Journal Information
Vol. 36. Num. 4.October - December 2016
Pages 185-276
Share
Share
Download PDF
More article options
Visits
653
Vol. 36. Num. 4.October - December 2016
Pages 185-276
Original Article
DOI: 10.1016/j.jcol.2016.04.007
Open Access
Effects of hydroalcoholic extract of Ziziphus jujuba on acetic acid induced ulcerative colitis in male rat (Rattus norvegicus)
Efeitos do extrato hidroalcoólico de Ziziphus jujuba na colite ulcerativa induzida pelo ácido acético em rato macho (Rattus norvegicus)
Visits
653
Nader Tanideha,b, Akram Jamshidzadehc, Ali Ghanbari Sagheslooc,
Corresponding author
articlepublishers93@gmail.com

Corresponding author.
, Farhad Rahmanifard, Maral Mokhtarie, Omid Koohi-Hosseinabadif, Mahmood Omidic, Asma Najibic
a Shiraz University of Medical Sciences, Stem Cell and Transgenic Technology Research Center, Shiraz, Iran
b Shiraz University of Medical Sciences, School of Medicine, Department of Pharmacology, Shiraz, Iran
c Shiraz University of Medical Sciences, School of Pharmacy, Department of Pharmacology Toxicology, Shiraz, Iran
d Shiraz University, School of Veterinary Medicine, Department of Anatomy, Shiraz, Iran
e Shiraz University of Medical Sciences, School of Medicine, Department of Pathology, Shiraz, Iran
f Shiraz University of Medical Sciences, Center of Comparative and Experimental Medicine, Shiraz, Iran
This item has received
653
Visits

Under a Creative Commons license
Article information
Abstract
Full Text
Bibliography
Download PDF
Statistics
Figures (3)
Show moreShow less
Tables (1)
Table 1. Experimental setup and treatments which used in this study.
Abstract
Objective

To investigate the effects of hydroalcoholic extract of Ziziphus jujuba on the histopathological, tissue oxidative stress and inflammation plus to antioxidant pathways of colon tissue in rat with induced Ulcerative colitis.

Materials and methods

Ulcerative colitis was induced in 80 rats those divided into 8 equal groups. Group 1 and 2 were negative controls receiving 1mL/day of normal saline in enema and oral; group 3 and 4 as positive control 1 and 2 received 10mg/kg of intra-colonic asacol and oral mesalazine; groups 5 and 6 received 20% and 40% of hydroalcoholic extract of Z. jujuba trans-rectally; group 7 and 8 received 1500 and 3000mg/kg of hydroalcoholic extract of Z. jujuba orally, respectively. After 7 days, animals were evaluated for colon tissue histopathology, levels of malondialdehyde and IL-1β, and activities of superoxide dismutase, glutathione peroxidase and myeloperoxidase in colon tissue.

Results

Hydroalcoholic extract of Z. jujuba in both forms of trans-rectal and oral administration especially in the higher doses could result into a more healing effect in damaged colonic tissue, more reduce glutathione peroxidase and IL-1β level. Also, these two doses (gel 40% and oral 3000mg/kg) could more decrease the myeloperoxidase activity and stimulate superoxide dismutase and glutathione peroxidase activities. Also, gel 40% in transrectal administration was more potent than administration 3000mg/kg in oral.

Conclusion

The results of the present study indicated that Z. jujube may be considered as a treatment of choice for Ulcerative colitis especially in gel form and also in dose-dependent pattern.

Keywords:
Ziziphus jujuba
Ulcerative colitis
Oxidative stress
Histopathology
Inflammation
Resumo
Objetivo

Investigar os efeitos do extrato hidroalcoólico de Ziziphus jujuba no estresse oxidativo em tecido ao nível histopatológico e na inflamação, juntamente com as vias antioxidantes em tecido de cólon em ratos com colite ulcerativa induzida.

