Antiulcerogenic and Ulcer Healing Effects of Indian Propolis in Experimental Rat Ulcer Models

Home , Gefarnate

Journal of ApiProduct and ApiMedical Science 2 (1): 21 - 28 (2010) © IBRA 2010 DOI 10.3896/IBRA.4.02.1.02

ORIGINAL RESEARCH ARTICLE

Antiulcerogenic and ulcer healing effects of Indian propolis in experimental rat ulcer models

S. Iyyam Pillai1, M. Kandaswamy1, and S. Subramanian2*

1Department of Inorganic chemistry, University of Madras, Guindy Campus,Chennai-600 025, Tamilnadu, India

2Department of Biochemistry, University of Madras, Guindy Campus, Chennai-600 025, Tamilnadu, India

Received 16 September 2009, accepted subject to revision 17 December 2009, accepted for publication 23 December 2009.

*Corresponding author: Email: [email protected]

Summary Propolis is a resinous hive product collected by worker bees from various parts of the plants. It is widely used in Indian folk medicine for the treatment of stomach ulcers. The preventive and curative effects of Indian propolis for ulcers were evaluated using models of acute gastric lesions induced by ethanol and indomethacin in rats. Moreover, the effects of ethanolic extract of propolis on gastric content volume, total acidity and pH, using the pylorus ligated model were also evaluated. Animals pretreated with propolis extract showed a significant reduction in lesion index in both ethanol and indomethacin induced ulcer models in a dose dependent manner when compared to the control group. Similarly, post-treatment with propolis (300 mg/kg body weight) for a period of 15 days revealed a statistically significant improvement in the ulcer healing process p <0.05. In the pylorus ligated model, it was observed that the Indian propolis extract displayed an antisecretory activity, which led to a significant reduction in the gastric juice volume, total acidity and pH. These findings indicate that Indian propolis displays both ulcer preventive and ulcer curative properties and provides a scientific rationale for the use of propolis in the traditional medicinal system.

Keywords: Indian propolis, ulcer index, ulcer preventive, ulcer curative, antisecretory

Introduction or NSAIDs has increased, and this affects the management of peptic The term ulcer was first coined by Quike in 1882 (Clinch, 1989) and ulcers (Chan and Leung, 2002). On rare occasions, a gastric ulcer it is now regarded as the new “plague” of the 21st century (O’Melley may become malignant. 2003). A peptic ulcer is a benign lesion in the lining of the stomach The first drug effective against gastric ulcer was or duodenum, where acid and pepsin bathes the surface. Gastric carbenoxolone, which was discovered as a result of research into a mucus is a highly hydrated viscoelastic gel that protects the commonly used indigenous plant, Glycyrrhiza glabra (Leguminosce) epithelium from mechanical stress, as well as from erosion by acid (Hossenbocus and Colin-Jones, 1974). Studies on cabbage, and pepsin (Allen et al., 1993). Peptic ulcers are caused when the previously employed as an antiulcer agent in folk medicine, has led to balance between aggressive factors (such as acid and pepsin) and the development of gefarnate (Barbara et al., 1974). Although defence mechanisms (such as mucus, bicarbonate, blood flow and histamine H2-receptor blockers (for example, ranitidine and mucosal turnover) are shifted in favour of the former (Lima et al., famotidine), proton-pump inhibitors (for example omeprazole and 2006). Factors such as stress, smoking, alcohol usage, nutritional lansoprazole), antibiotics (for example metronidazole, amoxicillin, deficiencies and frequent ingestion of non-steroidal-anti- clarithromycin, and tetracycline,) and other drugs are extensively inflammatory drugs (NSAIDs) have been shown to contribute to used in the management of peptic ulcers, there are reports of gastric ulcer incidence (Belaiche et al., 2002). Although there is adverse effects and relapse within one year (Wolfe and Sachs, 2000). evidence to implicate Helicobacter pyroli in the development of A rational therapy still remains elusive and the search for safer peptic ulcers, the proportion of ulcers not related to either H. pyroli potential drugs continues. 22 Iyyam Pillai, Kandaswamy, Subramanian

