Astragalus polysaccharides attenuate pulmonary�fibrosis by inhibiting the epithelial-mesenchymal�transition and NF-κB pathway activation

Abstract

Astragalus polysaccharides (APS), the active ingredients isolated from the plant Astragalus, have been reported to have numerous biological activities, including anti-inflammatory and antitumor activities. However, the effect of APS on pulmonary fibrosis (PF) remains unknown. The present study aimed to evaluate the protective effect of APS against PF and to explore its underlying mechanisms by using in vivo and in vitro models. A mouse in vivo model of bleomycin-induced PF and an in vitro model of transforming growth factor β1 (TGF-β1)-stimulated human lung epithelial A549 cells were established. Histopathologic examination and collagen deposition were investigated by hematoxylin and eosin staining and Masson staining, and by detecting the hydroxyproline content. The expression of related genes was analyzed by western blotting, reverse transcription-quantitative (RT-q) PcR, immunofluorescence and immunohistochemistry. The results from the in vivo mouse model demonstrated that treatment with APS could ameliorate collagen deposition and reduce fibrotic area and hydroxyproline content in the matrix. Furthermore, APS significantly inhibited the epithelial-mesenchymal transition (EMT), as evidenced by an increased level of E-cadherin and a decreased expression of vimentin and alpha smooth muscle actin. Furthermore, APS treatment significantly decreased TGF-β1-induced EMT and NF-κB pathway activation in vitro. The results from the present study provided new insights on PF regression via the anti-fibrotic effects of APS.

Therapeutic Effect of Astragali Radix Extract Injection Combined with Bone Marrow Mesenchymal Stem Cells in Bleomycin-Induced Pulmonary Fibrotic Rats

“…Its mechanism of action is associated with the inhibition of inflammatory factor expression and the modulated conversion of damaged alveolar cells to myofibroblasts in PF [ 37 ], as well as extracellular matrix deposition [ 38 ]. Astragalus polysaccharides inhibit the NF- κ B signaling pathway and the epithelial-mesenchymal transformation to reduce PF [ 13 ]. Astragali Radix extract injection contains astragaloside IV, Astragalus polysaccharides, and other chemical components.…”

“…Drugs such as Astragalus [ 11 ] that tonify Qi are the most popular drug type of herbs for treating PF. Astragalus can regulate the immune function of patients with PF and reduce inflammation and collagen content in lung tissues [ 12 , 13 ].…”

Multi-Pharmaceutical Activities of Chinese Herbal Polysaccharides in the Treatment of Pulmonary Fibrosis: Concept and Future Prospects

“…APS has been reported that have a variety of biological activities, including anti-inflammatory, (Lv et al, 2013;Yan et al, 2017;Feng et al, 2018;Zhan et al, 2020) APS Rha:Ara: Glc:Gal:GalA 0.03:1.00:0.27: 0.36:0.30 1,334 kDa Chemical structure of APS: 2 -(Chloromethyl)-4-(4-nitrophenyl)-1,3thiazole In vivo: BLM induced male C57BL/6 mice. In vitro: TGF-β1 induced A549 cells Regulate EMT and HYP content through the TGF-β1/NF-kB pathway, and reduce the area of a-SMA, COL deposition and fibrosis, and increase E-cadherin (Bao et al, 2018;Ren et al, 2018;Jia et al, 2019;Liu et al, 2019a;Zhang et al, 2020)…”

“…As expected, TCM polysaccharides have protective effects on PF. For example, astragalus polysaccharides (APS) can reduce the degree of PF by inhibiting transforming growth factor-β1 (TGF-β1) in vitro and in vivo ( Zhang, Xu, 2020 ). Ganoderma lucidum polysaccharides (GIP) inhibit bleomycin (BLM)-induced adult male SD rats by improving lung antioxidant capacity ( Chen et al, 2016 ).…”

“…The overproduction of TGF-β1 is always closely related to PF, and TGF-β1 plays a key role in inducing EMT ( Walton et al, 2017 ), nuclear factor-kB (NF-kB) regulates the expression of a variety of cytokines and inflammatory mediators, by inhibiting the expression of TGF-β1/NF-kB to block related signal pathways and prevent inflammation and reduce liver fibrosis ( Li et al, 2018a ). A recent observation proposed that APS can reduce PF through the TGF-β1/NF-kB pathway, which can effectively improve the deposition of COL-1, COL-3, and FN in vivo , APS reduce the area of fibrosis and HYP content in the matrix, and reduce the expression of a-SMA neutralizes E-cadherin, it significantly reduces the activation of the EMT and NF-kB pathways of TGF-β1 in vitro ( Zhang et al, 2020 ). Therefore, the mechanism of APS protecting PF is the regulation of TGF-β1/NF-kB pathway.…”