Dietary Sources and Bioactivities of Melatonin
Abstract
:1. Introduction
2. Dietary Sources of Melatonin
2.1. Animal Foods
2.2. Plant Foods
2.2.1. Cereals
2.2.2. Fruits
2.2.3. Vegetables
2.2.4. Legumes and Seeds (Raw and Germinated)
2.2.5. Nuts
2.2.6. Juices and Beverages
2.2.7. Medical Herbs
2.2.8. Edible Oils
2.2.9. Yeast
2.3. Other Issues about Melatonin Intake
2.3.1. The Alternation of Endogenous Melatonin along Life Cycle
2.3.2. Bioavailability of Exogenous Melatonin
2.3.3. Benefits of Consuming Melatonin-Containing Foods
2.3.4. Guidance on Regulating Dietary Supplement of Melatonin
3. Bioactivities of Melatonin
3.1. Antioxidant Activities
3.2. Anti-Inflammatory Activities
3.2.1. NF-κB Signaling Pathway Involved Mechanisms
3.2.2. SIRT1 Pathway Involved Mechanisms
3.3. Enhancing Immune Activities
3.4. Improving Circadian Rhythm and Sleep
3.5. Anticancer Activities
3.5.1. Effects on Tumor Cell Cycle, in Terms of Growth, Proliferation, Metabolism and Apoptosis
3.5.2. Effects on Invasion and Metastasis of Tumor Cells
3.5.3. Therapy Adjunct in Tumor Treatment
3.6. Cardiovascular Protection
3.7. Anti-Diabetic Activities
3.8. Anti-Obese Activities
3.9. Neuroprotective Activities
3.10. Other Bioactivities
3.11. Adverse Effects
4. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
Abbreviations
2-OHM | 2-hydroxymelatonin |
4-OHM | 4-hydroxymelatonin |
6-OHM | 6-hydroxymelatonin |
AAAD | aromatic L-amino acid decarboxylase |
Aβ | amyloid-beta |
ACC | acetyl-CoA carboxylase |
AD | Alzheimer’s disease |
AD-MSCs | adipose-derived mesenchymal stem cells |
AFMK | N1-acetyl-N2-formyl-5-methoxykynuramine |
AMK | N1-acetyl-5-methoxykynuramine |
AMPK | adenosine monophosphate-activated protein kinase |
AP-2β | activator protein 2β |
ARE | antioxidant responsive element |
ATF4 | activating transcription factor 4 |
BACE1 | β-APP-cleaving enzyme 1 |
Bax | Bcl-2-associated X protein |
BBB | blood-brain barrier |
Bcl-2 | B-cell lymphoma 2 |
BDNF | brain derived neurotrophic factor |
bFGF | basic fibroblast growth factor |
BMMNCs | bone marrow mononuclear cells |
BM-MSCs | bone marrow mesenchymal stem cells |
C3-OHM | cyclic 3-hydroxymelatonin |
CaMKIIα | calmodulin dependent protein kinase II alpha |
cAMP | cyclic AMP |
CAT | catalase |
CCL20 | chemokine C-C motif ligand 20 |
cGMP | cyclic GMP |
CNS | central nerve system |
COX-2 | cyclo-oxygenase 2 |
CVDs | cardiovascular diseases |
CXCL1 | chemokine C-X-C motif ligand 1 |
cyt c | cytochrome c |
DAG | diacylglycerol |
DS | diclofenac sodium |
DW | dry weight |
EBPβ | enhancer-binding protein beta |
eIF2α | eukaryotic initiation factor 2α |
EMF | electromagnetic fields |
EMT | epithelial mesenchymal transition |
eNOS | endothelial nitric oxide synthase |
ER | endoplasmic reticulum |
ERK | extracellular signal-regulated kinase |
ERR-α | estrogen-related receptor alpha |
FRAP | ferric reducing antioxidant power |
FSS | flow shear stress |
FW | fresh weight |
G6PD | glucose-6-phosphate dehydrogenase |
GAS | gamma-activated sequence |
γ-GCS | gamma-glutamylcysteine synthetase |
G-CSF | granulocyte colony-stimulating factor |
GFAP | glia and fibrillary acidic protein |
GM-CSF | granulocyte–macrophage colony-stimulating factor |
GPx | glutathione peroxidase |
GSH-Rd | glutathione reductase |
GSK3β | glycogen synthase kinase 3β |
H2-Ab1 | histocompatibility class II antigen A, beta 1 |
HDAC | histone deacetylase |
Hes1 | hairy and enhancer of split 1 |
HIOMT | hydroxyindole O-methyltransferase |
HOMA-IR index | homeostasis model assessment of insulin resistance index |
hTERT | human telomerase reserve transcriptase |
i.v. | intravenously |
i.p. | intraperitoneally |
IFN-γ | interferon gamma |
IGF-1 | insulin-like growth factor 1 |
IKK | inhibitor of nuclear factor kappa-B kinase |
IL-6 | interleukin 6 |
iNOS | inducible nitric oxide synthase |
IRI | ischemia/reperfusion injury |
JAK2 | Janus kinase 2 |
JNK | Jun N-terminal kinase |
LAN | light at night |
LPS | lipopolysaccharide |
MAPK | mitogen-activated protein kinase |
MDH | malondialdehyde |
MI | myocardial infarction |
MLHb | medial lateral habenula |
MMP-9 | matrix metalloproteinase-9 |
Mst1 | mammalian Ste20-like kinase 1 |
MT1, MT2 | melatonin receptors |
NAD | Nicotinamide adenine dinucleotide |
NAT | N-acetyltransferase |
NDRG2 | N-myc downstream-regulated gene 2 |
NF-κB | nuclear factor kappa-light-chain-enhancer of activated B cells |
NK | natural killer |
NLRP3 | NOD-like receptor P3 |
NO | nitric oxide |
NOMela | N-nitrosomelatonin |
Nrf2 | nuclear factor-erythroid 2-related factor 2 |
OA | osteoarthritis |
ON | optic neuritis |
ORAC | oxygen radical antioxidant capacity |
Oxa | oxaliplatin |
p-Akt | phosphorylated protein kinase B |
PARP | poly-ADP-ribose polymerase |
pCREB | phosphorylated cAMP response element-binding protein |
PD | Parkinson’s disease |
PDGF | platelet-derived growth factor |
PGC-1α | peroxisome proliferator-activated receptor gamma coactivator-1 alpha |
PI3K | phosphatidyl inositol 3-kinase |
PKB | protein kinase B |
PLR | pupil light reflex |
PPAR-γ | peroxisome proliferator-activated receptor gamma |
PRDX1 | peroxiredoxin 1 |
PS1 | presenilin 1 |
PUMA | p53 upregulated modulator of apoptosis |
RNS | reactive nitrogen species |
ROCK-1 | Rho-associated kinase protein |
ROS | reactive oxygen species |
S100B | S100 calcium-binding protein B |
SAH | subarachnoid hemorrhage |
SCN | suprachiasmatic nucleus |
SE | standard error |
SEEMs | selective estrogen enzyme modulators |
SIRT1 | sirtuin 1 |
SOD | superoxide dismutase |
STAT | signal transducer and activator of transcription |
TBI | traumatic brain injury |
TGF-β | transforming growth factor β |
TIMP-1 | tissue inhibitor of metalloproteinases 1 |
TNF-α | tumor necrosis factor α |
TPH | tryptophan hydroxylase |
UCP1 | uncoupling protein 1 |
UPS | ubiquitin/proteasome system |
VEGF | vascular endothelial growth factor |
VEP | visual evoked potentials |
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Name | Scientific Name/Variety/Origin | MT Value or Range ng/g or pg/mL | No. of Samples | Quantified by | Reference |
---|---|---|---|---|---|
Animal Foods | |||||
Meat | |||||
Lamb | Not specified | 1.6 ± 0.14 ng/g | 5 | HPLC | [22] |
Beef | Not specified | 2.1 ± 0.13 ng/g | 5 | HPLC | [22] |
Pork | Not specified | 2.5 ± 0.18 ng/g | 5 | HPLC | [22] |
Fish | |||||
Salmon | Not specified | 3.7 ± 0.21 ng/g | 5 | HPLC | [22] |
Chicken | |||||
Meat and skin | Not specified | 2.3 ± 0.23 ng/g | 5 | HPLC | [22] |
Liver and heart | Not specified | 1.1 ± 0.01 ng/g | 5 | HPLC | [22] |
Egg | |||||
Dried solids | Not specified | 6.1 ± 0.95 ng/g | 5 | HPLC | [22] |
Raw, whole | Not specified | 1.54 ng/g | 5 | HPLC | [22] |
