INTRODUCTION :

An ulcer is defined as disruption of the mucosal integrity of the stomach and/or duodenum leading to a local defects or excavation due to active inflammation, ulcer occur within the stomach and/or duodenum and are often chronic in nature, peptic disorders are very common in India, with 4 Million individuals (new Cases and recurrences) affected per year, Life time prevalence of PUD in the India is approximately 12% in men and 10% in women. Move over an estimated 15,000 deaths per year occur as a consequence of complicated PUD. The Financial impact of these common disorders has been substantial, with an estimated burden on health care costs of >$ 15 billion per year in India (Agreus and Tally, 1997). Peptic ulcer is a term used to refer to a group of ulcerative disorders of the upper gastrointestinal tract involving principally the most proximal portion of the duodenum and stomach. The frequent ulceration of the small intestine, when attached surgically to actively secreting gastric mucosa and corrosion at the skin predictably produced with gastro cutaneous fistulas (Bardhan et al., 1979).Although a number of antiulcer drugs such as H2 receptor antagonists, protonpump inhibitors and cytoprotectants are available for ulceration all these drugs have side effects and limitations (Ariyoshi et al., 1986).

Herbal medicine deals with plants and plant extracts in treating diseases. These medicines are considered safer because of the natural ingredients with no side effects (Clouatre and Rosenbaum, 1994).

The plant Mukia maderasapatana was reported to have activities such as hepato protective (Thabrew, et. al., 1996), diuretic, stomachic (a digestive tonic), gentle aperients, antipyretic and antiflatulent, antiasthmatic, anti-inflammatory, antidiabetic and antibronchitis and is used for tooth-ache besides its use in vertigo and biliousness (Chopra, 2002 and Kirthikar and Basu, 1980). This study was undertaken to assess the efficacy of Mukia maderasapatana leaf extract in the treatment of gastric ulcer.

MATERIALS AND METHODS:

Animals: Male albino rats of wistar strain approximately weighing 150-125g were fed with standard pelleted diet (M/s Hindustan Lever Foods, Bangalore, India) and water ad libitum and housed under standard environmental conditions. The animals were deprived of food for 24 h prior to ulcer induction.

Chemicals: Thiobarbituric acid (TBA), 2.4 Dinitrophenylhydrazine (DNPH), and reduced glutathione were purchased for Sigma Chemical Company, Mumbai. All other chemicals and reagents used in this study were of analytical grade with high purity and were obtained from Glaxo laboratories and Sisco Research Laboratories, Mumbai, India.

Plant Material and Preparation of Drug: The leaf of Mukia maderasapatana were collected from Vettikadu. The leaf were dried and make a fine powder. The fine powder of Mukia maderasapatana leaf was dissolved in distilled water just before oral administration.

Stress Induced Ulcer: Stress induced by animals were not fed with standard pellet diet and water were provided and libitum for the period of 5 days.

Experimental Designs: Body weight of animals recorded and they dividing into 3 groups of 6 animals each as follows: Group I-Normal animal received normal diet and water ad libitum; Group II- Stress induced ulcer in rats; Group III- Rats treated with Mukia maderasapatana (500mg/kgb,wts) only (no feed) using an intragastric tube for 7 days.The Experimental protocol was subjected to the scrutiny of Institutional Animal Ethics Committee and was cleared by the same before starting.

After completed the experimental regimen, the rats were sacrificed and the stomach was removed. The gastric content was collected and centrifuge for 5 min at 2000xg and the supernatant was separated. The volume, pH and total acidity and free acidity gastric fluid were determined.

Preparation of homogenate: The stomach was then weighed and homogenized in chilled Tris buffer (10 mm, pH 7.4) at a concentration of 10% (w/v). The homogenates were centrifuged at 3000xg for 20 min using centrifuge. The clear supernatant was used for the assays of lipid peroxidation (MDA content) and reduced glutathione (GSH).

Biochemical Parameter: The following bio chemical parameter was estimated, Reduced glutathione -GSH (moron et. al., 1979); Malondialdehyde - MDA (Beuge and Aust 1978); Gastric juice, volume and pH. (Hirohashi et. al.,1993).

RESULT AND DISCUSSION:

Ulcer is a major health hazard both in terms of morbidity and mortality. The pathophysiology of gastric ulcer has generally focused on imbalance between aggressive and protective factors in the stomach, such as acid – pepsin secretion, mucosal barrier, mucus secretion, blood flow, cellular regeneration, prostaglandins and epidermal growth factors (Lima et al., 2006). The reactive oxygen species especially hydroxyl radical plays a major role in causing oxidative damage of mucosa in all types ulcers (Das, et al., 1997) worldwide interest in natural products as preventive and therapeutic agents has led to a greater appreciation of the rich heritage of traditional systems of medicine. Dietary and life style modifications are the basis of Ayurvedic medicine, Herbal drugs obtained from the plant source are relatively less expensive, safe and good tolerability even in higher doses (Goel and Sairam, 2002).

The present study was carried out to evaluate the anti ulcer activity of Mukia maderasapatana. The observations made on different groups of experimental and control animals were compared as follows.