Traditionally plants have not only provided food and shelter Preparation of Propolis extract for mankind, but have also been used to cure many different Propolis samples were collected in Mudivaithanendal, Tamil Nadu, ailments (Gilani and Rahman, 2005). Propolis is the generic name India from Apis mellifera hives and kept desiccated in the dark until for a strongly adhesive resinous material gathered by honey bees processing. Samples were air-dried at 40°C for 48 h. 100g of propolis (Apis mellifera L.) from various plant sources (Moreno et al., 2000). powder was extracted in 500 ml of ethanol by stirring overnight at Etymologically, the Greek word propolis is comprised of pro, (for room temperature (Gekker et al., 2005). After filtration, the extract before) and polis, (for the city), which means “defence of the hive”. was concentrated in a rotary evaporator under reduced pressure at Bees use propolis to seal the holes in their honey combs, smooth 60°C and the residue was stored in the dark at room temperature out internal walls and to cover carcasses of intruders that died inside until further use. The yield of the ethanolic extract was 8.5% (w/w). the hive, in order to avoid their decomposition. Propolis also protects A known amount of the solvent free extract was suspended in water the colony from diseases because of its antiseptic efficacy and to obtain the desired concentration of the propolis. antimicrobial properties (Salatino et al., 2005). Propolis contains more than 300 components, including Experimental animals phenolic aldehydes, polyphenols, sequiterpene quinines, coumarins, Healthy, male rats of Wistar strain (160–180 g) were selected for the steroids, amino acids and inorganic compounds (Khalil, 2006). Plant present study. The animals were provided by the Central Animal origin and the region of collection bear great significance with House of the Tamil Nadu Veterinary and Animal Sciences University, respect to the composition of propolis (Christov et al., 2006). Chennai. The animals were housed in cages with raised floors of wide Despite the chemical differences, it is well known that samples of mesh to prevent coprophagy and maintained on sterile, standard different geographical origin and chemical composition usually pellet diet (Hindustan Lever Ltd., Bangalore, India) and water ad demonstrate similar pharmacological properties (Marquele et al., libitum. The light cycle was automatically controlled and room 2005). The chemical properties of propolis are not only beneficial to temperature regulated to 22 ± 1°C. The experiments were designed bees but have general pharmacological value as a natural mixture and conducted to meet the ethical norms approved by the Ministry of (Teixeira et al., 2005). Administration of propolis to mice or humans Social Justice and Empowerment, Government of India and does not seem to have side effects (Jasprica et al., 2007). Propolis is Institutional Animal Ethics Committee Guidelines (IAEC No. still a frequently used remedy for internal and external complaints in 01/032/04) on animal care. Before initiating the experiments, the many parts of India. Recently, propolis has been extensively used in animals were allowed to acclimatize to animal house conditions for a food and beverages to improve health and prevent disorders such as period of one week. heart disease, diabetes, inflammation and cancer. (Hirota et al., 2000; Na et al., 2000). The ethnopharmacological approach to propolis combined Acute oral toxicity studies with chemical and biological methods may provide useful The acute oral toxicity studies were conducted in the rat model (both pharmacological leads. In view of recent reports of therapeutic sexes), according to the method of Litchfield and Wilcoxon (1949) properties, the present study was designed to investigate the and as described in “Guidelines for Testing of Chemicals-Acute Oral preventive (pretreatment) and curative (post-treatment) potential of Toxicity-Fixed Dose Procedure” (OECD 420, 2001). In this study, an ethanolic extract of Indian propolis using experimental models of propolis extract was orally administered to a group of at least 10 rats gastric ulcer in rats, to suggest a mechanism for its pharmacological after a 12 h fast. The control group received equal amount of water action. Both antisecretory and cytoprotection effects were evaluated. by gavage with the aid of a metal gastric cannula. The signs and symptoms associated with a single dose of 7000 mg/kg body weight