Materiais e métodos: Induzimos colite ulcerativa em 80 ratos, divididos em 8 grupos iguais. Os grupos 1 e 2 eram controles negativos que receberam 1mL/dia de salina normal em enema e por via oral; os grupos 3 e 4 eram controles positivos para 1 e 2 e receberam 10mg/kg de asacol por via intracolônica e mesalazina oral; os grupos 5 e 6 receberam gel a 20% e 40% de extrato hidroalcoólico de Z. jujuba por via trans-retal; os grupos 7 e 8 receberam 1500 e 3000mg/kg de extrato hidroalcoólico de Z. jujuba por via oral, respectivamente. Transcorridos 7 dias, os animais foram avaliados para histopatologia de tecido de cólon, níveis de malonildialdeído e IL-1β, e atividades de superóxido dismutase, glutátion peroxidase e mieloperoxidase no tecido colônico.

Resultados

O uso do extrato hidroalcoólico de Z. jujuba, tanto na forma transretal como oral, e em especial nas doses mais altas, resultou em um efeito de cicatrização mais intensa no tecido colônico lesionado, e em maior redução nos níveis de glutátion peroxidase IL-1β. Além disso, essas duas doses (gel a 40% e 3000mg/kg por via oral) diminuíram ainda mais a atividade de mieloperoxidase e estimularam as atividades de superóxido dismutase e glutátion peroxidase. Outro achado do estudo foi que o gel a 40% por administração trans-retal se mostrou mais potente do que a administração oral de 3000mg/kg.

Conclusão

Os resultados do presente estudo sugerem que Z. jujuba pode ser considerado como tratamento de escolha para colite ulcerativa, sobretudo em forma de gel e também em um padrão proporcional à dose administrada.

Palavras-chave:
Ziziphus jujuba
Colite ulcerativa
Estresse oxidativo
Histopatologia
Inflamação
Full Text
Introduction

Inflammatory bowel diseases (IBDs) include two parts, ulcerative colitis (UC) and Crohn's disease (CD). UC affected the superficial layer of all parts of the large intestine specially descending colon and rectum.1 Incidence of UC is 1.2–20.3 cases and its prevalence is 7.6–240 cases per 100000 peoples in each year.2 The basis of the UC is genetically susceptibility to inflammation and also environmental triggers.3 These environmental factors include microbiological,4,5 immunological,6 smoking and psychological factors.5 So, some treatments can be applicable to overcome these environmental factors. In addition, besides the cost of treatment, the impact of UC on quality of life is staggering.7 Therefore, finding effective and cost benefit treatment for UC is necessary.

Before each study for finding good therapeutic agents for UC, it is necessary to simulate the conditions similar to human UC in animal models. There are several models for induction of UC in animals such as use of trinitrobenzene sulfonic acid (TNBS) (7), dextran sodium sulfate,8 and acetic acid.9 Rectal administration of acetic acid can mimic the conditions which occurred in human UC10 and related UC is a reproducible laboratory animal model and is useful for screening of effectiveness of drugs.11

Use of medicinal plants and their derivatives has an ancient basis. Ziziphus jujube is a herbal plant belongs to the Rhamnaceae family and is one of the most important Ziziphus species.12 The jujube fruit contains many bioactive compounds, including triterpenic acids, flavonoids, cerebrosides, phenolic acids, α-tocopherol, β-carotene, and polysaccharides. Each constituent of the jujube presents some health benefits, thus making it a healthy food choice and also as therapeutic agent.13 The beneficial effects of administration of Z. jujuba as alternative treatment in oral mucositis (OM) has been reported previously.14 The objective of present investigation was to evaluate the therapeutic effects of hydroalcoholic extract of Z. jujuba in experimentally induced UC in male rat as an animal model for human studies.

Materials and methodsEthical statement

The protocol of the presented study is approved by the Ethical Committee of Shiraz University of Medical Sciences. All efforts were made to prevent the harmful handling of the animals and also the lowest but statistically significant number of the animals was allocated in each group.

