On the Effect of "Piper nigrum" and "Ferula foetida"

LIST OF CONTENTS

1.Introduction

2.Review of Literature
1.Plant Review

3.Aim and Objectives

4.Materials and Methods

5.Results
Discussion

6. Conclusion

Bibliography

LIST OF TABLES

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LIST OF FIGURES

LIST OF ABBREVIATIONS

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ABSTRACT

In the present study, the gastroprotective mechanism of aqueous extract of Piper nigrum and Ferula foetida (AEPF) was investigated. The current knowledge is clearly incontestable that AEPF pent-up the aggressive issue, gastric acid secretion. The anti-ulcerogenic impact of the AEPF is also associated with its antisecretory action since acid may be a major consideration the event of ulceration. The current data also clearly demonstrated that the 400 mg/kg is more effective than the 200 mg/kg and 100mg/kg dose of AEPF and has shown increased pH and decreased total acidity of gastric fluid. The ulcerogenic effect of cysteamine-induced duodenal ulcers was developed in rats that received cysteamine HCl 400mg/kg. The exact mechanism of pathological process within the cysteamine-induced peptic ulcer model isn't totally known however but hypersecretion of gastric acid, deterioration of mucosal resistance and promotion of gastric emptying are among the possible mechanisms. In cold restraint stress induced ulcer model blood parameters such as Glucose, cholesterol and Triglycerides were estimated. The significant increase in blood sugar level was discovered because; beneath nerve-racking conditions, ductless gland secretes corticosterone in man and glucocorticoid in rats. AEPF significantly reduced the elevated serum cholesterol and triglycerides levels, which may be due to inhibition of stimulation of the sympathetic nervous system. Therefore it could act as a potent therapeutic agent against peptic ulcer disease.

Keywords: Antisecretory activity, Piper nigrum, Ferula foetida , Immobilisation stress, Ulcer activity.

ACKNOWLEDGEMENT

C ompletion of this dissertation was possible with the support of several people. We have taken efforts in this project. However, it would not have been possible without the kind support and help of many individuals and organizations. We would like to express my sincere gratitude to all of them.

We would like to thank our Principal, Dr.P.Suresh, Associate director, School of pharmacy, GNITC, who has been always there to listen and give advice. We are grateful to him for the long discussions that helped us sort out the practical details of work. Thank you sir, for encouraging us on this thesis work.

W e would like to express our special gratitude and thanks to, Dr.Sagar pamu, Assistant professor, Department of pharmacy practice, School of pharmacy, for being very kind and patient and always there to help and sort out the problems whenever we approached him.

The thesis would not have come to a successful completion, without the help we received from the statistician regarding the results, as he meticulously carried out the analysis of the data. We would like to thank Dr.Deepak Pawar, Assistant professor, Department of pharmacy practice, School of pharmacy.

We would like to thank Mr.Venkatesh, lab technician, Department of pharmacy practice, School of pharmacy, for his support in our project.

Most importantly we take this opportunity to thank our friends and family for their help, trust, silent hope, prayers and sacrifice for us. Last but not the least our friends have helped us, their support and care helped us on the study. We greatly value their friendship and we deeply appreciate their belief in us.

DEDICATION

EVERY BIT AND PARCEL OF THIS PROJECT IS DEDICATED TO MY PARENTS WHO GAVE ME LIFE, GREW ME UP, WERE ALWAYS SUPPORTIVE AND ENCOURAGED ME TO GO ON EVERY ADVENTURE ESPECIALLY THIS ONE.

I OWE THEM EACH MOMENT IN MY LIFE AND PRAISE THEM IN EVERY BREATH.

CHAPTER-1

Introduction

1 .INTRODUCTION

1.1. HERBAL PLANTS- SIGNIFICANCE:

The history of herbal medicine is as old as the human civilization. Human beings seem to be afflicted with additional diseases than the other animal species. Man sought to alleviate his suffering from injury and disease by taking advantage of plants growing around him. In the past, almost all the medicines used by man were from the plants.

India is one of the oldest, richest and most diverse cultural traditions associated with the use of medicinal plants 1. The World Health Organization (WHO) has recently outlined traditional drugs (including herbal drugs) as comprising therapeutic practices that are alive, typically for many years, before the development and spread of modern medicine and are still in use today 2, 3. Or, traditional medicine is the synthesis of therapeutic experience of generations of practicing physicians of indigenous systems of medicine. The traditional preparations comprise medicative plants, minerals, organic matter, etc. herbal medication represent solely those ancient medicines that primarily use medicative plant preparations for medical aid.