(bw) were observed carefully after 0, 30, 60, 120, 180 and 240 min and then once a day for the subsequent 14 days to record toxic

manifestations. Observations included changes in body mass, food Methods and materials and water consumption, hair loss, eyes and mucus membrane and autonomic (salivation, lacrimation, perspiration, piloerection, urinary Drugs and chemicals incontinence and defecation) and the central nervous system Indomethacin, omeprazole and cimetidine were purchased from (optosis, drowsiness, gait, tremors and convulsion). On the 14th day Sigma Aldrich, (St Louis, MD, USA). All other used reagents and both control and propolis treated animals were sacrificed, blood was solvents were of analytical grade. All the drugs and reagents were collected and analysed for haematological parameters such as red prepared freshly before use. and white blood cell counts, haemoglobin, haematocrit (HCT) and Antiulcerogenic properties of Indian propolis 23

mean corpuscular volume (MCV). Biochemical parameters, such as After 15 days, all animals were sacrificed by cervical blood glucose, blood urea, protein, creatine, cholesterol and lipid dislocation, the stomachs was dissected out and opened along the profile were also assessed. The activity of pathophysiological greater curvature. Stomachs were gently rinsed with water to remove enzymes such as Aspartate transaminase (AST), Alanine the gastric contents and blood clots for subsequent ulcer scoring. transaminase (ALT), Alkaline phosphatase (ALP) and Lactate dehydrogenase (LDH) were also assayed. Vital organs such as liver, kidney, heart and lungs were observed macroscopically. The effect of propolis pre-treatment using the indomethacin induced ulcer model Four groups of at least six rats each were set-up. Group I was the The effect of propolis pre-treatment using the ethanol control which received 1 ml water only. Ulcers were induced in all induced ulcer model rats in groups II, III and IV by indomethacin (100 mg/kg bw) by oral The study was performed according to the method of Büyükokuroğlu gavage. Rats in group III were treated with 300 mg/kg bw propolis et al., (2002). After 12 h of fasting, the rats were randomly divided extract daily for 15 days and rats in group IV were treated with into six groups of eight rats each. Group 1 represented the control cimetidine (100 mg/kg bw) daily for 15 days. group which received water only and the group 2 was given 1 ml of After 15 days, all animals were sacrificed and ulcers assessed 99.5% ethanol by oral gavages to induce gastric ulcer (Süleyman et as before. The sum of length of lesions (mm) was calculated and al., 2002). Groups 3, 4 and 5 received 100, 200 and 300 mg/kg bw expressed as lesion index. of propolis extract respectively and group 6 animals were treated with omeprazole (30 mg/kg bw). All pretreatments were administered orally. One hour later all of the animals in groups 3, 4, Shay ulcer model 5 and 6 were given 1 ml of 99.5% ethanol by oral gavages to induce In this model, the rats were divided into three groups each gastric ulcers (Süleyman et al., 2002). After a lapse of 1 h the comprising of a minimum of ten rats each. The rats were fasted for animals were sacrificed by cervical dislocation and stomachs were 24 h with free access to water. Thirty minutes after oral removed and opened along the greater curvature. The stomach was administration of single dose of propolis extract (300 mg/kg bw), gently rinsed with water to remove the gastric contents and blood cimetidine (100 mg/kg bw) as a positive control or water (10 ml/kg clots for subsequent ulcer scoring. bw) as a negative control, the pylorus ligature was performed under phenobarbital anesthesia at a dose of 35 mg/kg bw (Shay et al., 1945). Animals were allowed to recover and stabilize in individual The effect of propolis pre-treatment using the indomethacin cages and were deprived of water during the postoperative period. induced ulcer model Four hours later, the animals were sacrificed by cervical dislocation Six groups of eight rats each were tested as above (Nwafor et al., and the abdomen was opened to place another ligature at the 2000), except that group 6 animals were pretreated with cimetidine oesophageal end. The stomachs were removed and gastric content (100 mg/kg bw) and ulcers were induced in group 2, with was carefully collected and centrifuged at 3000 rpm for 10 min. The indomethacin. One hour after pretreatment, all of the animals in amount of gastric juice and pH was determined by titration with groups 3, 4, 5 and 6 were given indomethacin (100 mg/kg bw) by 0.01N NaOH solution and phenolphthalein as an indicator. Gastric oral gavages to induce gastric ulcers. After 1 h animals were lesions were evaluated by examining the inner gastric surface as sacrificed by cervical dislocation and gastric ulcers determined as described separately. before.

