TABLE 1.
Antifibrotic role of curcumin in respiratory fibrosis.
| Disease | Animal/cell model | Inducer | Dosage and duration | Described effects | Reference |
|---|---|---|---|---|---|
| IPF | LMSCs | H2O2, 600 μM | Curcumin (2.5, 5, and 10 µM) | ↑: MMP, Bcl-2/Bax, NRF2, HO-1, and p-AKT/AKT ↓: Apoptosis, ROS, and cleaved caspase-3 |
Ke et al. (2020) |
| PF/ALI | C57BL/6 male mice | BLM, 3 units/kg | Curcumin (75 mg/kg) | ↑: MCH, platelet counts, uPA, and uPAR ↓: MCV and HGB counts, P-p53, p53, PAI-1, α-SMA, cleaved caspase-3, p-ERK, Ki-67-positive cell, IL-17A, PAI-1, and STAT3 |
Gouda et al. (2024) |
| ALI | Park’s strain mice | Paraquat, 50 mg/kg | Curcumin (5 mg/kg, i.n.) | ↑: uPA and uPAR ↓: MMP-2, MMP-9, PAI-1, IL-17A, TNF-α, and IL-6 |
Muneesa et al. (2022) |
| ALI/LF | In vitro: A549 | BLM (40 μg/mL) | Curcumin (20 µM) | ↓: Ki 67, p-EGFR, and EGFR | Shaikh et al. (2020) |
| In vivo: C57BL/6 mice | Curcumin (75 mg/kg) | ||||
| PF | In vitro: human embryonic WI-38 lung fibroblast cell | ET-1 and thrombin induce | Curcumin (5 µM) | ↓: ET-1, α-SMA, CCN 2, vimentin protein, p-MAPK (ERK, JNK, and p38), p-ERK, and collagen IV | Chen et al. (2019a) |
| In vivo: BALB/c mice | BLM, 0.05 U/50 µL | Curcumin (30 mg/kg) | ↓: ET-1, α-SMA, CCN 2, vimentin protein, p-MAPK (ERK, JNK, and p38), p-ERK, and collagen IV | Chen et al. (2019a) | |
| Lung fibrosis | In vivo: 57BL/6 mice | BLM, 0.1 mU/mL | Curcumin (200 mg/kg) | ↑: Cathepsins K and L in the lungs and apoptotic cells ↓: Collagen deposition, TGF-β1, and cell proliferation and migration |
Zhang et al. (2011) |
| In vitro: HFL-1 | Curcumin (3, 10, 20, and 30 µM) | ↑: Cathepsins K and L, caspase-3, and Bax/Bcl-2 ↓: TGF-β1 |
Zhang et al. (2011) | ||
| IPF | In vitro: normal human fetal lung fibroblasts | TGF-β, 6 ng/mL | Curcumin (1, 5, 10, and 20 µM) | ↓: Proliferation of lung fibroblasts, inflammation, collagen deposition, α-SMA, TGF-β1, p-Smad2, p-Smad3, and p-ERK/ERK | Smith et al. (2010) |
| In vivo: C57BL/6 mice | BLM | Curcumin (300 mg/kg) | ↓: HYP | Smith et al. (2010) | |
| ALI/ARDS | Female CBA/J mice | Reovirus 1/L (107 PFU) 15 mL in each nostril | Curcumin (50 mg/kg) | ↑: p-p38 ↓: Procollagen I mRNA, IL-6, IL-10, IFNγ, MCP-1, α-SMA, E-cadherin, Tenascin-C, TGF-β RII, and P-p 65 NF-κB |
|
| PF | C57BL/6 | BLM, 2 mg/kg | Curcumin (75 mg/kg), i.p. | ↑:↑: uPA and uPAR ↓: MMP-2, MMP-9, and PAI-1 |
Muneesa et al. (2022) |
| PF | In vivo: ICR mice | BLM, 5 mg/kg or SiO2, 100 mg/kg | Curcumin (75 and 150 mg/kg) | ↑: HGF (lungs and large intestine) and Klotho | Miao et al. (2021) |
| In vitro: CCD-18Co cells, RAW264.7, and L929 cells | - | ↑: PPARγ, CREB, HGF, PGD 2, and 15 d-PGJ 2 | Miao et al. (2021) | ||
| IPF | In vivo: male SD rats | BLM | Curcumin LPMPs (5 mg) | ↓: lung injuries, infiltration of pulmonary mesenchyme and the variation of alveoli, high lung deposition, macrophage uptake, HYP, collagen I, TNF-α, TGF-β1, NF-κB p65, and MMP-9 | Hu et al. (2018) |
| PF | BALB/c mice | OVA, 50 μg | Curcumin (5 mg/kg) | ↓: HYP, MMP-9, eotaxin, and α-SMA | Chauhan et al. (2016) |
