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Astragaloside IV is a biologically active substance derived from the traditional Chinese medicine Astragalus mambranaceus Bunge, and has antioxidant, anti-inflammatory, and anti-apoptotic properties. In this study, we aimed to investigate the effects of astragaloside IV on Klebsiella pneumonia rats and the underlying mechanisms. Klebsiella pneumoniae (K. pneumoniae) rats were treated with different dosages of astragaloside IV (5, 10, and 20 mg/kg) by intragastric administration. The levels of pro-inflammatory cytokines interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α in bronchoalveolar lavage fluid (BALF) were determined. Pathological changes of lung tissue were inspected by HE staining. The expression of transforming growth factor (TGF)-β1 in lung tissue was determined with immunohistochemistry, and the expression levels of TGF-β1, p-Smad2/Smad2, p-Smad3/Smad3, IκBα/p-IκBα, and p65/p-p65 in lung tissue were determined by western blot. The mechanism was further investigated with TGF-β1 inhibitor SB-431542. Astragaloside IV reduced the elevated levels of pro-inflammatory cytokines caused by K. pneumoniae and improved lung tissue damage in a dose-dependent manner. Astragaloside IV also decreased the expression of TGF-β1/Smad signaling pathway-related proteins and decreased the protein levels of inflammation-related p-IκBα and p65 in lung tissues induced by K. pneumoniae. Additionally, it was found that the effects of 20 mg/kg astragaloside IV were similar to SB-431542, which could improve pulmonary fibrosis induced by K. pneumoniae, decrease the levels of TGF-β1/Smad signaling pathway-related proteins in lung, and reduce inflammation at the same time. Astragaloside IV could alleviate the inflammation of rat pneumonia induced by K. pneumoniae through suppressing the TGF-β1/Smad pathway. Bunge antioxidant antiinflammatory, antiinflammatory anti inflammatory, inflammatory anti-inflammatory antiapoptotic apoptotic properties study mechanisms K (K 5, 5 (5 10 2 mgkg mg kg administration proinflammatory pro IL6, IL6 IL 6, 6 (IL)-6 IL1β, IL1β ILβ 1β, 1β β IL-1β TNFα TNF α BALF (BALF staining TGFβ1 TGFβ TGF β1 (TGF)-β immunohistochemistry TGFβ1, β1, pSmad2/Smad2, pSmad2Smad2 pSmadSmad p Smad2/Smad2, Smad2 Smad p-Smad2/Smad2 pSmad3/Smad3, pSmad3Smad3 Smad3/Smad3, Smad3 p-Smad3/Smad3 IκBα/pIκBα, IκBαpIκBα IκBα/p IκBα, IκBα IκBα/p-IκBα p65/pp65 p65pp65 ppp p65/p p65/p-p6 blot TGF-β SB431542. SB431542 SB 431542. 431542 SB-431542 dosedependent dose dependent manner TGFβ1/Smad TGFβ1Smad TGFβSmad β1/Smad pathwayrelated pathway related inflammationrelated pIκBα p6 Additionally SB431542, 431542, time ( 1 (IL)- pSmad2 pSmad pSmad2/Smad2 pSmad2Smad Smad2Smad2 SmadSmad Smad2/Smad2 p-Smad2/Smad pSmad3 pSmad3/Smad3 pSmad3Smad Smad3Smad3 Smad3/Smad3 p-Smad3/Smad IκBα/pIκBα IκBαp pp65 pp p65/pp6 p65pp6 p65p p65/p-p SB43154 43154 SB-43154 β1Smad βSmad (IL) pSmad2/Smad Smad2Smad Smad2/Smad pSmad3/Smad Smad3Smad Smad3/Smad pp6 p65/pp p65pp SB4315 4315 SB-4315 (IL SB431 431 SB-431 SB43 43 SB-43 SB4 4 SB-4 SB-