Worenine attenuates pulmonary fibrosis potentially through modulation of PBK/SRC-associated TGF-β1/Smad and NF-κB signaling pathways - 20/09/26
, Na Chen c, Yijie Zhang c, Juanjuan Xiao a, b, d, Shuang Zhao a, b, d, Qiuhong Duan a, e, ⁎ , Feng Zhu a, b, d, ⁎ Abstract |
Objective |
To elucidate the pharmacological mechanisms of worenine in pulmonary fibrosis (PF) through an integrative strategy combining network pharmacology, molecular docking, and experimental validation.
Methods |
Potential targets of worenine and PF-related genes were obtained from public databases and integrated to construct interaction networks. Protein-protein interaction (PPI), GO, and KEGG enrichment analyses were performed to identify key targets and pathways. Molecular docking evaluated binding affinities between worenine and hub targets. The anti-fibrotic effects and mechanisms of worenine were validated in bleomycin-induced PF mice and in TGF-β1-stimulated A549 and MRC-5 cells.
Results |
A total of 116 overlapping targets were identified. Key targets included SRC, IL6, TNF, NFKB1, and PIK3CA. Enrichment analyses indicated that worenine regulates pathways related to inflammation and cellular stress, including TNF, IL-17, and HIF-1 signaling. Molecular docking showed strong binding affinities between worenine and core targets such as EZH2, PTGS2, PBK, SRC, NFKB1, and IL6. In vivo, worenine alleviated PF, reducing collagen deposition and improving histopathology. In vitro, worenine inhibited EMT and FMT, accompanied by suppression of PBK/SRC-associated TGF-β1/Smad, ERK, and NF-κB signaling, as well as decreased secretion of IL-6, IL-8, and VEGFA.
Conclusion |
Worenine attenuates experimental pulmonary fibrosis, potentially through modulation of PBK/SRC-associated signaling and the TGF-β1/Smad, ERK, and NF-κB pathways. These findings provide a rationale for further investigation of Worenine as a potential therapeutic candidate for PF.
Le texte complet de cet article est disponible en PDF.Graphical Abstract |
Worenine attenuates pulmonary fibrosis through PBK/SRC-associated signaling, suppressing EMT, FMT, and inflammatory responses and improving bleomycin-induced lung injury with a favorable in vivo safety profile.
Worenine attenuates pulmonary fibrosis through PBK/SRC-associated signaling, suppressing EMT, FMT, and inflammatory responses and improving bleomycin-induced lung injury with a favorable in vivo safety profile. Le texte complet de cet article est disponible en PDF.
Highlights |
• | Worenine attenuates pulmonary fibrosis via PBK/SRC signaling. |
• | Network pharmacology and docking reveal Worenine’s multi-target anti-fibrotic effects. |
• | Worenine significantly improves BLM-induced pulmonary fibrosis in animal models. |
• | Worenine inhibits EMT, FMT, and inflammation, supported by experimental validation. |
Keywords : Worenine, Pulmonary fibrosis, Network pharmacology, Molecular docking, EMT, FMT, PBK
Plan
Vol 203
Article 119868- octobre 2026 Retour au numéro
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