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Table 1 Characteristics of studies that reported the roles of Propolis in kidney disease

From: A comprehensive insight into the molecular and cellular mechanisms of the effects of Propolis on preserving renal function: a systematic review

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
Zhu et al. [29, 30] China 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
Zhu et al. [29, 30] China 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
  1. Bold used to make it easy distinguishing the results of different groups
  2. AKI, acute kidney injury; CKD, chronic kidney disease; T2DM, type 2 diabetes mellitus; g. gram; mg, milligram; kg, kilogram; FBS, fasting blood sugar; HOMA‑IR, homeostasis model assessment of insulin resistance; TC, total cholesterol; TG, triglyceride; LDL-C, low-density lipoprotein cholesterol; VLDL-C, very low-density lipoprotein cholesterol; SCr, serum creatinine; HOMA-β, homeostasis model assessment of β-cell function; QUICKI, quantitative insulin sensitivity check index; HDL-C, high-density lipoprotein cholesterol; Na+, Sodium; K+, Potassium; Cl, Chloride; DM, diabetes mellitus; i.p., intraperitoneally; STZ, streptozotocin; mL, milliliter; BW, body weight; I/R, ischemic-reperfusion; n, number; MDA, malondialdehyde; 8-OHdG, 8-hydroxy-2′-deoxyguanosine; TNF-α, tumor necrosis factor α; SOD, superoxide dismutase; GSH, glutathione; HTN, hypertension; NOS, nitric oxide synthetase; L‐NAME, Nω‐nitro‐L‐arginine methyl ester; HT, hypertensive; CAPE, caffeic acid phenethyl ester; TOS, total oxidant status; OSI, oxidative stress index; NF‐κB, nuclear factor kappa B; ADMA, asymmetric dimethylarginine; TAS, total antioxidant status; PON1, paraoxonase; CML, Carboxymethyl Lysine; IL-6, interleukin-6; Ig, Immunoglobulin; UAE, urinary albumin excretion; CAT, catalase; GST, glutathione-S-transferase; Cr, creatinine; T1DM, type 1 diabetes mellitus; GBM, glomerular basement membrane; GA, glomerular area; GPx, glutathione peroxidase; FRAP, ferric-reducing ability of plasma; EEP, ethanolic extract of Propolis; NO, nitric oxide; Nx, 5/6 renal ablation; RP, red Propolis; Tbars, urinary levels of reactive oxygen metabolites; ED-1, interstitial and glomerular macrophage infiltration; GS, percentage of Sclerotic glomeruli; IG, glomerulosclerosis Index; INT, masson positive cortical interstitial area; AII, angiotensin II; FENa+, absolute excretion of sodium; FEK+, absolute excretion of potassium; eNOS, endothelial nitric oxide synthetase; HO-1, heme-oxygenase-1; ClCr, creatinine clearance; WSDP, water-soluble derivative of Propolis; UAER, urinary albumin excretion rate; HbA1C, hemoglobin A1C; BUN, blood urea nitrogen; CCR, creatinine clearance rate; MCP-1, monocyte chemoattractant protein-1; eGFR, estimated glomerular filtration rate; UACR, urinary albumin-to-creatinine ratio; BP, blood pressure; 2hpp Glc, 2-h postprandial glucose; hs-CRP, high sensitivity C-reactive protein; IL-1 β, interleukin-1β; RLP-C, remnant-like particle cholesterol
  3. *RCT: Randomized clinical trials