| IPF | Primary human lung fibroblasts from a patient with IPF | | Curcumin (10, 15, and 20 µM) | ↑: KLF 10 and cell cycle arrest ↓: proliferation/viability of IPF fibroblasts and hsa-miR-6724-5 p |
Chang et al. (2020) |
| ALI | Mice (Park’s strain) | PQ, 50 mg/kg, i.p., single dose | Curcumin (5 mg/kg) | ↑: FITC B220 and PE CD4+ ↓: inflammatory cell count, reactive oxygen species (ROS), HYP, α-SMA, MMP-9, TIMP-1, FITC Gr1, and PE CD11 |
Tyagi et al. (2016) |
| PF | Female C57BL/6 mice | Irradiation, 13.5 Gy (8-min irradiation session) | 1% or 5% (weight/weight, w/w) dietary curcumin | ↑: HO-1 ↓: ROS and TNF-α |
Lee et al. (2010) |
| LLC cells or PMVEC | 1.7 Gy/min | Curcumin (10 μM, 4 h) | ↑: HO-1 ↓: ROS and TNF-α |
Lee et al. (2010) | |
| PF | | | | ↓: fibrosis, inflammation, oxidative, HYP, MPO, and MDA | Hanyu et al. (2023) |
| PF | In vivo: Wistar rats | BLM (0.75 U/100 g, 3, 5, 7, 14, and 28 days post-BLM) | Curcumin (300 mg/kg; 28 days) | ↓: Total cell counts in BALF, ACE, AKP, superoxide anion, and nitric oxide | Durairaj Punithavathi (2000) |
| In vitro: AM | BLM (3, 5, 7, 14, and 28 days) | - | ↓: Total cell counts in BALF, ACE, AKP, superoxide anion, and nitric oxide | Durairaj Punithavathi (2000) | |
| PF | Male Wistar rats | BLM (0.75 U/100 g body) | Curcumin (300 mg/kg) | ↓: fibronectin level, total hexose, sialic acid, fucose, hexosamine, N-acetyl-β-d-glucosaminidase, and β-glucosidase | Durairaj et al. (2020) |
| PF | Fischer 344 rats | Amiodarone, 6.25 mg/kg | Curcumin (50, 100, and 200 mg/kg) | ↓: MPO, TGF-β1, HYP, collagen I, c-Jun, TNF-α, and PMA | Punithavathi et al. (2009) |
| PF | In vivo: SD rats | BLM, 1.5 mg/kg | Curcumin (250 and 500 mg/kg; 28 days) | ↓: collagen I, iNOS, and TGF-β1 | Xu et al. (2007) |
| IPF | In vitro: pulmonary fibroblasts | Four patients with advanced IPF (IPF-F) and four normal lungs (NHLF) | Curcumin (20 µM) | ↑: P21, P53, and ROS ↓: ACTA2, PCNA, collagen type I α1, CCND1, hypoxia-inducible factor 1α (HIF-1α), superoxide dismutase 2 (SOD2), and catalase (CAT), nuclear factor-like 2 (NRF2) |
Rodriguez et al. (2019) |
| In vitro: normal fibroblasts | Curcumin (20 µM) | ↑: P21, P53, and ROS ↓: HIF-1 and SOD 2 -: CAT and NRF2 |
Rodriguez et al. (2019) | ||
| In vitro: pulmonary epithelial | Curcumin (20 µM) | ↑: P21, P53, and ROS ↓: HIF-1α, superoxide dismutase 2 (SOD2), CAT, and NRF2 |
Rodriguez et al. (2019) | ||
| IPF | In vitro: A549 | Curcumin (20 µM) | ↑: P21, P53, HIF-1, NRF2, CAT -: ROS |
Rodriguez et al. (2019) | |
| PF | Male albino Wistar rats | Cyclophosphamide (150 mg/kg b.w., i.p.) | Curcumin (200 mg/kg) | ↑: NO and GSH ↓: HYP, elastin, MPO, MDA, TGF-β1, IL-1β, histamine, LT-C4, total protein, and N-acetyl-β-D-glucosaminidase, fibroblastic cells proliferation, and collagen |
Hamdy et al. (2012) |
| IPF | In vitro: macrophages | 2.5 U/kg BLM; immune inhibitor BLZ-945, M1: 100 ng/mL of LPS; and M2: 10 ng/mL of recombinant mouse IL-4 | Mn-curcumin metal– organic frameworks | ↓: M1, M2, pCSF-1R, HYP, TGF-β1, IL-11, IL-6, TNF-α, and ROS | Hou et al. (2024) |
| Cystic fibrosis | In vitro: HFF and mouse macrophages (J774A.1) cell lines | P. aeruginosa 106 PFU reovirus 1/L | Curcumin-loaded lipid-polymer hybrid nanoparticles (termed CG-HNPs) | ↑: Solubility and bioavailability and CTCF against P. aeruginosa biofilm and against intracellular bacteria | Sadeghi Mohammadi et al. (2021) |