Milk and dairy products | |||||
Human milk | |||||
Indian human milk | Not specified | 15.92 ± 1.02 pg/mL | 6 | LC-MS/MS | [37] |
Breast milk | Not specified | 0–42 pg/mL | 5 | ELISA | [41] |
Bovine milk | |||||
Fresh colostrum, | Not specified | 0.06 ng/g | 5 | HPLC | [22] |
Cow milk | Not specified | 14.45 ± 0.12 pg/mL | 6 | LC-MS/MS | [37] |
Cow Milk | Holstein cows | 4.03–39.43 pg/mL | 3 | EIA | [38] |
Colostrum powder | Not specified | 0.6 ± 0.06 ng/g | 5 | HPLC | [22] |
Toned milk | Not specified | 18.41 ± 0.62 pg/mL | 6 | LC-MS/MS | [37] |
Yoghurt | Not specified | 0.13 ± 0.01 ng/mL | 5 | LC-MS/MS | [42] |
Artificial formulas | Not specified | nd | 15 | ELISA | [41] |
Fermented milk drink | Kefir | nd | 5 | LC-MS/MS | [42] |
Plant foods | |||||
Cereals | |||||
Corn | |||||
Corn (whole, yellow) | Not specified | 1.3 ± 0.28 ng/g | 5 | HPLC | [22] |
Corn (germ meal) | Not specified | 1.0 ± 0.10 ng/g | 5 | HPLC | [22] |
Corn (YM001-) | 58 cultivars | 10–2034 ng/g DW | N/A | HPLC | [31] |
Corn | Not specified | 1.88 ng/g FW | N/A | GC/MS | [47] |
Sweet corn | Not specified | 1.37 ng/g FW | N/A | HPLC-FD | [83] |
Rice | |||||
Rice | Oryza sativum L. ssp. japonica | 1.50 ng/g FW | N/A | GC/MS | [47] |
Rice (SD001-) | 25 cultivars | 0–264 ng/g DW | N/A | HPLC | [31] |
Black glutinous | Long grain, waxy, Thailand (Bran) | 73.81 ± 0.07 ng/g DW | 9 | PLE HPLC-FD | [17] |
Black | Not specified | 182.04 ± 1.62 ng/g DW | 9 | PLE HPLC-FD | [17] |
Red | Not specified | 212.01 ± 1.37 ng/g DW | 9 | PLE HPLC-FD | [17] |
Whole short grain | Not specified | 47.83 ± 0.12 ng/g DW | 9 | PLE HPLC-FD | [17] |
Whole semi-long grain | Not specified | 42.95 ± 0.64 ng/g DW | 9 | PLE HPLC-FD | [17] |
Polished short grain | Not specified | 31.99 ±0.31 ng/g DW | 9 | PLE HPLC-FD | [17] |
Polished long grain | Not specified | 27.61 ± 1.16 ng/g DW | 9 | PLE HPLC-FD | [17] |
Basmati | Not specified | 38.46 ± 0.07 ng/g DW | 9 | PLE HPLC-FD | [17] |
Parboiled rice | Not specified | 28.33 ± 0.61 ng/g DW | 9 | PLE HPLC-FD | [17] |
Rice | Oryza sativa cv. Dongjin | 0.04 ng/g DW | 20 | HPLC | [84] |
Rice (transgenic) | Oryza sativa cv. Dongjin | 0.07–1.25 ng/g DW | 20 | HPLC | [84] |
Rice | Oryza sativum L. ssp. japonica | 1.01 ng/g FW | N/A | HPLC-FD | [83] |
Wheat | |||||
Wheat | Triticum aestivum L. | 124.7 ± 14.9 ng/g FW | N/A | HPLC-ECD | [85] |
Whole grain | Not specified | 2–4 ng/g | N/A | Not specified | [86] |
Purple wheat | Not specified | 4 ng/g DW | 3 | HPLC-UV | [87] |
Purple (heat stressed) | Not specified | 2 ng/g DW | 3 | HPLC-UV | [87] |
Barley | |||||
Barley | Hordeum vulgare L. | 0.87 ng/g FW | N/A | GC/MS | [47] |
Barley | Hordeum vulgare L. | 82.3 ± 6.0 ng/g FW | N/A | HPLC-ECD | [85] |
Barley | Hordeum vulgare L. | 0.38 ng/g FW | N/A | HPLC-FD | [83] |
Oats | |||||
Oats | Avena sativa L. | 90.6 ± 7.7 ng/g FW | N/A | HPLC-ECD | [85] |
Oat | Avena sativa L. | 1.80 ng/g FW | N/A | HPLC-FD | [83] |
Bread | |||||
Crumb | Specific ingredients | 0.19–0.63 ng/g DW | 3 | LC-ESI-MS/MS | [20] |
Crumb | Not specified | 0.34 ± 0.03 ng/g DW | 5 | LC-MS/MS | [42] |
Crust | Specific ingredients | 0.14–0.82 ng/g DW | 3 | LC-ESI-MS/MS | [20] |
Crust | Not specified | 0.14 ± 0.02 ng/g DW | 5 | LC-MS/MS | [42] |
Fruits | |||||
Pineapple | |||||
Pineapple | Ananas comosus L. | 0.28 ng/g FW | N/A | GC/MS | [47] |
Pineapple | Ananas comosus L. | 0.04 ng/g FW | N/A | HPLC-FD | [83] |
Kiwi fruit | Actinidia chinensis L. | 0.02 ng/g FW | N/A | HPLC-FD | [83] |
Strawberry | |||||
Strawberry | Fragaria magna L. | 0.14 ng/g FW | N/A | GC/MS | [47] |
Strawberry | Fragaria ananassa L. cv. Camarosa | 5.58 ± 0.01 ng/g FW | 3 | LC-MS/LC-FD | [44] |
Strawberry | Fragaria ananassa L. cv. Candonga | 5.5 ± 0.6 ng/g FW | 3 | LC-MS/LC-FD | [44] |
Strawberry | Fragaria ananassa L. cv. Festival | 11.26 ± 0.13 ng/g FW | 3 | LC-MS/LC-FD | [44] |
Strawberry | Fragaria ananassa L. cv. Primoris | 8.5 ± 0.6 ng/g FW | 3 | LC-MS/LC-FD | [44] |
Strawberry | Fragaria magna L. | 0.01 ng/g FW | N/A | HPLC-FD | [83] |
Banana | Musa ensete | 0.66 ng/g FW | N/A | GC/MS | [47] |
Apple | |||||
Apple | Malus domestica | nd | N/A | HPLC-FD | [83] |
Apple | Malus domestica Borkh. cv. Red Fuji | 5 ng/g FW | 3 | HPLC | [88] |
Apple | Malus domestica | 0.16 ng/g FW | N/A | GC/MS | [47] |
Pomegranata | Punica granatum | 0.17 ng/g FW | N/A | GC/MS | [47] |
Mulberry | |||||
Mulberry | Hongguo2 Morusnigra, black | 1.41 ng/g FW | 3 | HPLC-ESI-MS/MS | [36] |
Mulberry | Baiyuwang Morus alba, white | 0.58 ng/g FW | 3 | HPLC-ESI-MS/MS | [36] |
Cherry | |||||
Tart cherries (frozen) | Prunus cerasus L. cv. Balaton | 2.9 ± 0.6 ng/g DW | 3 | HPLC-EMS | [60] |
Tart cherries (dry) | Prunus cerasus L. cv. Balaton | nd | 3 | HPLC-EMS | [60] |
Tart cherries | Prunus cerasus L. cv. Balaton | 13.46 ± 1.10 ng/g FW | 3 | HPLC-ECD | [46] |
Tart cherries (frozen) | Prunus cerasus L. cv. Montmorency | 12.3 ± 2 ng/g DW | 3 | HPLC-EMS | [60] |
Tart cherries (dry) | Prunus cerasus L. cv. Montmorency | nd | 3 | HPLC-EMS | [60] |
Tart cherries | Prunus cerasus L. cv. Montmorency | 2.06 ± 0.17 ng/g FW | 3 | HPLC-ECD | [46] |
Cherry | Prunus avium L. cv. Hongdeng | 10–20 ng/g FW | 3 | SPE HPLC | [89] |
Cherry | Prunus avium L. cv. Rainier | 10–20 ng/g FW | 3 | SPE HPLC | [89] |
Cherry | Prunus avium L. cv. Burlat | 0.22 ng/g FW | 3 | HPLC-MS | [30] |
Cherry | Prunus avium L. cv. Navalinda | 0.03 ng/g FW | 3 | HPLC-MS | [30] |
Cherry | Prunus avium L. cv. Van | 0.01 ng/g FW | 3 | HPLC-MS | [30] |
Cherry | Prunus avium L. cv. Pico Limón Negro | 0.01 ng/g FW | 3 | HPLC-MS | [30] |
Cherry | Prunus avium L. cv. Sweetheart | 0.06 ng/g FW | 3 | HPLC-MS | [30] |
Cherry | Prunus avium L. cv. Pico Negro | 0.12 ng/g FW | 3 | HPLC-MS | [30] |
Cherry | Prunus avium L. cv. Ambrunés | nd | 3 | HPLC-MS | [30] |
Cherry | Prunus avium L. cv. Pico Colorado | 0.05 ng/g FW | 3 | HPLC-MS | [30] |
Grape | |||||
Grape | Albana, white | 1.2 ng/g | 3 | HPLC-FD | [43] |
Grape (skin) | Vitis vinifera L. cv. Merlot | 9.3 ± 0.14 ng/g grapes | 3 | UPLC-MS/MS | [90] |
Grape (fresh) | Vitis vinifera L. cv. Merlot | 3.9 ± 0.06 ng/g grapes | 3 | UPLC-MS/MS | [90] |
Grape (skin) | Vitis vinifera L. cv Malbec | 8.9–158.9 ng/g DW | 3 | HPLC-ESI-MS/MS | [45] |
Grape (skin) | Vitis vinifera L. cv. Nebbiolo | 0.97 ng/g | 3 | HPLC-ELISA | [35] |
Grape (skin) | Vitis vinifera L. cv. Croatina, | 0.87 ng/g | 3 | HPLC-ELISA | [35] |
Grape (skin) | Vitis vinifera L. cv. Barbera | 0.63 ng/g | 3 | HPLC-ELISA | [35] |
Grape (skin) | Vitis vinifera L. cv. Cabernet Sauvignon | 0.42 ng/g | 3 | HPLC-ELISA | [35] |
Grape (skin) | Vitis vinifera L. cv. Cabernet Franc | 0.01 ng/g | 3 | HPLC-ELISA | [35] |
Grape (skin) | Vitis vinifera L. cv. Marzemino, | 0.03 ng/g | 3 | HPLC-ELISA | [35] |
