Abstract Pulmonary fibrosis is a chronic, progressive and irreversible heterogeneous disease of pulmonary interstitial tissue. Its incidence is increasing year by year in the world, and it will be further increased due to the pandemic of COVID-19. However, at present, there is no safe and effective treatment for this disease, so it is very meaningful to find drugs with high efficiency and less adverse reactions. The natural astragalus polysaccharide has the pharmacological effect of anti-pulmonary fibrosis with little toxic and side effects. At present, the mechanism of anti-pulmonary fibrosis of astragalus polysaccharide is not clear. Based on the network pharmacology and molecular docking method, this study analyzes the mechanism of Astragalus polysaccharides in treating pulmonary fibrosis, which provides a theoretical basis for its further clinical application. The active components of Astragalus polysaccharides were screened out by Swisstarget database, and the related targets of pulmonary fibrosis were screened out by GeneCards database. Protein-protein interaction network analysis and molecular docking were carried out to verify the docking affinity of active ingredients. At present, through screening, we have obtained 92 potential targets of Astragalus polysaccharides for treating pulmonary fibrosis, including 11 core targets. Astragalus polysaccharides has the characteristics of multi-targets and multi-pathways, and its mechanism of action may be through regulating the expression of VCAM1, RELA, CDK2, JUN, CDK1, HSP90AA1, NOS2, SOD1, CASP3, AHSA1, PTGER3 and other genes during the development of pulmonary fibrosis. Keywords: Astragalus polysaccharides, pulmonary fibrosis, network pharmacology, molecular docking, mechanism Introduction Pulmonary fibrosis is caused by many causes, and it is a chronic, progressive and irreversible heterogeneous disease of pulmonary interstitial tissue ([30]Raghu et al., 2011). Including pulmonary fibrosis caused by secondary factors and idiopathic pulmonary fibrosis. The pathological features of pulmonary fibrosis are mainly the proliferation of lung fibroblasts and excessive deposition of extracellular matrix, which leads to the destruction of lung tissue structure and eventually leads to chronic respiratory failure ([31]Datta et al., 2011; [32]King et al., 2011). There are many factors leading to pulmonary fibrosis, mainly including smoking and environmental exposure, genetic factors, virus infection and complications ([33]Renzoni et al., 2014; [34]Zaman and Lee, 2018). The data show that the incidence of pulmonary fibrosis is increasing year by year in the world and is similar to that of liver cancer, gastric cancer and cervical cancer ([35]Hutchinson et al., 2015). At present, with the global spread of Coronavirus Disease 2019 (COVID-19), there may be more patients with pulmonary fibrosis. COVID-19 can cause severe lung injury and may lead to pulmonary fibrosis. Previous data of coronavirus infection (SARS-CoV or MERS-CoV) and new data of COVID-19 pandemic indicate that severe fibrosis may occur after SARS-CoV-2 infection ([36]George et al., 2020). Early diagnosis of pulmonary fibrosis is difficult and incurable, and the prognosis is very poor. The median survival time after diagnosis is 2–3 years, The 5-year survival rate is less than 30% ([37]Vancheri and du Bois, 2013; [38]Wuyts et al., 2020). At present, the main treatments for pulmonary fibrosis are drug therapy and lung transplantation. Lung transplantation is the most effective treatment at present, but it is limited by the supply of donor organs, economic situation and patients’ situation ([39]Kistler et al., 2014). As for drug therapy, so far only Pirfenidone and Nidanib have been approved by FDA for the treatment of pulmonary fibrosis worldwide ([40]Mora et al., 2017; [41]Lederer and Martinez, 2018). These two anti-fibrosis drugs can improve patients’ lung function, but they still can’t cure pulmonary fibrosis and have obvious side effects, such as diarrhea and drug-induced liver injury, anorexia, vomiting and photosensitive rash, etc. ([42]Richeldi et al., 2014; [43]King et al., 2014). At present, the pathogenesis of pulmonary fibrosis is not clear, but the incidence of pulmonary fibrosis is on the rise, especially with the pandemic of