Astragalus polysaccharides and astragaloside IV alleviate inflammation in bovine mammary epithelial cells by regulating Wnt/β-catenin signaling pathway

Abstract

The Wnt/β-catenin signaling regulates cell renewal and repair and is closely associated with inflammation. Astragalus polysaccharides (APS) and astragaloside IV (AS-IV), which are the main active substances extracted from Radix Astragali, protect cells by regulating Wnt signaling in cells, exerting antiinflammatory, antioxidant, and antistress effects. However, the mechanisms by which APS and AS-IV interact with Wnt signaling to achieve their therapeutic effects in bovine mammary epithelial cells (BMECs) are not understood. In this study, we used lipopolysaccharide (LPS)-stimulated BMECs as an in vitro model of inflammation to investigate the effects of APS and AS-IV on Wnt signaling in inflamed BMECs. Drug concentrations were screened using the CCK-8 method, the effect on protein expression was analyzed using immunoblotting, the effect on inflammatory factors using enzyme-linked immunosorbent assay, and the effect on oxidative factors using enzyme labeling and flow cytometry. LPS activated the expression of inflammatory and oxidative factors in cells and inhibited Wnt/β-catenin signaling. APS and AS-IV antagonized the inhibitory effect of LPS, protecting BMECs. They inhibited the expression of the IL-6, IL-8, and TNF-α inflammatory factors, and that of the MDA oxidative factor, and activated Wnt signaling in LPS-stimulated BMECs. Silencing of β-catenin abolished the protective effect of APS and AS-IV against LPS-stimulated BMECs. Thus, APS and AS-IV mediate protective effects in inflammatory BMECs model through activation of the Wnt signaling pathway. Wnt signaling pathway is one of the targets of the inhibitory effects of APS and AS-IV on inflammation.

Astragaloside IV Alleviates Acute Liver Failure Induced by D-GalN/LPS by Upregulating Autophagy and Reducing Inflammation

“…Previous studies have shown that AS-IV has an anti-inflammatory effect and is negatively correlated with inflammatory factors, such as TNF-α, IL-6 and IL-1β 24,25 . In this study, we used a cytometric bead array method to assess the effect of AS-IV on inflammatory cytokines in response to D-GalN/LPS.…”

“…Previous studies have shown that AS-IV has an anti-inflammatory effect and is negatively correlated with inflammatory factors, such as TNF-α, IL-6 and IL-1β. 24,25 In this study, we used a cytometric bead array method to assess the effect of AS-IV on inflammatory cytokines in response to D-GalN/LPS. The results showed that monocyte chemoattractant protein-1 (MCP-1) was significantly decreased, while IL-10, IL-6, IFN-β, granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-12p70, IL-1β and IL-23 ( P < 0.05) were significantly increased in the AS-IV group compared to the D-GalN/LPS group (all P < 0.05) (Figure 3).…”

Research state of the herbal medicine Huangqi (Radix Astragali): A global and bibliometric study

“…[29] Huangqi reduced oxidative stress by restraining ROS production, [30] improving mitochondrial dysfunction, [31] and enhancing Nrf2 activation and HO-1 and NQO1 expression. [32] Inflammation: Huangqi mediated multiple signaling pathways to exert anti-inflammatory effects, such as mediating the TLR-4/ NF-kb p65 pathway [33] and regulating the Wnt/β-catenin signaling pathway, [34] down-regulating the expression of inflammatory factors IL-1, IL-6, and TNF-α, and inhibiting the JNK signaling pathway associated with oxidative stress, reducing the expression of transcriptional level of the puc gene. [35] These 3 pathological processes may be the main pharmacological mechanism of Huangqi, which was also the focus of the research area of Huangqi.…”

Fufang shenhua tablet, astragali radix and its active component astragaloside IV: Research progress on anti-inflammatory and immunomodulatory mechanisms in the kidney

“…Other studies have also found that AS-IV and APS can decrease the expression of inflammatory factors, such as IL-6, IL-8, and TNF-α, oxidative factors like ROS and MDA, and the apoptotic factor caspase-3 in inflammatory cells. Furthermore, the expression of β-catenin is activated in inflammatory cells for cytoprotection (Fan, 2021). AR treatment (2.1 g/kg for 12 weeks) in STZ-induced DN rats can reduce 24-hour urine protein quantification, attenuate interstitial pathological damage, and inhibit the expression of wnt4, β-catenin, and TGF-β1 in the renal interstitium, thus playing a role in kidney protection and slowing down the process of interstitial fibrosis in DN rats (Deng and Fang, 2012).…”