Grape (skin) | Vitis vinifera L. cv. Sangiovese | 0.33 ng/g | 3 | HPLC-ELISA | [35] |
Grape (skin) | Vitis vinifera L. cv. Merlot, | 0.26 ng/g | 3 | HPLC-ELISA | [35] |
Grape (skin) | Vitis vinifera L. cv. Malbec, | 1.2 ng/g | 5 | CEC | [56] |
Grape (skin) | Vitis vinifera L. cv. Cabernet Sauvignon | 0.8 ng/g | 5 | CEC | [56] |
Grape (skin) | Chardonnay | 0.6 ng/g | 5 | CEC | [56] |
Cranberry | |||||
Cranberry | Vaccinium oxycoccos L. | 40 ± 10 ug/g DW ** | 5 | UPLC-MS | [91] |
Cranberry | Vaccinium vitis-idaea L. | 25 ± 3 ug/g DW ** | 5 | UPLC-MS | [91] |
Cranberry | Vaccinium macrocarpon Ait. | 96 ± 26 ug/g DW ** | 5 | UPLC-MS | [91] |
Vegetables | |||||
Onion | Allium cepa L. | 0.30 ng/g FW | N/A | GC/MS | [47] |
Onion | Allium fistulosum L., Welsh | 0.09 ng/g FW | N/A | HPLC-FD | [83] |
Onion | Allium cepa L. | 0.03 ng/g FW | N/A | HPLC-FD | [83] |
Garlic | Allium sativum L. | 0.59 ng/g FW | N/A | GC/MS | [47] |
Cabbage | Brassica oleraceae L. var. capitata | 0.31 ng/g FW | N/A | GC/MS | [47] |
Cauliflower | Brassica oleraceae L. var. botrytis | 0.82 ng/g FW | N/A | GC/MS | [47] |
Turnip | Brassica rapa L. | 0.50 ng/g FW | N/A | GC/MS | [47] |
Cucumber | Cucumis sativus L. | 0.59 ng/g FW | N/A | GC/MS | [47] |
Cucumber | Cucumis sativus L. | 0.03 ng/g FW | N/A | HPLC-FD | [83] |
Cucumber | Not specified | 0.01 ng/g | 1 | GC/MS | [48] |
Carrot | Daucus carota L. | 0.49 ng/g FW | N/A | GC/MS | [47] |
Carrot | Paucus carota L. | 0.06 ng/g FW | N/A | HPLC-FD | [83] |
Radish | Raphnus sativus L. | 0.76 ng/g FW | N/A | GC/MS | [47] |
Japanese radish | Bassica campestris L. | 0.66 ng/g FW | N/A | HPLC-FD | [83] |
Potato | Solanum tuberosum L. | nd | N/A | GC/MS | [47] |
Potato | Not specified | nd | 1 | GC/MS | [48] |
Ginger | Zingiber officinale Rosc. | 1.42 ng/g FW | N/A | GC/MS | [47] |
Black olive | Not specified | 0.01 ng/g DW | 5 | LC-MS/MS | [42] |
Beetroot | Beta vulgaris | 0.002 ng/g | 1 | GC/MS | [48] |
Purslane | Portulaca oleracea L. | 19 ng/g WW | N/A | GC/MS | [92] |
Spinach | Not specified | 0.04 ng/g WW | N/A | GC/MS | [92] |
Indian spinach | Basella alba L. | 0.04 ng/g FW | N/A | HPLC-FD | [83] |
Asparagus | Asparagus officinalis L. | 0.01 ng/g FW | N/A | HPLC-FD | [83] |
Pepper | Capsicum annuum L. cv. Barranca | 4.48 ng/g FW/31.01 ng/g DW | 4 | UHPLC-MS/MS | [49] |
Pepper | Capsicum annuum L. cv. F26 | 11.9 ng/g FW/93.4 ng/g DW | 4 | UHPLC-MS/MS | [49] |
Tomato | Solanum lycopersicum L. cv. Ciliegia | 0.64 ng/g FW/7.47 ng/g DW | 4 | UHPLC-MS/MS | [49] |
Tomato | Solanum lycopersicum L. cv. Optima | 14.77 ng/g FW/249.98 ng/g DW | 4 | UHPLC-MS/MS | [49] |
Tomato | Solanum lycopersicum L. cv. Micro-Tom | 1.5–66.6 ng/g FW | N/A | EIA | [93] |
Tomato | Lycopersicon pimpinellifolium | 0.11 ng/g | 1 | GC/MS | [48] |
Tomato | Lycopersicon esculentum Mill. cv. Sweet 100 | 0.51 ng/g | 1 | GC/MS | [48] |
Tomato | Lycopersicon esculentum Mill. cv. Rutgers California Supreme | 0.17 ng/g | 1 | GC/MS | [48] |
Tomatoes | Lycopersicon pimpinellifolium | 0.30 ng/g FW | N/A | GC/MS | [47] |
Tomatoes | Lycopersicon esculentum cv. Bonda | 23.87 ± 2.02 ng/g FW | 3 | LC-MS/LC-FD | [44] |
Tomatoes | Lycopersicon esculentum cv. Borsalinaa | 8.2 ± 0.6 ng/g FW | 3 | LC-MS/LC-FD | [44] |
Tomatoes | Lycopersicon esculentum cv. Catalinaa | 4.1 ± 0.9 ng/g FW | 3 | LC-MS/LC-FD | [44] |
Tomatoes | Lycopersicon esculentum cv. Gordala | 17.10 ± 1.21 ng/g FW | 3 | LC-MS/LC-FD | [44] |
Tomatoes | Lycopersicon esculentum cv. Lucindaa | 4.45 ± 0.05 ng/g FW | 3 | LC-MS/LC-FD | [44] |
Tomatoes | Lycopersicon esculentum cv. Marbonea | 18.13 ± 2.24 ng/g FW | 3 | LC-MS/LC-FD | [44] |
Tomatoes | Lycopersicon esculentum cv. Myriadea | 8.0 ± 1.3 ng/g FW | 3 | LC-MS/LC-FD | [44] |
Tomatoes | Lycopersicon esculentum cv. Pitenzaa | 14.0 ± 2.5 ng/g FW | 3 | LC-MS/LC-FD | [44] |
Tomatoes | Lycopersicon esculentum cv. Santonioa | 7.73 ± 1.22 ng/g FW | 3 | LC-MS/LC-FD | [44] |
Tomatoes (wild type) | Solanumlycopersicum L. cv. Micro-Tom | 6.58 ng/g FW | 3 | HPLC | [94] |
Tomatoes (transgenic) | Solanumlycopersicum L. cv. Micro-Tom | 7.39–10.34 ng/g FW | 3 | HPLC | [94] |
Tomatoes | Not specified | 0.03 ± 0.01 ng/g DW | 5 | LC-MS/MS | [42] |
Tomato | Lycopersicon esculentum L. | 0.03 ng/g FW | N/A | HPLC-FD | [83] |
Japanese butterbur | Patasites japonicus 50 | nd | N/A | HPLC-FD | [83] |
Taro | Colocasis escutenta | 0.06 ng/g FW | N/A | HPLC-FD | [83] |
Cabbage | Brassica oleracea | 0.11 ng/g FW | N/A | HPLC-FD | [83] |
Chinese cabbage | Raphamus sativas | 0.11 ng/g FW | N/A | HPLC-FD | [83] |
Chungitsu | Chrysanthemum cororarum | 0.42 ng/g FW | N/A | HPLC-FD | [83] |
Ginger | Zinigiber officinale | 0.58 ng/g FW | N/A | HPLC-FD | [83] |
Japanese ashitaba | Angelica keiskei | 0.62 ng/g FW | N/A | HPLC-FD | [83] |
Mushrooms | |||||
Mushroom | Agaricus bisporus* | 4300–6400 ng/g DW | 3 | RP-HPLC | [50] |
Basidiomycota | Armillaria mellea | <10 ng/g DW | 3 | HPLC | [19] |
Basidiomycota | Boletus badius | <10 ng/g DW | 3 | HPLC | [19] |
Basidiomycota | Boletus edulis | 6800 ± 60 ng/g DW | 3 | HPLC | [19] |
Basidiomycota | Cantharellus cibarius | 1400 ± 110 ng/g DW | 3 | HPLC | [19] |
Basidiomycota | Lactarius deliciosus | 12,900 ± 770 ng/g DW | 3 | HPLC | [19] |
Basidiomycota | Pleurotus ostreatus | <10 ng/g DW | 3 | HPLC | [19] |
Legumes and seeds (raw) | |||||
Legumes | |||||
Lentils | Lens culinaris L. | 0.5 ng/g DW | 3 | HPLC-MS/MS | [53] |
Kidney beans | Phaseolus vulgaris L | 1.0 ng/g DW | 3 | HPLC-MS/MS | [53] |
Soybean | Glycine max | 0.45 ± 0.03 ng/g DW | N/A | RIA | [52] |
Seeds | |||||
Lupin (seed-cotyledons) | Lupinus albus L. | 3.83 ± 0.21 ng/g FW | 5 | HPLC-FD | [32] |
Lupin (seed-coat) | Lupinus albus L. | 37.50 ± 2.3 ng/g FW | 5 | HPLC-FD | [32] |
Lupin (seed-flour) | Lupinus albus L. | 0.53 ± 0.04 ng/g DW | 5 | HPLC-FD | [32] |
Grape (seed) | Vitis vinifera L. cv. Merlot | 10.04 ± 0.49 ng/g grapes | 3 | UPLC-MS/MS | [90] |
Barley (seed) | Hordeum vulgare L. | 0.58 ± 0.05 ng/g FW | 5 | HPLC-FD | [32] |
Barley(seed-flour) | Hordeum vulgare L. | 0.09 ± 0.01 ng/g DW | 5 | HPLC-FD | [32] |
Black mustard | Brassica nigra | 129 ng/g DW | 2 | HPLC-ECD | [51] |
White mustard | Brassica hirta | 189 ng/g DW | 2 | HPLC-ECD | [51] |
Fenugreek | Trigonella faena-graecum | 43 ng/g DW | 2 | HPLC-ECD | [51] |
Milk thistle | Silybum marianum | 2 ng/g DW | 2 | HPLC-ECD | [51] |
Celery | Apium gravolens | 7 ng/g DW | 2 | HPLC-ECD | [51] |
Alfalfa | Medicago sativa | 16 ng/g DW | 2 | HPLC-ECD | [51] |
Coriander | Coriandrum sativum | 7 ng/g DW | 2 | HPLC-ECD | [51] |
Green cardamom | Elettaria cardamomum | 15 ng/g DW | 2 | HPLC-ECD | [51] |
Fennel | Foeniculum vulgare | 28 ng/g DW | 2 | HPLC-ECD | [51] |