COVID-19, the incidence of pulmonary fibrosis secondary to COVID-19 will further increase, and seriously affect the health of patients. Although many treatments have been used to treat pulmonary fibrosis, there is still no safe and effective treatment. Therefore, it is of great significance to find drugs with high efficiency and less adverse reactions to improve the quality of life and survival rate of patients with pulmonary fibrosis. A large number of clinical and experimental studies show that traditional Chinese medicine can obviously improve many pathological links of pulmonary fibrosis, and the toxicity of traditional Chinese medicine is relatively small, which can improve the quality of life of patients and reduce the mortality rate, and has a good application prospect ([44]Zhao et al., 2017). Among them, Astragalus membranaceus plays an important role in treating fibrosis ([45]Ma et al., 2020). Astragalus membranaceus has been used in Chinese medicine for nearly 2000 years and is one of the most popular Chinese medicines in the world ([46]Shahrajabian et al., 2019). As one of the traditional Chinese medicines commonly used in clinic, Astragalus membranaceus can improve and treat various diseases, and has many pharmacological effects, such as antioxidation ([47]Shahzad et al., 2016), immunomodulation ([48]Block and Mead, 2003), antifibrosis ([49]Zhou et al., 2016), antitumor ([50]Zhou et al., 2018) and analgesia ([51]Di Cesare Mannelli et al., 2017). The main bioactive components in Astragalus membranaceus include polysaccharides, saponins, flavonoids and alkaloids ([52]Shahrajabian et al., 2019). Among them, Astragalus polysaccharide is the most abundant component in Astragalus membranaceus, which has a variety of pharmacological activities ([53]Zheng et al., 2020). The main components of Astragalus polysaccharides include dextran, heteropolysaccharide, acidic polysaccharide, and neutral polysaccharide. The monosaccharide components of Astragalus polysaccharide include glucose, glucuronic acid, arabinose, rhamnose, fructose, mannose, galactose, galacturonic acid, fucose, etc ([54]Wang et al., 2019). Studies have shown that Astragalus polysaccharide has anti-fibrosis pharmacological activity, and the main active ingredient of Astragalus membranaceus in anti-pulmonary fibrosis may be Astragalus polysaccharide. However, due to the complex components of Astragalus polysaccharide, the research on the anti-pulmonary fibrosis mechanism of Astragalus polysaccharide is relatively lacking at present, and the anti-pulmonary fibrosis mechanism of Astragalus polysaccharide is still unclear ([55]Li et al., 2011). Network pharmacology is a new discipline of multi-target drug molecular design by network construction and selecting specific signal Nodes. Emphasis is placed on the multi-channel regulation of signal pathway, improving the therapeutic effect of drugs and reducing the toxic and side effects, thus opening up new ways for drug development and utilization and saving the research and development cost of drugs ([56]Zhang et al., 2019). Molecular docking is a computer simulation of the recognition process between two or more molecules, which involves spatial matching and energy matching between molecules. Molecular docking methods are widely used in drug design, screening and other fields ([57]Morris and Lim-Wilby, 2008). Based on network pharmacology and molecular docking technology, this study preliminarily explored the mechanism of Astragalus polysaccharides in anti-pulmonary fibrosis, provided possible therapeutic drugs for the treatment of pulmonary fibrosis, and laid a theoretical foundation for the clinical application of Astragalus polysaccharides in anti-pulmonary fibrosis. Methods Screening of Key Active Components and Targets in Astragalus Polysaccharides HERB ([58]http://herb.ac.cn/) is a platform for pharmacology of Chinese herbal medicines. The database mainly includes the chemical substances, targets and drug target networks of Chinese herbal medicines ([59]Ru et al., 2014). We searched the HERB database for related chemical components with “Astragalus membranaceus” as the key word, and finally screened the components of Astragalus membranaceus polysaccharides from the above-mentioned searched compounds by combining with references.