Cytoprotective Effect of Zingiber Officinale extract on Alcohol Induced Gastric Lesion in Mice

Ginger is a perennial plant that grows in India, China, Mexico and several other countries. The rhizome is used as both spice and in herbal medicine...


Introduction
Spices, the predominant flavoring, coloring, and aromatic agents in food and beverages are now gaining importance for their diversified uses. Ginger (Zingiber Officinale) is a medicinal plant that has been widely used in Chinese, and Tibb Unani herbal medicines all over the world, since antiquity, for a wide array of unrelated ailments that include muscular aches, sore throat, constipation, arthritis, indigestion, vomiting and infectious diseases. Currently, there is a renewed interest in ginger, and several scientific investigations aimed at isolation and identification of active constituents of ginger, scientific verification of its pharmacological actions and of its constituents, and verification of the basis of the use of ginger in several diseases and conditions Ali et al. [1].
Ginger grows best in tropical and subtropical areas, which have good rainfall with hot and humid conditions during the summer season. It is a member of Zingiberaceae family originated in Southeast Asia and has been introduced to many parts of the globe where it proliferates in suitable environment. Belief in the medicinal properties of ginger existed in ancient Indian and oriental cultures where ginger has been used alone or as a component in herbal remedies. This practice continues today in many areas of the world including Africa, Brazil, China and, Mexico. Ginger has introduced to Europe and other areas by Dutch, Portuguese Arab and Spanish explorers or traders from around the 13 th to 16 th centuries.
steroidal anti-inflammatory drugs, and ethanol) and defensive factor of gastric mucosa (prostaglandin, mucus, bicarbonate). The antiulcerogenic activity of many plant products is reported due to an increase in mucosal defensive factors rather than decrease in the aggressive factors Goel, et al. [2]. Numbers of an antiulcer drugs like gastric antisecretory drugs H2-receptor antagonist, antimuscarinic agents, proton pump inhibitors, and mucosal protective agents, carbenoxolone sodium, sucralfate, and prostaglandin analogous are available which are shown to have side effects and limitation Baowman et al. [3].
There are several herbal ayuvedic preparation which have a protective effect against gastric mucosal injury Shetty et al. [4]. Herbal medicine is now used by up to 50% of the Western population in a number of instances 10% for treatment or prevention of digestive disorders Langmead and Rampton [5].
Today, pharmacopoeias of a number of different countries list ginger extract for various digestive disease, Aromatic, spasmolytic and carminative properties of ginger are probably responsible for the therapeutic application in digestive tract ailments Sertie et al. [6].

Mechanism of Gastric Effect of Ginger
Several studies have shown that ginger extract, essential oils and glycolipids possess a number of pharmacological actions, which at least in part for some of them anti-ulcerogenic or ulcer preventive efficacy may be suggested. Common side effects of treating inflammation with modern drugs is that ulcer in the digestive system can be created or their condition made worse Wallace [7]. Ginger not only relieves the symptoms of inflammation but also protects the creation of digestive ulcers. Ginger may protect the stomach from the damaging effect of alcohol and non-steroidal anti-inflammatory drugs and may help prevent ulcers Villegas et al. [8]. A study was done in Isfahan university by Miniaiyan et al. [9] for anti-ulcerogenic effect of ginger on cysteamine-induced duodenal ulcer in rats. The results obtained in positive control groups indicated that ginger possesses its anti-ulcerative properties through a mechanism mainly related to acid-pepsin inhibition.
The effect of ginger (acetone extract) and zingiberene on hydrochlochloric acid/ethanol-induced gastric lesions in rats have been examined (6)-gingerol and zingiberene, both 100mg/ kg oral), significantly inhibited gastric lesions by 54.5% and 53.6% respectively. The total extract inhibited lesions by 97.5% at 1g/kg.