Poppy | Popaver somniferum | 6 ng/g DW | 2 | HPLC-ECD | [51] |
Anise | Pimpinella anisum | 7 ng/g DW | 2 | HPLC-ECD | [51] |
Sunflower | Helianthus annuus | 29 ng/g DW | 2 | HPLC-ECD | [51] |
Flax | Linum usitatissimum | 12 ng/g DW | 2 | HPLC-ECD | [51] |
Almond | Prunus amydalus | 39 ng/g DW | 2 | HPLC-ECD | [51] |
Chinese wolfberry | Lycium barbarum | 103 ng/g DW | 2 | HPLC-ECD | [51] |
Cucumber | Cucumissativus L. cv. Jingyu-1 | 5.1 ng/g FW | 3 | UPLC-ESI-MS/MS | [95] |
Alfalfa | Medicago sativa L. | 0.05 ± 0.00 ng/g DW | 3 | ELISA | [23] |
Lentil | Lens sculenta L. | 0.07 ± 0.01 ng/g DW | 3 | ELISA | [23] |
Mung bean | Vignaradiata L. | 0.01 ± 0.0 ng/g DW | 3 | ELISA | [23] |
Onion | Allium cepa L. | 0.22 ± 0.01 ng/g DW | 3 | ELISA | [23] |
Broccoli | Brassica oleraceae L. | 0.41 ± 0.04 ng/g DW | 3 | ELISA | [23] |
Red cabbage | Brassica oleraceae capitate rubra L. | 0.34 ± 0.04 ng/g DW | 3 | ELISA | [23] |
Radish (mixed) | Raphanus sativus japonicum L. | 0.28 ± 0.01 ng/g DW | 3 | ELISA | [23] |
Raphanus sativus rambo L. | |||||
Raphanus sativus sinicum rosae L. | |||||
Legumes and seeds (germination) | |||||
Legumes sprouts | |||||
Lentils | Lens culinaris L. | 1089.8 ng/g DW | 3 | HPLC-MS/MS | [53] |
Lentil | Not specified | 0.92 ± 0.06 ng/g DW | N/A | RIA | [52] |
Kidney beans | Phaseolus vulgaris L. | 529.1 ng/g DW | 3 | HPLC-MS/MS | [53] |
Soya bean | Glycine max L. | 1.89 ± 0.11 ng/g DW | N/A | RIA | [52] |
Vetch | Vicia sativa L. | 1.91 ± 0.11 ng/g DW | N/A | RIA | [52] |
Seedling | |||||
Rice | Oryza sativa cv. Dongjin | 1.9 ng/g DW | 3 | HPLC | [96] |
Rice (transgenic) | Oryza sativa cv. Dongjin | 2.7–5.2 ng/g DW | 3 | HPLC | [96] |
Cucumber | Cucumis sativus L. cv. Jingyu-1 | 17.3 ng/g FW | 3 | UHPLC-ESI-MS/MS | [95] |
Alfalfa | Medicago sativa L. | 0.13 ± 0.01 ng/g DW | 3 | ELISA | [23] |
Lentil | Lens sculenta L. | 0.22 ± 0.0 1 ng/g DW | 3 | ELISA | [23] |
Mung bean | Vignaradiata L. | 0.17 ± 0.01 ng/g DW | 3 | ELISA | [23] |
Onion | Allium cepa L. | 0.30 ± 0.02 ng/g DW | 3 | ELISA | [23] |
Broccoli | Brassica oleraceae L. | 0.44 ± 0.01 ng/g DW | 3 | ELISA | [23] |
Red cabbage | Brassica oleraceae capitate rubra L. | 0.86 ± 0.05 ng/g DW | 3 | ELISA | [23] |
Radish | Raphanus sativus japonicum L. | 0.54 ± 0.04 ng/g DW | 3 | ELISA | [23] |
Raphanus sativus rambo L. | |||||
Raphanus sativus sinicum rosae L. | |||||
Nuts | |||||
Pistachio | |||||
Pistachio | Pistacia vera L. cv. Ahmad Aghaei | 233,000 ng/g DW | N/A | GC/MS | [28] |
Pistachio | Pistacia vera L. cv. Akbari, Kalle | 226,900 ng/g DW | N/A | GC/MS | [28] |
Pistachio | Pistacia vera L. cv. Qouchi | 231,400 ng/g DW | N/A | GC/MS | [28] |
Pistachio | Pistacia vera L. cv. Fandoghi | 228,400 ng/g DW | N/A | GC/MS | [28] |
Walnuts | |||||
Walnuts | Juglans regia L. cv. Serr | 1.02 ± 0.06 ng/g FW | 4 | HPLC–MS | [97] |
Walnuts | Juglans regia L. cv. Hartley | 1.77 ± 0.14 ng/g FW | 4 | HPLC–MS | [97] |
Walnuts | Juglans regia L. cv. Chandler | 1.37 ± 0.37 ng/g FW | 4 | HPLC–MS | [97] |
Walnuts | Juglans regia L. cv. Howard | 1.9 ± 0.4 ng/g FW | 4 | HPLC–MS | [97] |
Walnuts | Not specified | 0.14 ± 0.03 ng/g DW | 5 | LC–MS/MS | [42] |
Walnuts | Juglans regia L. | 3.5 ± 1.0 ng/g | 5 | HPLC-ECD | [78] |
Juices and beverages | |||||
Beer | Not specified | 0.09 ± 0.01 ng/mL | 5 | LC-MS/MS | [42] |
Wine | |||||
Albana must | Albana, Romagna | 1.1 ng/mL | 3 | HPLC-FD | [43] |
Albana wine | Albana, Romagna | 0.6 ng/mL | 3 | HPLC-FD | [43] |
Albana grappa | Albana, Romagna | 0.3 ng/mL | 3 | HPLC-FD | [43] |
Red wine | Not specified | 0.26 ± 0.18 ng/mL | 3 | UHPLCMS/MS | [59] |
Dessert ice wine | Not specified | 0.17 ± 0.11 ng/mL | 3 | UHPLCMS/MS | [59] |
Groppello wines | Vitis vinifera L. cv. Groppello Gentile | 5.2 ng/mL | 3 | UHPLCMS/MS | [59] |
Merlot wines | Merlot | 8.1 ng/mL | 3 | UHPLCMS/MS | [59] |
Wine | Cabernet Sauvignon | 14.2 ± 0.2 ng/mL | 3 | HPLC-MS/MS | [55] |
Wine | Cabernet Sauvignon | 0.23 ± 0.01 ng/mL | 3 | ELISA | [55] |
Wine | Jaen Tinto | nd | 3 | HPLC-MS/MS | [55] |
Wine | Jaen Tinto | 0.16 ± 0.01 ng/mL | 3 | ELISA | [55] |
Wine | Vitis vinifera L. cv. Merlot | nd | 3 | HPLC-MS/MS | [55] |
Wine | Vitis vinifera L. cv. Merlot | 0.21 ± 0.02 ng/mL | 3 | ELISA | [55] |
Wine | Palomino Negro | nd | 3 | HPLC-MS/MS | [55] |
Wine | Palomino Negro | 0.28 ± 0.00 ng/mL | 3 | ELISA | [55] |
Wine | Petit Verdot | 5.1 ± 0.6 ng/mL | 3 | HPLC-MS/MS | [55] |
Wine | Petit Verdot | 0.22 ± 0.01 ng/mL | 3 | ELISA | [55] |
Wine | Prieto Picudo | 49.0 ± 4.7 ng/mL | 3 | HPLC-MS/MS | [55] |
Wine | Prieto Picudo | 0.19 ± 0.01 ng/mL | 3 | ELISA | [55] |
Wine | Syrah | 86.5 ± 2.6 ng/mL | 3 | HPLC-MS/MS | [55] |
Wine | Syrah | 0.22 ± 0.02 ng/mL | 3 | ELISA | [55] |
Wine | Tempranillo | 129.5 ± 3.5 ng/mL | 3 | HPLC-MS/MS | [55] |
Wine | Tempranillo | 0.14 ± 0.01 ng/mL | 3 | ELISA | [55] |
Wine | Vitis vinifera L. cv. Malbec | 0.24 ng/mL | 5 | CEC | [56] |
Wine | Cabernet Sauvignon | 0.32 ng/mL | 5 | CEC | [56] |
Wine | Chardonnay | 0.16 ng/mL | 5 | CEC | [56] |
Wine | Sangiovese, red | 0.5 ng/mL | 3 | HPLC-FD | [43] |
Wine | Trebbiano, white | 0.4 ng/mL | 3 | HPLC-FD | [43] |
Coffee beans | |||||
Green coffee | Not specified | 0.040 ± 0.01 ng/g DW | 5 | LC-MS/MS | [42] |
Green beans | Coffea canephora L. (robusta) | 5800 ± 800 ng/g DW | 3 | LC-MS-ESI | [58] |
Green beans | Coffea arabica L. (arabica) | 6800 ± 400 ng/g DW | 3 | LC-MS-ESI | [58] |
Roasted beans | Coffea canephora L. (robusta) | 8000 ±.900 ng/g DW | 3 | LC-MS-ESI | [58] |
Roasted beans | Coffea arabica L. (arabica) | 9600 ± 800 ng/g DW | 3 | LC-MS-ESI | [58] |
Decoction (Brew) | Coffea canephora L. (robusta) | 60 ± 12 ng/mL | 3 | LC-MS-ESI | [58] |
Decoction (Brew) | Coffea arabica L. (arabica) | 78 ± 5 ng/mL | 3 | LC-MS-ESI | [58] |
Juices | |||||
Orange juice | Citrus sinensis L. var. Navel late (Huelva, Spain) | 3.15–21.80 ng/mL | 3 | UHPLC-QqQ-MS/MS | [98] |
Grape juice | Not specified | 0.5 ng/mL | 3 | HPLC-FD | [43] |
Cacao powder | Not specified | 0.01 ng/g DW | 5 | LC-MS/MS | [42] |
Concentrate | |||||
Tart cherries | Prunus cerasus L. cv. Balaton | nd | 3 | HPLC-EMS | [46] |
Tart cherries | Prunus cerasus L. cv. Montmorency | nd | 3 | HPLC-EMS | [46] |
Sour cherries | Not specified | nd | 5 | LC-MS/MS | [42] |
Tea | |||||
Green tea | Not specified | nd | 5 | LC-MS/MS | [42] |
Black tea | Not specified | nd | 5 | LC-MS/MS | [42] |
Balsamic vinegars | 0.12 ± 0.014 ng/mL | 3 | UHPLCMS/MS | [59] | |
Medical Herbs | |||||
Huang-qin | Scutellaria biacalensis | 7110 ng/g DW | 2 | Not specified | [29] |
St John’s Wort (flowers) | Hypericum perforatum | 4490 ng/g DW | 2 | Not specified | [29] |
Chantui | Periostracum cicadae | 3771 ng/g DW | 3 | SPE-HPLC-FD | [61] |
