Table 1.
In vitro and in vivo actions of curcumin.
| Curcumin Concentrations | Experimental Models | Outcomes | References |
|---|---|---|---|
| Fertilization and Fetal Development | |||
| 24 μM for 24 h | Mouse blastocyst | Increased ROS, apoptosis and embryo resorption; decreased fetal weight | [51] |
| 24 μM for 24 h | Mouse blastocyst | Increased apoptosis at blastocyst stage or early egg stage and trophoblastic giant cell | [52] |
| 20 μM for 24 h | Mouse blastocyst | Increased apoptosis, p21 and p53; decreased oocyte maturation and fertilization | [53] |
| 1500, 3000 and 10,000 ppm for 70 days | Rat | No gross or microscopic changes in organs: no reproductive parameters changes; small reduction in pre-weaning body weight gain of the F2 pups at 10.000 ppm dose level. | [54] |
| 0.015% of diet | Mouse and Rat | No effects on chromosomes, pregnancy rate, number of live and dead embryos | [55] |
| 31.25–500 µM | Human and mouse spermatozoa | Decreased sperm motility starting from 62.5 µM but decreased capacitation/acrosome reaction at all concentrations tested | [57] |
| 1 nM, 100 nM, 1 mM, 1 M | Human spermatozoa | Increased spermatozoa motility, reduced ROS formation and MDA production at 100 nM; decreased total and progressive motility at 1 mM and 1 M | [56] |
| Protection against Cytotoxic and Teratogenic Agents | |||
| 10 mg/Kg Curcumin ± 60 mg/Kg Retinoic Acid (RA) for 10 days | Mouse | Increased crown rump (CR) length and embryos weight; decreased cell number and sinusoid diameter in the embryonic liver tissue | [44] |
| 250 mg/kg Curcumin (for 1 h) ± 1 mg/kg Aroclor1254 for 28 days | Rat | Decreased 8-(OH)DG, 5-methycytosine and 5-hydroxymethycytosine levels; decreased karyopyknotic nuclei and shrunken or swollen cytoplasm in the migrating neurons | [68] |
| 16 g/Kg Curcumin ± 3 g/L Lead (Pb) for 82 days | Rat | Improved sensory and motor functions in neonatal rats | [73] |
| 75 mg/kg/d Curcumin ± 6 g/kg/d alcohol for 8 days | Mouse | Decreased HAT activity, DHAND; increased H3K14ac, EHAND; inhibited H3K14ac connection with DHAND and EHAND | [75] |
| 25 μM Curcumin ± 200 mM alcohol for 24 h | Cardiac progenitor cells | Decreased H3K9 acetylation and apoptosis reducing cleaved caspase-3 and cleaved caspase-8; increased bcl-2 | [76] |
| 100 mg/kg Curcumin ± 85 ppm Arsenic (As) for 10 days | Mouse | Increased number of EpASCs; decreased chromosomal aberrations; decreased AS accumulation in liver, skin, hair and kidney; decreased Nrf2, NFkB and IkB | [79] |
| 500 nmol/kg Curcumin ± 30 mg/kg Celecoxib for 4 days | Mouse | Increased neurogenesis upregulating GSK-3B and β−Catenin | [84] |
| 150 or 300 ppm Curcumin ± 10 ppm of HgCl2 for 35 days | Mouse | Increased body weight, anticipated hairgrowth and eye opening; increased memory, learning ability, and levels of dopamine, serotonin and acetylcholinesterase in forebrain of pups | [87] |
| 5, 10 and 20 μM (for 1 h) Curcumin ± 200 μM Methylglyoxal (MG) for 3 h | Mouse embryonic stem cells and blastocyst | Decreased DNA fragmentation, caspase-3 activation, cleavage of PARP, JNK activation and apoptosis; decreased ROS production | [46] |
| Viral and Bacterial Infections | |||
| 5 μM for 2 h | HeLa, BHK-21, Vero-E6 cells; CHIKV, VSV, ZIKV viruses | Reduced infectivity of ZIKV and CHIKV viruses by blocking the binding of viruses to cell surface | [88] |
| 0.2, 0.4 and 0.8 µg/mL for 2 days | HELF cells; HCMV virus | Reduced infectivity of HCML by decreasing Hsp90 protein expression | [90] |
| 20 μM for 2 h | HeLa and Vero cells; HSV-1 virus | Reduced HSV-1 infectivity and replication by decreasing ICP4 and ICP27 genes in a p300-independent way | [91] |
| 50 μM for 12 h | HEK-293T, J1.1, TZM-bl cells; HIV-1 virus | Inhibited HIV activity by degrading unfolded Tat protein in a proteasomal dependent way | [92] |
| 0.25 μM for 30 min | Recombinant HIV-1 integrase | Inhibited HIV-1 activity by blocking integrase function | [93] |
| 8 μg/mL for 30 min 200 mg/kg curcumin for 8 h |
