Table 1 Characteristics of studies that reported the roles of Propolis in kidney disease
Articles | Cause of AKI or CKD | Samples | Study design | Main results |
|---|---|---|---|---|
A. Animal studies | ||||
Laaroussi et al. [19] Morocco | T2DM: Induced by 10% D-glucose in drinking water throughout the study | Sixty-six male Wistar rats (weighing 173 ± 3 g) were randomly allocated into eleven groups of six rats (groups 1–5: non-diabetic controls; groups 6–11: diabetics): Group 6: untreated; Group 7: Propolis extract (200 mg/Kg); Group 8: bee pollen extract (200 mg/kg); Group 9: Propolis extract (100 mg/kg); Group 10: bee pollen extract (100 mg/kg); Group11: 100 mg/kg of Propolis extract + 100 mg/kg of bee pollen extract | Administration of Moroccan Propolis: 100 or 200 mg/kg/day, by oral gavage for 16 weeks | Comparison between groups 7 and 9 with group 6: Significant decrease: FBS, insulin, HOMA-IR, TC, TG, LDL-C, VLDL-C, SCr, urea, uric acid, kidney weight Significant increase: HOMA-β (only at a dose of 200 mg/kg/day), QUICKI, HDL-C, total serum protein, serum albumin Insignificant: Na+, K+, Cl− *Data regarding the comparison between groups 10 and 11 were not presented in the article |
El Adaouia Taleb et al. [20] Algeria | DM: Induction by i.p. injection of a single dose of STZ solution (65 mg/kg) | Twenty male Wistar rats (weighing 250–300 g) were randomly assigned into four groups of five animals each: Control group, untreated diabetic group, and two diabetic groups treated with Propolis (Group DP30% and Group DP15%) | Administration of the 30% or 15% Turkish Propolis ethanolic extract: 0.5 mL/100 g BW/day, by oral gavage for 4 weeks | Comparison between Propolis receiving groups with untreated Diabetic group: Significant decrease: FBS Significant increase: renal tissue improvement |
El Menyiy et al. [21] Morocco | DM: Induction by a single dose intravenous injection of STZ (60 mg/kg) | Forty-eight adult male Wistar rats (weighing 150–220 g) were divided into eight groups, six rats in each (groups 1–4 non-diabetic; groups 5–8 diabetic): Group 5: untreated; Group 6: glibenclamide; Groups 7 and 8: Propolis (50 or 100 mg/kg/day) | Administration of hydroalcoholic extract of Moroccan Propolis: 50 or 100 mg/kg/day, by oral gavage for 15 days | A) Comparison between Diabetes given single dose of Propolis with untreated Diabetic group: Significant decrease: FBS B) Comparison between groups 7 and 8 with group 5: Significant decrease: FBS, TC, TG, LDL-C, VLDL-C, urea (only at a dose of 100 mg/kg/day), SCr Significant increase: HDL-C, albumin Insignificant: serum protein |
Geyikoglu et al. [22] Turkey | I/R | Thirty-five Sprague–Dawley rats (weighing 250–300 g) were randomly divided into five groups: 1. Control -Sham group, 2. I/R group, 3. The Propolis intervention group, 4. Boric acid intervention group, 5. Propolis + boric acid intervention group (n = 7 per group) | Administration of water-soluble Propolis: 200 mg/kg intra-gastric, one hour before ischemia | Comparison between I/R given Propolis with untreated I/R group: Significant decrease: renal MDA, renal 8-OHdG formation, renal TNF-α, renal congestion, renal hemorrhage, renal hydropic degeneration, necrosis of tubules Significant increase: renal SOD, renal GSH, improvement of kidney tissue Insignificant: Bax Immunoreactivity |
Salmas et al. [23] Turkey | HTN: Induction of HTN by i.p. injection of non‐specific NOS inhibitor L‐NAME (40 mg/kg) for 28 days | Thirty-five male Sprague–Dawley rats (weighing 250–300 g) were separated into five groups of 7 rats each: Group I (control), Group II (L‐NAME = HT), Group III (L-NAME + Propolis), Group IV (L‐NAME + CAPE), and Group V (L‐NAME + pollen) | Administration of Propolis: 200 mg/kg/day, by gavage for 2 weeks | Comparison between L-NAME given Propolis with untreated L-NAME group: Significant decrease: renal TOS, renal OSI, renal NF-κB, renal ADMA Significant increase: renal TAS, renal PON1 |
El Rabey et al. [24] Saudi Arabia | DM: Induction of DM by intravenous injection of STZ 65 mg/kg | Forty male Albino rats (weighing 180–200 g) were separated into four groups (10 rats in each group): negative control (G1), positive diabetic control (G2), the Nigella sativa group (G3), and the Propolis group (G4) | Administration of Saudi Arabian Propolis methanol extract: 20% w/w (200 g of Propolis in one liter of methanol; 20 g of it in 100 ml distilled water with 2 mL of tween 80 (suspending agent) to prepare a 20% solution), orally, for 4 weeks | Comparison between Diabetes given Propolis with untreated Diabetic group: Significant decrease: FBS, percentage of CML, serum and renal MDA, serum and renal IL-6, serum IgG, serum IgA, serum IgM, UAE, urea, SCr, uric acid Significant increase: Serum CAT, serum SOD, serum GST, improvement of the kidney tissue, urine Cr, serum electrolytes levels (Na+ and K+) |
