Abstract
Neutrophils are the primary immune cells in innate immunity, which are related to various inflammatory diseases. Astragalus mongholicus Bunge is a Chinese medicinal herb used to treat various oxidative stress-related inflammatory diseases. However, there are limited studies that elucidate the effects of Astragalus mongholicus Bunge in human neutrophils. In this study, we used isolated human neutrophils activated by various stimulants to investigate the anti-inflammatory effects of Astragalus mongholicus Bunge water extract (AWE). Cell-free assays were used to examine free radicals scavenging capabilities on superoxide anion, reactive oxygen species (ROS), and nitrogen-centered radicals. Imiquimod (IMQ) induced psoriasis-like skin inflammation mouse model was used for investigating anti-psoriatic effects. We found that AWE inhibited superoxide anion production, ROS generation, and elastase release in human neutrophils, which exhibiting a direct anti-neutrophil effect. Moreover, AWE exerted a ROS scavenging ability in the 2,2’-Azobis (2-amidinopropane) dihydrochloride assay, but not superoxide anion in the xanthine/xanthine oxidase assay, suggesting that AWE exhibited anti-oxidation and anti-inflammatory capabilities by both scavenging ROS and by directly inhibiting neutrophil activation. AWE also reduced CD11b expression and adhesion to endothelial cells in activated human neutrophils. Meanwhile, in mice with psoriasis-like skin inflammation, administration of topical AWE reduced both the affected area and the severity index score. It inhibited neutrophil infiltration, myeloperoxidase release, ROS-induced damage, and skin proliferation. In summary, AWE exhibited direct anti-inflammatory effects by inhibiting neutrophil activation and anti-psoriatic effects in mice with IMQ-induced psoriasis-like skin inflammation. Therefore, AWE could potentially be a pharmaceutical Chinese herbal medicine to inhibit neutrophilic inflammation for anti-psoriasis.
Highlights
Astragalus mongholicus Bunge (AM; “Huang Qi” in Chinese) is one of the most important and widely used traditional Chinese medicines, having anti-inflammatory effects and multiple bioactivities such as protecting viral myocarditis injury, regulating blood sugar, and promoting wound healing (Chen et al, 2012; Agyemang et al, 2013; Piao and Liang, 2014; Qi et al, 2017)
Astragaloside IV in Astragalus mongholicus Bunge water extract (AWE) was identified according to the peak retention time and two product ion fragments in multiple reaction monitoring (MRM) channels (Figure 1C)
Our results revealed that AWE significantly reduced the oxidative stress generated by fMLF-activated human neutrophils, and this effect might have resulted from regulating the activation of human neutrophils and directly scavenging reactive oxygen species (ROS) by AWE
Summary
Astragalus mongholicus Bunge (AM; “Huang Qi” in Chinese) is one of the most important and widely used traditional Chinese medicines, having anti-inflammatory effects and multiple bioactivities such as protecting viral myocarditis injury, regulating blood sugar, and promoting wound healing (Chen et al, 2012; Agyemang et al, 2013; Piao and Liang, 2014; Qi et al, 2017). AM contains several bioactive ingredients, such as polysaccharides, flavonoids, and saponins (Fu J. et al, 2014), that are reported to provide anti-inflammatory effects and other benefits against many diseases or pathological conditions in various models (Shahzad et al, 2016). Excessive production of ROS from neutrophils may cause tissue damage (Glennon-Alty et al, 2018). Aside from that, activated neutrophils release granules containing proteolytic enzymes, such as neutrophil elastases, MPO, and cathelicidin (Faurschou and Borregaard, 2003), that contribute to tissue damage. Overproduction of ROS, proteolytic enzymes, and cytokines by neutrophils can cause several pathological conditions, which could aggravate many clinical diseases (Papayannopoulos, 2018)
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