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. 2021 Feb 13;22(4):1883. doi: 10.3390/ijms22041883

Table 1.

Pharmacological effects of natural antioxidants in iron deficiency anemia.

Bioactive Compound Doses In Vitro/
In Vivo/
Clinical Study
Model Bioactive Effect References
Iron from Moringa leaves 10% and 20% dehydrated
Moringa leaves
in vivo iron-deficient diet in Wistar rats ↑ serum iron, ferritin, and transferrin concentration
Dietary iron from Moringa leaf was found to be superior compared with ferric citrate (35 mg/kg) in overcoming the effects of iron deficiency in rats
[61]
Sulfate Ulva polysaccharide (SUE)
Low-dose group (SUE-iron (III) with iron concentration of 0.8 mg/mL, 0.7 mg kg−1 BW, Fe)
High-dose group (SUE-iron (III) with iron concentration of 2.3 mg/mL, 2.0 mg kg−1 BW, Fe)
in vivo iron deficiency anemia in Wistar rats ↑ RBC number
↑ serum iron
↓ TIBC
↓ IL-4
returnes Hb to the normal levels
[47]
Astragalus membranaceus polysaccharide-iron (III) complex APS-iron (III) complex with the iron content 12.5, 25, 50, 75, and 100 mg/kg in vivo Iron-deficiency anemia rodent model ↑ Hb
↑ SOD and CAT
↓ MDA
[62]
Ginger + iron supplem. 215 mg clinical study iron deficiency anemia
62 pacients
18–65 years
↑ plasma iron
↑ plasma ferritin
↓ TIBC
[63]
Quercetin + FeSO4 50 mg·kg−1 quercetin + 50 mg·kg−1 FeSO4 in vivo Iron deficiency anemia rat model ↑ Hb
↑ serum iron level
↑ iron stores in spleen
↑ expression of SLC40
-improve red blood cells level
-↓ CD68 macrophage activation
-↓ iNOS expression in splenic red pulp
[64]
Low-molecular-weight polysaccharide from Enteromorpha prolifera (LPE)-iron (III) complex Low LPE-iron (III) complex group (0.7 mg Fe/kg body weight)
High LPE-iron (III) complex group (2 mg Fe/kg body weight)
in vivo iron deficiency anemia rat model - improved the growth of rats with IDA
↑ Hb
↑ RBC numbers
↑ HTC
↑ serum iron
↓ TIBC level
↑ EPO level
-alleviated the hypertrophy of spleen
-improved the liver coefficient
[65]
Aqueous extract of Mangifera indica stem bark 25, 50, and 75 mg/kg body weight in vivo iron deficiency anemia rat model ↑ PCV, Hb and RCB count
↑ lactase and sucrase activity
[66]
Aqueous extract of the stem bark of Theobroma cacao (TC) 25, 50, and 75 mg/kg body weight in vivo iron deficiency anemia model
albino rats
↑ PCV, Hb and RCB count
↑ intestinal lactase and sucrase activity
[67]
Caulis spatholobi (CS) cells treated with 400 mg/mL of extract
AIN-76A diet containing 10.8% dried CS
in vitro
in vivo
Human hepatocellular carcinoma cell lines Huh7 and HepG2
C57BL/6 mice
diet containing 108 g dried CS per kilogram (10.8%)
↓ HAMP expression in Huh7 and HepG2 cells
↓ BMP-6-induced HAMP expression
↓ IL-6-induced HAMP expression
↑ iron mobilization in mice
↓ phosphorylation of Smad1/5/8
↓ hepatic iron levels
↑ serum iron levels in mice
[68]
Angelica sinensis polysaccharide (ASP) 1 g/kg in vivo iron deficiency anemia in Sprague Dawley rats ↓ hepcidin expression [50]
Angelica sinensis polysaccharide (ASP) 1 g kg−1 in vivo iron deficiency anemia
Sprague Dawley rats
↓ hepcidin expression [51]
Beetroot juice (Beta vulgaris L.) 200 mL clinical study Twenty female soccer players
23.13 ± 0.77 years old
↑ Hb, HTC, RBC, iron, and ferritin levels
↓ TIBC
[58]
Beetroot juice (Beta vulgaris L.) 100 mL clinical study adolescent girls ↑ Hb [59]
Beet powder (Beta Vulgaris L.) with Fe supplementation 8 g beetroot powder clinical study 30 pregnant women with anemia ↑ Hb, HTC,
↑ the number of erythrocytes
[60]
Carica papaya 110 g of papaya clinical study 42 pregnant women ↑ Hb
↑ HTC
[69]
Sweet potato (Ipomoea Batatas L.) 100 g clinical study first trimester pregnant women ↑ Hb [70]
Baobab fruit (Adansonia digitata) 60, 80, and 100 g clinical study 32 pregnant with iron deficiency anaemia ↑ Hb, PCV
↑ serum ferritin
[71]
Aqueous extract of Hibiscus sabdariffa seeds 400 mg of the extract/kg body weights -nutritional anemia model
-hemorrhagic anemia ratmodel
↑ HB, PCV, and RBC count of hemorrhagic anemic rats
↑ the Hb level of the nutritionally iron-deficient rats
[72]
Red beetroot (Beta vulgaris L.) 8 g clinical study healthy female volunteers (age range, 22 to 24) ↑ Hb
↓ TIBC
↑ ferritin
↓ transferrin
↑ serum iron levels
[57]

↑ increase/upregulated; ↓ decrease/downregulated; SUE, sulfate Ulva polysaccharide; RBCs, red blood cells; Hb, hemoglobin; TIBC, total iron-binding capacity; IL-4, interleukin 4; APS, Astragalus membranaceus polysaccharides; SOD, superoxide dismutase; CAT, catalase; MDA, malonyldialdehyde; TBARS, thiobarbituric acid reactive substances; LOOH, lipid hydroperoxide; GSH-Px, glutathione peroxidase; HTC, hematocrit; LPE, low-molecular-weight polysaccharide from Enteromorpha prolifera; EPO, erythropoietin; PCV, packed cell volume; TC, aqueous extract of the stem bark of Theobroma cacao; HAMP, hepcidin antimicrobial peptide; CS, Caulis spatholobi; ASP, Angelica sinensis polysaccharide; SMAD4, SMAD family member 4; BMP-6, bone morphogenic protein 6; FeSO4, ferrous sulfate.