Sameni et al. [25] Iran | T1DM: Induction of T1DM by a single dose of STZ 60 mg/kg by i.p. injection | Forty male Wistar rats (weighing 200–220 g) were divided into five groups (8 rats per group): control, untreated DM, DM with vehicle treatment (10% ethanol), DP100, and DP200 | DP100: DM with administration of 100 mg/kg/day ethanol extract of Iranian Propolis DP200: DM with administration of 200 mg/kg/day ethanol extract of Iranian Propolis All by oral gavage, for 6 weeks | Comparison between Diabetes given Propolis with untreated or vehicle-treated Diabetes: Significant decrease: In both groups: FBS, GBM thickness, In the DP200 group: renal MDA, kidney weight, GA Significant increase: In both groups: renal SOD, renal GPx In the DP200 group: renal FRAP Insignificant: In the DP100 group: renal MDA, renal FRAP, kidney weight *With adjusting blood glucose level, the significance for GA, GBM, MDA, FRAP and GPx (except SOD) were impaired |
Jabir et al. [26] IRAQ | DM: Stimulating diabetes in fasting rats by injection of a single dose of STZ (i.p.) concentration of 60 mg/kg for more than sixteen hours | Seventy-five Sprague–Dawley rats (weighing 150 ± 10 g) were divided randomly into five groups: (1) control (intact rats drenched orally with drinking water), (2) diabetic rats (rats were drenched drinking water), (3) EEP treated intact rats, (4) diabetic with pre-treated of EEP, 5. Post-treated of EEP in diabetic rats (n = 15 per group) | Administration of ethanol extract of Iraqi Propolis: 200 mg/kg/day by drenching for three or 6 weeks | Comparison between EEP pre-treated and Post-treated diabetic rats with untreated Diabetic group: Significant decrease: FBS, serum MDA, serum NO, uric acid Significant increase: serum SOD, serum CAT, serum GST, improvement of the renal tissue, concentration of total serum protein |
Teles et al. [10] Brazil | 5/6 renal ablation (Nx) | Thirty-two adult male Wistar rats (aged 2 months, weighing 220–250 g) were divided into five groups: Sham (n = 8) and Nx (n = 11) untreated rats; Sham + RP (n = 8) and Nx + RP (n = 8) treated rats after 30 days of surgery | Administration of alcoholic extract of Brazilian RP: 150 mg/kg/day orally, for 2 months | Comparison between Nx given RP with untreated Nx group: Significant decrease: Tbars, renal ED-1+ cells, GS, IG, INT, proteinuria, SCr, HTN Significant increase: improvement of renal damage Insignificant: renal AII+ cells |
da Costa et al. [27] Brazil | Unilateral nephrectomy and contralateral renal I/R | Thirty-two male Wistar Rats (weighing 250–300 g) were divided into four groups: 1. Sham + tap water, 2. Sham + RP, 3. I/R + tap water, 4. I/R + RP (n = 8 in each group) | Administration of RP: 150 mg/kg/day by gastric gavage, 3 days before the procedure, and one hour prior to surgical procedure or ischemia | Comparison between I/R given RP with untreated I/R group: Significant decrease: urine MDA, renal MDA, tubular necrosis score, urea, SCr, FENa+, FEK+, Significant increase: renal GSH, renal eNOS score, renal HO-1 score, improvement of kidney damage, ClCr |
Oršolić et al. [28] Croatia | DM: Induction of DM by a single intravenous injection of alloxan 75 mg/kg | Seventy male and female Swiss Albino mice (2–3 months old, weighing 20–25 g) were divided into four groups: control, alloxan control, WSDP-treated diabetic group, EEP –treated diabetic | Administration of Croatian WSDP: 50 mg/kg/day Administration of Croatian EEP: 50 mg/kg/day All by i.p. injection for 7 days | Comparison between Diabetes given Propolis with untreated Diabetic group: Significant decrease: In both groups: liver MDA By WSDP: renal MDA Insignificant: In both groups: FBS, TG, TC, improvement of renal histopathology By WSDP: urea (decreased) By EEP: urea (increased), renal MDA |
