Review Article

Antiulcer Effect of Honey in Nonsteroidal Anti-Inflammatory Drugs Induced Gastric Ulcer Model in Rats: A Systematic Review

Table 1

Characteristics of Studies in this Review.

Study 1Ulcer-Induced / DoseRats / FastedGroup / Treatment Dose and DurationMethodologyResult

Adnyana et al. (2014)Aspirin
405 mg in 1% Carboxymethyl cellulose sodium (CMC-Na)
Ethanol
95% (1 ml/200 g)
35 Male albino Wistar 150 – 250 g
1 night before sacrificed
7 Groups of 5 animals each.
(1) Control group – water given
(2) Induced ulcer for 10 days without treatment
(3) Treatment group – honey 2125 mg/kg
(4) Treatment group – honey 4250 mg/kg
(5) Treatment group – Turmeric 135 mg/kg
(6) Treatment group – honey 2125 mg/kg + Turmeric 135 mg/kg
(7) Treatment group – Omeprazole 1.8 mg/kg
Total 10 days experiment
405 mg in 1% CMC-Na, from day 1 – 10, and on day 5 and 95% ethanol (1 ml/200 g).
Treatment given from day 6 until day 10.
Turmeric Rhizome grinded and boiled at 90°C for 15 min.
Honey is diluted with distilled water.
Erosion and inflammation of mucosa lesser in test group than in control group.
Decline in body weight (BW) of rats in control group but not in honey and/or with turmeric group.
Healing ability in group 3, 4, 6 and 7 are consistent with histological result.
No significant difference in gastric acidity parameter except for group 7.
Diameter, number and index ulcer shown that treatment with lower dose honey is more significant in ulcer healing compare to treatment with higher dose honey.
31.51% ulcer healing obtained in group 6 (effect is lower than group 3 but higher than group 5).

Study 2Ulcer-Induced / DoseRats / FastedGroup / Treatment Dose and DurationMethodologyResult

Nasuti et al. (2006)Indomethacin
60 mg/kg.
Male Wistar 150 – 170 g
24 hours before sacrificed
9 groups of 18 animals each.
(1) Control group – water given
(2) Indomethacin (ulcerated group)
(3) Indomethacin + 1.2 g honey
(4) Indomethacin + 2 g honey
(5) Indomethacin + 1.2 g AS
(6) Indomethacin + 2 g AS
(7) Indomethacin + 1.2 g AM
(8) Indomethacin + 2 g AM
(9) Indomethacin + 100 mg Sucralfate
Total 7 days experiment.
Indomethacin 60 mg/kg is induced 30 minutes after daily treatment orally.
Alimento Supervis (AS) containing royal jelly 2%, ginseng powder 4%, ginseng liquid extractive 4% and hydroalcoholic propolis extract 4%.
Alimento Mieleucalipto (AM) containing hydroalcoholic propolis 4% and eucalyptus 4%.
Both AS and AM derived from same chestnut honey.
Evaluation of gastric lesions by UI.
Honey, AS, and AM solubilized in distilled water (4% solution). Ginseng, propolis, eucalyptus, and royal jelly dissolved in hydroalcoholic solution (4%, 16%, and 32% respectively).
UI value
(1) In indomethacin group is 35.6 ± 1.04 vs 0.0 ± 0.00 in control group.
(2) Sucralfate, 2 g/kg of honey, AS, and AM decrease UI to (3.5 ± 1.04, 4.33 ± 2.27, 4.25 ± 0.95 and 3.25 ± 0.25 respectively)
(3) With low honey dose of 1.2 g/kg of honey, AS and AM represent of (23.55 ± 3.63, 18.46 ± 3.39 and 15.08 ± 2.72 respectively)
MPV value
(1) 5.09 ± 0.37 μg EB/g tissue is obtained in indomethacin group vs 2.08 ± 0.47 μg EB/g tissue from control group.
(2) In sucralfate group, 3.27 ± 0.55 μg EB/g tissue.
(3) 2 g/kg of honey, AS, and AM shown (3.44 ± 0.61, 3.04 ± 0.78, 3.15 ± 0.31 μg EB/g tissue respectively)
(4) No reduction of value in 1.2 g/kg of honey, AS, and AM observed compared with indomethacin group.
MPO value
(1) Increase MPO activity in indomethacin compared to control (11.82 ± 0.31 vs 7.54 ± 0.61 U/g tissue respectively)
(2) 2 g/kg of honey, AS, and AM shown (9.21 ± 0.67, 1.31 ± 0.19, 2.07 ± 0.20 U/g tissue respectively)
(3) 1.2 g/kg of honey, AS, and AM shown (5.8 ± 0.24, 8.03 ± 0.25, 6.02 ± 0.87 U/g tissue respectively)

Study 3Ulcer-Induced / DoseRats / FastedGroup / Treatment Dose and DurationMethodologyResult

