Table 2.
The protective effects of propolis against prooxidant action of different harmful factors.
| Source | Toxic or harmful factor | Harmful effects of an applied factor | The type of propolis and the way of application | Effects 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 blood | Chrysin; 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 expression | Brazilian 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 ROS | Two 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.