Medicinal Plant Research 2025, Vol.15, No.5, 224-232 http://hortherbpublisher.com/index.php/mpr 226 2.4 Regulation of respiratory system-related signaling pathways Astragalus and active ingredients regulate several important signaling pathways related to respiratory disease. These include inhibition of the TLR4/NF-κB/MyD88 signal pathway, decreasing inflammation and oxidative damage, regulation of the PI3K/Akt/mTOR signal pathway, restoring autophagic flux and reduction of lung damage. The Nrf2/SLC7A11/GPX4 signal pathway is triggered to suppress ferroptosis and oxidative injury, and the Ras/Raf/MEK/ERK pathway is associated with the induction of autophagy and anti-fibrosis. Moreover, Astragalus modulates the JAK2/STAT6 and HMGB1/RAGE/NF-κB pathways and restrains airway inflammation and remodeling in asthma. Through these multi-target and multi-pathway mechanisms, Astragalus evokes extensive protective effects on many respiratory diseases (Pei et al., 2021; Wang et al., 2022; Yu et al., 2022; Wei et al., 2023). 3 Clinical Applications of Astragalus in Acute Respiratory Diseases 3.1 Acute upper respiratory tract infections Astragalus membranaceus has been traditionally long used in preventing and treating acute upper respiratory tract infection (URTIs), particularly in Chinese traditional medicine. Recent pharmacological studies have demonstrated that Astragalus polysaccharides can activate innate immunity by inducing expression of antimicrobial peptides such as LL-37 in respiratory epithelial cells and thereby having direct anti-infective activity. Its immunomodulatory activity is mediated through activation of p38 MAPK, JNK, and NF-κB signaling pathways that play central roles in host defense against infection. These findings offer a rationale for the therapeutic use of Astragalus in the prevention and treatment of acute URTIs. However, systematic reviews of randomized controlled trials revealed no adequate evidence of high quality to prove the efficacy and safety of oral Astragalus alone as an intervention for the prevention of recurrent episodes of acute respiratory tract infections in children, calling for more rigorous clinical trials (Su et al., 2016; Zhao et al., 2018). 3.2 Acute bronchitis Immunomodulatory and anti-inflammatory actions of Astragalus membranaceus suggest potential therapeutic advantages in the treatment of acute bronchitis. Astragalus saponins and polysaccharides are able to inhibit pro-inflammatory cytokine gene expression and airway inflammation, the two primary pathological features of acute bronchitis. At the same time, Astragalus is capable of modulating immune response and inducing mucosal repair to achieve symptom relief and earlier recovery. Whereas preclinical and mechanistic studies substantiate these activities, there is no strong direct clinical evidence to support the use of Astragalus in acute bronchitis, and good clinical trials would be required to establish its safety and efficacy in this indication (Chen et al., 2020; Tan et al., 2023). 3.3 Community-acquired pneumonia Astragalus membranaceus has been explored as an adjuvant therapy in community-acquired pneumonia due to its immunostimulatory, anti-inflammatory, and antioxidant properties. Bioactive molecules in it are able to modulate immune cell function, stimulate the clearance of pathogens, and inhibit over-inflammation-induced lung injury. Some clinical trials and reviews of literature report that Astragalus-containing products may improve clinical outcome, reduce the severity of symptoms, and reduce complications in patients with pneumonia. However, the evidence currently available is based primarily on studies on more inclusive respiratory infections or traditional Chinese medicine formulations, and no high-quality large-scale randomized controlled trials targeting community-acquired pneumonia are present. Accordingly, while Astragalus is presented positively as adjunctive therapy, more robust clinical trials need to be conducted to define its role in the management of community-acquired pneumonia (Law et al., 2020; Zheng et al., 2020). 4 Clinical Applications of Astragalus in Chronic Respiratory Diseases 4.1 Chronic obstructive pulmonary disease (COPD) Astragalus membranaceus and its bioactive molecules, astragalosides, and polysaccharides have been documented to have therapeutic potential in COPD by anti-inflammatory, antioxidant, and immunomodulatory effects. Cigarette smoke- and particulate matter-induced models of COPD in animals show that Astragalus
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