The effect of propolis post-treatment using the ethanol Determination of degree of ulceration (ulcer index) induced ulcer model The surface area (A) mm2 covered by each lesion was measured Male Wistar rats weighing about 160-180 g were divided into four (Murakami et al., 1992) and the sum of erosion areas per rat groups of at least 6 rats each. Group I was the control group which stomach was calculated. Percentage ulcerated surface (US) was received 1 ml water only. Ulcers were induced in all rats in groups calculated as II, III and IV by 1 ml 99.5% ethanol by oral gavages ( Süleyman et Total area covered by ulcer al., 2002). Rats in group III were treated with 300 mg /kg bw % US = ------X 100 propolis extract for each of 15 successive days. Rats in group IV Total corpus mucosal surface were treated with 30 mg / kg bw omeprazole for each of 15 successive days. Ulcer index was calculated from percentage ulcerated surface as 24 Iyyam Pillai, Kandaswamy, Subramanian

described by Tan et al., (1996). The following score was used in significant alterations in food and water consumption or body weight order to calculate ulcer index: gain during the experimental period. Analysis of both haematological 0. No ulcer 6. 15 - 20 and biochemical parameters indicated no significant changes in the 1. US <0.5 7. 20 - 25 propolis treated group of rats when compared to animals in the 2. 0.5 - 2.5 8. 25 - 30 control (untreated) group. Oral administration of propolis extract 3. 2.5 - 5 9. 30 - 35 showed no effect on serum pathophysiological enzyme activities. 4. 5-10 10. US >35 Macroscopic observation on vital organs also confirmed the non-toxic 5. 11-15 nature of propolis. These preliminary studies indicate the absence of acute toxic effects of Indian propolis.

Statistical analysis The values are expressed as mean ± SEM for six rats in each group. Proplis Pretreatment studies All the data were analyzed with SPSS/13 student software. The ulcer preventive effect of the propolis extract on both ethanol Hypothesis testing method included one way analysis of variance and indomethacin induced gastric lesions in experimental rats is (ANOVA) followed by post hoc performed with Least Significant summarized in Tables 1 and 2. Pretreatment with propolis resulted in Difference (LSD) teat. A p value of less than 0.05 was considered to a significant reduction of the gastric lesions induced by two indicate statistical significance. damaging agents (ethanol and indomethacin) in a dose dependent manner and the efficacy was found to be similar in both cases. The ulcer preventive effects of propolis in both models were comparable Results to standard antiulcerogenic drugs omeprazole and cimetidine,

The acute oral toxicity evaluated after a single oral administration of respectively. The results obtained suggest that the crude extract of 7000 mg/kg bw of propolis revealed non-toxicity (results not propolis has a significant antiulcer effect in each of these ulcer shown). All of the animals survived for 14 days. There were no induced models.

Table 1. Effect of propolis pretreatment on ethanol induced ulcerated rats.

Groups Ulcerated surface (%) Ulcer Index

Control 0.0 0

Ethanol induced ulcer 27.18 ± 1.09 a* 8

Ethanol + Propolis extract (100 mg/kg bw) 11.27 ± 0.83 b* 5

Ethanol + Propolis extract (200 mg/kg bw) 4.88 ± 0.51 b* 3

Ethanol + Propolis extract (300 mg/kg bw) 1.93 ± 0.27 b* 2

Ethanol + Omeprazole (30 mg/kg bw) 1.66 ± 0.31 b* 2

Values of ulcerated surfaces (%) are expressed as mean ± SEM of eight rats in each group. * p<0.05. Using one way ANOVA followed by post hoc test LSD. Comparisons are made between Control a, Ethanol induced ulcer b.

Table 2. Effect of propolis pretreatment on indomethacin induced ulcerated rats

Groups Ulcerated surface (%) Ulcer Index

Control 0.0 0

Indomethacin induced ulcer 51.24 ± 5.49 a* 10

Indomethacin + Propolis extract (100 mg/kg bw) 24.18 ± 2.07 b* 7

Indomethacin + Propolis extract (200 mg/kg bw) 12.97 ± 1.21 b* 5

Indomethacin + Propolis extract (300 mg/kg bw) 2.44 ± 0.68 b* 2

Indomethacin + Cimetidine (100 mg/kg bw) 2.09 ± 0.71 b* 2

Values of ulcerated surfaces (%) are expressed as mean ± SEM of eight rats in each group. * p<0.05. Using one way ANOVA followed by post hoc test LSD sons are made between Control a, Ethanol induced ulcer b. Antiulcerogenic properties of Indian propolis 25

