Table 1.
Effects of curcumin on pregnancy and pregnancy-related disorders.
| Curcumin | Experimental Model | Outcomes | References |
|---|---|---|---|
| Altered glucose metabolism | |||
| 100 mg/kg/day (from 0 to 20 GD) | Mouse model of GDM | ↓Maternal glucose and insulin levels; improved oxidative stress (↑ GSH, SOD, CAT), and ↑AMPK and ↓HDAC4, in the liver; restored offspring litter size and body weight | Lu, X., 2019 [14] |
| 20 μM for 24 h | Mouse embryos (E8.5 of development) cultured for 24 h with 100 mg/dL glucose | ↓Neural tube defects by reducing oxidative stress (↓4-HNE, ↓LPO, ER stress (↓p-PERK, p-IRE1α, p-eIF2α, CHOP, BiP and XBP1 expression), and apoptosis (↓caspase-3 and -8 cleavage) | Wu, Y., 2015 [49] |
| Cardiovascular disorders | |||
| 0.36 mg/kg/day (from 0 to GD18) | Rat model of PE (LPS-induced) | Improved hypertension, proteinuria, and renal damage; ↓serum levels of IL-6 and MCP-1; ↓ placental TLR4, IL-6, and NFkB expression; improved trophoblast invasion and spiral artery remodeling | Gong, P., 2016 [50] |
| 0.36 mg/kg/day (from 0.5 to GD18) | Mouse model of PE (LPS-induced) | ↑Number of live pups, and fetal and placental weight; ↓inflammation (↓TNF-α, IL-1β, IL-6, MCP-1, and MIP-1 placental expression), ↑ Akt activation | Zhou, J., 2017 [51] |
| 5–10 µM for 24 h | HTR8/SVneotrophoblast cells (model for human first-trimester placenta) | ↑Proliferation associated with Akt activation, ↑tube formation; ↑proangiogenic factors VEGF, VEGFR2, and FABP4 expression; ↑ expression of NOTCH-signaling pathway mediators; ↑promoter hypomethylation of oxidative and metabolic stress genes | Basak, H., 2020 [15] |
| 5 µM for 24 h | HTR8/SVneo trophoblast cells (H2O2-treated) | ↑Cells viability; ↓oxidative stress (↑CAT, GSH-Px activities); ↑Nrf2 activation and ↓ caspase-3 activation | Qi, L., 2020 [52] |
| 60 µM for 24 h | Human placental and fetal membranes, LPS-treated | ↓IL-6, IL-8, and COX-2 mRNA expression; ↓PGE2 and PGF2a release; ↓MMP-9 expression and NFkB activation | Lim, R., 2013 [53] |
| 100 mg (single dose) | 47 pregnant women with PE | No differences in serum level of COX-2 and IL-10 | Fadinie, W., 2019 [54] |
| Fetal growth and development | |||
| 100 mg/kg/day (from 1.5 to 19.5 GD) | Mouse model of FGR (low-protein diet) | ↓Placental apoptosis and ↑ placental blood sinusoids area; ↑GSH-Px activity, Nfr2 mRNA expression; ↑antioxidant genes expression (SOD1, SOD2, CAT, Nrf2, and HO-1), in fetal liver | Qi, L., 2020 [16] |
| 400 mg/kg/day at 6 weeks of age for 6 weeks | FGR newborn rats | ↓TNF-α, IL-1β and IL-6 levels, ↓activity of AST, ALT, and MDA, ↑Gpx and GSH activity, in serum;↓NF-kB and JAK2 expression, ↑antioxidant genes (Nqo1, Hmox1, Gst, Gpx1 and Sod1), an Nfr2 activation, in the liver | He, J., 2018 [55] |
| 400 mg/kg/day at 6 weeks of age for 6 weeks | FGR newborn rats | ↓Glucose levels and IR; ↓TAG, NEFA, total cholesterol, ↑glycogen (↓IRS-1 and Akt phosphorylation, CD36, SREBP-1, and FASN expression, ↑PPARα), in the liver | Niu, Y., 2019 [56] |
| 100 mg/kg (single dose) | Mouse model of PTB, LPS-induced | ↓TNF-α, IL-8, MDA, and ↑SOD serum levels; ↓NFkB activation in placenta | Guo, Y.Z., 2017 [57] |
| Toxicant agents | |||
| 200 mg/kg/day (from 7 to PND28) | Pregnant rats, BPA-treated | Neuroprotective; ↑proliferation and differentiation of neuronal stem cells (↑neurogenin and neuroD1 expression); ↓apoptosis (↓Bax, ↑Bcl-2 expression); improvement in learning and memory | Tiwari, S.K., 2019 [58] |
| 150/300 ppm/day (from GD1 to 15PND) | Pregnant mice, HgCl2-treated | ↑Neurodevelopment and ↓anxiety (↑levels of DA, 5-HT, AChE, and GSH) | Abu-Taweel, G.M., 2019 [59] |
| 150/300 ppm/day (from GD1 to 15PND) | Pregnant mice, HgCl2-treated | ↑Pups body weight; ↑male genitalia weight, testosterone, and FSH levels; ↑ovary weight and progesterone, FSH and LH levels; improved sexual behavior in both sexes | Abu-Taweel, G.M., 2020 [60] |