Fruit and extraction

Z. jujuba fruits were purchased from local market and after genus and species confirmation by Botanist affiliated to Agriculture School of Shiraz University, were finely grounded by mixer. The hydroalcoholic extraction was performed according to previous report.15 The antioxidant content of this extract was evaluated using ferric reducing antioxidant power (FRAP) test as described previously.16

Animals

In this study, 80 male Sprague Dawley rats with mean and SD of weigh of 200±20g were purchased from the Center of Comparative and Experimental Medicine, Shiraz University of Medical Sciences. They kept under conventional conditions include 22±1°C, 55±5% relative humidity, and 12/12h light/dark cycles before the onset of the study for acclimation and during the study period. All rats were fasted for 24h and then UC was induced by rectal administration of 1mL of 3% acetic acid. Animals were randomly allocated into 8 equal separated groups and received different treatment after 24h, based on the Table 1.

Table 1.

Experimental setup and treatments which used in this study.

Group no.  Abbreviation  Treatment 
Negative control 1 (NC1)  1mL normal saline, enema 
Negative control 2 (NC2)  1mL normal saline, oral 
Positive control 1 (PC1)  Asacol 10mg/kg, enema 
Positive control 2 (PC2)  Mesalazine 10mg/kg, oral 
Gel 20%  1mL of gel 20% of ZJHE, enema 
Gel 40%  1mL of gel 40% of ZJHE, enema 
Oral 1500  1mL of solution of ZJHE as dose 1500mg/kg, oral 
Oral 3000  1mL of solution of ZJHE as dose 3000mg/kg, oral 

ZJHE, Z. jujuba hydroalcoholic extract.

At the end of the 7th day, all rats were sacrificed by cervical dislocation and samples from colon tissue were obtained and fixed in 10% buffered formalin. The tissue processing and histopathological slide preparation were performed according to previous procedures.17–19 The histopathological sections were evaluated for severity and extent of inflammation, crypt damage, percent of involvement and regeneration.

Measurement of malondialdehyde (MDA) level

Briefly, 500mg of tissue was homogenized in 5mL of 1.15% cold KCl. Then, 3mL of 1% phosphoric acid and 1mL of 0.6% tiobarbitoric acid were added to 500μl of homogenate and shake well. After indirect heating at 100°C for 45min, the centrifugation was performed at 10000rpm for 10min and the absorbance of the supernatant was measured in 532nm using UV-visible spectrophotometer.

Myeloperoxidase (MPO) activity

Two mL of phosphate buffer contain 0.5% hexadecyl trimethyl ammonium bromide (HTAB) was added to 100mg of colon tissue and homogenized on ice for six times of 45s. Then, 10s of sonication and freeze by liquid nitrogen were applied for three times. Centrifugation at 3000rpm and 4°C for 30min was performed and supernatant was harvested. 2.9mL of phosphate buffer contain o-Dianisidine and 0.005% hydrogen peroxide was added to 0.1mL of supernatant and after 5min, 0.1mL of 1.2M HCl was added to tube to orange color was appeared. The absorbance of the samples was measured at 460nm by UV–visible spectrophotometer and the activity of MPO was calculated using a standard curve.

Superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities

The activities of these two antioxidative enzymes were assessed using commercial kits (Biorexfars, Iran).

Interleukin (IL)-1β

The colon tissue content of IL-1β determined by commercial quantities enzyme linked immunosorbent assay (ELISA) kit (Biosource, USA) according to the manufacturer instruction.

Statistical analysis

Data were expressed as mean and SD and analyzed using SPSS version 21. One way analysis of variance (ANOVA) with using Tukey as Posthoc test were used to find statistical significant differences (p<0.05). GraphPad 6 was used for drawing the charts.

Results

Evaluation of damage and regeneration in the colon tissue showed that the severity and extent of inflammation, crypt damage, percent of involvement and regeneration in NC1 and NC2 were significantly higher than all other groups (p<0.05) but not statistically significant together (p>0.05). No significant differences were detected between other 6 groups in all pathological indices include inflammation severity and extent, crypt damage, percentage of involvement and regeneration (p>0.05) (Fig. 1).

Fig. 1.
(0.34MB).