Table 1 represents the levels of MDA and GSH in serum of normal and experimental rats. Group II stress induced rats showed a significant increased in the level of MDA when compared to Group I rats, Group III antiulcer activity rates treated with Mukia maderasapatana significantly decreased the level of MDA.

Group II stress induced rats showed a significant decreased in the level of GSH when compared to Group I rats. Group III stress induced rats treated with Mukia maderasapatana significantly increased in the level of GSH.

Table 1 - Effect of Mukia maderasapatana on MDA and GSH in experimental rats

Parameters	Group I	Group II	Group III
Serum MDA (nmol/dl)	1.8 ± 0.86	4.28 ± 1.20	1.14 ± 0.91*
GSH (mg/dl)	8.13 ± 0.50	4.01 ± 1.84	8.38 ± 1.22*
Stomach MDA (nmole/mg)	1.6 ± 1.04	7.06 ± 1.24	1.20 ± 2.37*
GSH (Mg/mg)	8.71 ± 1.65	4.61 ± 1.24	8.24 ± 1.77*

Values were expressed as mean ± SD for six rats in each group.

* Significantly different from Group II.

Oxygen derived free radicals cause lipid peroxidation, which leads to membrane fluidity, resulting in reduced membrance. Integrity of surface epithelial cells, thereby causing gastric ulcer (Bandyopadhyay et al., 1999). It has been found that oxygen – derived free radicals are implicated in the mechanism of acute and chronic ulceration and scavenging. These free radicals can play an appreciable role in healing gastric ulcers (Loguercio et al., 1993). The study revealed that the ulcer severity and lipid peroxidation were aggravated during cold resistance stress, which is also indicated by MDA content under stress as compared to control rat. Mukia maderasapatana exhibits a potent anti-peroxidative effect.

Glutathione Status is a highly sensitive indicator of cell functionally and viability. GSH depletion is linked to a number of diseases statuses including cancer, neurodegenerative diseases. Glutathione is a Ubiquitous thiol containing tri peptide, which plays a central role in cell biology; it is implicated in the cellular defense against Xenobiotics and naturally occurring deleterious compounds, such as Free radicals and hydro. Peroxides, kidneys are exposed to various cytotxic agents before the elimination of these agents in urine. Thus the GSH concentrations in kidneys cells are important (Pastore et al., 2003). In the present study, decreased content of GSH in stress induced rats as compared to control rats, the decreased plasma GSH content, implying, increased consumption for oxygen radicals scavenging activity. Administration of Mukia maderasaptana significantly increased in the levels of GSH in stress induced rats.

Table II - Effect of Mukia madaerasapatana on pH, Ulcer experimental rats

Parameters

Group I

Group II

Group III

Volume (ml)

Ulcer Index (mm)

Total acidity (mEq/L)

Free acidity (mEq/L)

1.80 ± 0.12

1.70 ± 0.14

1.03 ± 0.21

52.16 ± 0.59

38.21 ± 0.57

3.80 ± 0.26

4.5 ± 0.76

3.12 ± 0.32

85.12 ± 0.17

52.18 ± 0.83

2.00 ± 0.16*

1.80 ± 0.16*

1.31 ± 0.54*

53.01 ± 0.68*

38.72 ± 0.61*

Values were expressed as mean ± SD for six rats in each group.

* Significantly different from Group II.

Table II represents the levels of pH, Ulcer Index, Volume, Total acidity and Free acidity in gastric juice of normal and experimental rats. Group II stress induced rats showed a significant increased in pH, volume, free acidity, total acidity and ulcer index, when compared to Group I rats. Group III stress induced rats treated with Mukia maderasapatana significantly decreased in pH, volume free acidity, total acidity and ulcer index, when compared to group II untreated rats.

In the present study, significant increased in the level of gastric volume, total acidity and free acidity and increased pH of gastric juice were observed in ulcer control rats as compared to normal rats. The severity in terms of volume, pH, total acidity and free acidity showed marked decrease in Mukia madaerasapatana treated rats when compared to those in control rats. The restored pH of gastric juice was also observed in Mukia madaerasapatana treatment rats as compared with control rats. The increase in volume in the ulcer control rats is undoubtedly due to increased production of hydrochloric acid as is evident from the total acidity and decrease pH value of gastric juice. The decrease in volume of the gastric juice and concomitant decrease in the acidity and restored in pH providing the antiulcer activity of Mukia madaerasapatana.

CONCLUSION:

Gastric ulcers, one of the most widespread diseases, are believed to be due to an imbalance between acid and pepsin a long with weakness many drugs used for the treatment of gastric reactions, several plants and herbs have used to treat intestinal disorders, including gastric ulcers. Herbal medicines remain one of the common forms of therapy to world’s population. They are considered as safe since they are natural products. Mukia maderasaptana treated to ulcer prevents MDA and GSH accumulation in serum and tissue. Increase in the pepsin activity restore the pH, volume and activity in gastric juice.

Thus, Mukia maderasapnata can be standardized as a potent, herbal medicine in alleviating stress induced ulcer, the beneficial effect of Mukia maderasapanata due to the presence of phytochemical constituents.

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Received on 08.04.2012 Accepted on 10.05.2012

Asian J. Res. Pharm. Sci. 2(2): April-June 2012; Page 52-54