T1DM: Induction of T1DM by intravenously injection of a single dose of STZ 50 mg/kg | Forty male Sprague–Dawley rats (weighing 270 ± 40 g) were divided into the following groups: 8 healthy rats as normal group and 32 diabetic rats in four groups of model (untreated diabetes), Chinese Propolis, Brazilian Propolis, and positive (10 mg/kg glucobay) | Chinese group: Administration of 100 mg/kg/day ethanol extracted Chinese Propolis Brazilian group: Administration of 100 mg/kg/day ethanol extracted Brazilian Propolis All by oral intubation, twice daily, for 8 weeks | Comparison between Diabetes given Propolis with untreated Diabetic group: Significant decrease: In both groups: FBS, renal MDA, UAER Chinese group: HbA1C, TC, serum MDA Brazilian group: serum NOS, liver MDA, BUN Significant increase: In both groups: renal CAT In Brazilian group: serum and liver SOD, liver GPx Insignificant: In both groups: TG, LDL-C, HDL-C, serum NO, serum and renal GPx, serum and liver CAT, renal SOD, CCR, SCr, kidney weight In Chinese group: liver MDA, liver GPx, serum and liver SOD, serum NOS, BUN In Brazilian group: HbA1C, TC, serum MDA | |
DM (STZ-induced hepatorenal injury): Induction of diabetes by intravenously injection of STZ 50 mg/kg | Forty male Sprague–Dawley rats (5 weeks old, weighing 230–280 g) were divided into the following groups: 8 healthy rats as normal group and 32 diabetic rats in four groups of model (untreated diabetes), A, B, and positive (10 mg/kg glucobay) | Group A: Administration of 100 mg/kg/day ethanol extracted Chinese Propolis Group B: Administration of 100 mg/kg/day ethanol extracted Brazilian Propolis All by oral intubation, twice daily, continuously for 8 weeks | Comparison between Diabetes given Propolis with untreated Diabetic group: Significant decrease: In both groups: renal GPx, renal MDA, UAER, microalbuminuria, In group A: HbAlC In group B: serum and hepatic MDA, serum NOS Significant increase: In both groups: serum SOD, hepatic GPx, kidney tissue health (a better in kidney lesions in group A than group B) In group B: renal CAT improvement Insignificant: In both groups: serum NO, serum CAT, serum GPx, liver and renal SOD, liver CAT, CCR, BUN, SCr In group A: serum NOS, serum and hepatic MDA, renal CAT In group B: HbA1C | |
Abo-Salem et al. [31] Egypt | T1DM: Induction of T1DM by i.p. injection of STZ 60 mg/kg for three successive days | Fifty adult male Albino Wistar rats (weighing 190–200 g) were divided into five groups (10 animals/ group): control (G1), diabetic control (G2), three groups of EEP (G3, G4, G5) | Administration of ethanol extract of Brazilian green Propolis: 100, 200, 300 mg/kg/day, via oral gavage, for 40 days | Comparison between Diabetes given Propolis with untreated Diabetic group: Significant decrease: FBS, TC, LDL-C, TG, serum and renal MDA, kidney weight, UAE, BUN, SCr (at doses of 200 and 300 mg/kg) Significant increase: HDL-C (at doses of 200 and 300 mg/kg), renal GSH, renal SOD, renal CAT Insignificant: HDL-C (at dose of 100 mg/kg), SCr (at dose of 100 mg/kg), |
B. Human studies (RCTs)* | ||||
Silveira et al. [13] Brazil | CKD caused by diabetes or another etiology | Thirty-two CKD patients were randomized to receive Brazilian green Propolis extract (n = 18) or a placebo (n = 14) | Supplementation with Propolis 500 mg/day (4 tablets of 125 mg each) or placebo 500 mg/day (4 tablets of 125 mg each), for 12 months | Comparison between patients given Propolis with the placebo group: Significant decrease: urinary MCP-1, proteinuria Insignificant: HbA1C, eGFR, UACR, BP |
Zakerkish et al. [32] Iran | T2DM | Ninety-four Patients with T2DM (35–85 years old, receiving treatment with oral hypoglycemic agents) were randomized to receive: Iranian Propolis (n = 50) or placebo (n = 44) | Supplementation with ethanol extract of Iranian Propolis 1000 mg/day (2 capsules of 500 mg each) or placebo 1000 mg/day, for 90 days | Comparison between patients given Propolis with the placebo group: Significant decrease: HbA1C, 2hpp Glc, insulin, HOMA-IR, HOMA-β, serum hs-CRP, serum TNF-α Significant increase: HDL-C Insignificant: FBS, TG, TC, LDL-C, VLDL-C, serum IL-6, serum IL-1β, eGFR, BUN, SCr, uric acid |
Fukuda et al. [33] Japan | T2DM | Eighty patients with T2DM were randomly assigned to receive Brazilian green Propolis (n = 41) or the placebo (n = 39) | Supplementation with Brazilian green Propolis or placebo 226.8 mg/day, once a day for 8 weeks | Comparison between patients given Propolis with placebo group: Insignificant: FBS, HbA1C, insulin, HOMA-IR, TC, TG, HDL-C, LDL-C, RLP-C, serum TNF‑α, serum IL-6, serum hs-CRP, eGFR, UACR, uric acid, urine pH *Values of blood uric acid and eGFR in patients taking the placebo became worse at 8 weeks compared to the baseline, whereas this did not occur in patients consuming Brazilian green Propolis |