TABLE 2.
Antifibrotic role of curcumin in circulatory system fibrosis.
| Disease | Animal/Cell model | Inducer | Dosage and duration | Described effects | Pathway | Reference |
|---|---|---|---|---|---|---|
| DCM | Male Wistar rats | HFD + STZ (40 mg/kg) | Curcumin (100 and 200 mg/kg for 5 weeks) | ↑: FS, EF, SOD, Bcl-2, f p-AKT, and p-GSK-3β ↓: Body weight, heart weight–body weight ratio, blood glucose, TG, TC, interventricular septal hypertrophy, IVSD, CK-MB, AST, LDH, IL-1β, MDA, TNF-α, glycogen lysis, cardiomyocyte hypertrophy, RAGE, gp91phox, p47phox, Rac1, NADP+/NADPH, Bax, and caspase-3 |
AKT/GSK-3β signaling pathway | Yu et al. (2012) |
| Cardiac fibrosis | Rats | ABE (26 mg/kg/day) | Curcumin (30 mg/kg for 4 weeks) | ↓: Troponin I, total cholesterol, CK-MB, cardiac fibrosis, cardiac vessels, myofibril degeneration, karyolytic myocardiocytes, and fibrosis | CK-MB | Huyut et al. (2023) |
| Atrial fibrillation | Male SD rats | Ach (66 μg/mL)–CaCl2 (10 mg/mL) for 28 days | Curcumin (50 mg/mL for 24 days) | ↓: AF duration, left atrial fibrosis, myocardial fibrosis, IL-17A, IL-1β, IL-6, TGF-β1, collagen type I α1, FASN, PCK1, BMP10, IL-33, and FIGF | IL-17 | Yue et al. (2022) |
| MI | In vivo: Male C57BL/6 mice | Left anterior descending coronary artery ligation | Curcumin (50 and 100 mg/kg) for 4 weeks | ↓: CD68+, CD3+, cardiac myofibroblast enrichment, collagen deposition, periostin, vimentin, and α-SMA | IL18–p-SMAD2/3 signaling pathway | Zhao et al. (2022) |
| In vitro: Raw RAW264.7 cells | LPS 1 μg/mL | Curcumin (10 and 20 μM) | ↑: IL-10 ↓: Proliferation, apoptotic, IL-6, IL-1β, TNF-α, and CD86+ |
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| In vitro: primary neonatal rat cardiac fibroblasts | TGF-β 10 ng/mL | Curcumin (20 μM) | ↓: α-SMA, vimentin, periostin, and EDA–fibronectin, p-SMAD2/3, and IL-18 | |||
| Cardiac hypertrophy | Male SD rats | Isoprenaline (5 mg/kg/day) | Curcumin (200 mg/kg/day for 4 weeks) | ↑: MYH6, β-MHC (MYH7B), and mTOR ↓: Cardiac hypertrophy, interstitial fibrosis, heart weight–body weight ratio, ANP, MYH7, collagen I, collagen III, LC3, Beclin-1, and p-mTOR -: BNP |
mTOR/autophagy | Liu R. et al. (2018) |
| CF (chronic kidney disease) | In vivo: male SD rats | Remove the right kidney and select ligation of the posterior branch and the anterior segmental artery of the anterior branch | Curcumin (100 mg/kg for 5 weeks) | ↓: Left kidney weight, proteinuria, high blood pressure, LV mass, interstitial fibrosis, cardiomyocyte hypertrophy, ED-1 (heart), NLRP3, caspase-1, IL-1β, TGF-β1, p-Smad2, collagen I, and β-MHC -: Glomerulosclerosis, urinary protein, blood urea nitrogen levels, ED-1 (kidney), and ASC |
NLRP3 | Bugyei-Twum et al. (2016) |
| DCM | In vivo: male SD rats | HFD + STZ (30 mg/kg) | Curcumin (20 mg/kg for 8 weeks) | ↑: SOD, NRF2, NQO 1, and CAT ↓: MDA, TGF-β1, and collagen type I α2 |
NRF2/ARE pathway | Xiang et al. (2020) |
| CF | In vitro: HCFs | TGF-β1 10 ng/mL | Curcumin (20 µM) | ↓: α-SMA, collagen I, collagen III, cyclin B, CDK1, p-Smad2/3, p38 MAPK, and p-ERK | p38 MAPK/ERK signaling pathway | Fang et al. (2018) |
