Endocannabinoid signalling/cannabinoid receptor 2 is involved in icariin-mediated protective effects against bleomycin-induced pulmonary fibrosis

Du, Wenjing; Zhang, Ting; Yang, Feng; Gul, Aman; Tang, Zhao You; Zhang, Hu; Jiang, Shan; Wang, Shiqiang; Dong, Jingcheng

doi:10.1016/j.phymed.2022.154187

Cited by 5 publications

(1 citation statement)

References 37 publications

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“…Meanwhile, infiltrating inflammatory cells in pulmonary interstitium and alveolar spaces also indicated strong CB2R positive signals. These features are consistent with the latest literature indicating that CB2R in the lung tissues could be a signature of PF [ 41 ]. Furthermore, the expression of CB2R was examined in A549 (human type II alveolar epithelial cell line) and RLE-6TN (rat alveolar type II cell line).…”

Section: Resultssupporting

confidence: 92%

Discovery of a pyrano[2,3-b]pyridine derivative YX-2102 as a cannabinoid receptor 2 agonist for alleviating lung fibrosis

Liu

Yuan

et al. 2022

J Transl Med

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Background Pharmacological modulation of cannabinoid 2 receptor (CB2R) is a promising therapeutic strategy for pulmonary fibrosis (PF). Thus, to develop CB2R selective ligands with new chemical space has attracted much research interests. This work aims to discover a novel CB2R agonist from an in-house library, and to evaluate its therapeutic effects on PF model, as well as to disclose the pharmacological mechanism. Methods Virtual screening was used to identify the candidate ligand for CB2R from a newly established in-house library. Both in vivo experiments on PF rat model and in vitro experiments on cells were performed to investigate the therapeutic effects of the lead compound and underlying mechanism. Results A “natural product-like” pyrano[2,3-b]pyridine derivative, YX-2102 was identified that bound to CB2R with high affinity. Intraperitoneal YX-2102 injections significantly ameliorated lung injury, inflammation and fibrosis in a rat model of PF induced by bleomycin (BLM). On one hand, YX-2102 inhibited inflammatory response at least partially through modulating macrophages polarization thereby exerting protective effects. Whereas, on the other hand, YX-2102 significantly upregulated CB2R expression in alveolar epithelial cells in vivo. Its pretreatment inhibited lung alveolar epithelial-to-mesenchymal transition (EMT) in vitro and PF model induced by transforming growth factor beta-1 (TGF-β1) via a CB2 receptor-dependent pathway. Further studies suggested that the Nrf2-Smad7 pathway might be involved in. Conclusion These findings suggest that CB2R is a potential target for PF treatment and YX-2102 is a promising CB2R agonist with new chemical space.

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Section: Resultssupporting

confidence: 92%