| 16 g/kg/day during pregnancy and lactation | Pregnant rats, Pb-treated | Prevented central nervous system dysfunction allowing normal locomotor behavior | Benammi, H., 2017 [61] |
| Pretreatment with curcumin 500 nmol/kg/day (from ED 13.5 to E16.5) | Pregnant mice, celecoxib-treated | ↑Neurogenesis in fetal frontal cortex (↑Cyclin D1 expression, and activation of Wnt/βcatenin signaling in neural progenitor cells) | Wang, R., 2017 [62] |
| Single-dose curcumin (1 g/kg) in neonatal rats | Pregnant rats, VPA-treated | ↑Body and brain weight in pups; ↓IL-6, IFN-γ, and ↑GSH, CYP450 expression, in brain pups | Al-Askar, M., 2017 [63] |
| Offsprings 100 mg/kg/day (from 28 to 35 PND | PLAE-pregnant mice (offspring peri-adolescence period) | Improved offspring anxiety and memory deficits; ↓Neuroinflammation (↓IL-6, TNF-α, and NF-kB expression) | Cantacorps, L., 2020 [64] |
| Embryos 25 µM for 24 h | PAE-pregnant mice (embryos E17.5) | Improved offspring anxiety and memory deficits; ↓neuroinflammation (↓IL-6, TNF-α, and NF-kB expression) | Yan, X., 2017 [65] |
| Adverse effects on embryos | |||
| 24 μM for 24 h | Mouse blastocysts | ↑Apoptosis (↑Bax and ↓Bcl-2 expression); ↓ implantation rate and development | Chen, C.C., 2010 [66] |
| 24 μM for 24 h | Mouse oocytes | ↑Apoptosis; ↓ oocytes fertilization; ↓implantation rate and development | Chen, C.C., 2012 [67] |
| 6–24 μM for 24 h | Mouse blastocysts (at implantation stage and during the early post-implantation stage) | Dose-dependent damage, 24 μM lethal for all blastocysts | Huang, F.J., 2013 [68] |
| Curcuma longa extract (7.80–125 µg/mL) for 5 days | Zebrafish embryos and larvae at different hours of post-fertilization (24–120 h) | Dose-dependent toxic effects: malformations above 62.50 µg /mL, and mortality at 125.0 µg/mL | Alafiatayo, A.A., 2019 [19] |
Abbreviations: ↑ Increases; ↓ Decreases; GDM, gestational diabetes mellitus; GD, gestational day; GSH, glutathione; SOD, superoxide dismutase; CAT, catalase; AMPK, 5′ AMP-activated protein chinasi; HDAC4, histone deacetylase 4; 4-HNE, 4-hydroxynonenal; LPO, lipid peroxidation; ER, endoplasmic reticulum; p-PERK, phospho-protein kinase-like endoplasmic reticulum kinase; p-IRE1α, phospho-inositol-requiring kinase 1α; p-eIF2α, phospho-eukaryotic Initiation Factor 2α; CHOP, C/EBP homologous protein; BiP, binding immunoglobulin protein; XBP1, X-box-binding protein-1; PE, preeclampsia; LPS, lipopolysaccharides; IL6, interleukin-6; MCP-1, monocyte chemoattractant protein-1; TLR4, toll-like Receptor 4; NFkB, nuclear transcriptor factor kappa B; TNFα, tumor necrosis factor α; IL1β, interleukin-1β; MIP-1, macrophage inflammatory protein-1; Akt, protein kinase B; VEGF, vascular endothelial growth; VEGFR2, vascular endothelial growth factor receptor 2; FABP4, fatty acid binding protein 4; GSH-Px, glutathione peroxidase; Nrf2, nuclear factor erythroid-2-related factor-2; IL-8, interleukin-8; COX-2, cyclooxigenase-2; PGE2, prostaglandin E2; PGF2a, prostaglandin F2α; MMP-9, metalloproteinase-9; IL-10, interleukin-10; FGR, fetal growth restriction; HO-1, heme oxygenase-1(enzyme); AST, aspartate aminotransferase; ALT, aminotransferase; MDA, malondialdehyde; JAK2, Janus kinase 2; Nqo1, quinone dehydrogenase; Hmox1, heme oxygenase 1 (gene); Gst, glutathione S-transferase; Gpx1, glutathione peroxidase; IR, insulin resistance; TAG, triglycerides; NEFA, Non-Esterified Fatty Acids; IRS-1, insulin receptor substrate-1; PTB, preterm birth; CD36, cluster of differentiation 36; SREBP-1, stearoyl CoA desaturase-1; FASN, Fatty acid synthase; PPARα, Peroxisome Proliferator Activated Receptors-α; PND, postnatal day; BPA, bisphenol-A; DA, dopamine; 5-HT, serotonin; AChE, acetylcholinesterase; FSH, follicle stimulating hormone; LH, luteinizing hormone; ED, embrionic day; Pb, plumbum (lead); VPA, valproic acid; IFN-γ, interferon γ; CYP450, cytochromes P450; PLAE, prenatal and lactational alcohol exposure; PAE, prenatal alcohol exposure; PND, postnatal day; B-cell lymphoma protein 2 (Bcl-2)-associated X (Bax); B-cell lymphoma protein 2 (Bcl-2).