Gouteng | Uncaria rhynchophylla | 2460 ng/g DW | 3 | SPE-HPLC-FD | [61] |
Diding | Viola philipica Cav. | 2368 ng/g DW | 3 | SPE-HPLC-FD | [61] |
Shiya tea-leaf | Babreum coscluea | 2120 ng/g DW | 3 | SPE-HPLC-FD | [61] |
Feverfew (fresh leaves) | Tanacetum parthenium | 1920–2450 ng/g DW | 2 | Not specified | [29] |
St John’s Wort (leaves) | Hypericum perforatum | 1750 ng/g DW | 2 | Not specified | [29] |
Sangye | Morus alba L. (Leaf) | 1510 ng/g DW | 3 | SPE-HPLC-FD | [61] |
Huangbo | Phellodendron amurense Rupr. | 1235 ng/g DW | 3 | SPE-HPLC-FD | [61] |
Sangbaipi | Mori Albae (Cortex) | 1110 ng/g DW | 3 | SPE-HPLC-FD | [61] |
Yinyanghuo | Epimedium brevicornum Maxim | 1105 ng/g DW | 3 | SPE-HPLC-FD | [61] |
Black pepper | Piper nigrum L. | 1092.7 ng/g DW | 5 | SPE HPLC ELISA | [62] |
Huanglian | Coptis chinensis Franch | 1008 ng/g DW | 3 | SPE-HPLC-FD | [61] |
Mulberry leaves | Morus spp. cv. Buriram 60 | 279.6 ng/g DW | 3 | HPLC-FD | [99] |
Morus spp. cv. Sakonnakhon | 100.5 ng/g DW | 3 | HPLC-FD | [99] | |
Morus spp. cv. Khunphai | 40.7 ng/g DW | 3 | HPLC-FD | [99] | |
Edible oil | |||||
Virgin Argan oil | Not specified | 0.06 ± 0.05 ng/g | 2 | HPLC-FD | [64] |
Refined sunflower | Not specified | 0.03–0.08 ng/g | 2 | HPLC-FD | [64] |
Primrose, | Not specified | 0.03–0.08 ng/g | 2 | HPLC-FD | [64] |
Refined grape seed | Not specified | 0.03–0.08 ng/g | 2 | HPLC-FD | [64] |
Refined walnut | Not specified | 0.03–0.08 ng/g | 2 | HPLC-FD | [64] |
Virgin walnut | Not specified | 0.03–0.08 ng/g | 2 | HPLC-FD | [64] |
Virgin linseed | Not specified | 0.03–0.08 ng/g | 2 | HPLC-FD | [64] |
Linseed oils | Not specified | 0.03–0.08 ng/g | 2 | HPLC-FD | [64] |
Refined linseed | Not specified | 0.29 ± 0.00 ng/g | 2 | HPLC-FD | [64] |
Virgin sesame | Not specified | 0.03–0.08 ng/g | 2 | HPLC-FD | [64] |
Wheat germ | Not specified | 0.03–0.08 ng/g | 2 | HPLC-FD | [64] |
Virgin soybean | Not specified | 0.19 ± 0.00 ng/g | 2 | HPLC-FD | [64] |
Olive oil | Extra virgin | 0.03 ± 0.00 ng/g | 2 | HPLC-FD | [64] |
D.O. Sierra Ma′gina | Not specified | 0.11 ± 0.04 ng/mL | 3 | ELISA | [63] |
D.O. Siurana | Not specified | 0.10 ± 0.02 ng/mL | 3 | ELISA | [63] |
D.O. Bajo Arago′n | Not specified | 0.07 ± 0.02 ng/mL | 3 | ELISA | [63] |
D.O. Montes de Toledo | Not specified | 0.11 ± 0.01 ng/mL | 3 | ELISA | [63] |
D.O. Baena | Not specified | 0.12 ± 0.00 ng/mL | 3 | ELISA | [63] |
D.O. Sierra de Segura | Not specified | 0.09 ± 0.00 ng/mL | 3 | ELISA | [63] |
D.O. Les Garrigues | Not specified | 0.10 ± 0.00 ng/mL | 3 | ELISA | [63] |
D.O. Toscano | Not specified | 0.11 ± 0.02 ng/mL | 3 | ELISA | [63] |
Refined olive oil sample 1 | Not specified | 0.05 ± 0.01 ng/mL | 3 | ELISA | [63] |
Refined olive oil sample 2 | Not specified | 0.08 ± 0.01 ng/mL | 3 | ELISA | [63] |
Refined sunflower oil sample | Not specified | 0.05 ± 0.01 ng/mL | 3 | ELISA | [63] |
Microorganisms | |||||
Yeast (dried brewer) | Saccharomyces cerevisae | 2.2 ± 0.14 ng/g | 5 | HPLC | [22] |
Study Type | Subjects | Dose (mg/kg b.w.)/(Dose Dependent) | Potential Mechanisms (Melatonin (Mel) and/or Its Metabolites) | Reference |
---|---|---|---|---|
Antioxidant Activities | ||||
Directly scavenging free radical | ||||
In vivo | Mouse | 10 mg/kg b.w. | Increasing the efficiency of electron transport chain: - lowering electron leakage and reducing free radical generation | [122] |
In vitro | Human umbilical artery segment | 10−6, 10−5, 10−4 M (dose dependent) | Significantly scavenging the hydroxyl radical | [127] |
Cascade effects: removing free radicals efficiently than other reductants: | ||||
In vivo | Rat | 43 μmol/kg b.w. | - more efficient than Vitamin C | [128] |
Rat | 2 μmol/kg b.w. | - more efficient than Vitamin E | [125] | |
Mouse | 5 mg/kg b.w. | - more efficient than Vitamin E | [325] | |
In vitro | Incubation medium | 1–1000 mM | - more efficient than Vitamin C & Vitamin E | [123] |
Some metabolites more potent than its precursor in reducing oxidative stress: | ||||
Fenton reaction-based assay | AFMK: 0.017–0.067 mM AMK: up to 0.2 mM | - the order of efficacy of scavenging ∙OH: AMK > AK > AFMK | [130] | |
N/A | N/A | N/A | - C3-OHM is 2–3 fold more potent than Mel in reducing hypervalent hemoglobin (Tan & Reiter, unpublished observations). | [131] |
Modulating and activating other enzymes | ||||
Downregulating pro-oxidative enzymes | ||||
In vitro & in vivo | Rat striatum | M & AMK: 10−11–10−3 M (dose dependent in vitro) | - Mel & AMK inhibiting nNOS activity - AMK more potent in inhibiting nNOS activity than Mel (in vivo) | [142] |
In vitro | MCF-7 cells | 1 nM | Inhibiting the mRNA expression of COX 1 and COX-2 in MCF-7 cells | [143] |
Stimulating the synthesis of other antioxidants | ||||
In vitro | ECV304 cells | 1 μM | - Inducing γ-GCS expression to promote GSH synthesis | [124] |
In vitro | 2 neuronal cell lines: PC12 cells & SK-N-SH | 1 nM | - Regulating AOEs gene expression - Increasing mRNA of SODs and GPx | [144] |
Preventing antioxidant enzymes from oxidative stress | ||||
In vitro | human BM-MSCs | 0 to 1000 μM (dose dependent 10–100 μM) | - significantly restoring SOD (p < 0.05) and CAT (p < 0.01) - increasing GSH (p < 0.01) with pre-treatment of Mel | [145] |
In vivo | Sprague-Dawley rats | 10 mg/kg b.w. | GSH-Rd activity was completely or partially restored by Mel treatment | [146] |
In vitro & in vivo | Sprague–Dawley rats | 0–0.1 mM (dose dependent in vitro) 10 mg/kg b.w. | G6PG activity dose-dependent in vitro (increased below 0.08 mM Mel concentration and reached a plateau above 0.1 mM) G6PG activity time-dependent (in vivo) | [147] |
Synergistically working with other reductants | ||||
Combining with other antioxidants to remove radicals synergistically | ||||
In vitro | Rat liver homogenates | 2.5–1600 μM | - dramatically enhancing the protective effects after combining | [148] |
Anti-inflammatory Activities | ||||
NF-κB signaling pathway involved mechanisms | ||||
Modulating NF-κB and its downstream pro-inflammatory target genes | ||||
In vitro | Human colon cancer cell lines SW620 and LOVO | 1 mmol/L | - iNOS | [70] |
In vitro | RAW 264.7 macrophages | 0.5, 1, 2 mM (dose dependent) | - COX-2, PGE2 | [158] |
In vitro | Human neuroblastoma dopamine SH-SY5Y cell lines | 1, 10, 100 or 1000 nM | - TNF-α | [159] |
In vitro | Rat astrocytoma C6 cells | 50–200 μM (dose dependent) | - GFAP | [160] |
In vitro & in vivo | CHON-001 human chondrocyte cell line Rabbit with osteoarthritis (OA) | 0.1, 1, 10, 100 ng (dose- and time-dependent) 20 mg/kg | Protecting cells by blocking the activated NF-κB as well as the phosphorylation of PI3K/Akt, p38, ERK, JNK and MAPK | [161] |
