ARTICLE INFO

Article Type

Original Research

Authors

Paseban   M. (1)
Mousavi Fayzabadi   V. (2 )
Tayyebi Meibodi   N. (3)
Yousefi   M. (4)
Hosseini   A. (5)
Rakhshandeh   H. (*)






(*) Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran
(1) Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
(2 ) Department of Biochemistry, Faculty of Basic Science, Mashhad University of Payam Noor, Mashhad, Iran
(3) Department of Pathology, Imam Reza Hospital, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad , Iran
(4) Department of Persian Medicine, School of Persian and Complementary Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
(5) Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran

Correspondence

Address: Pharmacology Department, Faculty of Medicine, Ferdowsi University campus, Azadi Square, Mashhad, Iran
Phone: +9155036929
Fax: 05138828565
RakhshandehH@mums.ac.ir

Article History

Received:  February  25, 2018
Accepted:  September 22, 2018
ePublished:  January 27, 2019

BRIEF TEXT


Gastrointestinal disorders such as gastric ulcer, duodenal ulcer, gastritis and dyspepsia is one of the problems that is remarkable in modern societies [1]. With 10-15% of people in the community with peptic ulcer disease, the economic impact of this disease is also significant as statistics show that in the United States more than $ 10 billion a year is spent on the disease [2].

... [3-7]. Many studies have been carried out on Plantago herb and these studies have shown the effects of hypoglycemic [8], strong antioxidant [9], hematopoietic activity in bone marrow and spleen cells [10], antibacterial and anti-inflammatory [12, 11], anti-tumor, analgesic, antihypertensive, antiviral, and therapeutic effects for skin, respiratory, digestive, cancer, infections, colds, as well as weak antibiotic effects for this plant [13-15]. In traditional medicine, this plant is used to treat stomach ulcers and in recent studies, the anxiolytic effects of the stomach resulted by aspirin have been reported for this plant [16].

The aim of this study was to determine the effect of plantago hydro-alcoholic extract on indomethacin induced gastric ulcer.

This research is an experimental study.

This research was carried out on Wistar male rats from the animal house of the Medical school of Mashhad University of Medical Sciences.

72 Wistar male rats weighing 220-280 gram were collected from the animal house of the Faculty of Medicine of Mashhad University of Medical Sciences. The rats were randomly divided into 12 groups [17]: Group 1: Carboxymethyl cellulose receptor group 1% (10 mg / kg) (indomethacin solution) for 3 days Group 2: Distilled water for three days receptor group (healthy control group) Group 3 distilled water for three days and then indometacin at a dose of 35 mg / kg receptor group (wound control group = indomethacin group) Group 4: Group receiving 200 mg / kg extract for 3 days and then indomethacin (35 mg / kg) Group 5: Group receiving 400 mg / kg of extract for three days and then indomethacin (35 mg / kg) Group 6: Group receiving 800 mg / kg extract for 3 days and then indomethacin (35 mg / kg) Group 7: Group receiving ranitidine (50 mg / kg) for 3 days and then indomethacin (35 mg / kg) Group 8: Group receiving Indomethacin (35 mg / kg) and then distilled water for three days Group 9: Group receiving Indomethacin (35 mg / kg) and then extract (200 mg / kg) for three days Group 10: Group receiving Indomethacin (35 mg / kg) and then extract (400 mg / kg) for three days Group 11: Group receiving Indomethacin (35 mg / kg) and then extracts (800 mg / kg) for three days Group 12: Group receiving Indomethacin (35 mg / kg) and then ranitidine (50 mg / kg) for three days

First, a50% hydrochloric extract of plantago was prepared by soaking. In all treatment groups, indomethacin was first gavaged in a single dose and then administered for three days with ranitidine and various doses of the extract (200, 400, 800 mg/kg). In the prevention groups, initially, three days of ranitidine administration and various doses of extract (200, 400, 800 mg / kg) were injected, then on the fourth day, indometacin was gavaged and six hours later, the mice were surgically treated. For surgery, the pyloric portion of the stomach was first blocked by suturing for one hour. After an hour, the stomach juice was collected and the stomach was removed. Gastric juice was titrated with NaOH 0.01. Acid normality was calculated by the formula N1V1 = N2V2 and the amount of acid was expressed in mEq / ml of the extract and the amount of the exogenous acid expressed in mEq / ml / h. Evaluation of wound index and therapeutic index: Macroscopic examination of gastric ulcers was performed using microscopy. The gastric ulcers were counted and their numbers and diameters were noted. The wound index was determined based on the area of the wounds (in mm2) in each group and then, based on the formula, the prevention and treatment index was determined for each group. Prevention or Therapeutic Index (%) = {A / (A-B)} × 100 A = Wound index in the control group, B = Wound index in the group receiving the plantgo extract or ranitidine Histopathologic study: The stomach of each group was fixed and numbered in 10% formalin for 72 hours. Then in the pathology section of the stomach tissue, paraffin blocks were prepared and stained with micrometers of 4 micron sections and stained with hematoxylin-eosin. The rats were randomly selected from the gastric tissue of each rat and examined histopathologically. Grading of the lesion was carried out according to Melchiorri et al. article [18]: In this study, statistical analysis of variance and Tukey post hoc test were used.