Gharzouli et al. (2002)Indomethacin
30 mg in 0.25% carboxymethyl cellulose (CMC) + 2 drops of Tween 80 per 10 ml
Aspirin -HCL (ASA-HCL)
300 mg dissolved in 0.15 N HCL containing 0.25% w/v
100% ethanol
5 ml/kg
Either sex Wistar 200 – 250 g
48 hours before sacrificed
8-10 animals per groups
Indomethacin induced ulcer
(1) Indomethacin + 2.5 g/kg of monofloral honey
(2) Indomethacin + 2.5 g/kg of polyfloral honey
(3) Indomethacin + GFSM mixture 50% w/v
(4) Control group receive 5 ml water /kg
Ethanol induced ulcer
(5) Ethanol + 2.5 g/kg of monofloral honey
(6) Ethanol + 2.5 g/kg of polyfloral honey
(7) Ethanol + GFSM mixture 50% w/v
(8) Control group receive 5 ml water /kg
ASA-HCL induced ulcer
(9) ASA-HCL + 2.5 g/kg of monofloral honey
(10) ASA-HCL + 2.5 g/kg of polyfloral honey
(11) ASA-HCL+ GFSM mixture 50% w/v
(12) Control group receive 5 ml water /kg
Honey or glucose – fructose – sucrose – maltose (GFSM) mixture is given just before injection of indomethacin.
Aspirin, by oral gavage 30 minutes after pretreatment with test solution. Killed after 3 hours.
100% ethanol (5ml/kg) by oral gavage 30 minutes after pretreatment with test solution. Killed after 15 min.
Transmural potential difference (PD) obtained between gastric lumen and peritoneal cavity with potentiometric recorder. Acid output evaluated by titration to pH 7 using 0.01 N NaOH.
Model study 1
(1) 30 min require for PD stabilization. 210 min perfusion of saline in control group.
(2) In treated group, 60 min infuse with saline, then 60 min with isotonic honey, then again with saline for 90 min.
(3) At 120 min, histamine dihydrochloride (10 mg/kg) is injected by bolus via superior vein of the penis.
Model study 2
(1) 30 min require for PD stabilization.
(2) Then perfuse with isotonic honey for 60 min.
(3) During period of 15 min, absolute ethanol is added for 5 min to give final 70% concentration. Then, replace the solution with the same preceding preparation.
(4) Control group receive saline with the same protocol of honey.
Total lesions length (mm)
(1) In control group, 52.7 ± 6.9, 11.4 ± 2.2, and 37.8 ± 9.7 observed from ethanol, indomethacin and ASA-HCL respectively.
(2) Indomethacin-induce group (6.7 ± 1.2 from GFSM mixture group, 4.1 ± 0.6 from monoflora honey group and 5.1 ± 0.6 from polyflora honey group) are measured.
(3) ASA_HCL induce group, 4.6 ± 1.5, 3.1 ± 0.6 and 2.8 ± 1.7 are obtained from GFSM mixture, monoflora honey and polyflora honey respectively.
(4) In ethanol induce group, GFSM mixture group shown 1.0 ± 0.4, monoflora honey 0.8 ± 0.5, and polyflora honey 1.0 ± 0.5.

Study 4Ulcer-Induced / DoseRats / FastedGroup / Treatment Dose and DurationMethodologyResult

Gharzouli et al. (2001)Indomethacin
30 mg/kg
50 female Wistar of 210 – 220 g
24 hours before sacrificed
5 animals per group.
(1) Absolute (abs) control – normal saline given
(2) Indomethacin control
(3) 300 mOsm honey
(4) 600 mOsm honey
(5) 1800 mOsm honey
(6) 3600 mOsm honey
(7) 300 mOsm mannitol
(8) 600 mOsm mannitol
(9) 1800 mOsm mannitol
(10) 3600 mOsm mannitol
Indomethacin dose is 30 mg/kg by i.p suspended in normal saline with 30 mg/ml given to animals at the beginning (0 min)
In treated with honey or mannitol groups, doses are given at 0. Min and 2 hours.
At 4th hour, animal sacrificed by cervical dislocation and stomach is taken for UI scoring.
Endogenous prostaglandin 1-2 (PG-1-2) determined by radioimmunoassay (RIA) of oxyntic cell (antrum and fundus of stomach)
UI value
(1) Absent in abs control group
(2) Indomethacin group shows 13.3 ± 4.2
(3) In honey treated group, (5.5 ± 2.9, 1.2 ± 0.5, 1.6 ± 0.7, 1.0 ± 0.5 are observed from dose of 300 mOsm, 600 mOsm, 1800 mOsm and 3600 mOsm respectively.
(4) In mannitol treated group, (5.3 ± 2.4, 1.5 ± 0.7, 1.5 ± 0.6, 1.0 ± 0.4 are observed from dose of 300 mOsm, 600 mOsm, 1800 mOsm and 3600 mOsm respectively.

Study 5Ulcer-Induced / DoseRats / FastedGroup / Treatment Dose and DurationMethodologyResult

Bukhari et al. (2011)Aspirin
200mg
100 male albino rats of 200 - 250 g5 groups with 20 animals each.
Group A: Control group 2ml of 2% gum tragacanth (GT)
Group B: Nigella sativa group (30 mg/kg)
Group C: Natural honey group (30 mg/kg).
Group D: Cimetidine group (0.2 g/kg)
Group E: Acetylsalicylic group (0.2 g/kg)
20 rats from 2ml of 2% GT
2 rats from all groups (group A given 2ml of 2% GT, group B, C, D, and E given 0.2 g/kg of acetylsalicylic) and sacrificed after 3 days for gastric lesions confirmation.
The remaining rats divided into subgroups (1, II, and III and sacrificed after 2 weeks, 4 weeks, and 6 weeks respectively) and give the treatment accordingly.
All chemical used suspended in 2% GT aqueous solution.
Honey diluted in distilled water and administered orally with 0.5 ml/100 g BW.
By the gross examination, number of animals with lesion from each group:
(1) AI – AIII = 0
(2) BI = 1, BII = 1, and BIII = 1
(3) CI = 1, CII = 1, and CIII = 1
(4) DI = 0, DII = 1, and DIII = 0
(5) EI = 5, EII = 6, and EIII = 6
By the gross examination, number of animals with lesion from each group:
(1) AI – AIII = 0
(2) BI = 2, BII = 1 and BIII = 2
(3) CI = 2, CII = 2 and CIII = 1
(4) DI = 1, DII = 1, and DIII = 0
(5) EI = 5, EII = 6 and EIII = 6