Comparison of histopathological indices of damage and regeneration between different groups. Significant statistical differences between groups in each index are indicated by different superscript letter (p<0.05).

Comparison of MDA level as oxidative stress index and activities of two antioxidative enzymes, SOD and GPx, in colon tissue are presented in Fig. 2. As shown, the colon tissue MDA concentration in NC1 and NC2 were significantly higher than all other groups (p<0.05) but not statistically significant together (p>0.05). The tissue MDA concentration in gel 20% was significantly higher than gel 40% and oral 3000 groups and significantly lower than all other groups (p<0.05). Despite of the NC1 and NC2, the MDA level in oral 1500 group was significantly higher than all other groups (p<0.05) but not significantly differ with PC2 (1.85±0.04μnol/L vs. 1.83±0.06μnol/L, p>0.05). Lowest MDA level was detected in gel 40% group (0.86±0.03μnol/L) followed by oral 3000 group (1.07±0.04μnol/L) (Fig. 2A). Changes in the activities of both SOD and GPx showed approximately similar pattern. This included higher activities of enzymes in all groups in comparison to both NC groups, highest and lowest activities of both enzymes between treatment group in gel 40% and PC2, respectively, and highest activities of both enzyme in response to oral mesalazine in comparison to enema asacol. Other differences and their significances are shown in Fig. 2B and C.

Fig. 2.
(0.2MB).

Comparison of mean and SD of A, malondialdehyde level; B, glutathione peroxidase activity and C, superoxidase dismutase activity in colon tissues of different experimental groups. Significant statistical differences between groups in each index are indicated by different superscript letter (p<0.05).

Comparison of inflammatory biomarkers of IL-1β and MPO activity in colon tissue of different groups are presented in Fig. 3. As shown, these two inflammatory indices were decreased in response to treatments in comparison to both NC groups (p<0.05). The most declines were belonged to the gel 40% group (210.00±22.47pg/mL for IL-1β and 1.19±0.05IU/L for MPO) followed by oral 3000 group (318.20±31.49pg/mL for IL-1β and 1.37±0.03IU/L for MPO). Other values and their significances can be seen in Fig. 3A and B.

Fig. 3.
(0.14MB).

Changes of inflammatory indices in colon tissues of rats in different groups. A, IL-1β level; B, myeloperoxidase activity. Significant statistical differences between groups in each index are indicated by different superscript letter (p<0.05).

Discussion

In the present study antioxidative, anti-inflammatory and regenerative effects of hydroalcoholic extract of Z. jujuba in 4 doses of 20% and 40% in gel form and enema route and 1500mg/kg and 3000mg/kg in oral route in acetic acid induced UC in rat model were investigated. Overall, stimulatory effects on the activities of SOD and GPx, decreasing effects on IL-1β and MDA level plus MPO activity and healing and regenerative effects in histopathological features were detected in response to use of plant extract. Also, enema route is better than oral administration in all effects and dose-dependent response was detected in both routes of administration.

In previous studies, different plants and derivatives were explored for treatment of UC. It has been reported that hydroalcoholic extract of Teucrium polium could increase healthy cells in the colon tissue, decrease the inflammation severity and resolve the inflammation of colon tissue.20 Effects of different doses and routes of administration of hydroalcoholic extract of licorice for 7 day in treatment of UC in rat were investigated. It is found that these treatment decreased the intestinal epithelium damages, TNF-α, IL-6 and NO and increased SOD activity in dose-response pattern.21 Improving of pathological conditions of colon, increase of weight and decline in MDA level were seen in rat suffered from UC in response to strawberry extract in dose-response type.22 Similar findings are reported by our group and other scientists for Berberis vulgaris,23Melilotus officinalis,9Hypericum perforatum,24,25Calendula officinalis26 and Pistachia atlantica27 in line with findings of this study. However, the reports about the beneficial effects of using of Z. jujuba in inflammatory diseases are scarce. Hydroalcoholic extract of Z. jujube can reverse oxidative stress induced by pentylenetetrazole (PTZ) and electroshock in experimental models of epilepsy in rats.28 Also, the beneficial effects hydroalcoholic extract of Z. jujuba as alternative treatment in OM as another inflammatory diseases was reported by our group previously.14