Table 3. Effect of propolis on the extent of ulceration in ethanol induced ulcerated rats

Groups Ulcerated surface (%) Ulcer Index Control 0.0 0

Ethanol induced ulcer 49.68 ± 5.17 a* 10

Ethanol + Propolis extract (300 mg/kg b.w) 4.18 ± 0.56 b* 3

Ethanol + Omeprazole (30 mg/kg b.w) 3.95 ± 0.31 b* 3 Values of ulcerated surfaces (%) are expressed as mean ± SEM of eight rats in each group. * p<0.05. Using one way ANOVA followed by post hoc test LSD. Comparisons are made between Control a, Ethanol induced ulcer b.

Table 4. Effect of propolis on the extent of ulceration in indomethacin induced ulcerated rats

Groups Ulcerated surface (%) Ulcer Index

Control 0.0 0

Indomethacin induced ulcer 78.83 ± 6.41 a* 10

Indomethacin + Propolis extract (300 mg/kg bw) 4.59 ± 0.73 b* 3

Indomethacin + Cimetidine (100 mg/kg bw) 3.19 ± 0.54 b* 3

Table 5. Effect of propolis on the extent of ulceration in pylorus-ligated rats

Groups Dose (mg/kg bw) Total gastric volume (ml) Gastric acidity (mEq/L) pH

Control - 2.61 ± 0.73 5.69 ± 0.83 2.17 ± 0.41 Propolis 300 1.63 ± 0.08 a* 3.49 ± 0.21 a* 4.23 ± 0.34 a*

Cimetidine 100 1.48 ± 0.06 a* 3.27 ± 0.25 a* 4.08 ± 0.22 a*

Values are expressed as mean ± SEM of ten rats in each group. One way ANOVA followed by post hoc test LSD. * p<0.05. Comparisons are made between Control a .

Propolis Post-treatment studies Discussion The rats receiving water only showed no lesions in their gastric mucosa. Treatment of rats with ethanol as well as indomethacin In this propolis antiulcerogenic study, acute toxicity in rats was produced typical acute mucosal lesions with ulcer index scores of 10. investigated and a single oral administration of propolis at a Oral administration of propolis extract at a concentration of 300 mg/ concentration of 7000 mg/kg indicated the non-toxic nature of Indian kg bw for 15 days significantly (p <0.05) reduced the ulcer index in propolis. After treatment of rats with different concentrations of both ethanol as well as indomethacin induced experimental ulcer in propolis (up to 6 mg/kg/day) different extracts (water or ethanol) rats and the results were comparable with standard drugs (Tables 3 and varying time of administration (30, 90 and 150 days) has been and 4). In the gastric secretion determination model, using ligated demonstrated not to induce significant alterations in haematological pylorus, the treatment with propolis extract, as well as cimetidine, or biochemical parameters (Mani et al., 2006). Administration of reduced the volume of the gastric juice, total acidity and raised propolis to mice or humans does not seem to have side effects gastric pH significantly in comparison with control groups (Table 5). (Cuesta et al., 2005; Jas Prica et al., 2007). Burdock (1998) reported that the safe dose of propolis for humans could be 70 mg/day. Here dosage fixation studies indicate that the Indian propolis extract at a concentration of 300mg/kg bw/p.o showed the maximum antiulcerogenic activity in both alcohol and indomethacin induced experimental ulcer models in rats. 26 Iyyam Pillai, Kandaswamy, Subramanian

