Selected Herbal Remedies of Gastric Ulcer and their Possible Mechanism of Action
By Rita Soludo
ABSTRACT
From the ancient times, plants have been used for the treatment of a wide variety of disease. This herbal basket of nature has been explored in this review to highlight some of its potential herbs for the cure of Gastric ulcer. They are aim of this review on gastric ulcer was due to the wide spreading nature of this disease in all class of population, which may be due to rapidly changing food habits and stress, causing an imbalance between the gastric offensive and defensive factors. Plants are becoming more reliable in recent times, because they lack significant side effects and are safe. On the other hand, the synthetic antiulcer drugs are constantly reported to possess critical adverse effects like arrhythmia, gynaecomastia, impotency, and arthralgia. The relapse rate of ulcer has been reported to be high in such molecules. A few plants have been reviewed to bring their mechanism of anti-ulcerogenic properties to light. Some phytoconstituents have been discussed along with the research conducted by researchers in different ulcer models for better understanding the activity of the plants. This review would throw more light on this particular section of research oriented towards searching new herbal moieties to treat Gastric ulcer.
INTRODUCTION
The use of medicinal plants in the treatment of diseases has been an age long practice [Sofowora. A, 2005]. Medicines derived from plants are largely used because they are relatively safe, easily available and cheaper than their synthetic alternatives[Iwu et al,2006]. Plants provide a rich source of raw materials for traditional medicines in Africa and other developing parts of the world . Many Africans still depend on traditional medicine practioners and the use of medicinal plants for the maintenance of their health and health related problems [Sonibare et al ,2008]. Also due to appearance of various side effects by usage of conventional drugs for numerous disease, medicinal plants are considered the major reservoir of potentially new drugs .Plants extracts and their crude are the most significant sources of new drugs and have been shown to cause promising results in the treatment of diseases[Falcao et al ,2008].The two main causes of peptic ulcer are infection with gram negative bacteria helicobacter pylori and the prolonged use of non steroidal anti inflammatory drugs [NSAIDS) other factors that have been implicated in the development of ulcer are Increased hydrochloric acid(HCL) secretion, Inadequate mucosal defense, stress ,smoking, caffeine ,alcohol ,inadequate dietary habits(Carol motyka,2015). Gastric ulcer develops from continuous erosion and injury of the stomach wall which may worsen and results into bleeding(Wallace,J.L, 2008).There is an increase in research studies on the treatment of ulcer from natural products(Ukwe et al,2010)(Ubaka et al,2010).
Many medicinal plants are known to exhibit antiulcer properties and are found useful in the treatment of peptic ulcer (Kumar et al,2011). Some of these medicinal plants have been confirmed scientifically to possess gastroprotective and antiulcer property(Singhet al,2008)(Kayode et al,2015).The plant drugs possessing the active principles such as flavonoids, tannins, terpenoids are found to show antiulcer activity(Gadekar et al,2010).The use of phytoconstituents as drug therapy to treat major ailments has proven to be clinically effective and less relatively toxic than the existing drugs and also reduces the offensive factors serving as a tool in the prevention of peptic ulcer. In this modern era also majority of the world population still use herbal medicine mainly in developing countries, for primary health care because of better acceptability, compatibility with the human body and lesser side effects. The chemical constituents present in herbal medicine or plant are a part of the physiological functions of living flora and hence they are believed to have better compatibility with human body.
EPIDEMIOLOGY
About 5% of the worlds population is affected by peptic ulcer(Debashis et al,2009).70 – 90% of patients with gastric ulcer and 80 – 90% of patients with duodenal ulcer are infected with H.pylori (Girish et al,2001). In the United states, peptic ulcer disease affects approximately 4.6 million people annually with an estimated 10% of the US population having evidence of a duodenal ulcer at some time, H.pylori infection accounts for 90% of gastric ulcers(Malik, Singh, 2019). The proportion of people with H.pylori infection and peptic ulcer disease increases with age. The prevalence of peptic ulcer disease has shifted from predominance in males and females. The lifetime prevalence is approximately 11-14 % in men and 8-11% in women (PubMed). Age trends for ulcer occurrence reveal declining rates in younger men, particularly for duodenal ulcer, and increasing rates in older women. Duodenal ulcers usually appear between ages 30 and 50 and are more common in men than in women . Gastric ulcers tend to occur later in life, after age 60 and affects women than men.