There are several possible mechanisms for these observations. The most important of them is the role of oxidative stress in the pathophysiology of UC. In UC, primary increase of free radicals and secondary hypoxic conditions and chemokines production induced neutrophils and mast cell migration to the colon tissue and increased inflammation and oxidative stress in this organ by help of arachidonic acid metabolites, cytokines and other chemokines.29Z. jujuba contains several polyphenolic compounds such as gallic acid, catechins, caffeic acid, chlorogenic acid, cinnamic acid, coumarin and coumaric acid.30–32 These compounds express antiinflammatory and antioxidative effects by blocking the arachidonic acid pathway and inhibiting phospholipase-1, cyclooxygenase and lipooxygenase.30

Conclusion

Inflammatory diseases such as UC are currently treated with steroidal and non-steroidal anti-inflammatory drugs (NSAIDs), but our findings suggest hydroalcoholic extract of Z. jujuba as a new therapeutic agent for UC. This can be concluded from stimulation of healing process and inhibition of the inflammatory and oxidative pathways.

Conflicts of interest

The authors declare no conflicts of interest.

Acknowledgments

Authors wish to thank all staffs of Department of Pharmacology Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran for their cooperation in experimental procedure and analysis. This article was extracted from MSc Thesis of Mr. Ali Ghanbari Saghesloo with supervision of Dr. Nader Tanideh and Dr. Akram Jamshidzadeh. The authors also thanks The Articlepublishers group (www.articlepublishers.ir) for kindly help in article revision.

