Review Article

Antioxidant Potential of Propolis, Bee Pollen, and Royal Jelly: Possible Medical Application

Table 2

The protective effects of propolis against prooxidant action of different harmful factors.

SourceToxic or harmful factorHarmful effects of an applied factorThe type of propolis and the way of applicationEffects of propolis coadministration

Neuroprotective effect of propolis
Bazmandegan et al. [9]Cerebral ischemia-induced oxidative injury in a mouse model of stroke↑ MDA
↑ SOD and SOD/GPx ratio
↓ GPx in brain
Water-extracted Iran brown propolis; from two regions of Iran; 100 and 200 mg/kg; i.p. at 48, 24, and 1 h before and 4 h after the induction of ischemia↓ MDA
↓ SOD and SOD/GPx ratio
↑ GPx∗∗ in brain
Ni et al. [47]H2O2-induced neurotoxicity, human neuroblastoma SH-SY5Y cells (100 μM for 4 h or 1 h for ROS)↑ ROS in mitochondria
↑ 8-oxo-dG, the DNA oxidative damage marker
↓ Cell viability
Methanol extract of Brazilian green propolis, 10 μg/mL pretreatment for 2 h (or 1 h for ROS)↓ ROS in mitochondria
↓ 8-oxo-dG
↑ Cell viability
Nanaware et al. [48]β-Amyloid 25–35-induced Alzheimer’s disease model in rats, (10 μg/rat injected bilaterally)↓ SOD, GSH, CAT, NO
↑ MDA in brain
Macerated ethanolic extract of Indian propolis; 100, 200, and 300 mg/kg b.w., p.o. (posttreatment after 14 days); 21 days↑ SOD, GSH, CAT, NO
↓ MDA in brain
All doses were effective; the effect slightly increased with increasing dose
Jin et al. [6]6-Hydroxydopamine-induced oxidative stress in human neuroblastoma SH-SY5Y cells (50 μM for 24 h)↑ ROS
↑ MDA
↓ SOD
↓ Bcl-2/Bax ratio
Pinocembrin; 1, 5, and 25 μM pretreatment for 4 hours↓ ROS∗∗
↓ MDA∗∗
↑ SOD∗∗
↑ Bcl-2/Bax ratio∗∗
↑ Nrf2 translocation∗∗
↑ HO-1 and γ-GCS expression∗∗
de Oliveira et al. [49]Paraquat-induced neurotoxicity in SH-SY5Y cells (100 μM, 24 hours)↑ O2−• production, lipid peroxidation, protein carbonylation, and protein nitration in mitochondrial membranes
↓ Thiol content in mitochondrial membranes
↓ GSH in mitochondria
Pinocembrin; 25 μM pretreatment for 4 hours↓ O2−• production, lipid peroxidation, protein carbonylation, protein nitration, as well as oxidation of thiol groups in mitochondrial membranes
↑ Thiol content in mitochondrial membranes
↑ GSH in mitochondrial membranes
↑ Erk1/2-Nrf2 axis
↑ GCLM, GCLC, GSH, and HO-1
Barros Silva et al. [7]6-OHD-induced dopaminergic neuronal loss in rats, (3 μL, 8 mg/mL, s.i.)↑ Hydrogen peroxide in striatum
↑ Cu, Fe, Mn, and Zn in brain
Caffeic acid phenethyl ester (CAPE); 10 μM/kg, i.p., cotreatment for 5 days↓ Hydrogen peroxide in striatum
↓ Cu, Fe, Mn, and Zn in brain
Mahmoud et al. [50]K2CrO4-induced neurotoxicity in rats, (2 mg/kg b.w. for 30 days, i.p.)↑ MDA and NO
↓ SOD, GPx, and GSH in cerebrum
↑ JAK2, STAT3, and SOCS3 mRNA and protein in cerebrum
CAPE 20 mg/kg b.w. cotreatment for 30 days, orally↓ MDA and NO
↑ SOD, GPx, and GSH in cerebrum
↓ JAK2, STAT3, and SOCS3 mRNA and protein in cerebrum
Propolis role in mitigation of chemotherapy side effect
Kumari et al. [51]Mitomycin C-induced testicular toxicity in male mice, (8 mg/kg b.w., i.p., single dose)↑ MDA
↓ GSH, SOD, and CAT in testicular cells
Hydroethanolic extract of Indian propolis pretreatment (1 h prior) 400 mg/kg, i.p., single dose↓ MDA
↑ GSH and CAT in testicular cells
Alyane et al. [5]Doxorubicin-induced toxicity in rat heat mitochondria, (20 mg/kg b.w., i.p., single dose)↑ Mitochondrial MDA
↓ RCR (respiratory chain ratio) and P/O ratio
↑ O2 (evaluated in vitro)
Propolis extract pretreatment with 100 mg/kg/day, p.o. for four days prior↓ Mitochondrial MDA
↑ RCR (respiratory chain ratio) and P/O ratio
↓ O2 (evaluated in vitro)
Propolis as a modulator of cardiovascular disease markers
Salmas et al. [52]Nω-nitro-L-arginine methyl ester- (L-NAME-) induced hypertension in rats, (40 mg/kg b.w.; i.p. for 28 days)↓ TAS, PON1
↑ TOS, ADMA, and NF-κB
