International immunopharmacology · 2025
Baicalin inhibits the Akt/mTOR/ULK1 signaling pathway to activate autophagy and ameliorate pulmonary fibrosis.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Hu Xu-Liang, Liang Qing, Jie Zhi-Jun, Chen Wan-Sheng, Deng Jiu-Ling, Sun Guang-Chun
Аннотация
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.
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.