References
[1]
M.W.M.D. Lutgens, M.G.H. van Oijen, G.J.M.G. van der Heijden, F.P. Vleggaar, P.D. Siersema, B. Oldenburg
Declining risk of colorectal cancer in inflammatory bowel disease: an updated meta-analysis of population-based cohort studies
Inflamm Bowel Dis, 19 (2013), pp. 789-799 http://dx.doi.org/10.1097/MIB.0b013e31828029c0
[2]
M. Economou, E. Zambeli, S. Michopoulos
Incidence and prevalence of Crohn's disease and its etiological influences
Ann Gastroenterol, 22 (2009), pp. 158-167
[3]
P. Heydarpour, R. Rahimian, G. Fakhfouri, S. Khoshkish, N. Fakhraei, M. Salehi-Sadaghiani
Behavioral despair associated with a mouse model of Crohn's disease: role of nitric oxide pathway
Progr Neuro-Psychopharmacol Biol Psychiatry, 64 (2016), pp. 131-141
[4]
J. Peterson, S. Garges, M. Giovanni, P. McInnes, L. Wang, J.A. Schloss
The NIH human microbiome project
Genome Res, 19 (2009), pp. 2317-2323 http://dx.doi.org/10.1101/gr.096651.109
[5]
T.E. Andreoli, J.G. Fitz, I. Benjamin, R.C. Griggs, E.J. Wing
Andreoli and Carpenter's Cecil essentials of medicine
Elsevier Health Sciences, (2010)
[6]
F. Seibold, S. Brandwein, S. Simpson, C. Terhorst, C.O. Elson
pANCA represents a cross-reactivity to enteric bacterial antigens
J Clin Immunol, 18 (1998), pp. 153-160
[7]
W.E. Cromer, C.V. Ganta, M. Patel, J. Traylor, C.G. Kevil, J.S. Alexander
VEGF-A isoform modulation in an preclinical TNBS model of ulcerative colitis: protective effects of a VEGF164b therapy
J Transl Med, 11 (2013), pp. 207 http://dx.doi.org/10.1186/1479-5876-11-207
[8]
X. Jiang, L. Zhong, D. Sun, L. Rong
Magnesium lithospermate B acts against dextran sodiumsulfate-induced ulcerative colitis by inhibiting activation of the NRLP3/ASC/Caspase-1 pathway
Environ Toxicol Pharmacol, 41 (2016), pp. 72-77 http://dx.doi.org/10.1016/j.etap.2015.10.009
[9]
A.R. Safarpour, F. Kaviyani, M. Sepehrimanesh, N. Ahmadi, O. Koohi Hosseinabadi, N. Tanideh
Antioxidant and anti-inflammatory effects of gel and aqueous extract of Melilotus officinalis L. in induced ulcerative colitis: a Rattus norvegicus model
Ann Colorect Res, 3 (2015), pp. e29511
[10]
A.D. Kandhare, K.S. Raygude, P. Ghosh, A.E. Ghule, T.P. Gosavi, S.L. Badole
Effect of hydroalcoholic extract of Hibiscus rosa sinensis Linn. leaves in experimental colitis in rats
Asian Pac J Trop Biomed, 2 (2012), pp. 337-344 http://dx.doi.org/10.1016/S2221-1691(12)60053-7
[11]
D.C. Baumgart, S.R. Carding
Inflammatory bowel disease: cause and immunobiology
[12]
Y.-L. Huang, G.-C. Yen, F. Sheu, C.-F. Chau
Effects of water-soluble carbohydrate concentrate from Chinese jujube on different intestinal and fecal indices
J Agric Food Chem, 56 (2008), pp. 1734-1739 http://dx.doi.org/10.1021/jf072664z
[13]
Z. Tahergorabi, M.R. Abedini, M. Mitra, M.H. Fard, H. Beydokhti
Ziziphus jujuba: a red fruit with promising anticancer activities
Pharmacogn Rev, 9 (2015), pp. 99-106 http://dx.doi.org/10.4103/0973-7847.162108
[14]
O. Koohi-Hosseinabadi, A. Andisheh-Tadbir, P. Bahadori, M. Sepehrimanesh, M. Mardani, N. Tanideh
Comparison of the therapeutic effects of the dietary and topical forms of Zizyphus jujuba extract on oral mucositis induced by 5-fluorouracil: a golden hamster model
J Clin Exp Dentist, 7 (2015), pp. e304-e309
[15]
M. Mardani, S.M. Afra, N. Tanideh, A. Andisheh Tadbir, F. Modarresi, O. Koohi-Hosseinabadi
Hydroalcoholic extract of Carum carvi L. in oral mucositis: a clinical trial in male golden hamsters
Oral Dis, 22 (2016), pp. 39-45 http://dx.doi.org/10.1111/odi.12375
[16]
N. Kazemipour, M. Nikbin, M.T. Maghsoudlou, M. Sepehrimanesh
Antioxidant properties of extracts of Scutellaria lute-caerulea in vitro
Online J Vet Res, 18 (2014), pp. 75-81
[17]
M. Panahi, N. Karimaghai, F. Rahmanifar, A. Tamadon, A. Vahdati, D. Mehrabani
Stereological evaluation of testes in busulfan-induced infertility of hamster
Comp Clin Pathol, 24 (2015), pp. 1051-1056
[18]
A. Tamadon, B. Nikahval, M. Sepehrimanesh, M. Mansourian, A.T. Naeini, S. Nazifi