In both treatment and prevention groups, the wound index in the indomethacin group was significantly higher than the healthy control group (p <0.001). Ranitidine (50 mg / kg) and various doses of Plantago extract (200 mg / kg, 400 mg / kg, 00 mg / kg) in the prevention groups and doses of 200 mg / kg and 800 mg / kg in the treatment groups showed significant decrease in the wound index in comparison with the group receiving Indomethacin (p <0.01 and p <0.05; Figures 1 and 2). In the prevention groups, ranitidine was 55.4% (p <0.01) and doses of 200, 400 and 800 mg / kg extract showed 55.4, 32.6 and 35.8 percent (p <0.01 and p <0.05) of the effect of preventive action against gastric ulcer induced by indomethacin. Also, in the treatment groups, the percentage of treatment index was 48% in the ranitidine group (p <0.05) and in the groups receiving 200 mg / kg and 800 mg / kg doses, respectively, were 40 and 45% (p <0.01) and in the group receiving the dose of 400 mg / kg of extract, it was 15%. In both prevention groups and treatment groups, acid extract was significantly increased in indomethacin group than healthy control group (p <0.01). Also, ranitidine (50 mg / kg) and various doses of plantago (200 mg / kg, 400 mg / kg, 800 mg / kg) in the preventive groups and dose of 200 mg / kg of extract in the treatment groups, significantly decreased (p <0.05) acid extract compared to the group receiving indomethacin (Figures 3 and 4). The degree of mucosal damage in the ranitidine receptor groups and the different dose of the extract significantly decreased compared to the indomethacin group. Ranitidine and dose of 200mg / kg of extract at a dose of 35% and 400 mg / kg and 800 mg / kg dosage of extract reduced the amount of mucosal damage by 30%.

In this study, Plantago extract reduced the secretion of gastric acid, the number of ulcers and mucosal damage induced by indomethacin. In a study, Kubis et al. showed the effects of gastric acid and gastric acid antagonists on gastric ulcer resulting from aspirin, which confirms the results of our study [17]. ... [19-22]. The study of Melseh et al. showed the anti-inflammatory and protective effects of Plantago extract on gastric ulcer induced by acid acetic, which confirmed the results of our study (23). Studies have shown that another mechanism involved in indomethacin induced gastric ulcer is the production of active oxygen species, which causes lipid peroxidation [24]. Regarding the fact that active oxygen species and lipid peroxidation are one of the causative agents of gastric mucus, and according to the study by Melo et al., who have shown the antioxidant effects of Plantago herb [25], it can be said that another possible mechanism of the protective effect of the extract Plantago from indomethacin induced gastric ulcer is due to the antioxidant effects of this plant.

A research is proposed to investigate the effect of plantago on the factors mentioned in the constraints.

One of the limitations of the present study was the non-measurement of total protein secretion, total hexosis, mucus, prostaglandin E2, superoxide dismutase and catalase levels, and the expression of anti-apoptotic protein expression.

Plantago extract with reducing acid secretion has a protective effect against indomethacin induced gastric ulcer, and a dose of 200 mg / kg has a better protective effect.

The authors would like to thank and appreciate the support of the vice president of research and the Student Research Committee of Mashhad University of Medical Sciences.

The authors state that there was no conflict of interest.

The plan was approved in Mashhad University of Medical Sciences in 2011 and at that time there was no need for the ethics committee to approve animal designs. Therefore, the present proposal does not have the Ethics Code. However, at all stages of this study, the ethics of animal work has been respected. Approved Code: 910559

This research is the result of the research work of the authors and its funding is personal.

TABLES and CHARTS

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