Propolis CAPE coadministration: propolis: 200 mg/kg/d; 28 days, by gavage; CAPE: 50 μM/kg/d; 14 days, i.p.↑ TAS
↑ PON1—only propolis
↓ TOS, ADMA
↓ NF-κB—only propolis
Ahmed et al. [53]Isoproterenol-induced myocardial infarction in rats, (85 mg/kg injection for 2 days—on the 29th and 30th days)↓ SOD, GPx, GRx, and GST in myocardium
↑ TBARS in myocardium
Malaysian propolis ethanol extract, pretreatment with 100 mg/kg/day, orally, 30 days↑ GPx, GRx, and GST in myocardium
↓ TBARS in myocardium
Sun et al. [54]H2O2-induced rat cardiomyocytes (H9c2) oxidative injury, (700 μM, 6 h)↑ MDA
↓ SOD and GPx
CAPE, benzyl caffeate, and cinnamyl caffeate pretreatment with 1, 5, and 10 μM for 12 h↓ MDA—doses of 5 and 10 μM
↑ SOD and GPx—doses of 5 and 10 μM
El-Awady et al. [58]High glucose-induced vascular endothelial dysfunction, isolated rat aorta, (44 mM for 3 hours)↑ TBARS in rat aorta
↓ SOD and GSH in rat aorta
Propolis extract pretreatment 400 μg/mL, 30 min prior↓ TBARS in rat aorta
↑ SOD and GSH in rat aorta
Propolis as protective agent against prooxidants’ toxicity
Yonar et al. [59]Trichlorfon-induced oxidative stress in fish, environmental exposure, 11 and 22 mg/L, 14 days↑ MDA in the liver, kidney, and gill
↓ GSH, SOD, CAT, and GPx in the liver, kidney and gill
Propolis cotreatment 10 mg/kg of fish weight, 14 days↓ MDA in the liver, kidney, and gill
↑ GSH, SOD, CAT, and GPx in the liver, kidney, and gill
Ferreira et al. [12]Tebuconazole-induced oxidative stress in fish, environmental exposure (0.88 mg/L)↑ MDA and carbonyl protein in brain, liver, and kidney
↑ GST in liver
↓ GST in brain
↑ CAT in kidney and brain
↓ SOD in liver
Propolis; 0.01, 0.05, and 0.1 g/L↓ MDA and carbonyl protein in brain, liver and kidney
↑ GST in brain, liver∗∗ and kidney
↑ CAT in liver∗∗
↓ CAT in kidney∗∗ and brain
↑ SOD in liver
Aksu et al. [60]Paracetamol- (PRC-) induced reproductive toxicity in rats, (500 mg/kg b.w., by oral gavage)↓ SOD, CAT, GPx, and GSH in testicular tissue
↑ MDA in testicular tissue
Chrysin; pretreatment with 25 mg/kg and 50 mg/kg b.w., by oral gavage, 7 days↑ GSH, CAT∗∗, GPx∗∗, SOD (only the higher dose) in testicular tissue
↓ MDA in testicular tissue
Manzolii et al. [61]Methylmercury-induced oxidative stress (30 μg/kg b.w., by gavage, 45 days)↓ GSH in bloodChrysin; cotreatment (0.10, 1.0, and 10 mg/kg b.w., by gavage, 45 days)↑ GSH in blood
Saito et al. [62]UVA irradiation, human skin fibroblast cells—NB1-RGB (10 J/cm2)↑ HO-1 expressionBrazilian green propolis; 3, 10, or 30 μg/mL 3,5-di-O-caffeoylquinic acid, 3,4-di-O-caffeoylquinic acid, and chlorogenic acid; 1 or 3 μg/mL↑ HO-1 expression
↑ Nrf2 nuclear translocation to the nuclei (only propolis extract was studied)
Cao et al. [63]H2O2-induced oxidative stress, mouse L929 fibroblast cell lines, (600 μM H2O, 12 hours)↑ ROS
↓ Cell viability
Ethanol extract of Chinese propolis; pretreatment with 5, 7.5, and 10 μg/mL per 3 hours prior↓ ROS∗∗
↑ Cell viability∗∗
↑ HO-1, GCLM, and GCLC at mRNA level (the highest dose was studied)
↑ HO-1 and GCLM at protein level (the highest dose was studied)
Arabameri et al. [64]Maternal separation-induced stress, the neonatal rats, separated 6 hours per day, 15 days↑ MDA in ovarian tissue
↓ SOD, GPx, and FRAP in ovarian tissue
Iranian propolis; cotreatment 50, 100, or 200 mg/kg b.w.; 15 days↓ MDA∗∗ in ovarian tissue
↑ SOD∗∗, GPx, and FRAP∗∗ in ovarian tissue
All three doses exerted a positive effect, but the most effective was 200 mg/kg
Zhang et al. [66]H2O2-induced oxidative stress, RAW264.7 cells, 300 μM for 13 hours↑ Intracellular ROSTwo ethanol extracts of Chinese propolis, pretreatment for 0.5 hour before↓ Intracellular ROS
RAW264.7 cells not subjected to any factor————Two ethanol extracts of Chinese propolis↓ Intracellular ROS
↑ HO-1, GCLM, and TrxR1 on both the mRNA∗∗ and protein levels∗∗
The most effective for HO-1

