Astragalin inhibits airway eotaxin-1 induction and epithelial apoptosis through modulating oxidative stress-responsive MAPK signaling

Abstract

BackgroundEotaxin proteins are a potential therapeutic target in treating the peribronchial eosinophilia associated with allergic airway diseases. Since inflammation is often associated with an increased generation of reactive oxygen species (ROS), oxidative stress is a mechanistically imperative factor in asthma. Astragalin (kaempferol-3-O-glucoside) is a flavonoid with anti-inflammatory activity and newly found in persimmon leaves and green tea seeds. This study elucidated that astragalin inhibited endotoxin-induced oxidative stress leading to eosinophilia and epithelial apoptosis in airways.MethodsAirway epithelial BEAS-2B cells were exposed to lipopolysaccharide (LPS) in the absence and presence of 1–20 μM astragalin. Western blot and immunocytochemical analyses were conducted to determine induction of target proteins. Cell and nuclear staining was also performed for ROS production and epithelial apoptosis.ResultsWhen airway epithelial cells were exposed to 2 μg/ml LPS, astragalin nontoxic at ≤20 μM suppressed cellular induction of Toll-like receptor 4 (TLR4) and ROS production enhanced by LPS. Both LPS and H2O2 induced epithelial eotaxin-1 expression, which was blocked by astragalin. LPS activated and induced PLCγ1, PKCβ2, and NADPH oxidase subunits of p22phox and p47phox in epithelial cells and such activation and induction were demoted by astragalin or TLR4 inhibition antagonizing eotaxin-1 induction. H2O2-upregulated phosphorylation of JNK and p38 MAPK was dampened by adding astragalin to epithelial cells, while this compound enhanced epithelial activation of Akt and ERK. H2O2 and LPS promoted epithelial apoptosis concomitant with nuclear condensation or caspase-3 activation, which was blunted by astragalin.ConclusionsAstragalin ameliorated oxidative stress-associated epithelial eosinophilia and apoptosis through disturbing TLR4-PKCβ2-NADPH oxidase-responsive signaling. Therefore, astragalin may be a potent agent antagonizing endotoxin-induced oxidative stress leading to airway dysfunction and inflammation.

4′-Demethyl-deoxypodophyllotoxin glucoside isolated from Podophyllum hexandrum exhibits potential anticancer activities by altering Chk-2 signaling pathway in MCF-7 breast cancer cells

“…The compound 5 has shown its promising and consistent cytotoxic activity in almost all cell lines (PC-3, HeLa, HCT-116, HEK-293 and MCF-7) tested within an IC 50 concentration range of 208-291 nM ( Table 1). The other potent molecules 3 [29], 4 [30] and 9 [31] were well studied for their various biological activities and cytotoxic potential that fully complies with our data in Table 1. Further, 5 was found to be more active against breast cancer MCF-7 cells with an IC 50 value of 208 nM in comparison to 1 (3.2 lM), indicating a 15-fold more potency than 1 (Fig.…”

Epigallocatechin gallate protects BEAS-2B cells from lipopolysaccharide-induced apoptosis through upregulation of gastrin-releasing peptide

“…BEAS-2B cells were grown to 80-85% confluence at 37°C in an atmosphere of 5% CO 2 . LPS at the concentration of 1-2 lg/ml was applied to BEAS-2B cells for up to 12 h [21]. In another set of experiment, EGCG at a concentration of 100 lM was also added to the culture to analyse its cytoprotective role against LPS-induced toxicity [22].…”

Astragalin inhibits IL-1β-induced inflammatory mediators production in human osteoarthritis chondrocyte by inhibiting NF-κB and MAPK activation

“…Astragalin, a bioactive component isolated from Rosa agrestis, has been reported to have various pharmacological activities including anti-inflammatory and antioxidant effects [10,11]. It has been reported that astragalin inhibited iNOS and COX-2 expression in macrophages [11].…”