, these results suggest that L-theanine alleviates airway inflammation in asthma, which likely occurs via the oxidative stress-responsive NF-κB pathway, highlighting its potential as a useful therapeutic agent for asthma management.
... Cells treated with IL-1β only served as the control. The dose of L-theanine (≥98% (high-performance liquid chromatography, HPLC), Sigma-Aldrich, St. Louis, MO, USA) was determined according to previous studies which L-theanine showed inhibition of NF-κB [25] and anti-inflammation activities [26]. ...
... This study was the first to demonstrate the effects of L-theanine on articular cartilage in experimentally induced OA and IL-1β-induced chondrocytes. The present study was designed based on previous reports that showed that cartilage and synovial inflammation occurs in OA progression [10,31,32], and that L-theanine can prevent inflammatory responses by suppressing the NF-κB signaling pathway [33][34][35], and reduces the release of downstream pro-inflammatory mediators [26,36] in inflammatory-related diseases. ...
... Animal models of OA which was induced by surgery was demonstrated mimic human posttraumatic OA, including partial or total meniscectomy, destabilization of the medial meniscus (DMM), anterior cruciate ligament (ACL) or posterior cruciate ligament transection. Rat OA model was broadly used and disease progression in rat surgical models is much faster than in human OA [26]. Except for rapid progression and low cost, a rat ACLT induced OA model exhibits mild cartilage destruction 4 weeks post-surgery. ...
The etiology of osteoarthritis (OA) is multifactorial, with no effective disease-modifying-drugs. L-theanine has been reported to inhibit inflammatory responses in some diseases and this study aimed to investigate the effect of L-theanine on Interleukin-1(IL-1)β-stimulated chondrocytes, and in an injury-induced OA rat model. Primary chondrocytes were stimulated by IL-1β (10 ng/mL) for 24 h and then co-cultured with L-theanine for 24 h. The effects of L-theanine on IL-1β-stimulated expression of pro-inflammatory cytokines and hydrolytic enzyme were analyzed using Western blotting, quantitative polymerase chain reaction (q-PCR) and enzyme-linked immunosorbent assay (ELISA) kits. An immunofluorescence assay was used to detect nuclear factor kappa B (NF-κB) phosphorylation. OA was induced by anterior cruciate ligament transection (ACLT) surgery in rats and celecoxib was used as a positive control. OA severity was measured using the Osteoarthritis Research Society International (OARSI) grading system to describe histological changes. The results showed that L-theanine decreased the expression of pro-inflammatory mediators, including cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE-2), inducible nitric oxide synthase (iNOS), and nitric oxide (NO), both in vivo and in vitro. L-theanine treatment inhibited IL-1β-induced upregulation of matrix metalloproteinases (MMP)-3 and MMP-13, as well as inhibited NF-κB p65 activation. In vivo animal model showed that L-theanine administration (200 mg/kg) significantly alleviated OA lesions and decreased OARSI score. Our data indicated that L-theanine decreased inflammatory cytokines and protected extracellular matrix degradation through inhibition of the NF-κB pathway, and L-theanine may be considered a promising therapeutic strategy in OA prevention.
... Zeng et al. figured out that high-fat diet-induced oxidative stress, inflammation, and injury in the heart were significantly compromised by curcumin through inactivation of NF-κB both in vivo and in vitro [46]. Additionally, MCP-1, a CC chemokine also named as chemokine (C-C motif) ligand 2 (CCL2), is an important inflammatory molecule in the airway epithelium in asthma [47]. It has been confirmed that the NF-κB signaling pathway is essential for the regulation of MCP-1 expression in the airway epithelium in inflammatory conditions, including asthma, in both mice and BEAS-2B cells [47][48][49][50]. ...
... Additionally, MCP-1, a CC chemokine also named as chemokine (C-C motif) ligand 2 (CCL2), is an important inflammatory molecule in the airway epithelium in asthma [47]. It has been confirmed that the NF-κB signaling pathway is essential for the regulation of MCP-1 expression in the airway epithelium in inflammatory conditions, including asthma, in both mice and BEAS-2B cells [47][48][49][50]. Hwang et al. revealed that l-theanine markedly inhibited OVA-induced airway inflammation and upregulation of MCP-1 in the lungs by inactivation of NF-κB in a murine model of asthma [47]. ...
... It has been confirmed that the NF-κB signaling pathway is essential for the regulation of MCP-1 expression in the airway epithelium in inflammatory conditions, including asthma, in both mice and BEAS-2B cells [47][48][49][50]. Hwang et al. revealed that l-theanine markedly inhibited OVA-induced airway inflammation and upregulation of MCP-1 in the lungs by inactivation of NF-κB in a murine model of asthma [47]. Huang TNF-α-induced overexpression of MCP-1 was remarkably reduced by conjugated linoleic acids (CLAs) through blocking NF-κB transcription regulation in BEAS-2B cells [48]. ...
Asthma is characterized by airway inflammation and mucus hypersecretion. Curcumin possessed a potent anti-inflammatory property involved in the PPAR γ -dependent NF- κ B signaling pathway. Then, the aim of the current study was to explore the value of curcumin in asthmatic airway inflammation and mucus secretion and its underlying mechanism. In vivo, mice were sensitized and challenged by ovalbumin (OVA) to induce chronic asthma. Airway inflammation and mucus secretion were analyzed. In vitro, BEAS-2B cells were obtained. MCP-1, MUC5AC, and PPAR γ expression and the phosphorylation of NF- κ B p65 and NF- κ B p65 DNA-binding activity were measured in both the lungs and BEAS-2B cells. shRNA-PPAR γ was used to knock down PPAR γ expression. We found that OVA-induced airway inflammation and mucus hypersecretion in mice, OVA and IL-4-induced upregulation of MCP-1 and MUC5AC, suppression of PPAR γ , and activation and translocation of NF- κ B p65 were notably improved by curcumin both in vivo and in vitro. Our data also showed that these effects of curcumin were significantly abrogated by shRNA-PPAR γ . Taken together, our results indicate that curcumin attenuated OVA-induced airway inflammation and mucus hypersecretion in mice and suppressed OVA- and IL-4-induced upregulation of MCP-1 and MUC5AC both in vivo and in vitro, most likely through a PPAR γ -dependent NF- κ B signaling pathway.
... Previous studies in mouse also found that pre-treatment of L-theanine can prevent ethanol-induced (Li et al., 2012) and Escherichia coli-induced (Deng et al., 2016) oxidative stress injury of liver through restoring the antioxidant capability of hepatocytes including glutathione content, and superoxide dismutase (SOD), CAT and glutathione peroxidase (GSH-PX) activities and expression levels. In addition, several studies in rodents have shown that L-theanine has anti-inflammatory activity and can down-regulate the aroclor 1254-induced mRNA expressions of inflammatory cytokines (Sumathi et al., 2016) and attenuate the ovalbumin-induced activation of nuclear factor κ B (NFκ B) pathway (Hwang et al., 2017). In a recent review, Liang et al. (2015) reviewed the other health benefits of L-theanine such as anti-tumor effects, anti-fatigue effects, anti-diabetic effects and hypotensive activity (Liang et al., 2015). ...
... Saeed et al. (2018) also observed that briolers fed diets supplemented with L-theanine at 200 mg/kg has significantly higher spleen and bursa of Fabricius relative weight, and lower serum pro-inflammatory cytokine (IL-2 and IFN-γ) contents. Moreover, some researches in rodent and human reported that serum inflammatory cytokines contents and blood immunocompetent cells could be positively regulated by L-theanine administration (Murakami et al., 2010;Takagi et al., 2010;Hwang et al., 2017). However, no experimental study has been published on the effect of L-theanine on the immune function of ducks. ...
... Therefore, L-theanine may be used as an effective feed additive for improving the immune function of duck. Nuclear factor κ B is a transcription factor which is closely related to the regulation of various inflammatory genes expression, its activation may lead to inflammatory reaction and immune dysfunction (Kim et al., 2009;Hwang et al., 2017). Previous studies reported that the mRNA expression levels of cytokines in immune tissues of broilers (Saeed et al., 2018) and NFκ B protein level in lung of mice (Hwang et al., 2017) could be down-regulated by L-theanine. ...
l-theanine is a unique nonproteinogenic amino acid found in tea, and has recently received considerable attention because of its various biological activities. However, there is no available research report on the use of l-theanine as a feed additive in ducks. This study was conducted to investigate the potential benefits and appropriate dosages of l-theanine on the growth performance, immune function, serum biochemical parameters, and jejunum morphology and antioxidant capacity of ducks. A total of 600 1-day-old Chaohu ducks were randomly allocated into five dietary treatment groups supplemented with 0 (control group), 300, 600, 900 and 1500 mg/kg of l-theanine. Each group included five replicates of 24 birds each. Body weight at day 28 was increased (P
... Research has shown that oral co-administration of Ltheanine and L-cystine suppressed neutrophilia and excessive inflammatory reactions to promote postoperative recovery [22,23], reduce the adverse events of anticancer drugs [24], and protect against influenza virus infection [25,26]. Moreover, several recent works have reported that L-theanine owns anti-inflammatory actions to ameliorate airway inflammation [27] or bladder hyperactivity [28]. Interestingly, all the research on health benefits of L-theanine was performed by oral or intragastrical administration. ...
... Interestingly, all the research on health benefits of L-theanine was performed by oral or intragastrical administration. Moreover, two in vitro studies showed that L-theanine inhibited TNF-α-induced NF-kB activation in Human lung carcinoma cell line [27] or the upregulation of adhesion molecule ICAM-1 (the intercellular adhesion molecule-1), VCAM-1 (vascular cell adhesion molecule-1) expression in endothelial cells, indicating the anti-inflammatory effect of L-theanine in vitro [29]. However, the topical anti-inflammatory activity of L-theanine in skin acute inflammation have not been studied. ...
... Several works have proved the anti-inflammatory effect of L-theanine administered orally or intragastrically at the dose range from 10 to 200 mg/kg to heal gastric ulcer [61], substance P-induced hyperactive bladder [28], allergic asthma [27] and even oxidative stress [62]. The highest concentration of topical applied L-theanine (250 mM, 20 μl) per mice ( ± 30 g) used in our study was equal to ± 290 mg/kg body weight (b.w.). ...
l-theanine, the most abundant free amino acid in tea, has been documented to possess many different bioactive properties through oral or intragastrical delivery. However, little is known about the effect of topical delivery of l-theanine on acute inflammation. In the present study, by using 12-O-tetradecanoylphorbol-13-acetate (TPA, 2.5 μg/ear)-induced ear edema model in mice, we first found that single-dose local pretreatment of l-theanine 30 min before TPA time- and dose-dependently suppressed the increases in both skin thickness and weight. Subsequently l-theanine ameliorated TPA-induced erythema, vascular permeability increase, epidermal and dermal hyperplasia, neutrophil infiltration and activation via downregulating the expression of PECAM-1 (a platelet endothelial adhesion molecule-1) in blood vessels and the production of pro-inflammatory cytokines IL-1β, TNF-α, and mediator cyclooxygenase-2 (COX-2), which is mainly expressed in neutrophils. It highlighted the potential of l-theanine as a locally administrable therapeutic agent for acute cutaneous inflammation.
... Oolong tea ethanol extract Inhibited activity of NO, COX-2, TNF-α, IL-6 and IL-1β in LPS-induced murine macrophage cell line [99] L-theanine Topically delivered, reduced skin inflammation via inhibition of IL-1β, TNF-α and COX-2 [103]. Alleviated airway inflammation via suppression of NFκB pathway, reduced production of MCP-1, IL-4, IL-5, IL-13, TNF-α and interferon-gamma, attenuated trafficking of inflammatory cells into bronchoalveolar lavage fluid [104]. ...
... One dose of topically delivered L-theanine was shown to reduce acute skin inflammation in a mouse model by inhibiting production of IL-1β, TNF-α and COX-2 [103]. An ovalbumin-induced murine model of asthma showed that L-theanine alleviated airway inflammation and dramatically attenuated extensive trafficking of inflammatory cells into bronchoalveolar lavage fluid (BALF) [104]. This study found L-theanine administration significantly decreased the production of MCP-1, IL-4, IL-5, IL-13, TNF-α, and interferon-gamma in BALF, exhibiting strong anti-inflammatory activity through suppression of the NFκB pathway. ...