Herbal drugs remains the mainstay of regarding 75-80% of the planet population, principally within the developing countries, for primary health care due to higher cultural acceptableness, better compatibility with the body and lesser side effects. However, last few years have seen a major increase in their use in the developing world 3.

Herbal medicines also offer therapeutics for age-related disorders like memory loss, osteoporosis, immune disorders, etc. for which no modern medicine is available. India, despite its wealthy content, heritage for herbal medicines and large biodiversity has a dismal share of the world market due to export of crude extracts and drugs. Development of herbal based products has increased manifold in the past few years in all parts of the world and thus the present age is also referred to as ‘the age of herbal products 4.

In Deutschland and France, many herbs and herbal extracts are used as prescription drugs and their sales in the countries of European Union were around $ 6 billion in 1991 and may be over 20 billion now. In USA, flavourer medication area unit presently oversubscribed in food stores with a flipover of regarding $ four billion in 1996 that is anticipated to double by the turn of the century 5. In India, the herbal drug market is about $ 1 billion and the export of plant-based crude drugs is around $ 80 million 6.

Medicinal plants are reservoir of drugs and lead compounds for many therapeutic agents 7, 8. There are avalanche of scientific support on the efficacy of medicinal plants in the treatment of gastrointestinal disorders and in the management of ulcers of different etiologies 9.

In the recent years, a widespread search has been launched to identify new anti-ulcer drugs from synthetic and natural sources. A large number of dietary nutrients, spices and condiments, namely banana 10, ginger 11, cinnamon, α tocopherol 13 and Selenium 14 have been shown to possess significant antisecretory and gastroprotective activity 15.

The typical anti-ulcer treatment of today’s mainstream medicine is triple therapy regimen: it includes two antibiotics combined with one drug from either of two other classes of drugs – one designed to inhibit acid secretion and one designed to shield the internal organ mucous membrane from chemical attack. Now-a-days, Quadruple therapy is also suggested. But this treatment doesn’t work in everyone, and research from Michigan suggests that there may be more ulcer bacteria than Helicobacter 16.

These triple and quadruple regimens gladden the heart of the pharmaceutical industry, but not of Mother Nature, who prefers natural remedies without side effects. Nature has given mankind many remedies for almost all kind of diseases, peptic ulcer is no exception. Beneficial effects of a number of drugs like Drakshaghritham, Sitamundaram, Thriphalamundaram, Sathavareegritham, Taramanduram etc have claimed to be effective in the treatment of hyperacidity and peptic ulcers 17. Good amounts of work have been done on natural anti-ulcer remedy which includes Shankabhasma 18, Tephrosia purpurea 19, Tea root extracts 20, Deglycyrrhizinated Liquorice 21, Rhizomes of Curcuma longa 22 and many more.

This study is intended to evaluate the anti-ulcer activity of the Aqueous Extract of Piper nigrum and Ferula foetida (AEPF) in gastric ulcer induced models, Aspirin plus pylorus ligation induced gastric ulcer in rats, Cysteamine induced duodenal ulceration and Cold Restraint Stress induced gastric ulceration model.

1.2. ABOUT PEPTIC ULCER:

Peptic ulcer could be a conglomerate of heterogeneous disorders, which manifests itself as a break in the lining of the gastrointestinal mucosa bathed by acid and/or pepsin. NSAID ingestion is associated with Erosions, Petechiae, Type C gastritis, Ulceration, interference with ulcer healing, ulcer complications and injury to the small and large intestine 24. Although a number of anti-ulcer drugs such as H2 receptor antagonists, Proton pump inhibitors and Cytoprotectants are available for ulceration, all these drugs have side effects and limitations 25. Ethanol easily and rapidly penetrates into the gastric mucosa 26. By increasing membrane porousness and unleash of vasoactive merchandise, ethanol causes vascular damage and gastric cell necrosis, which in turn leads to ulcer formation 26, 27.

