2. Academic Validation
  3. Baicalin inhibits the Akt/mTOR/ULK1 signaling pathway to activate autophagy and ameliorate pulmonary fibrosis

Baicalin inhibits the Akt/mTOR/ULK1 signaling pathway to activate autophagy and ameliorate pulmonary fibrosis

  • Int Immunopharmacol. 2026 Jan 1;168(Pt 2):115883. doi: 10.1016/j.intimp.2025.115883.
Xu-Liang Hu 1,  Qing Liang 1,  Zhi-Jun Jie 1,  Wan-Sheng Chen 2,  Jiu-Ling Deng 3,  Guang-Chun Sun 4
Affiliations

Affiliations

  • 1 Department of Pharmacy, Shanghai Fifth People's Hospital, Fudan University, Shanghai 200240, China.
  • 2 Department of Pharmacy, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China. Electronic address: [email protected].
  • 3 Department of Pharmacy, Shanghai Fifth People's Hospital, Fudan University, Shanghai 200240, China. Electronic address: [email protected].
  • 4 Department of Pharmacy, Shanghai Fifth People's Hospital, Fudan University, Shanghai 200240, China. Electronic address: [email protected].
PMID: 41308360 DOI: 10.1016/j.intimp.2025.115883
Abstract

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disorder pathologically characterized by epithelial-mesenchymal transition (EMT) and aberrant extracellular matrix (ECM) accumulation. Autophagy dysfunction has recently been implicated in the pathogenesis of IPF. Baicalin (Bai), a natural flavonoid glycoside, has demonstrated anti-fibrotic potential, yet its role in modulating Autophagy in IPF remains unclear.

Objective: The study analyzed the protective effect of Baicalin on IPF, focusing on its ability to modulate Autophagy and inhibit EMT.

Methods: A classic murine model of IPF was induced by a single intratracheal injection of BLM and treated with Baicalin (50 mg/kg, 100 mg/kg, i.g.), pirfenidone (150 mg/kg, i.g.), or hydroxychloroquine (HCQ, 60 mg/kg, i.p.). In vitro, MLE-12 cells stimulated by TGF-β1 were subjected to Baicalin treatment. (10-40 μM). Fibrosis, Autophagy activity, and EMT markers were assessed using histopathology, Micro-CT, Western blot, immunofluorescence, and transmission electron microscopy. The Autophagy inhibitor 3-MA, activator rapamycin, and Akt Agonist SC-79 were employed for mechanistic validation.

Results: Baicalin treatment significantly ameliorated pulmonary fibrosis, inhibited EMT, reduced lung index, Collagen deposition, and inflammation, as well as enhanced Autophagy in BLM-challenged mice. In TGF-β1-stimulated MLE-12 cells, Baicalin reversed Autophagy impairment and EMT progression. Mechanistically, Autophagy inhibitors (3-MA, HCQ) counteracted Baicalin's anti-fibrotic effects. Baicalin suppressed Akt/mTOR/ULK1 signaling activation by decreasing p-Akt, p-mTOR, and p-ULK1 levels. The Akt Agonist SC-79 abrogated Baicalin-induced Autophagy restoration and EMT inhibition.

Conclusion: Baicalin alleviated pulmonary fibrosis by activating Autophagy and inhibiting EMT via the Akt/mTOR/ULK1 pathway. Our research offers new pharmacological insights into IPF treatment that targets Autophagy.

Keywords

Akt/mTOR/ULK1 pathway; Autophagy; Baicalin; Epithelial-mesenchymal transition; Pulmonary fibrosis.

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