This article is a comprehensive review of the literature pertaining to the antidepressant effects and mechanisms of regular tea consumption. Meta-data supplemented with recent observational studies were first analyzed to assess the association between tea consumption and depression risk. The literature reported risk ratios (RR) were 0.69 with 95% confidence intervals of 0.62–0.77. Next, we thoroughly reviewed human trials, mouse models, and in vitro experiments to determine the predominant mechanisms underlying the observed linear relationship between tea consumption and reduced risk of depression. Current theories on the neurobiology of depression were utilized to map tea-mediated mechanisms of antidepressant activity onto an integrated framework of depression pathology. The major nodes within the network framework of depression included hypothalamic-pituitary-adrenal (HPA) axis hyperactivity, inflammation, weakened monoaminergic systems, reduced neurogenesis/neuroplasticity, and poor microbiome diversity affecting the gut–brain axis. We detailed how each node has subsystems within them, including signaling pathways, specific target proteins, or transporters that interface with compounds in tea, mediating their antidepressant effects. A major pathway was found to be the ERK/CREB/BDNF signaling pathway, up-regulated by a number of compounds in tea including teasaponin, L-theanine, EGCG and combinations of tea catechins and their metabolites. Black tea theaflavins and EGCG are potent anti-inflammatory agents via down-regulation of NF-κB signaling. Multiple compounds in tea are effective modulators of dopaminergic activity and the gut–brain axis. Taken together, our findings show that constituents found in all major tea types, predominantly L-theanine, polyphenols and polyphenol metabolites, are capable of functioning through multiple pathways simultaneously to collectively reduce the risk of depression.
... At the same dosage (10 mg/kg/day), L-THE counteracted the deleterious effect of DOX on oxidative stress by normalising GSH levels in the heart and liver and potentially reducing oxidative damage, further highlighting the potential role of L-THE as an enhancer of cellular antioxidant defences (Sugiyama & Sadzuka, 2004). These antioxidant properties have also been reported by Hwang et al. (2017) ...
... who described the anti-inflammatory and antioxidant effects of L-THE in a murine model resulting from ovalbumin-induced asthma. This study provided evidence that L-THE (10-100 mg/kg/day) attenuated ovalbumin-induced airway inflammation in mice by reducing reactive oxygen species generation, decreasing inflammatory cells, and reducing IgE and the levels of proinflammatory mediators in bronchoalveolar lavage fluid(Hwang et al., 2017). Despite the consistent findings regarding the management of cancer drugs and their side effects, it is important to note that the majority of studies have been associated with cancer drug management. ...
l‐Theanine (l‐THE) is a nonproteinogenic amino acid derived from green tea (Camellia sinensis), which exhibits strong antioxidant‐like properties and contributes to the favourable umami taste sensation. Several studies have reported that the consumption of this amino acid has many therapeutic effects, including improvements in brain and gastrointestinal function, cancer drug therapeutic efficacies, antihypertensive effects, and improved immune function. Considering the recent Western commercialisation and popularity of green tea consumption as a nootropic agent in humans, the aims of this review were to consolidate the existing knowledge from ex vivo and in vitro animal models and attempt to highlight the applicability of l‐THE towards the human clinical trials. Considering the anti‐inflammatory and antioxidants effects of l‐THE presented in the current review, further research must translate the existing knowledge gained from animal and cell models to exploring the potential metabolic health benefits and moderating effects on the pathogenesis of conditions such as obesity, arthritis, depression, and type 2 diabetes in human trials. This will bridge the gap in literature and provide more insights into the mechanisms driving pathologies characterised by the inflammatory response and oxidative stress.
... Asthma is an inflammatory disorder that is characterized by pulmonary infiltration of eosinophils, neutrophils, and lymphocytes, as well as mucosal hypersecretion and airway hyper-responsiveness (AHR) (Elias et al. 2003). Importantly, MCP-1 (CCL2) is a critical inflammatory mediator in asthmatic airway epithelial cells (Hwang et al. 2017). Zhu et al. reported that curcumin significantly attenuated ovalbumin and IL-4-induced MCP-1 overexpression both in lung tissue of mice in a murine model of chronic asthma, as well as in the BEAS-2B cell line (human bronchial epithelial cells), and it appears that the inhibitory effects of curcumin were mediated by inactivation of the PPARγ-dependent NFκB signaling pathway (Zhu et al. 2019). ...
Chemokines belong to the family of cytokines with chemoattractant properties that regulate chemotaxis and leukocyte migration, as well as the induction of angiogenesis and maintenance of hemostasis. Curcumin, the major component of the Curcuma longa rhizome, has various pharmacological actions, including anti-inflammatory, immune-regulatory, anti-oxidative, and lipid-modifying properties. Chemokines and chemokine receptors are influenced/modulated by curcumin. Thus, the current review focuses on the molecular mechanisms associated with curcumin's effects on chemoattractant cytokines, as well as putting into context the many studies that have reported curcumin-mediated regulatory effects on inflammatory conditions in the organs/systems of the body (e.g., the central nervous system, liver, and cardiovascular system). Curcumin's effects on viral and bacterial infections, cancer, and adverse pregnancy outcomes are also reviewed.
... Thus, it helps animals improve their immune system under stress conditions. It is also intimately connected to the control of the expression of numerous inflammatory genes, because the activation of these genes may result in an inflammatory response and immunological dysfunction (Hwang et al., 2017). Wen et al. (2012) revealed that supplementing hens' daily diets with L-theanine boosts immunoglobin A (IgA) levels in serum levels of Interleukin-2 (IL2) and Interferon-γ (IFN-γ) and in the jejunum. ...
Theanine is a naturally occurring amino acid, including two forms: D-theanine and L-theanine. L-theanine is the most common nonprotein amino acid and is soluble in water. Theanine can be found in some plants, such as green tea and some mushrooms. Under stress conditions, theanine is proposed to be a naturally effective additive in preventing reactive oxygen species, thus reducing oxidative stress. In addition, as an immune booster in animal bodies, L-theanine can be applied in the diet to help animals improve their performance, especially their immunity during stress conditions. The digestion of L-theanine improves γδ T cell growth and development. Thus, it is considered an essential compound in boosting the immune function. Moreover, the immune function of L-theanine is also shown in immune-related organs through increasing their weights. Theanine seems to be widely used in pigs, mice, and humans. However, the study of theanine in poultry species is scarce. Therefore, to fill the knowledge gap regarding the use of theanine in enhancing poultry immunity, this study aims to synthesize all information on the application of theanine in poultry, focusing on its immune-boosting role.
... L-theanine was also found to reduce inflammation in lipopolysaccharide-induced mouse models, by normalizing the hyperactivity of the hypothalamus-pituitary-adrenal (HPA) axis and reducing the expression of inflammatory factors, including IL-1β, TNF-α, and IL-6, via inhibiting the NF-κB pathway (34). In ovalbumin-induced mouse asthma models, L-theanine treatment could reduce the transport of inflammatory cells to bronchoalveolar lavage fluid (BALF) and inhibit the infiltration of inflammatory cells via blocking the activation of NF-κB pathway and its downstream production of ROS, monocyte chemoattractant protein-1 (MCP-1), IL-4, IL-5, IL-13, TNF-α, and interferon (IFN)-γ in BALF (35). ...
Tea (Camellia sinensis L.) is a very popular health drink and has attracted increasing attention in recent years due to its various bioactive substances. Among them, L-theanine, a unique free amino acid, is one of the most important substances in tea and endows tea with a special flavor. Moreover, L-theanine is also a bioactive compound with plenty of health benefits, including antioxidant, anti-inflammatory, neuroprotective, anticancer, metabolic regulatory, cardiovascular protective, liver and kidney protective, immune regulatory, and anti-obesity effects. Due to the unique characteristics and beneficial functions, L-theanine has potential applications in the development of functional foods. This review summarized the influencing factors of L-theanine content in teas, the main health benefits and related molecular mechanisms of L-theanine, and its applications in food, understanding of which can provide updated information for the further research of L-theanine.
... It is synthesized in the roots and accumulates in tea leaves, with an average content of 1.2 to 6.2 mg/g fresh weight, 1 to 2.5% of total leaf weight, and represents about 50% of total free amino acids in teas [106]. Research on L-theanine has gained attention due to its numerous health benefits, including its growth promotion, anti-apoptosis, anti-oxidation, anti-stress, antianxiety, anti-carcinogenic, neuroprotection, antimicrobial, immunomodulation, and anti-inflammatory functions [18,[107][108][109][110]. It can cross the blood-brain barrier to afford neuroprotection against oxidative stress [111]. ...
Heat stress (HS) is an important environmental stress factor affecting poultry production on a global scale. With the rise in ambient temperature and increasing effects of global warming, it becomes pertinent to understand the effects of HS on poultry production and the strategies that can be adopted to mitigate its detrimental impacts on the performance, health, welfare, immunity, and survival of birds. Amino acids (AAs) have been increasingly adopted as nutritional modifiers in animals to ameliorate the adverse effects of HS. They are essential for protein synthesis, growth, maintenance, reproduction, immunity, stress response, and whole-body homeostasis. However, HS tends to adversely affect the availability, transport, absorption, and utilization of these AAs. Studies have investigated the provision of these AAs to poultry during HS conditions, and variable findings have been reported. Taurine, L-theanine, and L-citrulline are non-essential amino acids that are increasingly gaining attention as nutritional supplements in HS animals. Similarly, betaine is an amino acid derivative that possesses favorable biological properties which contributes to its role as a functional additive during HS. Of particular note, taurine is negligible in plants, while betaine, L-theanine, and L-citrulline can be found in selected plants. These nutrients are barely found in feed ingredients, but their supply has been shown to elicit important physiological roles including anti-stress effects, anti-oxidative, anti-inflammatory, gut promoting, and immunomodulatory functions. The present review provides information on the use of these nutritionally and physiologically beneficial nutrients as functional additives to poultry diets during HS conditions. Presently, although several studies have reported on the positive effects of these additives in human and murine studies, however, there is limited information regarding their utilization during heat stress in poultry nutrition. Therefore, this review aims to expound on the functional properties of these nutrients, their potentials for HS alleviation, and to stimulate further researches on their biological roles in poultry nutrition.
... l-Theanine, a unique free amino acid in tea plants, contributes 1-2% of the dry weight of green tea leaves [15]. It has been reported that l-theanine could decrease anxietylike behavior [16], airway inflammation [17], and neointimal hyperplasia [18]. As a derivative of glutamate, l-theanine robustly inhibits the apoptosis of liver cancer cells by mitochondrial pathway [19]. ...
Purpose
l-Theanine is a unique non-protein amino acid found in green tea, which has been identified as a safe dietary supplement. It has been reported that l-theanine exerts various biological activities. In this study, we explored the anti-cancer effects of l-theanine on melanoma cells.
Methods
A375, B16–F10, and PIG1 cell lines were used in the present study. EdU labeling, TUNEL and Annexin V/PI staining, wound-healing, and transwell migration assay were performed to detect the effects of l-theanine on melanoma cell proliferation, apoptosis, and migration. Brain and muscle Arnt-like protein 1 (BMAL1) was knocked down in melanoma cells to evaluate if l-theanine plays the anti-cancer role through regulating circadian rhythm of melanoma cells. The western blot, qRT-PCR, and dual luciferase assay were performed to explore the mechanism involved in the effects of l-theanine on melanoma cells.
Results
l-Theanine apparently reduced the viability of melanoma cells. Further experiments showed that l-theanine attenuated the proliferation and migration, and promoted apoptosis of melanoma cells. l-Theanine significantly enhanced the expression of BMAL1, a clock gene in melanoma cells. Down-regulation of BMAL1 suppressed the anti-cancer effects of l-theanine on melanoma cells. Further experiments indicated that the p53 transcriptional activity raised by l-theanine was dependent on BMAL1 expression in melanoma cells.
Conclusion
l-Theanine exerts the anti-cancer effect on melanoma cells through attenuating the proliferation and migration, and promoting apoptosis of them, which is dependent on the regulation of the clock gene Bmal1 in melanoma cells.
