Table 1 Animal experiments of representative hypoglycemic or lipid-lowering drugs for pulmonary fibrosis
Drug | Mechanism | Model | Control Group | Experimental Group | Ref |
|---|---|---|---|---|---|
Empagliflozin | Modulating Sesn2/AMPK/Nrf2 signaling Targeting ferroptosis and autophagy | BLM-induced PF in rats (BLM, I.P.) | Saline (I.P.) and 1% CMC (I.G.) BLM (I.P.) EMPA dissolved in 1% CMC (I.G.) | EMPA (I.G.) for 7d before BLM and continue for 4w after BLM (I.P.) | [131] |
Liraglutide | Reducing collagen interstitial deposition and production of precursor materials Reducing myofibroblasts in the tissues and the expression of pro-fibrotic cytokines | BLM-induced PF in rats (Intratracheal instillation of BLM) | VEH (S.C.) after intratracheal instillation of BLM | Liraglutide dissolved on 0.4% acetic acid (S.C.) after intratracheal instillation of BLM | [132] |
Metformin | Targeting S100A4 via AMPK-STAT3 axis | BLM-induced PF in mice (Intratracheal instillation of BLM) | Intratracheal instillation of Saline Intratracheal instillation of BLM | MET (I.P.) (Day 7 after treatment of BLM or saline) | [133] |
Rosiglitazone | Upregulating PTEN and downregulating the TGF-β1 expression in a PPAR-γ dependent manner | PQ-induced PF in rats (PQ, I.P.) | Distilled water (I.P.) RSG (I.P.) GW (I.P.) | PQ (I.P.) PQ + RSG (I.P.) PQ + RSG + GW (I.P) | [134] |
Fenofibrate and Rosiglitazone | Decreasing lung inflammation and down regulating TGF-b1-mediated collagen deposition | BLM-induced PF in rats (Intratracheal instillation of BLM) | No medications Intratracheal instillation of PBS Intratracheal instillation of BLM RSG orally Fenofibrate orally RSG and fenofibrate orally | RSG orally after intratracheal instillation of BLM Fenofibrate orally after intratracheal instillation of BLM RSG and fenofibrate orally after intratracheal instillation of BLM | [135] |
Pravastatin | Inhibiting TGF-β1, CTGF, RhoA and cyclin D1 pathways | BLM-induced PF in mice (Intratracheal instillation of BLM) | Intratracheal instillation of Saline Intratracheal instillation of BLM | Intratracheal instillation of BLM plus 30 mg ⁄ kg of pravastatin (I.P.) Intratracheal instillation of BLM plus 300 mg ⁄ kg of pravastatin (I.P.) | [136] |
Atorvastatin | Reducing the differentiation of lung fibroblast into myofibroblasts and inducing myofibroblast apoptosis | BLM-induced PF in mice (Intratracheal instillation of BLM) | Treatment of sterile vehicle solutions Intratracheal instillation of BLM (in PBS) ATR in DMSO/PBS (I.P.) for 10d from Day 7 | ATR(I.P.) for 10d after 7d from given BLM intratracheally | [137] |
Atorvastatin and Ezetimibe | Protecting against hypercholesterolemia-induced lung oxidative stress, inflammation, and fibrosis | Hypercholesterolemia-induced PF in rats | Standard diet(S) Standard diet + 1% cholesterol (SC) | SC with 30 mg/kg/day ATR (I.G.) SC with 10 mg/kg/day ezetimibe (I.G.) | [138] |
Probucol | Ameliorating EMT and lung fibrosis through restoration of SIRT3 expression | BLM-induced PF in mice (Intratracheal instillation of BLM) | Intratracheal instillation of BLM and CMC-Na (I.G.) Intratracheal instillation of probucol and probucol (I.G.) | Intratracheal instillation of BLM and probucol plus probucol (I.G.) | [139] |