Astragalin Attenuates Allergic Inflammation in a Murine Asthma Model

Liu, Jiping; Cheng, Yue; Zhang, Xiaoshuang; Zhang, Xue; Chen, Shuxian; Hu, Zongmiao; Zhou, Chuangbing; Zhang, Enhu; Ma, Shengming

doi:10.1007/s10753-015-0181-6

Cited by 24 publications

(26 citation statements)

References 21 publications

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“…The role of LTC 4 in allergic asthma has been extensively evaluated (85). LTC 4 is produced in mast cells by assembly of a biosynthetic complex at the nuclear envelope, consisting of cytosolic phospholipase A2 (cPLA2), (64) Oxi-CaMKII inhibitor KN-93 KN-93 significantly decreased goblet cell hyperplasia, bronchial epithelial thickness, airway eosinophilia, the eosinophil chemoattractant molecule, Ccl-11, and NF-κB activity in allergic asthma (61) Leukotriene C4 (LTC 4 ) inhibitor A LTC 4 inhibitor reduced NOX4 levels and attenuated cell death (32) Galangin Galangin demonstrated decreased airway remodeling, angiogenic activity, and ASMC proliferation through the TGF-β1-ROS-MAPK pathway (65)(66)(67) Astragalin Astragalin suppressed LPS-induced ROS production and eotaxin-1 expression in epithelial cells through the TLR4-PKCγ1-PKCβ2-NADPH signaling pathway (68,69) Glutathione GSH balances Th1/Th2 responses, alters nitric oxide metabolism and inhibits ROS (55,59,70) SOD SODs protects against the harmful effects of ROS and airway inflammation (71)(72)(73) Glutathione peroxidases Glutathione peroxidases prevent airway inflammation and alveolar destruction (74)(75)(76) Vitamins C and E Vitamins C and E reduce AHR, inflammation, and oxidative stress (77)(78)(79) TLR7, toll-like receptor 7; Oxi-CaMKII, oxidative-CaMKII; SOD, superoxide dismutase; AHR, airway hyper-reactivity; Nrf2, nuclear factor E2-related factor 2; Cu/Zn SOD, copper/zinc superoxide dismutase; ROS, reactive oxygen species; NOX4, NADPH oxidase 4; LPS, lipopolysaccharide; Th2, type 2 helper T.…”

Section: Ltc 4 Inhibitorsmentioning

confidence: 99%

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Recent developments in the role of reactive oxygen species in allergic asthma

Zhong

et al. 2017

J. Thorac. Dis.

132

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Allergic asthma has a global prevalence, morbidity, and mortality. Many environmental factors, such as pollutants and allergens, are highly relevant to allergic asthma. The most important pathological symptom of allergic asthma is airway inflammation. Accordingly, the unique role of reactive oxygen species It is well known that reactive oxygen species (ROS), endogenous nitric oxide (NO) and NO derived reactive nitrogen species (RNS) have been reported to mediate oxidative stress and airway inflammation and pathogenesis. However, ROS are more common in allergic asthma development (6,7). Hence, in our review, we mainly focus on the relationship between ROS and allergic asthma. ROS, such as hydrogen peroxide, may be directly or indirectly involved in epithelial cell apoptosis and inactivation of antioxidant enzymes and contribute to allergic asthma (8-11). ROS are derived from endogenous or exogenous oxidants. Endogenous ROS are composed of mitochondria, NADPH, and the xanthine/xanthine oxidase (XO) system. Exogenous sources of ROS production have been linked to strong oxidizing gases, such as ozone (O 3 ), sulfur dioxide (SO 2 ), nitrogen dioxide (NO 2 ) and particulate matter (PM), which are a major component of air pollution (12,13). The oxygen stress level in asthma is increased because of inflammatory cells in vivo, and cigarette smoke (CS) or PM produces ROS in vitro. For example, compared with normal subjects, the level of H 2 O 2 and superoxide that are produced by eosinophils and neutrophils are significantly increased in asthma patients (14). Increased levels of ROS can cause harmful pathophysiological disorders of allergic asthma. Studies have reported that excessive ROS can damage DNA, carbohydrates, proteins, and lipids, ultimately leading to an increased inflammatory response in allergic asthma (15,16). In this review, we will discuss the updated pathophysiological and mechanisms of oxidative stress relating to allergic asthma. Exogenous oxidants and allergic asthmaPatients' exposure to the environmental atmosphere is the main way that exogenous oxidative stress is induced (17). CS is a complex mixture including more than 4,000 different compounds. It has been demonstrated that inhaled CS can increase ROS levels. Most of these compounds have ability to generate ROS during their metabolism. The mechanism of CS induced inflammation is incorporated with oxidative stress leading to cell death and oxidative DNA damage via apoptosis and/or necrosis (7). It was reported that antioxidants have the ability to protect cells from cigarette smoke extract (CSE) induced apoptosis (18). Isolated human airway smooth muscle (hASM) cells were used to determine Ca 2+ responses and hASM proliferation, as well as ROS level and cytokine generation, by incubating these cells in the presence or absence of CSE. The results revealed that Ca 2+ regulatory proteins alter airway remolding and function in smoking-related airway disease, especially allergic asthma (19). CSE can damage bronchial epithelial cells from asthm...