... Heo et al., (2008) reported that aqueous extract of green tea (Camellia sinensis) exhibits potent anti-asthmatic activity by alleviating asthmatic symptoms in the lung of ovalbumin sensitized mice, by increasing the expression levels of T-helper 1 (Th1) cell-specific anti-asthmatic biomarkers (TNF-β and interferon-γ) and decreasing the expression of anti-asthmatic cytokines. In addition, Hwang et al., (2017) reported that a water-soluble amino acid namely L-theanine, isolated from green tea (Camellia sinensis), showed anti-inflammatory activity in an ovalbumin (OVA)-induced murine model of asthma giving protective effects on asthmatic responses, particularly airway inflammation and oxidative stress modulation. L-theanine represses OVA-induced mucus production and inflammatory cell infiltration in the respiratory tract and blood vessels. ...
Several plants have traditionally been used since antiquity to treat various gastroenteritis and respiratory symptoms similar to COVID-19 outcomes. The common symptoms of COVID-19 include fever or chills, cold, cough, flu, headache, diarrhoea, tiredness/fatigue, sore throat, loss of taste or smell, asthma, shortness of breath, or difficulty breathing, etc. This study aims to find out the plants and plant-derived products which are being used by the COVID-19 infected patients in Bangladesh and how those plants are being used for the management of COVID-19 symptoms. In this study, online and partially in-person survey interviews were carried out among Bangladeshi respondents. We selected Bangladeshi COVID-19 patients who were detected Coronavirus positive (+) by RT-PCR nucleic acid test and later recovered. Furthermore, identified plant species from the surveys were thoroughly investigated for safety and efficacy based on the previous ethnomedicinal usage reports. Based on the published data, they were also reviewed for their significant potentialities as antiviral, anti-inflammatory, and immunomodulatory agents. We explored comprehensive information about a total of 26 plant species, belonging to 23 genera and 17 different botanical families, used in COVID-19 treatment as home remedies by the respondents. Most of the plants and plant-derived products were collected directly from the local marketplace. According to our survey results, greatly top 5 cited plant species measured as per the highest RFC value are Camellia sinensis (1.0) > Allium sativum (0.984) > Azadirachta indica (0.966) > Zingiber officinale (0.966) > Syzygium aromaticum (0.943). Previously published ethnomedicinal usage reports, antiviral, anti-inflammatory, and immunomodulatory activity of the concerned plant species also support our results. Thus, the survey and review analysis simultaneously reveals that these reported plants and plant-derived products might be promising candidates for the treatment of COVID-19. Moreover, this study clarifies the reported plants for their safety during COVID-19 management and thereby supporting them to include in any future pre-clinical and clinical investigation for developing herbal COVID-19 therapeutics.
... A study in 2017 showed that theanine can modulate airway inflammation and oxidative stress of asthma in a murine model, and treatment with L-theanine attenuated the extensive infiltration of inflammatory cells into bronchi. It also inhibited mucus, MCP-1, IL-IL-4, IL-5, IL-13, TNF-α, INF-γ, and IgE production, attenuated the generation of ROS, and activates NF-κB and matrix metalloprotease-9 [24]. CsMYB73, which belongs to subgroup 22 of the R2R3-MYB family is a transcriptional repressor involved in L-theanine biosynthesis [25]. ...
Asthma is an important global health problem, and the main cause of asthma is allergic reaction and immune system dysregulation. Airway inflammation causes bronchial narrowing, and goblet cell hyperplasia leads to mucus hypersecretion that leads to airflow obstruction and difficulty breathing. The Th2 cytokines can induce allergic asthma. Camellia, Adhatoda, and Glycyrrhiza are the traditional medicines that are used in some countries. In the current study, we evaluated three herbal extracts on airway inflammatory responses in asthmatic mice. The asthma model was induced in mice that were divided into 6 groups: Phosphate-buffered saline (PBS) group, ovalbumin (OVA) group, OVA-budesonide group, OVA-Glycyrrhiza group, OVA-Camellia group, and OVA-Adhatoda group. Measurements of IL-4, IL-5, IL-13, glutamate oxaloacetate transaminase (GOT), glutamic pyruvic transaminase (GPT), IgE, histamine, percentages of eosinophils in bronchoalveolar lavage fluid (BALf), gene expression of COX-2, CCL24, CCL11, eotaxin, and histopathological study of lung were done. Adhatoda significantly attenuated the IL-4, IgE, and histamine levels. Glycyrrhiza attenuated the levels of IL-5, IL-13, GTP, GOT (on day 51), mRNA expression of eotaxin, CCL24, CCL11, and COX-2, eosinophil infiltration, mucus secretion, and goblet cell hyperplasia. Camellia decreased IL-13, GTP, COX-2 mRNA expression, mucus secretion, and goblet cell hyperplasia on day 31 and 51. We evaluated effect of three plants on allergic bio-factors. Glycyrrhiza as main anti-inflammatory treatment, Adhatoda as anti-allergic, and Camellia as anti-mucus releasing treatment can be used in attacks of allergic asthma.
... The major function of the inflammation is to defend the host from infectious pathogens and repair tissue injury through the action of leukocytes including macrophages, neutrophils, and lymphocytes [21,22]. However, immoderate or prolonged inflammation contribute to the development of chronic inflammation diseases such as arthritis, asthma, Crohn's, and inflammatory bowel disease (IBD), resulting in swelling, pain, and eventually damage of tissue or organ dysfunction [23,24]. Macrophage activated by antigen, pathogens, and endogenous inflammatory stimuli is associated with functional and physiological changes in the cells and generates proinflammatory and cytotoxic mediators such as nitric oxide (NO), tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), IL-6, reactive oxygen mediators, and hydrolytic enzymes [25,26]. ...
Celastrus orbiculatus Thunb has been known as an ethnopharmacological medicinal plant for antitumor, anti-inflammatory, and analgesic effects. Although various pharmacological studies of C. orbiculatus extract has been reported, an anti-inflammatory mechanism study of their phytochemical constituents has not been fully elucidated. In this study, compounds 1–17, including undescribed podocarpane-type trinorditerpenoid (3), were purified from C. orbiculatus and their chemical structure were determined by high-resolution electrospray ionization mass (HRESIMS) and nuclear magnetic resonance (NMR) spectroscopic data. To investigate the anti-inflammatory activity of compounds 1–17, nitric oxide (NO) secretion was evaluated in LPS-treated murine macrophages, RAW264.7 cells. Among compounds 1–17, deoxynimbidiol (1) and new trinorditerpenoid (3) showed the most potent inhibitory effects (IC50: 4.9 and 12.6 μM, respectively) on lipopolysaccharide- (LPS-) stimulated NO releases as well as proinflammatory mediators, such as inducible nitric oxide (iNOS), cyclooxygenase- (COX-) 2, interleukin- (IL-) 1β, IL-6, and tumor necrosis factor- (TNF-) α. Its inhibitory activity of proinflammatory mediators is contributed by suppressing the activation of nuclear transcription factor- (NF-) κB and mitogen-activated protein kinase (MAPK) signaling cascades including p65, inhibition of NF-κB (IκB), extracellular signal-regulated kinase (ERK), c-Jun NH2-terminal kinase (JNK), and p38. Therefore, these results demonstrated that diterpenoids 1 and 3 obtained from C. orbiculatus may be considered a potential candidate for the treatment of inflammatory diseases.
... l-Theanine has been used as a treatment for various diseases in China due to its anti-inflammatory and anti-oxidant effects (Di et al. 2010;Yan et al. 2017;Zeng et al. 2018). In a recent study, l-theanine was shown to suppress airway inflammation in ovalbumin-induced allergic asthma and inhibited TNF-α-induced NF-kB activation in Human lung carcinoma cells (Hwang et al. 2017). Another study showed that l-theanine inhibits proinflammatory signaling, apoptosis, and autophagy in substance P-induced bladder tissues (Tsai et al. 2017). ...
The aim of this study is to evaluate the anti-inflammatory and protective effects of l-theanine in inflammatory bowel disease (IBD) and to identify the underlying molecular mechanisms. Rats were pre-treated with l-theanine at 0, 50, 200, or 800 mg/kg/day. IBD was induced in rats using dextran sulfate sodium (DSS). Histopathological analysis suggests that l-theanine can suppress DSS-induced IBD with significant inhibition of inflammation in large and small intestinal tissues. Moreover, the 200 mg/kg/day l-theanine-treated DSS group had higher body and small intestine weights, a lower disease activity index and expression of inflammatory factors than the DSS group without pre-treatment. In RNA sequencing and tandem mass tag labeling analyses, large number of mRNAs and proteins expression level differed when compared with the DSS-induced rats with and without 200 mg/kg/day l-theanine pre-treatment. Moreover, Kyoto Encyclopedia of Genes and Genomes pathway analysis indicates the anti-inflammatory activities of l-theanine in DSS-induced IBD, with a high representation of genes in “Cholesterol metabolism” and “Retinol metabolism” pathways. Analysis of protein–protein interaction networks further indicates the involvement of these two pathways. These studies suggest that medium-dose l-theanine pre-treatment could ameliorate DSS-induced IBD through molecular mechanisms involving cholesterol and retinol metabolism.
... Amino acid NF-κB and MMP-9 levels are reduced leading to anti-inflammatory activity [33] Luteolin ...
COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is devastative to the humankind for which neither vaccines nor precise therapeutic molecules for treatment are identified. The search for new drugs and repurposing of existing drugs are being performed; however, at the same time, research on plants to identify novel therapeutic compounds or testing the existing ones is progressing at a slower phase. In this context, genomics and biotechnology offer various tools and strategies to manipulate plants for producing those complex biopharmaceutical products. This review enumerates the scope for research on plant-based molecules for their potential application in treating SARS-CoV-2 infection. Strategies to edit gene and genome, overexpression and silencing approaches, and molecular breeding for producing target biomolecules in the plant system are discussed in detail. Altogether, the present review provides a roadmap for expediting research on using plants as a novel source of active biomolecules having therapeutic applications.
... Numerous studies have confirmed that LT possesses anti-inflammatory, antioxidant, antitumor properties and exhibits protective effects against inflammatory injuries in the brain, stoma, liver, and kidney [11][12][13][14]. It can also enhance the body's antioxidant capacity under pathological conditions and reduce inflammatory responses by down-regulating mRNA expression of inflammatory factors in the nuclear factor kappa B (NFκB) pathway [15]. One recent study reported that LT is capable of replacing L-glutamine in E44813-stressed rats, thus ameliorating intestinal stress by reducing the expression of inflammatory factors, increasing the activities of antioxidant enzymes, and regulating glutamine metabolism [16]. ...
... Reduces the inflammatory cells count and 2 cytokines Shin et al. [123] 10 Evidence-Based Complementary and Alternative Medicine L-eanine Hwang et al. [132] Luteolin Isolated compound Perilla frutescens ...
Asthma, a disease classified as a chronic inflammatory disorder induced by airway inflammation, is triggered by a genetic predisposition or antigen sensitization. Drugs currently used as therapies present disadvantages such as high cost and side effects, which compromise the treatment compliance. Alternatively, traditional medicine has reported the use of natural products as alternative or complementary treatment. The aim of this review was to summarize the knowledge reported in the literature about the use of natural products for asthma treatment. The search strategy included scientific studies published between January 2006 and December 2017, using the keywords “asthma,” “treatment,” and “natural products.” The inclusion criteria were as follows: (i) studies that aimed at elucidating the antiasthmatic activity of natural-based compounds or extracts using laboratory experiments (in vitro and/or in vivo); and (ii) studies that suggested the use of natural products in asthma treatment by elucidation of its chemical composition. Studies that (i) did not report experimental data and (ii) manuscripts in languages other than English were excluded. Based on the findings from the literature search, aspects related to asthma physiopathology, epidemiology, and conventional treatment were discussed. Then, several studies reporting the effectiveness of natural products in the asthma treatment were presented, highlighting plants as the main source. Moreover, natural products from animals and microorganisms were also discussed and their high potential in the antiasthmatic therapy was emphasized. This review highlighted the importance of natural products as an alternative and/or complementary treatment source for asthma treatment, since they present reduced side effects and comparable effectiveness as the drugs currently used on treatment protocols.
