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Pulmonary fibrosis (PF) is a major public health issue with limited treatment options. As the active ingredient of the n-butanol extract of Amygdalus mongolica (BUT), amygdalin inhibits PF. However, its mechanisms of action are unclear and need further verification. Therefore, the purpose of the present studies was to investigate the anti-fibrotic effects of BUT on PF by serum metabolomics and the transforming growth factor β (TGF-β) pathway. Sixty male Sprague-Dawley rats were randomly divided into control, untreated PF, prednisone-treated (5 mg/kg), and BUT-treated (1.75, 1.25, 0.75 g/kg) groups, and the respective drugs were administered intragastrically for 21 days. The serum metabolomics profiles were determined by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS) and metabolism network analysis. The expression of TGF-β1, Smad-3, Smad-7, and α-smooth muscle actin (α-SMA) was measured using a real-time polymerase chain reaction in the lung tissue. BUT significantly alleviated fibrosis by reducing the mRNA expressions of TGF-β1 (from 1.73 to 1.13), Smad-3 (from 2.01 to 1.19), and α-SMA (from 2.14 to 1.19) and increasing that of Smad7 (from 0.17 to 0.62). Twenty-eight potential biomarkers associated with PF were identified. In addition, four key biomarkers were restored to baseline levels following BUT treatment, with the lowest dose showing optimal effect. Furthermore, A. mongolica BUT was found to improve PF by the pentose phosphate pathway and by taurine, hypotaurine, and arachidonic acid metabolism. These findings revealed the mechanism of A. mongolica BUT antifibrotic effects and metabolic activity in PF rats and provided the experimental basis for its clinical application. (PF options nbutanol n butanol BUT, , (BUT) However verification Therefore anti fibrotic TGFβ TGF (TGF-β SpragueDawley Sprague Dawley control prednisonetreated prednisone treated 5 ( mg/kg, mgkg mg/kg mg kg mg/kg) BUTtreated 1.75, 175 1 75 (1.75 125 25 1.25 075 0 0.7 g/kg gkg g groups 2 days ultraperformance ultra performance timeofflight time flight UPLCQTOF/MS UPLCQTOFMS UPLC QTOF/MS QTOF MS (UPLC-QTOF/MS analysis TGFβ1, TGFβ1 β1, β1 Smad3, Smad3 Smad 3, 3 Smad7, 7, 7 Smad-7 αsmooth α smooth αSMA SMA (α-SMA realtime real tissue TGF-β from 173 73 1.7 1.13, 113 1.13 13 1.13) Smad- 201 01 2.0 1.19, 119 1.19 19 214 14 2.1 017 17 0.1 0.62. 062 0.62 . 62 0.62) Twentyeight Twenty eight identified addition effect Furthermore A taurine hypotaurine application (BUT 1.75 (1.7 12 1.2 07 0. UPLCQTOF QTOFMS 1. 11 1.1 20 2. 06 0.6 6 (1. (1