ADMA: asymmetric dimethylarginine; Bax: Bcl-2-related ovarian killer protein; Bcl-2: B-cell lymphoma 2; CAT: catalase; GCLC: glutamate-cysteine ligase catalytic subunit; GCLM: glutamate-cysteine ligase regulatory subunit; Erk 1/2: extracellular signal-regulated kinase ½, FRAP: ferric reducing ability; GPx: glutathione peroxidase; GRx: glutathione reductase; GSH: reduced glutathione; GST: glutathione reductase; HO-1: heme oxygenase-1; JAK 2: Janus kinase 2; MDA: malondialdehyde; NF-κB: nuclear factor kappa B; Nrf2: nuclear factor erythroid 2-related factor 2 (Nrf2); NO: nitric oxide; 8-oxo-2′-deoxyguanosine, P/O: phosphate/oxygen ratio; PON1: paraoxonase; RCR: respiratory control ratio; ROS: reactive oxygen species; STAT3: signal transducer and activator of transcription 3; SOCS3: suppressor of cytokine signaling 3; SOD: superoxide dismutase; TAS: total antioxidant status; TBARS: thiobarbituric acid reactive substances; TOS: total oxidant status; TrxR1: thioredoxin reductase 1; γ-GCS: γ-glutamylcysteine synthetase. ↓: decrease; ↑: increase; ∗∗the effect depended on used dose.