Epididymis ligation: a minimally invasive technique for preparation of teaser rams
[19]
A. Yazdani, S.L. Poorbaghi, H. Habibi, S. Nazifi, F. Rahmani Far, M. Sepehrimanesh
Dietary Berberis vulgaris extract enhances intestinal mucosa morphology in the broiler chicken (Gallus gallus)
Comp Clin Pathol, 22 (2013), pp. 611-615
[20]
D. Mehrabani, F. Bahrami, S.V. Hosseini, M.J. Ashraf, N. Tanideh, A. Rezaianzadeh
The healing effect of Teucrium polium in acetic acid-induced ulcerative colitis in the dog as an animal model
Middle East J Diges Dis, 4 (2012), pp. 40-47
[21]
M. Allizadeh-Naeini, N. Tanideh, A. Zargari-Samadnejad, S. Mehrvarz
Healing effect of Licorice extract in acetic acid-induced ulcerative colitis in rat
Res Pharmaceut Sci, 7 (2012), pp. S837
[22]
N. Tanideh, F. Akbari Baseri, A. Jamshidzadeh, M.J. Ashraf, O. Kuhi, D. Mehrabani
The healing effect of strawberry extract on acetic acid-induced ulcerative colitis in rat
World Appl Sci J, 31 (2014), pp. 281-288
[23]
N. Tanideh, E. Afaridi, D. Mehrabani, N. Azarpira, M. Hosseinzadeh, M. Amini
The healing effect of Berberis vulgaris in acetic acid-induced ulcerative colitis in rat
Middle-East J Scient Res, 21 (2014), pp. 1288-1294
[24]
T. Dost, H. Ozkayran, F. Gokalp, C. Yenisey, M. Birincioglu
The effect of Hypericum perforatum (St. John's Wort) on experimental colitis in rat
Digest Dis Sci, 54 (2009), pp. 1214-1221 http://dx.doi.org/10.1007/s10620-008-0477-6
[25]
N. Tanideh, S.L. Nematollahi, S.V. Hosseini, M. Hosseinzadeh, D. Mehrabani, A. Safarpour
The healing effect of Hypericum perforatum extract on acetic acid-induced ulcerative colitis in rat
Ann Colorect Res, 2 (2014), pp. e25188
[26]
D. Mehrabani, M. Ziaei, S.V. Hosseini, L. Ghahramani, A.M. Bananzadeh, M.J. Ashraf
The effect of Calendula officinalis in therapy of acetic acid induced ulcerative colitis in dog as an animal model
Iran Red Crescent Med J, 13 (2011), pp. 884-890
[27]
N. Tanideh, S. Masoumi, M. Hosseinzadeh, A.R. Safarpour, H. Erjaee, O. Koohi-Hosseinabadi
Healing effect of pistacia atlantica fruit oil extract in acetic acid-induced colitis in rats
Iran J Med Sci, 39 (2014), pp. 522-528
[28]
M. Pahuja, J. Mehla, K.H. Reeta, S. Joshi, Y.K. Gupta
Hydroalcoholic extract of Zizyphus jujuba ameliorates seizures, oxidative stress, and cognitive impairment in experimental models of epilepsy in rats
Epilepsy Behav, 21 (2011), pp. 356-363 http://dx.doi.org/10.1016/j.yebeh.2011.05.013
[29]
J. Pravda
Radical induction theory of ulcerative colitis
World J Gastroenterol, 11 (2005), pp. 2371-2384
[30]
R.T. Mahajan, M.Z. Chopda
Phyto-pharmacology of Ziziphus jujuba mill – a plant review
Pharmacogn Rev, 3 (2009), pp. 320-329
[31]
M. Elaloui, A. Laamouri, J. Fabre, C. Mathieu, G. Vilarem, B. Hasnaoui
Distribution of free amino acids, polyphenols and sugars of Ziziphus jujuba pulps harvested from plants grown in Tunisia
[32]
J. Liu, B. Chen, S. Yao
Simultaneous analysis and identification of main bioactive constituents in extract of Zizyphus jujuba var. sapinosa (Zizyphi spinosi semen) by high-performance liquid chromatography–photodiode array detection–electrospray mass spectrometry
Idiomas
Journal of Coloproctology

Subscribe to our Newsletter

Article options
Tools
en pt
Cookies policy Política de cookies
To improve our services and products, we use "cookies" (own or third parties authorized) to show advertising related to client preferences through the analyses of navigation customer behavior. Continuing navigation will be considered as acceptance of this use. You can change the settings or obtain more information by clicking here. Utilizamos cookies próprios e de terceiros para melhorar nossos serviços e mostrar publicidade relacionada às suas preferências, analisando seus hábitos de navegação. Se continuar a navegar, consideramos que aceita o seu uso. Você pode alterar a configuração ou obter mais informações aqui.