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Section: Ltc 4 Inhibitorsmentioning

confidence: 99%

“…Histological studies demonstrated that astragalin substantially inhibited OVA-induced eosinophilia in lung tissue. All of these anti-inflammatory roles may occur through suppression of cytokine signaling (SOCS)-3 and enhancement of SOCS-5 expression in an asthma model (68).…”

Section: Astragalinmentioning

confidence: 99%

Recent developments in the role of reactive oxygen species in allergic asthma

Zhong

et al. 2017

J. Thorac. Dis.

132

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“…In addition, Ast can reduce acute lung injury in a murine asthma model and enhance survival from lethal endotoxemia [21]. Also, Ast has anti-allergic and anti-oxidant activities [22,23]. Nevertheless, the clinical applications of Ast are still limited because it has low water solubility.…”

Section: The Activation and Differentiation Of Th Cells Distinguishementioning

confidence: 99%

“…It has been reported to have various pharmacological effects including anti-oxidant, anti-HIV, anti-allergic, and anti-inflammatory activities[21][22][23]. Although astragalin has one glucosyl unit at the C-3 position of the flavonoid C-ring, it has low water solubility.…”

mentioning

confidence: 99%

Hydrophilic Astragalin Galactoside Induces T Helper Type 1-Mediated Immune Responses via Dendritic Cells

Jeon¹,

Lee²,

Kim³

et al. 2018

Preprint

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A flavonoid Astragalin (kaempferol-3-O-β-D-glucopyranoside, Ast) has several biological activities including anti-oxidant, anti-HIV, and anti-allergic effects. Nonetheless, its insolubility in hydrophilic solvents imposes restrictions on its therapeutic applications. In this study, we investigated the effects of water-soluble astragalin-galactoside (kaempferol-3-O- β-D-isomaltotrioside, Ast-Gal) on dendritic cell (DC) maturation and T helper (Th) cell-mediated immune responses. Ast-Gal significantly increased maturation and activation of DCs through up-regulation of surface markers, such as CD80, CD86, and MHC II in a dose-dependent manner, while Ast had little effects. Also, Ast-Gal-treated DCs markedly secreted immune-stimulating cytokines such as IL-1β, IL-6, and IL-12. Importantly, Ast-Gal strongly increased expression of IL-12, a polarizing cytokine of Th1 cells. In a co-culture system of DCs and CD4+ T cells, Ast-Gal-treated DCs preferentially differentiates naïve CD4+ T cells into Th1 cells. The addition of neutralizing IL-12 mAb to cultures of Ast-Gal-treated DCs and CD4+ T cells significantly increased IFN- γ production, thereby indicating that Ast-Gal-stimulated DCs enhance the Th1 response through IL-12 production by DCs. Injection with Ast-Gal-treated DCs in mice increased IFN-γ-secreting Th1 cell population. Collectively, these findings indicate that hydrophilically modified astragalin can enhance Th1-mediated immune responses via DCs, and point to a possible application of water-soluble astragalin-galactoside as an immune adjuvant.

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“…In addition, Ast can reduce acute lung injury in a murine asthma model and enhance survival from lethal endotoxemia [ 20 ]. Additionally, Ast has anti-allergic and anti-oxidant activities [ 21 , 22 ]. Nevertheless, the clinical applications of Ast are still limited because it has low water solubility.…”

Section: Introductionmentioning

confidence: 99%

Hydrophilic Astragalin Galactoside Induces T Helper Type 1-Mediated Immune Responses via Dendritic Cells

Jeon

Lee

Kim

et al. 2018

IJMS

View full text Add to dashboard Cite

A flavonoid Astragalin (kaempferol-3-O-β-d-glucopyranoside, Ast) has several biological activities including anti-oxidant, anti-HIV, and anti-allergic effects. Nonetheless, its insolubility in hydrophilic solvents imposes restrictions on its therapeutic applications. In this study, we investigated the effects of water-soluble astragalin-galactoside (kaempferol-3-O-β-d-isomaltotrioside, Ast-Gal) on murine bone marrow-derived dendritic cell (DC) maturation and T helper (Th) cell-mediated immune responses. Ast-Gal significantly increased maturation and activation of DCs through the upregulation of surface markers, such as cluster of differentiation (CD)80, CD86, and Major histocompatibility complex (MHC) II in a dose-dependent manner, while Ast had little effects. Additionally, Ast-Gal-treated DCs markedly secreted immune-stimulating cytokines such as interleukin (IL)-1β, IL-6, and IL-12. Importantly, Ast-Gal strongly increased expression of IL-12, a polarizing cytokine of Th1 cells. In a co-culture system of DCs and CD4+ T cells, Ast-Gal-treated DCs preferentially differentiates naïve CD4+ T cells into Th1 cells. The addition of neutralizing IL-12 monoclonal antibody (mAb) to cultures of Ast-Gal-treated DCs and CD4+ T cells significantly decreased interferon (IFN)-γ production, thereby indicating that Ast-Gal-stimulated DCs enhance the Th1 response through IL-12 production by DCs. Injection with Ast-Gal-treated DCs in mice increased IFN-γ-secreting Th1 cell population. Collectively, these findings indicate that hydrophilically modified astragalin can enhance Th1-mediated immune responses via DCs and point to a possible application of water-soluble astragalin-galactoside as an immune adjuvant.

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Astragalin Attenuates Allergic Inflammation in a Murine Asthma Model

Cited by 24 publications

References 21 publications

Recent developments in the role of reactive oxygen species in allergic asthma

Recent developments in the role of reactive oxygen species in allergic asthma

Hydrophilic Astragalin Galactoside Induces T Helper Type 1-Mediated Immune Responses via Dendritic Cells

Hydrophilic Astragalin Galactoside Induces T Helper Type 1-Mediated Immune Responses via Dendritic Cells

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