In vitro | BV2 murine microglial cell line | 1 mM | Downregulating chemokine expression | [162] |
In vivo | Rats | 5 mg/kg | Inhibiting the inflammatory reaction | [163] |
In vivo & in vitro | Female BALB/c mice MMECs | 5, 10, 20 mg/kg 25, 50, 100 μM (dose dependent) | Suppressing NF-κB activation and activating PPAR-γ | [164] |
In vitro | Mast cells (RBL-2H3) | 100 nM and 1 mM (dose dependent) | Inhibiting IKK/NF-κB signal transduction | [165] |
SIRT1 pathway involved mechanisms | ||||
In vitro & in vivo | BV2 cell lysates PND7 rat brain | 100 µM 10 mg/kg | Activating SIRT1/Nrf2 signaling pathway to reduce oxidative stress damage | [168] |
Other possible mechanisms | ||||
In vivo | Pediatric patients | 10 mg (09:00 h) 60 mg ( 21:00 h ) | Regulating the expression of other pro-inflammatory genes | [150] |
In vitro | Mouse Gsk3b knockout (Gsk3b−/−) and wild-type (Gsk3b+/+) MEF cells | 10 nM | Inhibiting the expression of inflammatory chemokines/cytokines | [169] |
In vivo | Plasmodium | 10 µM (time dependent) | Inducing temporal up-regulation of gene expression related to UPS | [170] |
In vivo | C57BL mice | 10 mg/kg i.p. | Downregulating mRNA of E2F2 and H2-Ab1 | [171] |
In vivo | Rats | 5, 15, and 25 mg/kg (dose-dependent) | Activating the expression of NDRG2, which was involved in cellular differentiation, development, anti-apoptosis, anti-inflammatory cytokine, and antioxidant | [172] |
In vivo | Carp | 10−4–10−12 M | Maintaining the pro- and anti- inflammatory balance during infection by influencing leukocyte migration and apoptosis | [151] |
Enhancing Immune Activities | ||||
Reciprocally regulating the nervous, endocrine, and immune systems | ||||
In vivo & In vitro | Mice Thymus and spleen cells | 4–5 mL/day/mouse 1.5 pg/ml to 1.5 pgg/ml | Regulating thymocyte apoptosis | [174] |
In vivo | Mice | 1.5 pg/mL to 1.5 pg/mL | The concentration of melatonin correspond with the change of seasons | [175] |
Inhibiting the production of cAMP, cGMP and DAG, and improving the immunity | ||||
In vitro | Human blood lymphocyte | N/A (dose-dependent) | Inhibiting adenylyl cyclase and the stimulating phospholipase C | [183] |
In vivo | Golden hamsters | 25 μg/100 g/hamster/day | Improving immune responses | [184] |
Protecting the immune organs, tissues and cells | ||||
Reversing the weight loss of thymuses and spleens in pinealectomized animals | ||||
In vivo & In vitro | Mice Thymus and spleen cells | 4–5 mL/day/mouse 1.5 pg/mL to 1.5 pg/mL | - thymus | [175] |
In vivo | Syrian hamsters | 25 μg | - spleen | [188] |
In vivo | Pediatric patients | N/A | Increasing tonsillar size | [189] |
Improving proliferation, increasing activity and inhibiting apoptosis of immune cells | ||||
In vitro | cultured monocytes | N/A | - monocyte | [190] |
In vivo | ICR mice | 10 or 50 mg/kg | - natural killer (NK) cells | [191] |
In vitro | Neutrophils & peripheral blood mononuclear cells | 10 mM | - neutrophils | [192] |
In vivo | Wistar albino rats | 10 mg/kg | Increasing the sensitivity of the immune cells to some cytokines | [193] |
In vitro & In vitro | Thymocytes of Barbari goats Thymus | 500 pg/mL 500 pg/mL | Restoring the suppressed immunity of T-cell cultured by developing some hormonal microcircuit (gonadal steroid and melatonin) in lymphatic organs | [194] |
Modulating immune mediator production | ||||
In vitro | Human mononuclear cells | 10−8 M | Increasing IL-2, IFN-γ and IL-6 in monocytes | [195] |
In vitro | Neutrophils & peripheral blood mononuclear cells | 10 mM | Mel & AFMK: decreasing IL-8 and TNF-α in neutrophils | [192] |
In vitro | RAW264.7 cells | 10, 100 or 1000 μM | Decreasing IL-1β, IL-6, IL-8, IL-10 and TNF-α in macrophages | [196] |
Regulating the ROS production in the essential immune cells | ||||
In vitro | Human monocytes | 10−12 M and above | Activating monocytes (above the activation threshold of 5 × 10−11 M) | [199] |
In vitro | Lung neutrophils | 0.01, 0.1, 1 mM (dose-dependent) | Activating neutrophils | [200] |
In vivo | Hamsters | 25 μg/100 g b.w. | Attenuating oxidative load | [201] |
In vivo | Wild birds | 25 μg/100 g/day | Alleviating oxidative damage and suppressing the immune status induced by stress | [202]. |
In vitro & in vivo | Heart tissue of C57BL/6 C57BL/6J mice | 3 or 4 doses of melatonin 30 mg/kg | Suppressing systemic innate immune activation by blocking the NF-κB/NLRP3 connection through a sirtuin1-dependent pathway | [154]. |
Improving Circadian Rhythm and Sleep | ||||
In vivo | C3H & C57BL mice | N/A | Being involved in the control of clock gene protein levels in the adrenal cortex of mice | [211] |
In vivo | Soay sheep | N/A | Resetting circadian rhythms in the pituitary pars tuberalis | [212] |
In vivo | Mice (C3H/HeJCrl and C57BL/6NCrl) | N/A | Influencing PER1 and CRY2 protein levels Playing a role in rhythmic regulation of pCREB levels in the mammalian retina | [213] |
In vitro & in vivo | COS7 cells Lambs | N/A | Activating Npas4 | [215] |
In vivo | Hamster | 20 μg/day | Coordinating the diurnal rhythm in neuronal remodeling | [217] |
In vivo | Mice | 6 μg/day for 2 weeks | Increasing amplitude in expressional rhythms Altering the expression of genes of serotonergic neurotransmission Improve the depression-like behavior | [218] |
In vivo | 23 patients | N/A | Being positive correlated with sleep parameters | [220] |
Anticancer Activities | ||||
Effects on tumor cell cycle, incl. growth, proliferation, metabolism and apoptosis | ||||
In vitro & In vivo | Human gastric cancer cell lines (AGS and MKN) Male BALB/c nude mice | 5 mg/kg/twice/week for 33 days 1 µM to 2 mM (dose-/time- dependent, 15 min to 24 h) | Inhibiting gastric tumor growth and peritoneal metastasis Inhibiting C/EBPβ and NF-κB Inducing ER stress and inhibiting EMT | [232] |
In vitro | T47D-BAF co-cultured | 20 nM | Suppressing breast cancer cell proliferation and inhibiting aromatase | [238] |
In vitro & in vivo | Prostate cancer cells TRAMP male mice | 1 mM 200 µg/mL | Reducing glucose uptake and modifying the expression of GLUT1 transporter Attenuating glucose-induced tumor progression and prolonging the lifespan | [233] |
In vitro | Hypoxic prostate cancer cell line PC-3 cells | 1 mM | Anti-angiogenic property Upregulating miRNA3195 and miRNA 374b and downregulating 16 miRNAs | [239] |
In vitro | Colorectal cancer LoVo cells | 0.1–2.0 mM (dose-dependent) | Suppressing cell proliferation and inducing apoptosis Inducing dephosphorylation and nuclear import of histone deacetylase 4 (HDAC4) Decreasing H3 acetylation by inactivating CaMKIIα and reducing bcl-2 expression | [240] |