In a systematic search of PubMed, EMBASE, and the Cochrane library, the annual incidence rates of peptic ulcer disease and 0.03 – 0.17% when based on hospitalization data(Sung et al,2009). The 1-year prevalence based on physician diagnosis was 0.12% -1.50% and that based on hospitalization data was 0.10- 0.19%. The majority of studies reported a decrease in the incidence or prevalence of peptic ulcer disease over time (sung et al,2009).
HERBAL TREATMENTS OF GASTRIC ULCER AND THEIR MECHANISM OF ACTIONS
Medicinal plants have achieved their therapeutic properties from their capability to produce renewable and various secondary metabolites, which are known as phytochemical constituents. Hence numerous plants have used these phytochemicals as a protective mechanism against pathogens (Abdallah, 2011). Examples of medicinal plants used in the treatment of gastric ulcer are
Carica papaya.
It commonly known as Papaya, belonging to the family Caricaceae. The methanolic extract of the seed shows gastroprotective and healing effects on ulcer in rats at a dose of 125, 250 and 500mg per kg . It significantly reduced the gastric lesion with 56,76 and 82 percent inhibition. The cytoprotective effect of papaya is responsible for its anti ulcerogenic activity. The enzyme P1G10 present in papaya has shown healing activity of chemically induced gastric ulcer(Pinto LA et al, 2015,Gomes et al,2010,Silva et al,2008).
Aloe barbadenicis.
It is commonly known as Aloe vera. It belongs to family Asphodelaceae (Liliaceae). Aloe vera gel has gastroprotective properties . The exisiting mucilage tissue at the center of leaves in this plant called aloe gel is used for various medicinal purposes. Its healing property is due to a compound called glucomannan, which is enriched with polysaccharide like mannose. The glucomannan affects fibroblast growth factor and stimulates the activity and proliferation of these cells.
The mucilage of aloe vera not only increases the amount of collagen on wound site but also increases tranversal connections among these bands rather than changing collagen structure fastening wound healing (Keshavarzi et al,2014)(Hashemi SA et al,2015).
Brassica oleraceae.
It is commonly known as Cabbage, belonging to family Brassicaceae. The aqueous extract of Brassica oleraceae var . capitata plant was used in the gastric disorders like ulcer at a dose of 0.25, 0.50 and 1.0mgperkg on Wistar rat. There is a chemical Lysophosphatidic acid (LPA), present in cabbage. It is a lipid mediator involved in a lot variety of physiological responses, like wound healing. This phospholipid shows an antiulcerogenic activity (Urikura et al,2012)(Jainu M,Devi CS, 2006).
Solanum nigrum.
It is commonly known as Potato, belonging to the family Solanaceae. It has gastric antiulcerogenic effects. Solanum nigrum was found to possess antiulcerinogenic as well as ulcer healing activities. Antiulcer activity was by blocking acid secretion through inhibition of H+ K+ATPase and decreasing secretion of gastrin hormone (Jainu M, Devi CS ,2006).
Ananas comosus.
It is commonly known as Pineapple, belonging to the family Bromeliaceae .The dichloromethane extract of pineapple has been found with the ability to protect the gastric mucosa against injuries caused 0.3M HCl, absolute ethanol, non steroidal anti inflammatory drugs (NSAIDS), and pylorus ligation ,in mice and rats. The mechanism of action of the DCM extract suggested that the effective gastroprotective action is due to the sulfhydryl group. Vianain present in pineapple has shown wound healing property in a guinea pig ischemic under model( Silva,2008)(Skrabut et al,1996).
Azadirachta indica A.
It is commonly known as Neem and belongs to the family Meliaceae . It has been identified to have potent gastroprotective and antiulcer effects. This was experimented in rats at a dose of 2.5g/kg. It is studied on various parameters of possible mechanism of treating ulcer.The main mechanism is to prevent acid pepsin secretion. Neem did not show any effect on mucin secretion though it improved life span of mucosal cells as evidenced by a decrease in cell shedding in the gastric juice. Thus the ulcer protective activity is due to its antisecretory and proton pump inhibitory activity rather than on defense mucin secretion. Bark extract of Azadirachta indica inhibits H+-k+-ATPase activity in vitro . It stops oxidative damage of the gastric mucosa by blocking lipid peroxidation and by scavenging the endogenous hydroxyl radical(OH), the major causative factor ulcer (Maity et al,2009)(Dorababu et al,2006)(Bandyopadhyay et al,2002).
Glycyrrhiza glabra.
