Table 2.
Pre-clinical studies about curcumin and its effects on diabetes and DCM.
| Animals/cells | Treatments | Main findings | Reference |
|---|---|---|---|
| Anti-inflammatory effects | |||
| STZ-induced diabetic SD rats | Curcumin (100 mg/kg/day) for 7 weeks | - Decreased blood levels of TNF-α, IL-6, MCP-1 | Jain et al., 2009 |
| - Decreased glucose and glycosylated hemoglobin | |||
| High glucose-treated monocytes | Curcumin incubation (0.01-1 μM) for 24 h | - Lower TNF-α, IL-6, IL-8, and MCP-1 secretion | Jain et al., 2009 |
| STZ-induced diabetic Wistar rats | Curcumin (100 or 200 mg/kg/day) for 8 weeks | - Attenuated diabetes-induced left ventricular dysfunction, cardiomyocyte hypertrophy and interstitial fibrosis | Yu et al., 2012 |
| - Inhibited AGEs accumulation | |||
| - Decreased inflammatory factors (TNF-α and IL-1β) | |||
| - Activated AKT/GSK-3β signaling pathway | |||
| STZ-induced diabetic Wistar rats | Curcumin (200 mg/kg/day) for 6 weeks | - Inhibited IL-6 and TNF-α levels | Abo-Salem et al., 2014 |
| STZ-induced diabetic SD rats | Curcumin (300 mg/kg/day) for 16 weeks | - Reduced TGF-β1 production | Guo et al., 2018 |
| - Suppressed TβR II levels and Smad2/3 phosphorylation | |||
| - Increased Smad7 expression | |||
| High glucose-treated human cardiac fibroblasts | Curcumin incubation (25 μM) for 24 h | - Inhibited TGF-β1- or HG-induced AMPK/p38 MAPK activation | Guo et al., 2018 |
| - Suppressed collagen synthesis in the fibroblasts | |||
| STZ-induced diabetic C57BL/6 mice | Curcumin (5 mg/kg/day) for 3 months | - Reduced hypertriglyceridemia in both serum and hearts | Wang et al., 2014 |
| - Improved cardiac function, inhibition of JNK signaling and cardiac inflammation | |||
| - Inhibited a high glucose-induced rise in pro-inflammatory cytokines via inactivation of NF-κB | |||
| STZ-induced diabetic C57BL/6 mice | Curcumin analog, J17 (10 mg/kg/day) for 42 days | - Suppressed hyperglycemia-induced inflammation, hypertrophy and fibrosis | Chen et al., 2017 |
| - Decreased TNF-α and ICAM-1 | |||
| High glucose-treated H9C2 cardiomyocytes | Curcumin analog, J17 (2.5 or 10 μM) for 30 min | - Decreased pro-inflammatory cytokines (TNF-α and IL-6) and adhesion molecules (VCAM-1 and ICAM-1) expressions | Chen et al., 2017 |
| - Decreased AKT phosphorylation | |||
| - Inhibited the HG-induced increase in fibrotic genes (collagen-IV, TGF-β, and collagen-I) | |||
| Antioxidant properties | |||
| STZ-induced diabetic Wistar rats | Curcumin (100 or 200 mg/kg/day) for 8 weeks | - Attenuated NADP+/NADPH ratio, Rac1 activity and the expression of NADPH oxidase subunits of gp91 phox, p47 phox | Yu et al., 2012 |
| STZ-induced diabetic Wistar rats | Curcumin (200 mg/kg/day) for 6 weeks | - Restored cardiac antioxidant enzymes (catalase, superoxide dismutase, and glutathione-S-transferase) | Abo-Salem et al., 2014 |
| STZ-induced diabetic SD rats | Curcumin (100 mg/kg/day) for 8 weeks | - Decreased NADPH oxidase subunits (p67phox, p22phox, gp91phox) | Soetikno et al., 2012 |
| - Decreased the mRNA expression of transcriptional co-activator p300 and atrial natriuretic peptide | |||
| - Decreased accumulation of ECM protein | |||
| - Reversed the increment of superoxide production | |||
| STZ-induced diabetic C57BL/6 mice | Curcumin (5 mg/kg/day) for 3 months | - Protection against diabetes-induced cardiac fibrosis, oxidative stress, and ER | Wang et al., 2014 |
| STZ-induced diabetic rats | Curcumin (20 mg/kg/day) for 45 days | - Prevented diabetes-induced upregulation of HO-1 expression and activity | Aziz et al., 2013 |
| Anti-apoptotic effects | |||
| STZ-induced diabetic Wistar rats | Curcumin (100 or 200 mg/kg/day) for 8 weeks | - Prevented diabetes-induced cardiomyocytes apoptosis | Yu et al., 2012 |
| STZ-induced diabetic C57BL/6 mice | Curcumin (5 mg/kg/day) for 8 weeks | - Prevented high glucose-induced apoptosis in cardiomyocytes and the development of diabetic cardiomyopathy | Pan et al., 2014 |
| - Inhibition of JNK phosphorylation | |||
| STZ-induced diabetic C57BL/6 mice | Curcumin (5 mg/kg/day) for 3 months | - Protection against diabetes-induced cardiac fibrosis, oxidative stress, and ER; | Wang et al., 2014 |
| High glucose-treated neonatal rat cardiomyocytes | Curcumin incubation (10 μM) for 24 h | - Inhibited the increased Bax/Bcl-2 ratio elicited by high glucose exposure | Yu et al., 2016 |
| - Increased AKT and GSK-3β phosphorylation | |||
DCM, diabetic cardiomyopathy; STZ, streptozotocin; SD, Sprague-Dawley; HG, high glucose; AGEs, advanced glycation end products; ICAM-1, intercellular adhesion molecule-1; VCAM-1, vascular cell adhesion molecule-1; IL-1β, interleukin-1β; IL-6, interleukin-6; IL-18, interleukin-18; TNF-α, tumor necrosis factor-α; TGF-β1, transforming growth factor; NF-κB, nuclear factor kappa-B; TβRII, type II transforming growth factor-β; Smad, sma- and mad-related protein; MCP-1, monocyte chemoattractant protein-1; AMPK, adenosine monophosphate activated protein kinase; MAPK, mitogen-activated protein kinase; JNK, Jun NH2-terminal kinase; AKT, protein kinase B; NADPH, nicotinamide adenine dinucleotide phosphate; Rac1, Ras-related C3 botulinum toxin substrate 1; PKC, protein kinase C; HO-1, heme-oxygenase-1; GSK-3β, glycogen synthase kinase 3β; ECM, extracellular matrix; ER, endoplasmic reticulum.