| Inflammation and fibrosis | Male SD rats | A single 18-Gy dose of thoracic irradiation | Curcumin (200 mg/kg) | ↓: TGF-β1, CTGF, TNF-α, collagen, TNFR 1, COX-2, and NF-κB p65 | Cho et al. (2013) |
| Cystic fibrosis | In vivo: bronchial epithelial cell, VA10 | - | Curcumin (1 and 10 mg/mL) | ↑: Transepithelial electrical resistance ↓: F-actin localization, E-cadherin, and claudin-1 -: Occludin |
Benediktsdottir et al. (2015) |
| PF | In vivo: Wistar rats | Paraquat, 20 mg/kg | Curcumin (200 mg/kg) | ↓: Smad4, Smurf 2, IL-4, and IFN-γ | Chen et al. (2019b) |
| PF | In vitro: mouse lung fibroblast cell | TGF-β2, 10 ng/mL | Curcumin (5, 25, and 50 µM) | ↑: PPARγ ↓: PDGFR-β, α-SMA, and proliferation -: FGFR 1 |
Liu D. et al. (2016) |
| Lung pneumonitis and fibrosis | Male Wistar rats | 15 Gy using a cobalt-60 gamma rays source | Curcumin (150 mg/kg) | ↓: IL-4, IL-13, IL4, Ra1, DUOX1, and DUOX2 | Amini et al. (2018) |
| Asthma | Mice | OVA + DBP (10 mg/kg) | Curcumin (5 mg/kg) | ↑: NQO-1, HO-1, and CAT ↓: CD 11b+, vimentin, E-cadherin, α-SMA, NRF2, and MMP-9/TIMP-1 |
Singh et al. (2025) |
| IPF | In vitro: A549 | BLM (3.5 μM) | Curcumin analog EF24 | ↑: ROS and LC 3B ↓: Myofibroblast markers (vimentin, α-SMA, and snail), mtDNA, TOM 20, P62, and VADC 1 |
Zhang et al. (2024) |
| In vitro: ATII cells | BLM (3.5 μM) | Curcumin analog EF24 | ↑: PTEN ↓: SA-β-Gal, collagen I, TGF-β, IL-6, PAI-1, P21, SASP, p-AKT`mTOR`NF-κB |
Zhang et al. (2024) | |
| In vivo: C57BL/6 mice | BLM (3.5 mg/kg) | Curcumin analog EF24 (20 mg/kg) | ↑: PTEN ↓: HYP, collagen I, SA-β-Gal, P21, and α-SMA |
Zhang et al. (2024) | |
| In vivo:C57BL/6 mice | TBI (5 Gy) | ↑: PTEN ↓: HYP, collagen I,, SA-β-Gal, P21, and α-SMA |
Zhang et al. (2024) | ||
| IPF | In vitro: NIH 3 T3 | TGF-β (5 ng/mL) | Curcumin (25 µM) | ↓: Migration of fibroblasts, basement membrane collagen, fibronectin, MMP-2, MMP-9, inflammatory cells, disrupted alveolar structure, and thickened alveolar septa | Moideen et al. (2024) |
| In vivo: C57BL/6 mice | BLM (2 mg/kg) | Curcumin (75 mg/kg) | ↓: Collagen, fibronectin, MMP-2, and MMP-9 | Moideen et al. (2024) | |
| ALI | In vivo: C57/B6 male mice | IL-17A recombinant protein (1 µg) | Curcumin (75 mg/kg) | ↑: uPA and uPAR ↓: IL-17A, JAK1, IL-27RA, HLA-DPA1, NFATC3, IL-2RB, GATA3, STAT3, p53, P-p53, PAI, and caspase-3 |
Gouda et al. (2024) |
| Asthma | BALB/c mice | OVA (50 µg) + Alum sensitization (i.p.) (days 0, 7, and 14); 1% OVA aerosol (days 19–22) | Curcumin (5 mg/kg) | ↓: Inflammatory cell infiltration, ROS, NO levels, EPO, IgE level in serum, histamine level in BALF, MPO, HYP, and MMP-2 -: MMP-9, HDAC 1, H3acK9, and NF-kB p65 |
Chauhan et al. (2016) |
| Asthma | BALB/c mice | OVA (50 µg) + 0.2 mL saline containing 4 mg alum (i.p.) (days 0, 7, and 14); 1% OVA aerosol (days 19–22) | Curcumin (10 mg/kg) | ↓: Oxidative stress (ROS and NO), MPO, EPO, IL-5, histamine, IgE, HYP, MMP-9, α-SMA, NF-κB p65, p-p38, p-JNK, and HDAC8 -: ALT, AST, creatinine, and pa-1 |
Islam et al. (2023) |