... It is notable that anti-amyloidogenic activity has been attributed to oxidized EGCG comparable to the intact molecule, as it has a disruptive effect on preformed fibrils more than the native form [202]. Green tea revealed a high potency in the prohibition of proMMP-9 and MMP-9 activities, which play an important role in the development of pulmonary hypertension [203]; meanwhile, L-theanine proved efficacy in the alleviation of oxidative stress-induced airway inflammation in asthma [204]. Recent studies showed that dietary supplementation enriched with green tea promotes the antioxidant defense system in plasma and thus provides protection against oxidative damage induced by both short-term muscular endurance test and long-term strength training [205]. ...
Tea, Camellia sinensis, which belongs to the family Theaceae, is a shrub or evergreen tree up to 16 m in height. Green tea is very popular because of its marked health benefits comprising its anticancer, anti-oxidant, and antimicrobial activities, as well as its effectiveness in reducing body weight. Additionally, it was recognized by Chinese people as an effective traditional drink required for the prophylaxis against many health ailments. This is due to the complex chemical composition of green tea, which comprises different classes of chemical compounds, such as polyphenols, alkaloids, proteins, minerals, vitamins, amino acids, and others. The beneficial health effects of green tea ultimately led to its great consumption and increase its liability to be adulterated by either low-quality or non-green tea products with concomitant decrease in activity. Thus, in this review, green tea was selected to highlight its health benefits and phytoconstituents, as well as recent approaches for its quality-control monitoring that guarantee its incorporation in many pharmaceutical industries. More research is needed to find out other more biological activities, active constituents, and other simple and cheap techniques for its quality assurance that ascertain the prevention of its adulteration.
... These results hinted that to some extent, allergic mice exposed to PM2.5 or FA alone, exhibited enhanced lung inflammation. These results are consistent with previous studies 31, 41 . The analyses of cytokines in BALF indicated that allergic mice exposed to a combination of PM2.5 and FA produced more serious lung inflammation than exposure to either of the pollutants alone. ...
Asthma is a complex pulmonary inflammatory disease that can be promoted by air pollutants such as PM2.5 and formaldehyde (FA). However, existent experimental evidence principally focuses on the negative influence of a single air pollutant, neglecting the possible synergistic effect in biological responses to mixture of these pollutants, a more common situation in our daily life. In this study, allergic Balb/c mice were exposed to a mixture of PM2.5 and FA, and their toxicological effects and mechanisms were explored. It is demonstrated that the combined exposure to PM2.5 and FA can greatly aggravate allergic asthma in mice. When compared with exposure to PM2.5 or FA alone, the co-exposure showed a certain synergistic effect. Increased levels of ROS, inflammatory factors and total serum immunoglobulin E were concomitant with this deterioration. Furthermore, results suggested that co-exposure exacerbated the activation of TRPV1 signal pathways, with an enhancement in substance P and calcitonin gene-related peptide production, which contributed to inflammation in asthma by neurogenic inflammation. The study also proved that capsazepine treatment could reduce the levels of not only pro-inflammatory neuropeptides, but also oxidative stress. It is concluded that co-exposure to PM2.5 and FA exacerbated allergic asthma through oxidative stress and enhanced TRPV1 activation.
Ovalbumin (OVA), a commonly consumed food protein, can cause severe allergies and intestinal immune disorders. L-theanine (LTA) and epigallocatechin gallate (EGCG) regulate intestinal immunity. However, it is unclear whether an...
Ovalbumin (OVA), a common food protein, can cause deadly allergies with intestine-specific immune reactions. L-Theanine (LTA) shows great potential for regulating intestinal immunity. To investigate the regulatory effect of LTA intervention on intestine-specific immunity, a 41 day experiment was performed on BALB/c OVA-sensitized mice. The results show that injecting female mice intraperitoneally with 50 μg of OVA and administering 30 mg of OVA 4 times can successfully establish an OVA-sensitized mouse model. LTA intervention significantly increased weight gain and thymus index (p < 0.05), decreased allergy and diarrhea scores (p < 0.05), and improved jejunum structure. Meanwhile, the histological score and degranulation of mast cells decreased. LTA intervention increased Clostridiales, Lachnospiraceae, Lactobacillus, Prevotella, and Ruminococcus abundance while decreasing Helicobacter abundance. Flow cytometry and Western blotting results indicated that 200 and 400 mg/kg of LTA upregulated the expression of T-bet and Foxp3 proteins (p < 0.05), thus promoting the differentiation of jejunum CD4+ T cells to Th1 and Tregs and increasing the cytokines IFN-γ, IL-10, and TGF-β (p < 0.05). We found that 200 and 400 mg/kg of LTA downregulated the expression of RORγt and GATA3, thus inhibiting the differentiation of Th2 and Th17 cells and decreasing cytokines IL-4, IL-5, IL-13 TNF-α, IL-6, and IL-17A (p < 0.05). LTA inhibited the degranulation of mast cells and significantly decreased the serum levels of OVA-IgE, HIS, and mouse MCPT-1 (p < 0.05). Therefore, LTA intervention alleviated OVA allergy by improving intestine-specific immunity.
The aim of this study was to explore the effects of dietary L-theanine (LT) supplementation on lipid metabolism and antioxidant capacity in weaned piglets. Twenty-one castrated DLY weaning piglets were randomly divided into three groups: a basal diet, a basal diet supplemented with 0.05% and 0.1% LT, respectively. Our data showed that dietary LT supplementation decreased T-CHO, TG, LDL-C and apoB levels and increased apoA and HDL-C levels in serum, but decreased the hepatic TG and T-CHO contents. Dietary LT supplementation increased the antioxidant capacity in serum and liver, and significantly increased the Nrf2 mRNA level and the nucleus Nrf2 protein level, but decreased the mRNA level of keap1 in the liver. In addition, dietary LT supplementation significantly increased HSL enzyme activity and the levels of CPT1 and TBA, while decreasing the enzyme activities of LPL and FAS in the liver. Furthermore, the mRNA levels HMG-CoAR, CPT-1a and PPARα and the protein levels of phosphorylated-AMPK and PGC-1α were increased by LT. Together, our data provide the first evidence that dietary supplementation of LT could improve lipid metabolism and antioxidant capacity in the liver of weaned piglets, and the effect might be mediated by activation of AMPK and Nrf2 signaling, respectively.
Acute alcoholic liver injury (AALI) refers to the inflammatory hepatic damage caused by alcohol. In severe cases, it can lead to steatohepatitis, alcoholic fibrosis and even cirrhosis. In this study, we analyzed the hepatoprotective activity of L-theanine on mice fed with a large amount of ethanol at one time, and the underlying molecular mechanism. The extensive liver injury caused by alcohol feeding was alleviated by L-theanine, which reduced tissue damage, decreased transaminase levels, and increased antioxidant activity. Mechanistically, L-theanine downregulated phosphorylated NF-κB, TNF-α and IKKα in the liver tissues and the LO2 normal hepatocyte cell line, which in turn lowered secretion of iNOS, IL-1β and IL-6. Taken together, L-theanine prevents alcohol-induced liver inflammation by blocking the intrahepatic TNF-α/NF-κB pathway, and is a promising treatment strategy against AALI.
The World Health Organization (WHO) has reported that chronic respiratory diseases such as asthma, chronic obstructive pulmonary disease, interstitial lung disease, and lung cancer are among the major chronic human diseases that posed a huge challenge to public health and socioeconomic growth. Pharmacotherapy is crucial in the management of these diseases; however, the utilization of conventional treatments is found to be futile, as most patients remained poorly controlled with low quality of life. This has prompted the discovery and development of novel therapeutic agents to improve treatment outcomes. Over the years, researchers have studied a vast range of natural products for their potential in managing chronic respiratory diseases. It has been demonstrated that chemical moieties obtained from plant sources improved pharmacokinetic and toxicological profiles, with a robust multi-prolonged action. Hence, they are held in high regard as possible replacements to address the limitations faced by current therapies. In this chapter, such a phytochemical approach with respect to their molecular mechanisms targeting signalling pathways involved in various chronic respiratory diseases will be discussed. We have also summarized some of the experimental evidence that supports the use of plant-based chemical moieties in chronic respiratory diseases.
Atherosclerosis is one of the most common cardiovascular diseases with highly mortality worldwide. The formation of foam cell plays an important role in the early stage of atherosclerosis pathogenesis. L-theanine is the most abundant free amino acid in tea, which possesses anti-inflammatory, anti-tumor and anti-atherosclerosis effects. However, little is known about the effects of L-theanine on the foam cell formation. In our study, RAW264.7 cells and primary mouse peritoneal macrophages were exposed to oxidized low density lipoprotein (ox-LDL) for inducing foam cell formation. We found that L-theanine significantly impeded cholesterol accumulation in macrophages, while inhibiting the formation of foam cell. Our further experiments showed that L-theanine attenuated the cholesterol uptake of RAW264.7 cells and primary mouse peritoneal macrophages by reducing the protein level of macrophage scavenger receptor A (SR-A), but not the level of mRNA suggesting that L-theanine regulates scavenger receptor A at the translational rather than transcriptional level. The present results demonstrated that L-theanine obviously promoted the degradation of scavenger receptor A protein and scavenger receptor A was degraded by ubiquitination dependent manner. Collectively, our research indicates that L-theanine suppresses the formation of macrophage foam cell by promoting the ubiquitination dependent degradation of scavenger receptor A.
Allergy is an immune-mediated disease with increasing prevalence worldwide. Regular treatment with glucocorticoids and antihistamine drugs for allergy patients is palliative rather than permanent. Daily use of dietary anti-allergic natural products is a superior way to prevent allergy and alleviate the threat. Tea, as a health-promoting beverage, has multiple compounds with immunomodulatory ability. Persuasive evidence has shown the anti-allergic ability of tea against asthma, food allergy, atopic dermatitis and anaphylaxis. Recent advances in potential anti-allergic ability of tea and anti-allergic compounds in tea have been reviewed in this paper. Tea exerts its anti-allergic effect mainly by reducing IgE and histamine levels, decreasing FcεRI expression, regulating the balance of Th1/Th2/Th17/Treg cells and inhibiting related transcription factors. Further research perspectives are also discussed.
Background. Mounting evidence, consistent with our previous study, showed that γ-aminobutyric acid type A receptor (GABAAR) played an indispensable role in airway inflammation and mucus hypersecretion in asthma. Monocyte chemotactic protein-inducing protein 1 (MCPIP1) was a key negative regulator of inflammation. Recent studies showed that inflammation was largely suppressed by enhanced MCPIP1 expression in many inflammatory diseases. However, the role and potential mechanism of MCPIP1 in airway inflammation and mucus hypersecretion in asthma were still not well studied. This study was to explore the role of MCPIP1 in asthmatic airway inflammation and mucus hypersecretion in both mice and BEAS-2B cells, and its potential mechanism.
Methods. In vivo, mice were sensitized and challenged by ovalbumin (OVA) to induce asthma. Airway inflammation and mucus secretion were analyzed. In vitro, BEAS-2B cells were chosen. Interleukin (IL)-13 was used to stimulate inflammation and mucus hypersecretion in cells. MCPIP1 Lentiviral vector (LA-MCPIP1) and plasmid-MCPIP1 were used to up-regulate MCPIP1 in lung and cells, respectively. MCP-1, thymic stromal lymphopoietin (TSLP), mucin 5AC (MUC5AC), MCPIP1, and GABAARβ2 expressions were measured in both lung and BEAS-2B cells. Immunofluorescence staining was performed to observe the expression of GABAARβ2 in cells.