Oral administration of both aqueous and methanol ginger extract
to rabbit has been reported to reduce gastric secretions (gastric juice volume, acid and pepsin output). Both extracts were found to be comparable with cimetidine (50mg/kg) with respect to gastric juice volume.
The aqueous extract was comparable with cimetidine and superior to the methanol extract for pepsin output, and the methanol extract superior to the aqueous extract and comparable to cimetidine for acid output. Roasted ginger decoction which showed an obvious inhibiting tendency on three gastric ulcer models. The plant contains active materials which for some of them

c)
Al-Yahya et al. [11] Studied the cytoprotective and gastric anti-ulcer effect of ginger in albino rats. Cyto destruction was produced by 80% ethanol, 0.6M HCL, 0.2 M NaOH and 25% Nacl. The animals were given a standard laboratory diet and free water Food was withdrawn 12h before and during the experimental hours:

Maceration method
In this method fresh ginger rhizome was cut into small pieces, dried, and then pulverized into coarse powder and weighing about 400g of powder. It was macerated in 1000ml hydroalcoholic solution (70% Ethanol, 30% distilled water) for seventy-two hours.
The extract was then shaked, filtered by using dryness filter paper

4.
Extract group: Given hydroalcoholic extract of ginger in a dose of (600mg/kg I.P) one hour before ulcer induction.

5.
Chronic extract group: Given hydroalcoholic extract of ginger. In a dose of (300mg/kg I.P) for five consecutive days before ulcer induction. The last dose was administered one hour before ulcer induction. 6. Reference group: Given rantidine (50mg/kg I.P) one hour before ulcer induction.
One hour after intragastric administration of absolute ethanol (95%, 0.2ml), the animals are euthanized with ether, the stomach were excised, cut along the greater curvature, and gently rinsed under tap water, and examined by 5-fold binocular magnifier to assess lesion in gastric mucosa.

Results
As shown in Figure 1 normal gastric mucosa Figure    In present paper ethanol administration provoked significant gastric mucosal injuries as evidence by necrosis, exfoliation and sloughing of gastric cells, congestion of blood vessels and infiltration of inflammatory cells. Cytoprotective action of ginger has been investigated using animal models of acute gastric injury induced by necrotizing agents such as ethanol. Ethanol serves as the most common ulcerogenic agent and produced sever gastric hemorrhagic erosions Robert et al. [12]; Szabo et al. [13]. The genesis of ethanol-induced gastric lesions is multifactorial with the depletion of gastric wall mucus content as one of the involved factors. Submucosal venular constriction by ethanol and eventual injury is caused due to perturbations of superficial mucosal cells, notably the mucosal mast cells leading to release of vasoactive mediators including histamine, that cause damage to gastric mucosa Hollander et al. [14]. Accumulation of activated neutrophil in gastric mucosa may be the source of free radicals Oxygen free radical which lead to increase to lipid peroxidation and damage to cell membrane are impacted in ethanol induced gastric mucosal injury Al-Harbi et al. [15]. In addition to its direct damage of gastric mucosal cells by development of free radicals, cause solubilization of mucus constituents and depressant tissue levels of protein leading to flow stasis in gastric blood. The present paper revealed parial cytoprotection by single oral dose of ginger (300mg/kg) in mice. More effective cytoprotection was elicited by (600mg/kg I.P).
The results obtained in the present paper indicated that ginger extract possess its anti-ulcerative properties through a mechanism mainly related to acid and pepsin inhibition Chronic I.P injection of plant extract in a dose of (300mg/kg) more effective in prevention lesion formation. The mechanism of ginger extract in chronic (I.P) protection may be due to counteracting the active oxidant radicals, decreasing mucosal cell shedding and thicking the mucus membrane. The mechanism of anti-ulcer effect of ginger may be due to presence of 6-Gingersulfonic acid and three monoacyldigalactosyl gylcerols including ginger glycolipid A. B. C have been isolated from dried rhizome of Zingiber Officinale which are potent anti-ulcer components Yoshikawa et al. [16]. 6-Gingerol and 6-shogaol are two other anti-ulcer components that are less potent but are mainly responsible for ginger pungency. The results of present paper in accordance with previous reports in which water and methanolic extract of eight Zingiberaceae herbs caused a significant decrease in gastric secretion in un-anesthetized rabbits and the effect of water extract was similar to cimetidine Sakai et al. [17].