Characteristically propolis is a lipophilic material that is hard unknown, but it has been reported that microcirculation damage can and brittle when cold, but soft, pliable and sticky when warm. Hence be prevented by prostaglandin administration (Guth et al., 1984). On the name bee glue (Hausen et al., 1987). The usual manner to the other hand, ethanol induced gastric lesions are thought to arise extract the fraction soluble in alcohol yields ‘propolis balsam’, leaving as a result of direct damage of gastric mucosal cells, resulting in the the alcohol insoluble or wax fraction (Ghisalberti, 1979). Since production of free radicals (Pihan et al., 1987) and hyperoxidation of ethanol has a low viscosity and readily solubilizes propolis, ethanolic lipids (Puurunen et al., 1980). These data suggest that ethanol is extract is found to be more effective than the aqueous extract in metabolized in the body and releases superoxide anion and eliciting biological properties (Kawabe et al., 2000). Therefore, the hydroperoxy free radicals. Pihan et al., (1987) reported that oxygen- present study was carried out with an ethanol extract of Indian derived free radicals are involved in the mechanism of acute and propolis. chronic ulceration in the gastric mucosa. Furthermore, disturbances In most cases, the stable incidence of ulcer in rat models in gastric secretions, damage of gastric mucosa, alterations in provides a powerful and convenient tool for the investigation of permeability, gastric mucus depletion and free radical production are therapeutic modalities for the disease and for its complications. The observed after the administration of ethanol (Salim, 1990). These ulcer preventive and ulcer curative activities of Indian propolis were data suggest that antioxidant compounds could be active in this evaluated using ethanol, indomethacin and pylorus ligated ulcer experimental model, producing antiulcerogenic effects. This effect is models; the most commonly used experimental models for the known as cytoprotection. evaluation of antiulcer activity is in rats. Based on the results The results of the present study indicate that propolis extract obtained, it is suggested that Indian propolis extract could prevent displays an antiulcerogenic effect related to its cytoprotective activity, and cure gastric lesions caused by necrotizing agents such as since it significantly reduced ethanol induced ulcers. Many reports alcohol, ulcerogenic agents such as indomethacin and the pylorus suggest that phytochemicals such as flavonoids and phenolic ligated model. Gastric mucosal damages induced by different compounds, which are well known for the antiulcer activity, and experimental ulcer models have different mechanisms (Samonina et other antioxidant compounds could be active in this experimental al., 2004). However, the net imbalance in offensive and defencive model producing antiulcerogenic effect (Havsteen, 2002; Repetto and factors brought about by them is thought to be the cause of Llesuy, 2002). Therefore the observed ulcer preventive and ulcer ulcerogenesis (Goel and Bhattacharya, 1991). curative activity of Indian propolis extract may be partially due to its Mucus serves as the first line of the defence against relative antioxidant activity. ulcerogens. The mucus is secreted by mucus neck cells and covers Chronic administration of non-steroidal antiinflammatory the entire gastrointestinal mucosa thereby preventing physical drugs (NSAIDs) such as indomethacin, during the course of anti- damage and back diffusion of hydrogen ions (Williams and inflammatory therapy, is often associated with the development of Turnberg, 1980). Gastric mucus consists of a viscous, elastic adverse gastrointestinal disorders such as gastric erosions, gastric or adherent and transparent gel formed by water and glycoproteins. duodenal ulceration and other severe complications such as The protective effects of mucous barrier depend not only on the gel gastrointestinal haemorrhage or perforation that often limited their structure but also on the amount or thickness of the layer covering wide spread clinical use (Villegas et al., 2004). Indomethacin is the mucosal surface. The ability of the gastric mucosa to resist known to induce gastric ulcer by inhibition of prostaglandins which injury caused by endogenous secretions (acid, pepsin and bile) and are cytoprotective to gastric mucosa (Wallace, 2001), particularly due by ingested irritants such as alcohol, aspirin and NSAIDs can be to the inhibition of cyclooxygenase pathway of arachidonic acid attributed to a number of factors that have been generally referred metabolism resulting in excessive production of leukotrienes and as mucosal defence (Wallace, 2001). other products of 5-lipoxygenase pathway (Rainsford, 1987). In the Ulcers caused by ethanol are due to superficial damage to stomach, prostaglandins play a vital protective role, stimulating the the mucosal cells (Miller and Henagan, 1984). Exposure to ethanol secretion of bicarbonate and mucus, maintaining mucosal blood flow, increases the extension of cellular damage in a dose dependent way and regulating mucosal cell turnover and repair (Hayllar and (Mutoh et al., 1990). Ethanol induced gastric damage may be due to Bjarnason, 1995). Thus, the suppression of prostaglandins synthesis stasis in gastric blood flow, which contributes to the development of by NSAIDs results in increased susceptibility to mucosal injury and haemorrhage and necrotic aspects of tissue injury (Guth et al., gastroduodenal ulceration. Several studies have indicated that 1984). This action is direct on the gastric epithelium also causing gastroduodenal protection by prostaglandins is due to increasing the perturbation of mast cells and release of a vasoactive mediator such mucosal resistance as well as the decrease in aggressive factors, as histamine (Oates and Hakkinen, 1988). Some reports show that mainly acid and pepsin (Aly, 1987). The observed antiulcerogenic changes in gastric circulation after ethanol administration remains property of propolis may be due to increased synthesis of mucous Antiulcerogenic properties of Indian propolis 27