Results. MCPIP1 was up-regulated by LA-MCPIP1 (P
Here, we aimed to investigate the role of Xanthatin in asthma and its underlying mechanism. BALB/c mice were treated with ovalbumin (OVA) to establish a mouse model of asthma. Our results showed that OVA injection significantly increased inflammatory cell infiltration and goblet cell hyperplasia in lung issues, while Xanthatin treatment and STAT3 inhibitor C188-9 administration relieved these symptoms. Moreover, OVA-induced OVA-specific IgE level in serum and the number of total cell, macrophages, lymphocytes neutrophils, and eosinophils in bronchoalveolar lavage fluid (BALF) were markedly reduced by Xanthatin treatment and STAT3 inhibition. Additionally, Xanthatin treatment and STAT3 inhibition was also significantly decreased the levels of inflammatory cytokines in BALF in asthmatic mice. We further demonstrated that the STAT3/NF-κB pathway was blocked by Xanthatin in asthmatic mice. Overall, we conclude that Xanthatin attenuates airway inflammation in asthmatic mice through blocking the STAT3/NFκB signaling pathway, indicating the potential of Xanthatin as a useful therapeutic agent for asthma.
Clinical and experimental studies show an association between maternal periodontitis and adverse outcomes during gestation. On the other hand, there were no studies evaluating the impact of maternal periodontitis on the offspring. Thus, our objective was to investigate the repercussion of maternal periodontitis on the development of asthma in the offspring. Pregnant rats were submitted or not to periodontitis by ligature technique. Thirty days after birth, the puppies were sensitized and challenged with ovalbumin (OVA) in order to induce asthmatic response. Our results showed that maternal periodontitis reduced cellular infiltrate in the parenchyma of offspring, tracheal responsiveness, lung edema, and anti-OVA antibodies, without alter mucus as well as cytokines production. We concluded that periodontitis has relevant impact on the offspring’s immune system, blunting the response to allergic and inflammatory stimulus. This study shows the important role of oral health during pregnancy and opens possibilities for future studies in order to explain the effects of periodontitis during pregnancy in the offspring.
Asthma is a chronic inflammatory airway disease. Icariside II has been reported to exert anti-inflammatory effect in multiple human diseases. The present study aimed to investigate the effects and mechanisms of Icariside II on airway inflammation and remodeling in asthma. We established an asthma mouse model with ovalbumin (OVA) immunization. Histological analysis using H&E, PAS and Masson staining showed that administration of Icariside II attenuated OVA-induced airway inflammation and remodeling. Icariside II reduced the numbers of total white blood cells and eosinophils in bronchoalveolar lavage fluid (BALF). The levels of interleukin (IL)-4, IL-5, IL-13 and transforming growth factor (TGF)-β1 in peripheral blood and the expression of α-smooth muscle actin (α-SMA), connective tissue growth factor (CTGF), eotaxin-1, CC-chemokine receptor-3 (CCR-3), Toll-like receptor (TLR)-2 and TLR-4 were significantly down-regulated in lung tissues of OVA-induced mouse model. These results suggested that Icariside II inhibited eosinophil activation and thus decreased eosinophils-induced airway inflammation and remodeling in asthma. Moreover, Icariside II suppressed TGF-β1-induced cell proliferation, migration, and CTGF expression in airway smooth muscle cells (ASMCs). In both OVA-induced mouse model of asthma and TGF-β1-induced ASMCs, Icariside II decreased IκBα degradation, nuclear translocation of NF-κB p65 and STAT3 phophorylation, indicating an inactivation of NF-κB and STAT3 in the presence of Icariside II. Therefore, we demonstrate that Icariside II attenuates eosinophils-induced airway inflammation and remodeling in asthmatic mice and inhibits TGF-β1-induced cell proliferation and migration in ASMCs via suppressing NF-κB and STAT3 signalings.
Aims:
Theanine, as a naturally occurring component in tea, has been shown to deliver benefits against various diseases. However, the exact molecular mechanisms underlying theanine's protective actions against cerebral ischemia/reperfusion (IR) injury still remains largely unknown.
Main methods:
In this study, rat cerebral IR injury model was established and were randomly divided into the following five groups: Sham (SH), IR, IR + Theanine (TH), IR + TH+ heme oxygenase-1 (HO-1) inducer cobalt protoporphyrin (Copp), and IR + Copp groups.
Key findings:
We found that theanine significantly inhibited neuron damage and apoptosis in the hippocampus during the 48 h detection period, as detected by hematoxylin and eosin (HE) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. Meanwhile, reduced levels of malondialdehyde (MDA) and elevated activities of superoxide dismutase (SOD), glutathione (GSH), and glutathione peroxidase (GSH-PX) were observed in the theanine-treated group. Enzyme-linked immunosorbent (ELISA) assay also revealed that theanine markedly decreased the levels of inflammatory cytokines, such as IL-6, IL-1β, and TNF-α, in IR rats. The anti-apoptotic effect of theanine on IR injury was further verified by flow cytometry assay. Besides, theanine dramatically inhibited HO-1 expression and activity but increased extracellular signal-regulated kinase 1/2 (ERK1/2) activity in hippocampal tissue from rats with cerebral IR injury. However, co-treatment with Copp remarkably abolished the protective effects of theanine on cerebral IR injury.
Significance:
These findings demonstrated that the neuroprotective role of theanine was associated with its anti-oxidative, anti-inflammatory, and anti-apoptotic properties, which might be through regulation of HO-1 activation in rats with cerebral IR injury.
Background:
L-theanine has multiple beneficial biological activities. However, there is little information about the use of L-theanine in broiler production. Therefore, this study investigated the effect of L-theanine on growth performance, intestinal development and health, and the mRNA levels of intestinal peptide and amino acid (AA) transporters of broilers.
Results:
Body weight and average daily gain were increased by L-theanine, while feed to gain ratio was decreased (quadratic, P<0.05). Notably, the relative weight of duodenum, jejunum and ileum, villus height, villus height to crypt depth ratio, the jejunal activities of glutathione peroxidase, total antioxidant capacity, catalase and total superoxide dismutase were increased linearly and/or quadratically by L-theanine (P<0.05), while crypt depth, serum D-lactic acid, and jejunal protein carbonyls and malondialdehyde contents were decreased linearly and/or quadratically (P<0.05). Moreover, L-theanine enhanced the jejunal mRNA levels of occludin, claudin-1, E-cadherin, zona occludens-1, di- and tri-peptide transporter, excitatory AA transporter 3, Na+ independent cationic AA transporter 1, Na+ independent cationic and zwitterionic AA transporter, Na+ and Cl- dependent neutral and cationic AA transporter, Na+ independent cationic and Na+ dependent neutral AA transporter (y+LAT) 1, y+LAT2, Na+ independent branched-chain and aromatic AA transporter, and heavy chain corresponding to the b°,+ transport system (linear and/or quadratic, P<0.05).
Conclusions:
L-theanine beneficially affected the growth performance of broilers by improving intestinal development and health, and the intestinal mRNA levels of AA and peptide transporters. Therefore, L-theanine is has the potential to be a promising feed additive for broilers This article is protected by copyright. All rights reserved.
Linalool is a natural product present in fruits and aromatic plants with biological activities. Researchers have reported that the inhalation of linalool exerts anti-inflammatory activities. In this study, we examined the therapeutic effects of linalool on airway inflammation and mucus overproduction in mice with allergic asthma. Oral administration of linalool significantly inhibited the levels of eosinophil numbers, Th2 cytokines and immunoglobulin E (IgE) caused by ovalbumin (OVA) exposure. Linalool exerted preventive effects against the influx of inflammatory cells and mucus hypersecretion in the lung tissues. Linalool also dose-dependently decreased the levels of inducible nitric oxide synthase (iNOS) expression and protein kinase B (AKT) activation in the lung tissues. Linalool effectively downregulated the activation of mitogen-activated protein kinases (MAPKs) and nuclear factor-κB (NF-κB) caused by OVA exposure. Furthermore, linalool exerted inhibitory effect on OVA-induced airway hyperresponsiveness (AHR). In the in vitro study, the increased secretion of MCP-1 was attenuated with linalool treatment in lipopolysaccharide (LPS)-stimulated H292 airway epithelial cells. In conclusion, linalool effectively exerts a protective role in OVA-induced airway inflammation and mucus hypersecretion, and its protective effects are closely related to the downregulation of inflammatory mediators and MAPKs/NF-κB signaling.
Theanine, a unique bioactive constituent from tea (Camellia sinensis) leaves, is widely used as a functional ingredient and dietary supplement. To evaluate the anti-inflammatory and hepatoprotective effects of theanine and its molecular mechanism, the lipopolysaccharide (LPS)-induced inflammation mouse model was employed in this study. The survival rate of mice in the theanine-treated group increased significantly compared with that of LPS-only group mice. Furthermore, ICR male mice were randomly divided into three or four groups: control, LPS (LPS treatment only), LPS + theanine (20 mg/kg/day), and theanine (theanine treatment only). The results showed that compared with the LPS group, the liver damage and oxidative stress of the theanine-treated group decreased significantly, based on plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) concentrations, hepatic total superoxide dismutase (T-SOD) and malondialdehyde (MDA) levels, and histological scores and apoptosis [terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate nick end-labeling (TUNEL) staining and caspase-3 activity] in the liver tissues. Furthermore, compared with no treatment, pretreatment with theanine significantly decreased the release of interleukin (IL)-1β and tumor necrosis factor (TNF)-α, inhibited the expression of several inflammatory factors (including IL-1β, TNF-α, and IL-6), and increased the IL-10/interferon (IFN)-γ ratio in the hepatic tissues. In the LPS-induced inflammation model, theanine inhibited the expression of proinflammatory mediators involved in the nuclear factor-kappa B (NF-κB) pathway, such as inducible nitric oxide synthase (iNOS) and matrix metalloproteinase-3 (MMP-3), and attenuated the phosphorylation of NF-κB in the hepatic tissues. Moreover, theanine suppressed the acute-phase response (elevated nitric oxide and C-reactive protein levels). Furthermore, theanine suppressed the LPS-induced inflammatory state by normalizing hypothalamic–pituitary–adrenal (HPA) axis hyperactivity. Taken together, the results suggest that theanine potentially ameliorates LPS-induced inflammation and acute liver injury; molecular mechanism of action may involve normalization of HPA axis hyperactivity and inactivation of the NF-κB signaling pathway.
Asthma is a common respiratory inflammatory disorder disease of childhood, and airway smooth muscle cells (ASMCs) play an important role in this disease. Recently, studies have found that interleukin (IL)-37 inhibits allergic airway inflammation of asthmatic mouse models. The aim of this study was to investigate the exact mechanism of IL-37 in asthma. In this study, we found recombinant human IL-37 protein significantly reduced ovalbumin (OVA)-induced airway hyperresponsiveness, inflammatory cell infiltration, the epithelial-mesenchymal-transition (EMT) process, and levels of IL-4, IL-6 and IL-13, but increased interferon (IFN)-γ expression. Moreover, IL-37 treatment remarkably inhibited transforming growth factor (TGF)-β1-induced cell proliferation, migration, EMT, and inflammatory response in ASMCs. IL-37 notably upregulated IκB expression and downregulated levels of NF-κB p65, phospho-NF-κB p65, STAT3 and phospho-STAT3 both in OVA-induced mice and in TGF-β1-stimulated ASMCs. The effects of IL-37 on TGF-β1-induced ASMCs were abrogated by STAT3 upregulation. Additionally, PDTC, a NF-κB inhibitor, showed the similar effects as IL-37 in ASMCs. In conclusion, IL-37 may alleviate airway inflammation and remodeling in asthma through suppressing the activation of NF-κB and STAT3.
Objectives: Artemisia scoparia Waldst. et Kit. (AS) has been used to treat inflammation, urticaria and hepatitis. However, the scientific studies of AS and its active compound for inflammatory reactions in activated human mast cell line, HMC-1 cells have not yet been elucidated.
Materials and methods: Here, we isolated 3,5-dicaffeoyl-epi-quinic acid (DEQA) from AS butanol fraction. The anti-inflammatory effect of AS and its new active compound, DEQA was examined in HMC-1 cells by studying the following markers: phorbol 12-myristate 13-acetate and calcium ionophore A23187 (PMACI)-induced thymic stromal lymphopoietin (TSLP), tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 secretion and mRNA expression by ELISA and RT-PCR, respectively. Furthermore, mechanism related to anti-inflammatory was examined by Western blotting.
