In vivo: |
J Pharmacol Exp Ther. 2017 May;361(2):268-279. | Mogroside IIIE, a Novel Anti-Fibrotic Compound, Reduces Pulmonary Fibrosis through Toll-Like Receptor 4 Pathways.[Pubmed: 28280123 ] | Idiopathic pulmonary fibrosis is a progressive fibrotic lung disease, and eventually most patients develop respiratory failure with a median survival rate of 2 to 3 years after diagnosis due to the lack of clinically effective therapies.
Mogroside IIIe (MGIIIE), a cucurbitane-type compound, was isolated from Siraitia grosvenorii MGIIIE has shown the strongest inhibition of nitric oxide release, a crucial inflammatory factor, from lipopolysaccharide (LPS)-treated RAW264.7 cells compared with other mogrosides. METHODS AND RESULTS:
In the pulmonary fibrosis mouse model induced by bleomycin,
MGIIIE treatment attenuated pulmonary fibrosis, indicated as a reduction in myeloperoxidase activity, collagen deposition, and pathologic score. MGIIIE also significantly suppressed expression of several important fibrotic markers, e.g., α-smooth muscle actin, collagen I, transforming growth factor-β (TGF-β) signal, and metalloproteinases-9/tissue inhibitor of metalloproteinase-1. Furthermore, MGIIIE blocked tansdifferentiation of lung resident fibroblasts into myofibroblast-like cells induced by TGF-β or LPS and subsequently inhibited collagen production in lung fibroblasts. These data indicate that MGIIIE is a potent inhibitor for pulmonary fibrosis. In vitro and in vivo mechanistic studies have shown that MGIIIE significantly decreased expression of toll-like receptor 4 (TLR4) and its downstream signals of myeloid differentiation factor 88 (MyD88)/mitogen-activated protein kinase (MAPK), an inflammatory signal essential for extracellular matrix (ECM) deposition in pulmonary fibroblasts.
CONCLUSIONS:
Taken together, these results demonstrate that MGIIIE significantly prevents pulmonary fibrosis by inhibiting pulmonary inflammation and ECM deposition through regulating TLR4/MyD88-MAPK signaling. Our study suggests that MGIIIE may have therapeutic potential for treating pulmonary fibrosis in clinical settings. |
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