It is commonly known as Licorice,belonging to the family Leguminosae. It showed effective healing on ethanol induced ulcers. It reduces stomach secretions and also produces thick protective mucus which covers the lining of stomach, therefore protects from peptic ulcers. Futhermore, it has been reported to increase the local concentration of prostaglandins which promotes mucous secretion and cell proliferation which promotes mucous and cell proliferation in the stomach(Khare CP,2004)(Bafina PA,Balaraman R, 2005).
Panax ginseng (Korean red ginseng).
It is a specie of Ginseng. It belongs to family Araliaceae. Korean red ginseng gives healing effect on gastic ulcer at a dose of 30, 100 and 300mg/kg, peroral , occurred 1hr before the ulcer induction in mice. The supposed mechanism of Ginseng species are significantly increase in mucin secretion and inhibited malondialdehyde(MDA) and H+/K+ATPase activity in the stomach( Oyagi et al,2010)(Jeong CS,2002).
Cynodon dactylon.
It is commonly known as Durva grass or Doob grass, belonging to family Poaceae. Doob grass was proved for anti ulcer activity in albino rats at a dose level of 200, 400 and 600mg/kg. Doob grass contains flavanoids. The alcoholic extract showed the presence of flavanoids, which is supposed to be responsible for antiulcer property(Dilpreet K et al,2012)(Patil et al,2011)(Nair GA,1995)
Bacopa monniera
It is commonly known as Brahmi, belonging to family Scrophulariacea .It is effective in treating various gastric ulcer models of rats. The main chemical constituent for curing the ulcer is bacoside A. It shows anti -ulcer and ulcer healing activities. There are multiple mechanism of bacoside A, which has been suggested. The first one for treating ulcer is anti H.pylori activity in the dose of 1000mg/ml and increasing prostanoids(PGE and PG12) in the dose of 10mg/ml. Other possible mechanism of action for this herb are mucosal offensive acid pepsin secretion and defensive factors like mucin secretion, mucosal cell shedding, cell proliferation and anti-oxidant activity in rats ( Dorababu et al,2004)( Goel RK et al,2003)( Sairam et al,2001).
Ficus religiosa.
It is commonly known as Pepal tree . It belongs to family Moraceae. The alcoholic extract of F.religiosa has been reported for anti-ulcer activity against pylorus ligation induced ulcers, ethanol induced ulcers and aspirin-induced ulcers at dose level of 250mg/kg and 560mg/kg in swiss albino rats. The stem bark ethanolic extract possess anti-ulcer activity due to endogenous production of prostaglandins , which in turn promotes mucus secretion,apart from this, the plant also possesses anti-inflammatory and anti-oxidant properties, which comes together to make the plant as a potential anti-ulcer drug (Khan et al,2011)(Pinto et al,2015).
Vaccinium oxycoccos.
It is commonly known as Cranberry, belonging to family Ericaceae . Cranberry juice is effective in peptic ulcer. Several H.pylori bacteria shows antibiotic resistance but can treated well by cranberry juice. Regular consumption of cranberry juice could help suppress H.pylori infection in endemically afflicted populations. The possible mechanism behind the anti-ulcer activity may be that, it causes immobilization of H.pylori strains in human mucus, erythrocytes and cultured gastric epithelia cells (LinYT et al,2005)(Zhang et al,2005)
Ceratonia siliqua.
It is commonly known as Carob, belonging to Fabaceae(Leguminoceae) family. Carob has shown to reduce the effect of gastroesophagel reflux and vomiting in infants. It works by several activities of its constituents mainly the Flavonoids content. It possesses demulcent property and the flavonoid content imparts gastroprotective and antioxidant properties, which together lend the drug to exhibit anti-ulcerogenic potential.
CONCLUSION
Research on natural products is often guided by ethnomedicinal knowledge, and their contribution to drug innovation by providing novel chemical structures and mechanisms of action is substantial. Large number of herbal extracts is used in folk medicine to treat various types of disorders. The synthetic drugs used to treat it are having side effects and it has been seen that some synthetic drugs have ulcer as their adverse effect. In that case, the herbal natural remedy is the obvious alternative, which is safe and equally effective as synthetic drug. Several plant sources have been highlighted in this article on the basis of traditional knowledge and reports of different researchers. Apart from this, searching for new pathways to treat ulcer can be developed only by understanding the mechanism of ulcerogenosis, by which it can be targeted. The investigative parameters which are the major aspects for herbal drug screening has been mentioned at required places in the article, which will hopefully help the researchers working in this area.
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