Results: We reported that AS and its new active compound, DEQA significantly reduced TSLP, TNF-α, IL-1β and IL-6 production levels through the reduction of caspase-1 activity. The mRNA expression of these inflammatory cytokine was also reduced via blocking nuclear factor-κB nuclear translocation by AS and DEQA. In addition, AS significantly reduced phosphorylated-c-Jun N-terminal kinase level and DEQA significantly reduced both phosphorylated-c-Jun N-terminal kinase and -p38 mitogen-activated protein kinase levels.
Conclusions: Therefore, these results indicated that AS and its active compound, DEQA may improve mast cell-mediated inflammatory diseases.
Background
This study aimed to investigate the regulatory effects of L-theanine on secretion of immune cytokines, hormones, and neurotransmitters, and mRNA expression of phospholipase C (PLC) in rats, and to explore its regulatory mechanism in immune function.
Material/Methods
Sixty-four Sprague-Dawley rats received daily intragastric infusion of different doses of L-theanine solution [0, 50 (LT), 200 (MT), and 400 (HT) mg/kg BW]. Cytokines, immunoglobulins, and hormones in the serum, neurotransmitters, and mRNA expression of PLC in the relevant tissues were assayed.
Results
L-theanine administration increased the splenic organ index and decreased the contents of ILs-4/6/10 and the ratio of IL-4/IFN-γ in the serum. High-dose L-theanine administration increased the levels of dopamine and 5-hydroxytryptamine in the pituitary and hippocampus, resulting in decrease in corticosterone level in the serum. L-theanine administration decreased the mRNA expressions of PLC isomers in the liver and PLC-γ1 and PLC-δ1 in the spleen. Interestingly, mRNA expressions of PLC-βf1 in the spleen and PLC isomers mRNA in the heart were up-regulated by L-theanine administration.
Conclusions
Administration of 400 mg/kg BWL-theanine improved immune function of the rats by increasing the splenic weight, altering the Th2/Th1 cytokine balance, decreasing the corticosterone level in the serum, elevating dopamine and 5-hydroxytryptamine in the brain, and regulating the mRNA expression of PLC isomers in the heart.
Asthma is a chronic obstructive airway disease that involves inflammation of the respiratory tract. Biological contaminants in indoor air can induce innate and adaptive immune responses and inflammation, resulting in asthma pathology. Epidemiologic surveys indicate that the prevalence of asthma is higher in developed countries than in developing countries. The prevalence of asthma in Korea has increased during the last several decades. This increase may be related to changes in housing styles, which result in increased levels of indoor biological contaminants, such as house dust mite-derived allergens and bacterial products such as endotoxin. Different types of inflammation are observed in those suffering from mild-to-moderate asthma compared to those experiencing severe asthma, involving markedly different patterns of inflammatory cells and mediators. As described in this review, these inflammatory profiles are largely determined by the involvement of different T helper cell subsets, which orchestrate the recruitment and activation of inflammatory cells. It is becoming clear that T helper cells other than Th2 cells are involved in the pathogenesis of asthma; specifically, both Th1 and Th17 cells are crucial for the development of neutrophilic inflammation in the airways, which is related to corticosteroid resistance. Development of therapeutics that suppress these immune and inflammatory cells may provide useful asthma treatments in the future.
Farrerol, isolated from rhododendron, has been shown to have the anti-bacterial activity, but no details on the anti-inflammatory activity. We further evaluated the effects of this compound in two experimental models of lung diseases.
For the asthma model, female BALB/c mice were challenged with ovalbumin (OVA), and then treated daily with farrerol (20 and 40 mg/kg, i.p.) as a therapeutic treatment from day 22 to day 26 post immunization. To induce acute lung injury, female BALB/c mice were injected intranasally with LPS and treated with farrerol (20 and 40 mg/kg, i.p.) 1 h prior to LPS stimulation. Inflammation in the two different models was determined using ELISA, histology, real-time PCR and western blot. Farrerol significantly regulated the phenotype challenged by OVA, like cell number, Th1 and Th2 cytokines levels in the BALF, the OVA-specific IgE level in the serum, goblet cell hyperplasia in the airway, airway hyperresponsiveness to inhaled methacholine and mRNA expression of chemokines and their receptors. Furthermore, farrerol markedly attenuated the activation of phosphorylation of Akt and nuclear factor-κB (NF-κB) subunit p65 both in vivo and in vitro. However, farrerol has no effect on the acute lung injury model.
Our finding demonstrates that the distinct anti-inflammatory effect of farrerol in the treatment of asthma acts by inhibiting the PI3K and NF-κB pathway.
Advances have been made in defining the mechanisms for the control of allergic airway inflammation in response to inhaled antigens. Several genes, including ADAM33, DPP10, PHF11, GPRA, TIM-1, PDE4D, OPN3, and ORMDL3, have been implicated in the pathogenesis and susceptibility to atopy and asthma. Growing evidence associates asthma with a systemic propensity for allergic T-helper type 2 cytokines. Disordered coagulation and fibrinolysis also exacerbate asthma symptoms. Balance among functionally distinct dendritic cell subsets contributes to the outcome of T-cell-mediated immunity. Allergen-specific T-regulatory cells play a pivotal role in the development of tolerance to allergens and immune suppression. The major emphasis on immunotherapy for asthma during the past decade has been to direct the immune response to a type 1 response, or immune tolerance. In this review, we discuss the current information on the pathogenesis of allergic airway inflammation and potential immunotherapy, which could be beneficial in the treatment of airway inflammation, allergy, and asthma.
In chronic inflammatory diseases, such as asthma, rheumatoid arthritis, inflammatory bowel disease, and psoriasis, several cytokines recruit activated immune and inflammatory cells to the site of lesions, thereby amplifying and perpetuating the inflammatory state.1 These activated cells produce many other mediators of inflammation. What causes these diseases is still a mystery, but the disease process results from an interplay of genetic and environmental factors. Genes, such as those for atopy in asthma and for HLA antigens in rheumatoid arthritis and inflammatory bowel disease, may determine a patient's susceptibility to the disease and the disease's severity, but environmental factors, often unknown, . . .
Substantial experimental evidence now supports the notion that allergic diseases are characterised by a skewing of the immune system towards a T-helper cell type-2 (Th2) phenotype. Studies using both human and mouse model systems have provided key evidence for the role that Th2 cytokines play in driving many of the hallmarks of allergic inflammation. Furthermore, the signalling pathways by which Th2 cytokines exert their effects on airway target cells are rapidly being elucidated, and antagonists of the Th2 pathway are under active development. In this review, the current knowledge of the role of T-helper cell type-2 cells in asthma is summarised, focusing on how and where T-helper cell type-2 cells differentiate from naïve precursors. The signalling molecules and transcription factors involved in T-helper cell type-2 differentiation will be reviewed in detail, in an attempt to translate studies using genetically modified mice into meaningful insights about asthma and other allergic diseases.
Asthma is an inflammatory disorder principally involving the conducting airways and characterised by infiltration of the airway wall with a range of inflammatory cells driven in large part by activation of Th2-type lymphocytes, mast cells and eosinophils. However a key component of asthma is the structural change that involves all of the elements of the airway wall. Here evidence is presented to suggest that the airway epithelium in asthma is fundamentally abnormal with increased susceptibility to environmental injury and impaired repair associated with activation of the epithelial-mesenchymal trophic unit (EMTU). In addition to adopting an activated phenotype, the barrier function of the epithelium is impaired through defective tight junction formation thereby facilitating penetration of potentially toxic or damaging environmental insults. Activated and repairing epithelial cells generate a range of growth factors that are involved in the early life origins of this disease as well as its progression in the form of mucous metaplasia and airway wall remodeling. By placing the epithelium at the forefront of asthma pathogenesis, different approaches to treatment can be devised focused more on protecting vulnerable airways against environmental injury rather than focusing on suppressing airway inflammation or manipulating the immune response.
The present study is aimed at evaluating the protective role of L-theanine on aroclor 1254-induced oxidative stress in rat brain. Intraperitoneal administration of Aroclor 1254 (2 mg/kg b.wt. for 30 days) caused oxidative stress in rat brain and also caused neurobehavioral changes. Oxidative stress was assessed by determining the levels of lipid peroxide (LPO), protein carbonyl content, and changes in activities of creatine kinase (CK), acetylcholinesterase (AchE), and ATPases in the hippocampus, cerebellum and cerebral cortex of control and experimental rats. Histopathological results showed that PCB caused neuronal loss in all three regions. PCB upregulated the mRNA expressions of inflammatory cytokines. Oral administration of L-theanine (200 mg/kg b.wt.) increased the status of antioxidants, decreased the levels of LPO, nitric oxide (NO) and increased the activities of CK, AchE and ATPases. L-theanine restored normal architecture of brain regions and downregulated the expression of inflammatory cytokines. In conclusion, L-theanine shows a protective role against PCBs-induced oxidative damage in rat brain.
Here we evaluated the ability of l-theanine in preventing experimental hepatic cirrhosis and investigated the roles of nuclear factor-κB (NF-κB) activation as well as transforming growth factor β (TGF-β) and connective tissue growth factor (CTGF) regulation. Experimental hepatic cirrhosis was established by the administration of carbon tetrachloride (CCl4) to rats (0.4 g/kg, intraperitoneally, three times per week, for 8 weeks), and at the same time, adding l-theanine (8.0 mg/kg) to the drinking water. Rats had ad libitum access to water and food throughout the treatment period. CCl4 treatment promoted NF-κB activation and increased the expression of both TGF-β and CTGF. CCl4 increased the serum activities of alanine aminotransferase and γ-glutamyl transpeptidase and the degree of lipid peroxidation, and it also induced a decrease in the glutathione and glutathione disulfide ratio. l-Theanine prevented increased expression of NF-κB and down-regulated the pro-inflammatory (interleukin (IL)-1β and IL-6) and profibrotic (TGF-β and CTGF) cytokines. Furthermore, the levels of messenger RNA encoding these proteins decreased in agreement with the expression levels. l-Theanine promoted the expression of the anti-inflammatory cytokine IL-10 and the fibrolytic enzyme metalloproteinase-13. Liver hydroxyproline contents and histopathological analysis demonstrated the anti-fibrotic effect of l-theanine. In conclusion, l-theanine prevents CCl4-induced experimental hepatic cirrhosis in rats by blocking the main pro-inflammatory and pro-fibrogenic signals.
© The Author(s) 2015.
We investigated the inhibitory effects of Platycodon grandiflorum root-derived saponins (Changkil saponins: CKS) on ovalbumin-induced airway inflammation in mice. CKS suppressed leukocytes number, IgE, Th1/Th2 cytokines, and MCP-1 chemokine secretion in bronchoalveolar lavage fluid. Also ovalbumin-increased MUC5AC, MMP-2/9, and TIMP-1/-2 mRNA expression, NF-κB activation, leukocytes recruitment, and mucus secretion was inhibited by CKS treatment. Moreover, the active component of CKS, platyconic acid A (PA), suppressed PMA-induced MUC5AC mRNA expression (from 2.1 ± 0.2 to 1.1 ± 0.1) by inhibiting NF-κB activation (from 2.3 ± 0.2 to 1.2 ± 0.1) via Akt (from 3.7 ± 0.3 to 2.1 ± 0.2) (respectively; p < 0.01) in A549 cells. Therefore, we demonstrate that CKS or PA suppressed the development of respiratory inflammation, hyperresponsiveness, and remodeling by reducing allergic responses, and they may be potential herbal drugs for allergen-induced respiratory disease prevention.
With the development of the Internet, Semantic search technology has been applied to various fields. In the pharmaceutical field, because of the huge number and wide range of the drugs on the market, an effective semantic retrieval system can bring great convenience for doctors. However, for doctors who have no background knowledge of semantic technologies, to write formal semantics search statement is still very difficult. Therefore, this paper proposes a pharmaceutical semantic database query mechanism which based on keywords. In this query mechanism, by analysis of ontology database and establishment of Chinese - English translation mapping, we can Transform Chinese keywords into English keywords. Then match the English keywords with ontology database to build a list of triples. And finally, formed Corresponding SPARQL query by analyze the list.
Airway remodeling is an important characteristic of asthma, linking inflammation with airway hyperresponsiveness. Baicalin, a major active component, was isolated from Radix Scutellariae. Many studies show that baicalin has anti-inflammatory, anti-bacterial, and anti-allergic effects. Here we investigate the influence of baicalin on asthmatic airway remodeling and the mechanism underlining the anti-remodeling effect in vivo.
