TABLE 1.
Drugs Related to NRF2 in Fibrotic Diseases.
| Type of fibrosis | Drugs | Model | Therapeutic mechanism | References | |
|---|---|---|---|---|---|
| Pulmonary fibrosis | Pirfenidone (PFD) | Bleomycin-induced lung fibrosis C57BL/6 mice TGF-β1 induced mouse lung fibroblasts | Regulation of NRF2/BACH1 equilibrium, such as the inhibition of BACH1, promotes NRF2 recovery | (Liu et al., 2017) | |
| Tanshinone IIA (Tan IIA) | Silica-induced lung fibrosis SD rats Silica-induced lung fibrosisWistar rats | Inhibiting EMT and the TGF-β1/Smad signaling pathway and activating NRF2 signaling pathway (silica-induced). By activating NRF2 and inhibiting NOX4, the ROS-mediated PKCδ/Smad3 signaling pathway is blocked to promote the degradation of KEAP1 and convert glutamine into GSH (bleomycin-induced) | (Feng et al., 2020; Zhu et al., 2020) | ||
| Sulforaphane (SFN) | Bleomycin-induced lung fibrosis C57/BL6 mice | By increasing the expression of the NRF2 gene and its downstream antioxidant enzymes | (Yan et al., 2017) | ||
| Hepatic fibrosis | Maresin-1 (MaR1) | DEN-induced hepatic fibrosis SD rats | Increasing KEAP1/NRF2 signaling pathway, inhibiting TGF-β1/NF-κB pathway and decreasing inflammatory cytokine expression levels in DEN-induced liver injury mouse model | (Serhan et al., 2000; Dalli et al., 2013; Rodríguez et al., 2021) | |
| Pleurotus geesteranus polysaccharides (PGPs) | Kunming strain mice | Upregulating NRF2/HO-1 signaling pathways in an ALD mouse model | (Song et al., 2022) | ||
| Myocardial fibrosis | 5,8-Dihydroxy-4′,7 -Dimethoxyflavone (DDF) | Human cardiac fibroblasts | Activating the P38 MAPK/NRF2 signaling pathway, increasing HO-1 expression, and decreasing CTGF expression in HCFs | (Pietta, 2000; Yang et al., 2020) | |
| Astragaloside IV (AsIV) | ADR-treated SD rats | Activating the NRF2 signaling pathway, inhibiting iron death, significantly improving adriamycin-induced myocardial fibrosis | (Tan et al., 2020; Luo et al., 2021) | ||
| Puerarin | Abdominal aortic banding SD rats | Puerarin downregulates KEAP1, promotes NRF2 expression and nuclear transfer, and can prevent and ameliorate myocardial fibrosis. Its therapeutic effect may be related to the upregulation of UGT1A1 in NRCF by NRF2 | (Cai et al., 2018; Zhou et al., 2021) | ||
| Renal fibrosis | Salvianolic acid B (SA-B) | Ureteral ligation induced renal fibrosis SD rats | Regulating the differentiation of fibroblasts and modulating the downstream antioxidant genes of NRF2 | (Lu et al., 2010; Chen et al., 2014) | |
| Dimethylfumarate | UUO-induced renal fibrosis C57BL/6 mice | Upregulating the expression of downregulated antioxidative genes (HO-1, NQO1, etc.) and modulating the activation of TGF-β | (Oh et al., 2012) | ||
| Intestinal fibrosis | Maggot extract | Human intestinal fibroblasts (CCD-18Co cells) DSS-induced chronic colitis C57BL/6 mice | Up-regulating NRF2 expression at transcription and translation levels, inhibits TGF-β1/SMAD pathway | Wang et al., 2021a | |
| Tert-butylhydroquinone (tBHQ) | TNBS-induced chronic colitis BALB/c mouse | Changing the conformation of the KEAP1-NRF2 complex, and the DEGRADATION of Nrf2 mediated by Keap1 fails. Increasing nuclear translocation of NRF2 | Xu et al., 2017b | ||