and/or prostaglandins or could possibly be due to its 5-lipoxygenase BÜYÜKOKUROGLU, M E; TAYSI, S; POLAT, F; GÖÇER, F (2002) inhibitory effect. Mechanism of the beneficial effects of dantrolene sodium on ethanol-induced acute gastric mucosal injury in rats. A review of antiulcer drugs of plant origin shows that Pharmacological Research 45: 421-425. triterpenes (because their ability to strengthen defencive factors DOI: 10.1006/ phrs.2002.0951 such as stimulation of mucous synthesis or maintenance of the CHAN, F K; LEUNG, W K (2002) Peptic-ulcer disease. The Lancet prostaglandins content of gastric mucosa at high levels) are 360: 933-941. DOI: 10.1016/S0140-6736(02)11030-0 CHRISTOV, R; TRUSHEVA, B; POPOVA, M; BANKOVA, V; potentially the compounds with antiulcer activity (Lewis and Hanson, BERTRAND, M (2006) Chemical composition of propolis from 1991). Canada, its antiradical activity and plant origin. Natural The ligature of the pyloric sphincter leads to an Product Research 20: 531-536. accumulation of gastric juice in the stomach. The pylorus ligated DOI:10.1080/14786410512331328159 CLINCH, J (1989) Perinatal mortality 1986 & 1987. Irish Journal of technique revealed that propolis extract possess anti-secretary Medical Sciences 158: 148-149. potency and this could suggest an anti-histaminic activity. CUESTA, A; RODRÍGUEZ, A; ESTEBAN, M A; MESEGUER, J (2005) Administration of propolis is found to inhibit both gastric output and In vivo effects of propolis, a honeybee product, on gilthead total acidity. seabream innate immune responses. Fish & Shellfish Immunology 18: 71-80. DOI: 10.1016/j.fsi.2004.06.002 In conclusion, the results of the present study show that DE BARROS, M P; SOUSA, J P; BASTOS, J K; DE ANDRADE, S F Indian propolis possesses antiulcer or cytoprotective activity, as (2007) Effect of Brazilian green propolis on experimental evidenced by its significant inhibition in the formation of ulcers by gastric ulcers in rats. Journal of Ethnopharmacology 110: different animal models, as well as ulcer curative properties by 567-571. DOI: 10.1016/j.jep.2006.10.022 GEKKER, G; HU, S; SPIVAK, M; LOKENSGARD, J R; PETERSON, P K decreasing the gastric secretions. These results were similar to the + (2005) Anti-HIV-1 activity of propolis in CD4 lymphocyte and results obtained with Brazilian green propolis extract, (de Barros et microglial cell cultures. Journal of Ethnopharmacology 102: al., 2007) suggesting that the observed effects of propolis is 158-163. DOI: 10.1016/j.jep.2005.05.045 probably a synergistic effect between reported phytochemicals. GHISALBERTI, E L (1979) Propolis: a review. Bee World 60: 59-84. GILANI, A H; RAHMAN, A U (2005) Trends in ethnopharmacology. Although the active compounds of Indian propolis are not identified Journal of Ethnopharmacology 100: 43- 49. quantitatively, the presence of flavonoids, triterpenes and DOI: 10.1016/j.jep.2005.06.001 glycosides (Kumar et al., 2009) may be regarded as possible active GOEL, R K; BHATTACHARYA, S K (1991) Gastroduodenal mucosal compounds against gastric lesions by increase of protective factors defence and mucosal protective agents. Indian Journal of Experimental Biology 29: 701-714. or antioxidant activity. GUTH, P H; PAULSEN, G; NAGATA, H (1984) Histologic and microcirculatory changes in alcohol-induced gastric lesions in the rat: effect of prostaglandin cytoprotection.

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