Asthmatic airway remodeling mice model was established by ovalbumin exposure. Seventy female BALB/c mice were randomly assigned to seven experimental groups: blank, ovalbumin, hexadecadrol, control, and baicalin (25 mg/kg, 50 mg/kg, 100 mg/kg) groups. Pulmonary function was measured using a whole-body plethysmograph in conscious and unrestrained mice. The lung pathology was observed and measured. The production of cytokines in bronchoalveolar lavage fluid and serum was measured using enzyme-labeled immunosorbent assay kits, and the expression levels of transforming growth factor-β 1 and vascular endothelial growth factor were detected by immunohistochemistry. The protein expression levels of transforming growth factor-β 1, vascular endothelial growth factor, extracellular signal–regulated kinase, and p21ras were measured using Western blot. The results show that ovalbumin exposure significantly increased the expression of interleukin-13 in BALF and serum, and transforming growth factor-β 1, vascular endothelial growth factor, extracellular signal–regulated kinase and p21ras expressions in the lungs. Baicalin attenuated the effects of ovalbumin significantly.
It can be concluded that baicalin has significant anti-remodeling effect on ovalbumin-induced asthmatic airway remodeling mice model by decreasing expression of transforming growth factor-β 1, interleukin-13, and vascular endothelial growth factor and inhibiting the activation of the extracellular signal–regulated kinase pathway.
Patients with severe asthma have asthma symptoms which are difficult to control, require high dosages of medication, and continue to experience persistent symptoms, asthma exacerbations or airflow obstruction. Epidemiological and clinical evidences point to the fact that severe asthma is not a single phenotype. Cluster analyses have identified subclasses of severe asthma using parameters such as patient characteristics, and cytokine profiles have also been useful in classifying moderate and severe asthma. The IL-4/IL-13 signalling pathway accounts for the symptoms experienced by a subset of severe asthmatics with allergen-associated symptoms and high serum immunoglobulin E (IgE) levels, and these patients are generally responsive to anti-IgE treatment. The IL-5/IL-33 signalling pathway is likely to play a key role in the disease pathogenesis of those who are resistant to high doses of inhaled corticosteroid but responsive to systemic corticosteroids and anti-IL5 therapy. The IL-17 signalling pathway is thought to contribute to 'neutrophilic asthma'. Although traditionally viewed as players in the defence mechanism against viral and intracellular bacterial infection, mounting evidence supports a role for Th1 cytokines such as IL-18 and IFN-γ in severe asthma pathogenesis. Furthermore, these cytokine signalling pathways interact to contribute to the spectrum of clinical pathological outcomes in severe asthma. To date, glucocorticoids are the most effective anti-asthma drugs available, yet severe asthma patients are typically resistant to the effects of glucocorticoids. Glucocorticoid receptor dysfunction and histone deacetylase activity reduction are likely to contribute to glucocorticoid resistance in severe asthma patients. This review discusses recent development in different cytokine signalling pathways, their interactions and steroid resistance, in the context of severe asthma pathogenesis.
l-Theanine is a unique amino acid in green tea. We here evaluated the protective effects of l-theanine on ethanol-induced liver injury in vitro and in vivo. Our results revealed that l-theanine significantly protected hepatocytes against ethanol-induced cell cytotoxicity which displayed by decrease of viability and increase of LDH and AST. Furthermore, the experiments of DAPI staining, pro-caspase3 level and PARP cleavage determination indicated that l-theanine inhibited ethanol-induced L02 cell apoptosis. Mechanically, l-theanine inhibited loss of mitochondrial membrane potential and prevented cytochrome c release from mitochondria in ethanol-treated L02 cells. l-Theanine also prevented ethanol-triggered ROS and MDA generation in L02 cells. l-Theanine restored the antioxidant capability of hepatocytes including GSH content and SOD activity which were reduced by ethanol. In vivo experiments showed that l-theanine significantly inhibited ethanol-stimulated the increase of ALT, AST, TG and MDA in mice. Histopathological examination demonstrated that l-theanine pretreated to mice apparently diminished ethanol-induced fat droplets. In accordance with the in vitro study, l-theanine significantly inhibited ethanol-induced reduction of mouse antioxidant capability which included the activities of SOD, CAT and GR, and level of GSH. These results indicated that l-theanine prevented ethanol-induced liver injury through enhancing hepatocyte antioxidant abilities.
The increasing occurrences of allergic disorders may be attributed to exposure to environmental factors that contribute to the pathogenesis of allergy. The health benefits of green tea have been widely reported but are largely unsubstantiated. Theanine is the major amino acid present in green tea. In this study, we investigated the role of theanine in both IgE- and non- IgE-induced allergic response. Theanine inhibited compound 48/80-induced systemic anaphylactic shock and ear swelling responses. IgE-mediated passive cutaneous anaphylaxis was inhibited by the oral administration or pharmaceutical acupuncture of theanine. Histamine release from mast cells was decreased with the treatment of theanine. Theanine also repressed phorbol 12-myristate 13-acetate and calcium ionophore A23187-induced TNF-α, IL-1β, IL-6, and IL-8 secretion by suppressing NF-κB activation. Furthermore, theanine suppressed the activation of caspase-1 and the expression of receptor interacting protein-2. The current study demonstrates for the first time that theanine might possess mast cell-stabilizing capabilities.
As a natural analogue of glutamate, l-theanine is the unique amino acid derivative in green tea. Although its underlining mechanisms are not yet clear, it has been suggested that l-theanine treatment may prove beneficial to patients with neurodegenerative diseases. In this study, we investigated the neuroprotective effect and its mechanism of l-theanine in an in vitro model of Alzheimer's disease by using the human APP (Swedish mutation) transgenic SH-SY5Y cell. Amyloid beta (Abeta) neurotoxicity was triggered by l-glutamate in this cell line. Additionally, l-theanine significantly attenuated l-glutamate-induced apoptosis at similar levels to those seen with the NMDA receptor inhibitor MK-801 in the stably expressing APP Swedish mutation SH-SY5Y cells which over-generated Abeta. Meanwhile, the activation of c-Jun N-terminal kinase and caspase-3 induced by l-glutamate was suppressed by l-theanine. We also found that cells treated with l-theanine showed decreased production of nitric oxide resulting from the down-regulated protein levels of inducible nitric oxide synthase (iNOS) and neuronal nitric oxide synthase (nNOS). These results indicate that the inhibition of the NMDA subtype of glutamate receptors and its related pathways is the crucial point of the neuroprotective effect of l-theanine in the cell model. Thus, our present study supports the notion that l-theanine may provide effective prophylaxis and treatment for Alzheimer's disease.
Amyloid beta (Abeta)-induced neurotoxicity is a major pathological mechanism of Alzheimer disease (AD). In this study, we investigated the inhibitory effect of l-theanine, a component of green tea (Camellia sinensis), on Abeta(1-42)-induced neuronal cell death and memory impairment. Oral treatment of l-theanine (2 and 4 mg/kg) for 5 weeks in the drinking water of mice, followed by injection of Abeta(1-42) (2 microg/mouse, icv), significantly attenuated Abeta(1-42)-induced memory impairment. Furthermore, l-theanine reduced Abeta(1-42) levels and the accompanying Abeta(1-42)-induced neuronal cell death in the cortex and hippocampus of the brain. Moreover, l-theanine inhibited Abeta(1-42)-induced extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase as well as the activity of nuclear factor kappaB (NF-kappaB). l-Theanine also significantly reduced oxidative protein and lipid damage and the elevation of glutathione levels in the brain. These data suggest that the positive effects of l-theanine on memory may be mediated by suppression of ERK/p38 and NF-kappaB as well as the reduction of macromolecular oxidative damage. Thus, l-theanine may be useful in the prevention and treatment of AD.
The aim of this study is to investigate the effects of theanine, a tea characteristic amino acid, on human lung cancer and leukemia cells. In the present study, we have demonstrated that theanine suppressed the in vitro and ex vivo growth of human non-small cell lung cancer A549 and leukemia K562 cell lines in dose- and time-dependant manners. In addition, theanine displayed the inhibitory effect on the migration of A549 cells. More importantly, theanine enhanced the anticancer activity of anticancer agents such as trichostatin A (the histone deacetylase inhibitor), berbamine and norcantharidin (the anticancer drugs in China) by strongly reducing the viability and/or migration rate in A549 cells. In addition, theanine significantly suppressed A549 cell invasion. Suppression of A549 cell migration may be one of the important mechanisms of action of theanine against the A549 cell invasion. Our present results suggest that theanine may have the wide therapeutic and/or adjuvant therapeutic application in the treatment of human lung cancer and leukemia.
Asthma is a multi-factorial inflammatory disease associated with increased oxidative stress and altered antioxidant defences. We have evaluated the effect of choline on oxidative stress in a mouse model of airway disease.
Balb/c mice were sensitised with 100 microg of ovalbumin on days 0 and 14, and challenged with aerosolized ovalbumin on days 25-27. Mice were administered 1 mg kg(-1) of choline via oral gavage or intranasal route on days 14-27. Mice were also administered 100 mg kg(-1) of alpha-lipoic acid as standard antioxidant. Total cell counts, eosinophils and eosinophil peroxidase (EPO) activity were determined in bronchoalveolar lavage (BAL) fluid. Reactive oxygen species (ROS), lipid peroxidation and isoprostanes levels were measured in BAL fluid. IL-13 and tumour necrosis factor-alpha (TNF-alpha) levels were also measured in BAL fluid and spleen cell culture supernatant. Nuclear factor kappaB (NFkappaB) p65 protein expression was measured after last ovalbumin challenge in nuclear and cytosolic extracts of lungs.
Compared with ovalbumin-challenged mice, choline and alpha-lipoic acid treated mice had significantly reduced eosinophilic infiltration and EPO activity in BAL fluid. Choline and alpha-lipoic acid treatment reduced ROS production and isoprostanes level significantly in BAL fluid and thus suppressed oxidative stress. Choline and alpha-lipoic acid administration by either route decreased lipid peroxidation levels and down regulated NFkappaB activity. Further, choline and/or alpha-lipoic acid treatment suppressed TNF-alpha level significantly as compared with that of ovalbumin-challenged mice.
Choline administration reduces oxidative stress possibly by modulating the redox status of the cell and inhibits inflammatory response in a mouse model.
Asthma is a common immune-mediated disorder characterized by reversible airway inflammation, mucus production, and variable airflow obstruction with airways hyperresponsiveness (AHR). In most cases the airway inflammation characteristic of asthma is thought to result from an allergic-type reaction to an inhaled substance from the environment (so-called allergic asthma). In allergic asthma, allergen exposure stimulates eosinophilic inflammation of the airways associated with infiltration of T cells. Although the recruitment of eosinophils into the airways is an important component in the pathogenesis of asthma, the trafficking of T lymphocytes into the airways is now believed to establish and orchestrate the asthmatic inflammatory response. This review explores the roles of various T cell subsets in the pathogenesis of allergic airway inflammation and highlights the contributions of these cells in regulating asthma.
An imbalance between oxidants and antioxidants is proposed in smokers and in patients with airways diseases. We tested this hypothesis by measuring the Trolox equivalent antioxidant capacity (TEAC) of plasma and the levels of products of lipid peroxidation as indices of overall oxidative stress. The plasma TEAC was markedly reduced (0.66 +/- 0.07 mmol/L; mean +/- SEM; n = 11), with increased levels of lipid peroxidation products, in healthy chronic smokers as compared with healthy nonsmokers (1.31 +/- 0.10 mmol/L, n = 14, p < 0.001), an effect that was exaggerated in those who had smoked 1 h before the study. Plasma TEAC was also low in patients presenting with acute exacerbations of chronic obstructive pulmonary disease (COPD) (0.46 +/- 0.10 mmol/L, n = 20, p < 0.001) or asthma (0.61 +/- 0.05 mmol/L, n = 9, p < 0.01) with increases in plasma lipid peroxidation products. There was a negative correlation between superoxide anion release by stimulated neutrophils and plasma antioxidant capacity (r = -0.73, p < 0.001) in patients with acute exacerbations of COPD. The profound decrease in TEAC was associated with a decreased plasma protein sulfhydryl concentrations in acute exacerbations of COPD but not in smokers or in asthmatic subjects. Therefore smoking, acute exacerbations of COPD, and asthma are associated with a marked oxidant/antioxidant imbalance in the blood, associated with evidence of increased oxidative stress. The decreased antioxidant capacity in plasma may result from different mechanisms in these conditions.