In vitro | Breast cancer cell line SK-BR-3 & MDA-MB-231 | 2 mM | Changing the protein levels of Survivin, Bcl-2, and Bax Affecting cyt c release from the mitochondria to the cytosol Enhancing apoptotic cell death via sustained upregulation of Redd1 expression and inhibition of mTORC1 upstream of the activation of the p38/JNK pathways | [234] |
Effects on invasion and metastasis of tumor cells | ||||
In vitro | HepG2 liver cancer cells | 1 mM | Exhibiting anti-invasive and antimetastatic activities by suppressing the activity of MMP-9 Reducing IL-1β-induced HepG2 cells MMP-9 gelatinase activity and inhibiting cell invasion and motility through downregulation of MMP-9 gene expression and upregulation of the MMP-9-specific inhibitor tissue inhibitor of TIMP-1 Suppressing IL-1β-induced NF-κB translocation and transcriptional activity | [241] |
In vitro | Renal cell carcinoma cells (Caki-1 and Achn) | 0.5–2 mM | Reducing the migration and invasion Inhibiting MMP-9 by reducing p65- and p52-DNA-binding activities Regulating MMP-9 transactivation and cell motility refer to the Akt-mediated JNK1/2 and ERK1/2 signaling pathways | [242] |
In vivo & in vitro | Female athymic nude mice Metastatic and non-metastatic breast cancer cell lines (MDA-MB-231) | 100 mg/kg/day 1 mM | Lowering the numbers of lung metastasis Decreasing ROCK-1 protein expression in metastatic foci Reducing cell viability and invasion/migration Decreasing ROCK-1 gene expression in metastatic cells and protein expression in non-metastatic cell line | [235] |
Therapy adjunct in tumor treatment | ||||
In vitro | Human non-small-cell lung cancer (NSCLC) cells lines H1299 and A549 | 1 mM | Enhancing the berberine-mediated growth inhibition of lung cancer cells through simultaneous modulation of caspase/cyt C, AP-2β/hTERT, NF-κB/COX-2, and Akt/ERK signaling pathways | [157] |
In vitro | Breast cancer cells | 1 nM | Mediating the sensitization to the ionizing radiation by decreasing around 50% the activity and expression of proteins involved in the synthesis of estrogens Reducing the amount of active estrogens at cancer cell level Inducing a 2-fold change in p53 expression compared to radiation alone | [243] |
In vivo | Female patients | Melatonin-containing cream for twice daily use | Significantly lowering the occurrence of grade 1/2 acute radiation dermatitis in patients with breast-conserving surgery for stage 0–2 breast cancer | [244] |
In vivo | Male Wistar rats | 10 mg/kg/week | Mitigating PVB-induced testicular dysfunction | [245] |
In vivo & in vitro | Female athymic nude mice Human colon cancer cell lines SW620 | 25 mg/kg 1 mmol/L | Exerting synergistic anti-tumor effect by inhibiting the AKT and iNOS pathway Enhancing the 5-FU-mediated inhibition of cell proliferation, colony formation, cell migration and invasion Synergizing with 5-FU to promote the activation of the caspase/PARP-dependent apoptosis pathway and induce cell cycle arrest Synergizing anti-tumor effect of 5-FU by targeting the PI3K/AKT and NF-κB/iNOS signaling | [70] |
In vitro | Human colorectal cancer cells | N/A | MT2 mRNA expression levels increased The profile of melatonin receptors gene expression and genes associated with their activity in colorectal cancer | [236] |
In vitro | Estrogen receptor-positive endometrial cancer cell line, Ishikawa | 1 × 10−9 M | MT1 receptor expressing but not MT2 Attenuating ERα mRNA expression Enhancing anti-tumor effects of paclitaxel among anticancer drugs tested | [237] |
Cardiovascular Protection | ||||
In vivo | Patients with confirmed nocturnal hypertension | 2 mg 2 h before bedtime for 4 weeks | Reducing nocturnal systolic and diastolic BP significantly (p = 0.01) | [249] |
In vivo | Spinal cord injury (SCI) mice model | 5, 10, 25, 50, 100 mg/kg i.p. | 50 mg/kg exhibiting significantly reduced blood spinal cord barrier permeability Restraining microvessel loss and attenuating edema Protecting the tight junction proteins, endothelial cells and pericytes Decreasing cell apoptosis and reducing MP3/AQP4/HIF-1α/VEGF/VEGFR2 expression | [251] |
In vivo | Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) | 30 mg/kg/day for 4 weeks | Decreasing reflex chronotropic responses to phenylephrine and sodium nitroprusside Reducing mean arterial pressure and heart rate Improving bradycardic and tachycardic baroreflex responses without modifying catecholamine responses Increasing glutathione peroxidase activity in plasma and erythrocytes | [252] |
In vivo | Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) | 30 mg/kg/day for 4 weeks | Decreasing mean arterial pressure (MAP) and heart rate Restoring the plasma noradrenaline concentrations, the chronotropic response to isoproterenol and the proportions of β1/β2-adrenoceptors in the heart in SHRs to the levels Decreasing the release of [3H] noradrenaline from isolated atria Improving the relaxation in the aorta | [253] |
In vivo | Rats | 50 mg/kg | Preventing vasculitis Decreasing elementary pathological lesions of radiation-induced heart disease (RIHD) like fibrosis and necrosis | [254] |
In vitro | BM-MSCs | 200, 20, and 2 µM(dose-dependent) | Reducing BM-MSC apoptotic death while increasing the levels of TGF-β, bFGF, VEGF, PDGF and Bcl-2, and decreasing Bax, p53 Upregulating modulator of apoptosis (PUMA) and caspase 3 Upregulating the phosphorylation of AMPK, which promotes ACC phosphorylation | [255] |
In vivo & in vitro | Female C57BL/6a mice with MI Adipose-derived MSCs | 20 mg/kg/day for 28 days 5 µM | Promoting functional survival of AD-MSCs in infarcted heart and provoking a synergetic effect with AD-MSCs to restore heart function associated with alleviated inflammation, apoptosis, and oxidative stress in infarcted heart Exerting cytoprotective effects against hypoxia/serum deprivation (H/SD) injury Attenuating inflammation, apoptosis, and oxidative stress Enhancing SIRT1 signaling, with the increased expression of anti-apoptotic protein Bcl-2, and decreased the expression of Ac-FoxO1, Ac-p53, Ac-NF-KappaB, and Bax. | [256] |
In vitro | Perfused isolated rat hearts and cultured neonatal rat cardiomyocytes | 5 µM | Improving postischemic cardiac function, decreasing infarct size, reducing apoptotic index, and diminishing lactate dehydrogenase release Upregulating the anti-apoptotic protein Bcl-2 and downregulating Bax Preserving mitochondrial redox potential and elevating SOD activity Decreasing formation of mitochondrial H2O2 and MDA | [257] |
In vivo | Rats with sepsis | 30 mg/kg | Improving survival rates and cardiac function, attenuating myocardial injury and apoptosis Decreasing the serum LDH, decreasing inflammatory cytokines TNF-α, IL-1β, and HMGB1 Increasing anti-oxidant enzyme activity and p-Akt and Bcl-2 levels | [258] |