Mouse; J774 cells; L. Monocytogenes | Inhibited bacterial growth by interfering with the activity of listeriolysin O; protective effects against infection in mice | [94] |
| 150 mg/kg for 14 days | S. agalactiae; silver catfish | Bactericidal action against S. agalactiae; prevented occurrence of clinical signs | [95] |
| 100 μM for 1 h | HeLa cells; Neisseria gonorrhoeae |
Interfered with bacterial binding to host cells in late infection; inhibited IkBa degradation and NF-kB activation; reduced TNFa, IL-8 and IL-6 secretion | [96] |
| 40 mg/kg for 2 h | Mouse; LPS | Restored neuronal cell morphology in fetal brain; reduced production of IL-6, Il-1B, COX-2, sICAM-1, sE-selectin, CCL-2, MCP-1 and CINC-1 | [97] |
| Gestational Diabetes | |||
| 100 mg/kg for 10 days | Mouse | Increased glucose tolerance by decreasing TBARS and increasing GSH, SOD and CAT; Enhanced AMPK activation and decreased HDAC4 and G6Pase expression | [105] |
| 20 μM for 24 h | Mouse embryos | Reduced neuronal tube defects and levels of 4-HNE and LPO; blocked ER stress by inhibiting pPERK, pIRE1α, peIF2α, CHOP, BiP and XBP1; reduced cleaved caspase3 and 8 | [106] |
| 10 μM for 1 h | RPEC cells | Reduced glucose‑induced toxicity and TNF‑α, IL‑6 and IL‑1β levels inhibiting AKT and mTOR activation | [45] |
| 7.5 mg/kg/day for 7 days | Endothelial progenitor cells (EPCs) from mouse | Restored tubule formation, and migration of EPCs; improved wound healing; reduced levels and activity of MnSOD. | [112] |
| Preeclampsia (PE) | |||
| 5 µM for 24 h | HTR8/SVneo cell line | Reduced apoptosis by increasing Bcl-2/Bax ratio and decreasing cleaved-caspase 3. Reduced oxidative stress by enhancing CAT and GSH-Px activity, and activating Nrf2. Increased HO-1, NQO1 expression. | [139] |
| 5 µM for 24 h | HTR8/SVneo, JEG3 and HMEC-1 cell lines | Increased cell growth, migration, proliferation and viability by activating AKT; increased tube formation, VEGFR2 HLA-G and FABP4 expression; increased DNMT3A and HSD11B2 expression | [47] |
| 100 µg/kg/d for 17 days | LPS-treated Mouse | Decreased systolic blood pressure, proteinuria, IL-6, IL-1B, TNFa, MCP-1 and MIP-1; increased live pups, fetal and placental weight; Decreased macrophages in placenta. | [134] |
| 360 µg/kg for 14 days | LPS-treated Rat | Decreased systolic blood pressure and proteinuria; improved trophoblast invasion and spiral artery remodeling; decreased TLR4, NF-κB, IL-6 and MCP-1 expressions | [135] |
| Fetal Growth Restriction (FGR) | |||
| 400 mg/kg/d for 18 days | Mouse | Decreased placental apoptosis; increased blood sinusoids area, CAT and GSH-Px in placenta; increased Nef2, HO-1, SOD2, CAT, NQO1 and GSH-Px in fetal liver | [139] |
| 400 mg/kg for 24 days | Pig | Decreased TNF-α, IL-1β and IL-6 serum levels; increased body weight; reduced insulin, glucose, and HOMA-IR levels by downregulating Irs1, Pik3c3, and Gsk3a | [30] |
| 200 mg/kg for 90 days | Pig | Increased Nrf2, SOD1, GCLC, GCLM, NQO1; decreased levels of TNFα, IL-6, IFNγ and caspase3, bax, bcl2, hsp70 mRNA expression. | [141] |
| 400 mg/kg for 24 days | Pig | Increased body-weight gain and Nrf2 and Hmox1 proteins in the liver of FGR piglets | [142] |
| 400 mg/kg for 6 weeks | Rat | Decreased TNF-α, IL-1β, IL-6, AST and ALT in the serum; decreased pNF-κB, pJAK2 and increased mRNA expression of genes of the Nfe2l2/ARE pathway in the liver. | [143] |
| 400 mg/kg for 6 weeks | Rat | Decreased insulin, glucose, HOMA-IR, pyruvate, TAG, total cholesterol and NEFA in the liver; decreased pIRS1, pAKT, pGSK-3, FASN and SREBP-1 in liver. | [144] |
| Preterm Birth | |||
| 100 mg/kg for 24 h | Mouse | Decreased NF-kBp65, TNFa and IL-8 in placental tissue; decreased serum levels of IL-8, SOD and MDA; increased live birth rate. | [147] |
| 30 and 60 µM for 24 h | Placental explants, Primary amnion cells and Myometrial cells | Decreased IL-6, IL-8, MMP-9, COX-2, PGE2 and PGF2a; decreased 8-Isoprostane and NF-kB/DNA binding. | [148] |
| 5, 10, 20, 30 and 40 µM for 1, 2 and 24 h | HuF and UIII cells | Decreased IL-6, gp130, pSTAT3, p50 and p65 expression | [150] |