Recent discoveries on the molecular and cellular basis of asthma have markedly altered our understanding of this common respiratory disorder. These insights have come during an unexplained period of rising disease incidence and severity and are now being applied to develop improved therapies. This review explores the latest advances in our understanding of the pathogenesis of allergic asthma, and provides insight into the expanding collaborations between research scientists, clinicians and the pharmaceutical industry in the race to control the asthma epidemic.
To determine the relative adverse symptomatic effects and benefits of therapy with oral corticosteroids at doses of 2 mg/kg vs 1 mg/kg daily in children with acute exacerbations of asthma.
Using a questionnaire that addressed symptoms, we conducted a prospective study of the adverse effects and benefits of therapy with prednisone or prednisolone at two dose levels in 86 children who were 2 to 16 years of age with mild persistent asthma during an acute exacerbation and were unresponsive to therapy with inhaled steroids and beta-adrenergic agents. Parents and physicians were blinded to the dose level. Children were assigned to either of the two doses by random allocation. Behavioral side effects were assessed via a questionnaire administered by a physician. Benefits were measured by the resolution of asthma symptoms (cough, shortness of breath, and wheeze) at the completion of the treatment with oral steroids.
Behavioral side effects, particularly anxiety (p < 0.02) and aggressive behavior (p < 0.002), were twice as common in patients receiving a dose of 2 mg/kg/d. Benefits were comparable in the two groups. The number needed to harm (ie, the number of patients receiving experimental treatment that would lead to one additional person being harmed vs patients receiving standard treatment) was 6.1 for anxiety, 8.6 for hyperactivity, and 4.8 for aggressive behavior.
Because the adverse side effects were greater at the higher dose but the benefits were comparable, we recommend using an oral corticosteroid dose of 1 mg/kg daily for children with mild persistent asthma who present with an acute exacerbation of asthma.
There is ample evidence that allergic disorders, such as asthma, rhinitis, and atopic dermatitis, are mediated by oxidative stress. Excessive exposure to reactive oxygen and nitrogen species is the hallmark of oxidative stress and leads to damage of proteins, lipids, and DNA. Oxidative stress occurs not only as a result of inflammation but also from environmental exposure to air pollution and cigarette smoke. The specific localization of antioxidant enzymes in the lung and the rapid reaction of nitric oxide with reactive oxygen species, such as superoxide, suggest that antioxidant enzymes might also function as cell-signaling agents or regulators of cell signaling. Therapeutic interventions that decrease exposure to environmental reactive oxygen species or augment endogenous antioxidant defenses might be beneficial as adjunctive therapies for allergic respiratory disorders.
Asthma is characterized by variable airflow obstruction and airway hyperresponsiveness in association with airway inflammation under the influence of T(H)2 cytokines. Eosinophilic bronchitis has similar immunopathology to asthma but without disordered airway physiology. Whether eosinophilic bronchitis is associated with increased expression of T(H)2 cytokines is unknown.
We sought to assess the expression of T(H)2 cytokines in eosinophilic bronchitis.
Expression of activation markers and chemokine receptors from blood and bronchoalveolar lavage (BAL) fluid T cells and the T(H)2 cytokine expression from these T cells and bronchial mucosa biopsy specimens were assessed from subjects with eosinophilic bronchitis, subjects with asthma, and healthy control subjects.
The proportion of resting (stimulated) CD4 BAL fluid T cells expressing intracellular IL-4 was significantly higher in the subjects with eosinophilic bronchitis 7.2% (11.4%) and subjects with asthma 5.3% (5.5%) than in healthy control subjects 2.8% (3.9%) (P =.03). The number of IL-4(+) (P <.001) and IL-5(+) (P =.003) cells per square millimeter of bronchial submucosa was significantly higher in the disease groups than in the healthy control subjects. Expression of intracellular IFN-gamma was significantly higher in stimulated blood CD8 T cells from subjects with eosinophilic bronchitis (24%) and asthma (17%) than in the healthy control subjects (5%; P =.003). There were no between-group differences in expression of IFN-gamma in the BAL fluid T cells or in the bronchial submucosa and no differences in expression of activation markers or chemokine receptors.
These findings support the concept of asthma as a disease associated with activation of T(H)2 lymphocytes in the airway and provide evidence that these cytokines play a role in the development of airway inflammation in eosinophilic bronchitis but suggest that the release of T(H)2 cytokines is not sufficient for the elaboration of disordered airway physiology in asthma.
Inflammatory lung diseases are characterized by chronic inflammation and oxidant/antioxidant imbalance. The sources of the increased oxidative stress in patients with chronic inflammatory lung diseases such as asthma and chronic obstructive pulmonary disease (COPD) derive from the increased burden of inhaled oxidants, and from the increased amounts of reactive oxygen species (ROS) generated by several inflammatory, immune and various structural cells of the airways. Increased levels of ROS produced in the airways is reflected by increased markers of oxidative stress in the airspaces, sputum, breath, lungs and blood in patients with lung diseases. ROS, either directly or via the formation of lipid peroxidation products such as 4-hydroxy-2-nonenal may play a role in enhancing the inflammation through the activation of stress kinases (JNK, MAPK, p38) and redox sensitive transcription factors such as NF-capital KJE, MacedonianB and AP-1. Recent evidences have indicated that oxidative stress and pro-inflammatory mediators can alter nuclear histone acetylation/deacetylation allowing access for transcription factor DNA binding leading to enhanced pro-inflammatory gene expression in various lung cells. Understanding of the mechanisms of redox signaling, NF-kappaB/AP-1 regulation, the balance between histone acetylation and deacetylation and the release and expression of pro- and antiinflammatory mediators may lead to the development of novel therapies based on the pharmacological manipulation of antioxidants in lung inflammation and injury. Antioxidants that have effective wide spectrum activity and good bioavailability, thiols or molecules which have dual antioxidant and anti-inflammatory activity, may be potential therapeutic agents which not only protect against the direct injurious effects of oxidants, but may fundamentally alter the underlying inflammatory processes which play an important role in the pathogenesis of chronic inflammatory lung diseases.
L-Theanine is an amino acid contained in green tea leaves which is known to block the binding of L-glutamic acid to glutamate receptors in the brain. Because the characteristics of L-Theanine suggest that it may influence psychological and physiological states under stress, the present study examined these possible effects in a laboratory setting using a mental arithmetic task as an acute stressor. Twelve participants underwent four separate trials: one in which they took L-Theanine at the start of an experimental procedure, one in which they took L-Theanine midway, and two control trials in which they either took a placebo or nothing. The experimental sessions were performed by double-blind, and the order of them was counterbalanced. The results showed that L-Theanine intake resulted in a reduction in the heart rate (HR) and salivary immunoglobulin A (s-IgA) responses to an acute stress task relative to the placebo control condition. Moreover, analyses of heart rate variability indicated that the reductions in HR and s-IgA were likely attributable to an attenuation of sympathetic nervous activation. Thus, it was suggested that the oral intake of L-Theanine could cause anti-stress effects via the inhibition of cortical neuron excitation.
Asthma is characterized by intense infiltration of eosinophils and CD4+ T cells into the submucosal tissue of airways. Accumulating evidence indicates that T helper type 2 cell-derived cytokines such as interleukin (IL)-4, IL-5 and IL-13 play critical roles in orchestrating and amplifying allergic inflammation in asthma. In addition, it has been suggested that newly identified cytokines including thymic stromal lymphopoietin, IL-25 and IL-33 are involved in the induction of allergic inflammation in asthma. In this review, we discuss the role of individual cytokines in the pathogenesis of asthma.
Asthma is a disease marked by chronic lung inflammation and the number of patients suffering from asthma increases annually. Both beta-sitosterol (BS) and beta-sitosterol glucoside exist in a variety of plants and have anti-tumor, anti-microbial, and immunomodulatory activities. However, the precise role of BS and beta-sitosterol glucoside in asthma has not been well understood. The aim of this study was to investigate the inhibitory effects of BS and lactose-BS (L-BS) on the pathophysiological process in ovalbumin-induced asthmatic mice. The total cells and eosinophils in the bronchoalveolar lavage (BAL) fluid markedly decreased (p<0.05) after L-BS or BS administration (1 mg/kg; i.p.), and the ROS production also decreased in comparison to the asthma control. Histopathological features were detected by performing histochemistry, including H&E and alcian blue & P.A.S staining. Both L-BS and BS mitigated the inflammation by eosinophil infiltration and mucus hypersecretion by goblet hyperplasia. These effects of L-BS were superior to those of BS. L-BS and BS inhibited the increased mRNA and protein expression of IL-4 and IL-5 in the lung tissue and BAL fluid, respectively. The IgE concentration in the BAL fluid and serum was measured by performing ELISA and the ovalbumin-specific IgE in the BAL fluid was uniquely inhibited by L-BS (p<0.05). The splenocytes were isolated from the normal and asthmatic mice and incubated in the absence and presence of 100 microg/ml ovalbumin, respectively. L-BS blocked the survival rate of the splenocytes of the mice (p<0.01). This finding indicates the possibility of L-BS and BS as potential therapeutic molecules in asthma and may contribute to the need to improve current therapeutic drugs.
Homeostasis of the reduction-oxidation (redox) state is critical to protection from oxidative stress in the lungs. Therefore, the lungs have high levels of antioxidants, including glutathione, heme oxygenase, and superoxide dismutase. The numbers of inflammatory cells -- particularly eosinophils -- are increased in the airways of asthma patients, and these pulmonary inflammatory cells release large amounts of harmful reactive oxygen species and reactive nitrogen species. Human thioredoxin 1 (TRX1) is a redox-active protein of approximately 12 kDa that contains a (32)Cys-Gly-Pro-(35)Cys sequence necessary for its activity. The strong reducing activity of the sequence results from the cysteine residues acting as proton donors and cleaving disulfide (S-S) bonds in the target protein. Endogenous or exogenous TRX1 or both protect the lungs against ischemia-reperfusion injury, influenza infection, bleomycin-induced injury, or lethal pulmonary inflammation caused by interleukin-2 and interleukin-18. We showed that exogenous TRX1 inhibits airway hyperresponsiveness and pulmonary inflammation accompanied by eosinophilia in mouse models of asthma. Recently, we reported that exogenous TRX1 improves established airway remodeling in a prolonged antigen-exposure mouse asthma model. Exogenous and endogenous TRX1 also prevents the development of airway remodeling. Here, we discuss the role and clinical benefits of TRX1 in asthma.
Saponins, especially platyconic acid A, from Platycodon grandiflorum reduce airway inflammation in ovalbumininduced mice and PMA-exposed A549 cells
- C E Brightling
- F A Symon
- S S Bradding
- P Pavord
- I D Wardlaw
- A J Choi
- J H Jin
- S W Kim
- H G Choi
- C Y Lee
- H S Ryu
- S Y Chung
- Y C Hwang
- Y J Um
- Y J Jeong
- T C Jeong
Brightling, C.E., F.A. Symon, S.S., Bradding, P., Pavord, I.D., Wardlaw, A.J., 2002. TH2
cytokine expression in bronchoalveolar lavage fluid T lymphocytes and bronchial submucosa is a feature of asthma and eosinophilic bronchitis. J. Allergy
Clin. Immunol. 110, 899e905.
Choi, J.H., Jin, S.W., Kim, H.G., Choi, C.Y., Lee, H.S., Ryu, S.Y., Chung, Y.C., Hwang, Y.J.,
Um, Y.J., Jeong, T.C., Jeong, H.G., 2015. Saponins, especially platyconic acid A,
from Platycodon grandiflorum reduce airway inflammation in ovalbumininduced mice and PMA-exposed A549 cells. J. Agric. Food Chem. 63, 1468e1476.