In vivo | Drosophila melanogaster | 5 µM | Increasing the regularity of heartbeat, rescuing rhythmicity in flies bearing mutations, increasing cardiac regularity independent of alteration of heart rate, which is mediated via a specific G-Protein-coupled receptor encoded by the CG 4313 gene | [259] |
In vivo | Patients with heart failure | N/A 1-year follow-up | As a predictors of left ventricular reverse remodeling (LVRR) and the adverse clinical events, increasing the area under of curve for the prediction LVRR | [260] |
In vivo | Mice with Mst1 transgenic (Mst1 Tg) and Mst1 knockout (Mst1−/− ) | 20 mg/kg/d for 1 week | Alleviating postinfarction cardiac remodeling and dysfunction by upregulating autophagy, decreasing apoptosis, and modulating mitochondrial integrity and biogenesis via Mst1/Sirt1 signaling | [261] |
Anti-diabetic Activities | ||||
In vivo | Albino Wistar rats | 10 mg/kg b.w. | Increasing the inhibited activity of catalase in liver cells Restoring the dysfunctional mitochondria related to diabetes | [274] |
In vivo | Rat | 2.8, 14, 28, and 140 nM | Inhibiting hepatic gluconeogenesis Activating hypothalamic Akt via membrane receptors MT1 and MT2 | [275] |
In vivo | Rat | 10 mg/kg/day | Increasing Ca2+ levels in lots of organs and tissues | [11] |
In vitro & in vivo | H9C2 cell line Rat | 0.1, 1, 10, 100, 1000 µM 20 mg/kg/day | Activating of SIRT1 signaling pathway (significant at 100 and 1000 µM) Inactivating PERK/eIF2α/ATF4 signaling pathway | [276] |
In vitro | INS 832/13 cells | 1–100 nM | Attenuating β-cell apoptosis, improving β-cell function, prolonging β-cell survival (particularly evident at 10 nM) | [277] |
In vivo | Rat | 10 mg/kg/day | Improving neurogenesis, synaptogenesis in hippocampi, increasing the receptors of melatonin and insulin, and restoring the downstream signaling pathway for insulin | [278] |
In vivo | Rat | 250 µg/animal/day/i.p. | Accelerating bone healing | [279] |
In vivo | Rat | 10 mg/kg/d, i.p. | Restoring the endothelial dysfunction and improving vascular responses | [271] |
Anti-obese Activities | ||||
In vivo | Rat | 10 mg/kg/day | Inducing white adipose tissue browning in rats with obesity-related type 2 diabetes | [282] |
In vivo | Rat | 20 mg/L | Benefiting homeostasis of renal glutathione | [283] |
In vitro | Mouse Gsk3b knockout (Gsk3b−/−) and wild-type (Gsk3b+/+) MEF cells | 10 nM | Inhibiting Akt activation Increasing GSK3B activity | [169] |
In vivo | Mice | 100 mg/kg/day | Ameliorating obesity-induced adipokine alteration | [285] |
In vivo | Women | N/A | Melatonin was involved in the development of obesity | [288] |
In vitro | Mice | 20 mg/kg/day | Promoting circadian rhythm-mediated proliferation in adipose tissue | [206] |
In vivo | Rat | 4 mg/kg/day | Decreasing myocardial infarct sizes and insulin resistant Increasing serum PKB/Akt, ERK42/44, GSK-3β and STAT3 | [289] |
In vivo | Mice | 100 mg/kg/day | Increasing mitofusin-2 expression | [290] |
In vivo | Mice | 10 mg/kg/day | Modulating the MAPK-JNK/p38 signaling pathway | [291] |
Neuroprotection | ||||
In vivo | Mice | 10 mg/kg | Increasing the activity of antioxidant enzymes Mediating the Nrf2-ARE pathway | [293] |
In vivo | C57BL/6J mice | 10 mg/kg given twice | Reducing IR-induced mitochondrial dysfunction Activating SIRT1 signaling | [294] |
In vivo | Rat | 150 mg/kg | Suppressing cortical expressions of proinflammatory cytokines | [295] |
In vivo | Mice | 5 mg/kg | Reducing oxidative damage by scavenging radicals | [296] |
In vivo | Rat | 10 mg/kg | Reversing the increased plasma TNF-α, IL-1β levels Decreasing BDNF, S100B and IL-10 values | [297] |
In vivo | Rat | 10 mg/kg and 50 mg/kg | Preventing the decrease of the number and the diameter of sciatic nerve axons | [298] |
In vivo | Rat | 20 mg | Preventing the decrease in VEPs and PLR Inhibiting microglial reactivity, astrocytosis, demyelination, and axon and retinal ganglion cell loss Preserving anterograde transport of cholera toxin β-subunit | [299] |
In vivo | Mice | 10 mg/kg | Restoring mRNA and protein levels of BACE1 and PS1 | [305] |
In vitro & in vivo | Rat hippocampal neurons Rat | 50 μM 500 mg/kg b.w. | Improving the soluble Abeta1–42-induced impairment of spatial learning and memory, synaptic plasticity and astrogliosis | [301] |
In vivo | Rat | 10 mg/kg | Improving motor activity and muscular strength | [306] |
In vitro | Mouse neuroblastoma cells | 1 μM | Activating transcription factor EB-dependent autophagy-lysosome | [136] |
In vivo | Rat | 100 mg/kg | Inhibiting caspase-3 | [307] |
In vivo | Rat | 50 mg/kg/day | Protecting the cell against neuronal damage in the hippocampus | [308] |
Other Bioactivities | ||||
In vivo | Rat | 10 mg/kg/day | Improving the microstructure and biomechanical properties of aged bones | [311] |
In vivo | Patients | 10 mg/day, 60 mg/day | Reducing the hyperoxidative and inflammatory process | [150] |
In vivo | Mice | 30 mg/kg/day | Decreasing plasma creatine kinase activity, increasing total glutathione content Lowering the oxidized/reduced glutathione ratio | [312] |
In vitro | NCI-H292 cells | 50, 100, 200, and 400 μM (dose-dependent) | Inhibiting mucin 5AC production | [313] |
In vivo | Rat | 4 mg/kg, i.p 10 mg/kg, i.p | Exhibits renoprotective effects against ischemia reperfusion induced AKI due to antioxidant properties and the involvement of progesterone receptors | [314] |
In vivo | Rat | 10 mg/kg/day | Scavenging free radicals | [315] |
In vivo | Rat | N/A | Activating SIRT1 signaling | [316] |
In vitro | Human ASCs | 100 μM for 3 h | Enhancing human ASCs’ survival and their therapeutic effectiveness on injured tissue | [317] |
In vivo | Rat | 10 mg/body | Interacting with other hormones | [319] |
In vivo | Rat | 10 mg/kg/day | Decreasing the increased myeloperoxidase activities and osteoclast and neutrophil densities | [322] |
In vivo | Rat | 10 mg/kg/day | Decreasing serum cyclophosphamide levels and increasing ALP levels | [323] |
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Meng, X.; Li, Y.; Li, S.; Zhou, Y.; Gan, R.-Y.; Xu, D.-P.; Li, H.-B. Dietary Sources and Bioactivities of Melatonin. Nutrients 2017, 9, 367. https://doi.org/10.3390/nu9040367
Meng X, Li Y, Li S, Zhou Y, Gan R-Y, Xu D-P, Li H-B. Dietary Sources and Bioactivities of Melatonin. Nutrients. 2017; 9(4):367. https://doi.org/10.3390/nu9040367
Chicago/Turabian StyleMeng, Xiao, Ya Li, Sha Li, Yue Zhou, Ren-You Gan, Dong-Ping Xu, and Hua-Bin Li. 2017. "Dietary Sources and Bioactivities of Melatonin" Nutrients 9, no. 4: 367. https://doi.org/10.3390/nu9040367
APA StyleMeng, X., Li, Y., Li, S., Zhou, Y., Gan, R. -Y., Xu, D. -P., & Li, H. -B. (2017). Dietary Sources and Bioactivities of Melatonin. Nutrients, 9(4), 367. https://doi.org/10.3390/nu9040367