| CF | In vitro: cardiac fibroblasts | TGF-β1 10 ng/mL | Curcumin (25 mM) | ↓: Proliferation, migration, collagen, MMP-2, p-Smad2/3, p-AKT, AT1R, and p-ERK1/2 | Smad/ERK | Chung (2014) |
| CF | In vitro: CFs from SD rats | TGF-β1 10 ng/mL | Curcumin (20 µM) | ↓: α-SMA, collagen I, Smad2, p-Smad2, P38, and p-P38 | Smad-2 and p38 MAPK signaling pathway | Liu L. et al. (2016) |
| CF | In vitro: cardiac ventricular fibroblasts | Ang II (10−5 mol/L) for 24 h | Curcumin (5, 10, and 20 µM) | ↓: collagen I, collagen III, TGF-β1, MMP-9, and TIMP-1 | TGF/MMP | Ma et al. (2016) |
| DCM | Male SD rats | HFD + STZ (35 mg/kg) | Curcumin (300 mg/kg for 16 weeks) | ↑: Smad7 ↓: collagen I, collagen III, TGF-β1, TβR II, and p-Smad2/3 |
TGF/Smad/AMPK | Guo et al. (2017) |
| DCM | In vitro: HCFs | HG (30 mmol/L) | Curcumin (25 µM for 24 h) | ↑: Smad7 ↓: collagen I, collagen III, TβR I, TβR II, and p-Smad2/3 |
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| TGF-β1 (5 ng/mL) | Curcumin (25 µM for 24 h) | ↓: collagen I, collagen III, p-P38, AMPKα, and p-AMPKα -: Smad7 |
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| CF | In vitro: HCFs | Ang II 0.1 μmol/L | Curcumin (5, 10, and 20 µM) | ↑: PPARγ ↓: CTGF, PAI-1, collagen III, FN, TGF-β1, and p-Smad2/3 |
TGF-β1/Smad2/3 | Meng et al. (2014) |
| CF | SHRs | - | Curcumin (100 mg/kg/day for 12 weeks) | ↑: PPARγ ↓: SBP, blood Ang II concentration, heart weight, heart weight–body weight ratio, left ventricle weight–body weight ratio, CTGF, PAI-1, collagen III, and FN |
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| Myocardial fibrosis | Male SD rats | Ang II (500 ng/kg/min) | Curcumin (150 mg/kg/day for 4 weeks) | ↑: AT 2, AT 2/AT 1, and ACE2 ↓: Arterial blood pressure, mean arterial pressure, AT 1, α-SMA, accumulated macrophages, proliferated myofibroblasts, TGF-β1, p-Smad2, p-Smad3, and collagen I |
TGF-β1/Smads signaling pathway | Pang et al. (2015) |
| MI | In vivo: Male C57BL/6J wild-type mice | Permanent ligation of the left anterior descending coronary artery | Curcumin (100 mg/kg/day for 4 weeks) | ↑: SIRT1 ↓: collagen I, collagen III, and TGF-β1 |
- | Ji et al. (2016) |
| In vitro: HCFs | Ang II (1, 10, and 100 nM) for 48 h | Curcumin (5, 10, and 15 µM) | ↑: SIRT1 ↓: collagen I, collagen III, TGF-β1, MMP-2, and MMP-9 |
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| CF | In vivo: male SD rats | Isoproterenol hydrochloride (5.0 mg/kg/day) | Curcumin (150 and 300 mg/kg/day for 4 weeks) | ↓: LVIDd, LVIDs, perivascular and cardiomyocyte fibrosis, fibroblast transformation, collagen I, collagen III, and α-SMA, -: EF |
- | Ma et al. (2016) |
| Takayasu’s arteritis | TAK patients (n = 12) and healthy controls (n = 8) | | Curcumin granules (60 g/day for 3 months) | ↑: Fatty acid oxidation ↓: Inflammation cells infiltration, thickening, necrosis and elastic fiber breakage, FABP3, α-SMA, ECM, AAF, CPT1A, CACT, ATP production, and cell proliferation |
- | Sifan Wu (2022) |
| Endothelial cell fibrosis | HUVECs | TGF-β1 | Curcumin (5 and 10 μM) | ↑: NRF-2, VE-cadherin, DDAH, and CD31 ↓: IL-1β, TNF-α, ADMA, vimentin, p-ERK1/2, EGFR, MMP-9, and α-SMA |
EndMT and ERK1/2 pathway | Chen et al. (2020) |