There is a balance in the stomach between the aggressive digestive capabilities of acid plus pepsin and the mucosal barrier. Ulceration happens once there's a disturbance of the traditional equilibrium caused by either increased aggression or diminished membrane resistance. Several factors are implicated in the pathogenesis of gastric ulcer. These include 29. Drug treatment of organic process ulcers is targeted at either counteracting aggressive factors (acid and enzyme, active oxidants, PAF, leukotrienes, endothelins, digestive juice or exogenous factors together with NSAIDs) or stimulating the mucosal defenses (mucus, bicarbonate, normal blood flow, Prostaglandins, Nitric Oxide) 30 (fig). The ideal aims of treatment of peptic ulcer disease are to relieve pain, heal the ulcer and delay ulcer recurrence 31. (Fig. 1)

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Figure: 1 Pathogenesis of Peptic Ulcer C LASSIFICATION OF ULCERS: (Fig. 2)

1. Gastric ulcer/ Peptic ulcer, present in the Stomach
2. Duodenal ulcer, present in the Duodenum
3. Esophageal ulcer, present in the Esophagus
4. Meckel’s Diverticulum ulcer, present on the Meckel’s Diverticulum

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Esophageal Ulcer Meckel’s Diverticulum

Ulcer

Figure: 2 Classifications of Ulcers

1.3. PREVALENCE:

The lifetime risk for developing a peptic ulcer is approximately 102. (Fig. 3)

In Western countries the prevalence of Helicobacter pylori infections roughly matches age (i.e., 2 hundredth at age twenty, half-hour at age thirty, 80% at age 80 etc). Prevalence is higher in third world countries. Transmission is by food, contaminated groundwater, and through human saliva (such as from kissing or sharing food utensils.)

A minority of cases of Helicobacter infection can eventually cause an lesion and a bigger proportion of individuals can get non-specific discomfort, abdominal pain or gastritis.

The methods used to assess the epidemiology of ulcers include Hospital data, mortality statistics, population studies, sickness benefit records. All of these methods have limitation and make comparative studies difficult.

In Australia, the number of prescriptions for H2 receptor antagonist has been used to assess the incidence of peptic ulcer33. In most European countries, USA, Australia, duodenal ulcers occur twice as frequently as gastric ulcers.

Sex ratio of peptic ulcer patients varies in different parts of the world; however these are more common in males than females. Ratio of duodenal ulcer varies from 18:1 in India34, 4:1 in Hong Kong35. The large geographic differences in sex ratio of ulcer disease strongly support the notion that environmental factors play an important etiological role in peptic ulcer.

Both duodenal and gastric ulcer diseases are closely associated with Helicobacter pylori infection. An infected individual has an estimated lifetime risk of 10-20% for the development of peptic ulcer disease, which is at least 3-4 folds higher than in non-infected subjects. H. pylori infection is diagnosed in 90-100% of peptic ulcer patients and in 60-100% of peptic ulcer patients. Subjects infected with a Cytotoxin-producing bacterial strain are at a higher risk of duodenal ulcer. Other factors that will influence the peptic ulceration risk in infected subjects area unit the number of internal organ acid production (which is exaggerated in peptic ulcer malady and faded in gastric ulcer disease), the presence of gastric metaplasia in the duodenal bulb, smoking, and genetic factors (e.g. blood group O and lack of the gland gene). After eradication of the infection, the risk of recurrence of ulcer disease is reduced to below 10% for gastric ulcer disease and to approximately 0% for duodenal ulcer disease36.

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Figure: 3 Disability adjusted life year for peptic ulcer per 100,000 inhabitants

CHAPTER-2

REVIEW OF LITERATURE

2. Review of literature

2.1 Botanical review:

Piper nigrum

About plant family: Piperaceae:

The family Piperaceae, additionally referred to as the Piperaceae, may be a massive family of flowering plants. The cluster contains roughly three,610 presently accepted species in 5 genera. The vast majority of peppers can be found within the two main genera: piper (2000 species) and peperomia (1600 species) [37].

Members of the family Piperaceae is also tiny trees, shrubs or herbs. The distribution of this cluster is best represented as equatorial. The most well -known species is piper nigrum whichyields most peppercorns that are used as spices, including black pepper although its relatives in the family include many other spices [38].

The name Piperaceae is likely derived from the Sanskrit term pippali, which was used to describe long peppers (like that of piper longum).

About Plant:

Black pepper (Piper nigrum) may be a flowering tracheophyte within the pepper family, cultivated for its fruit, which is usually dried and used as a spice [39] and seasonings. The fruit, referred to as a flavoring once dried, is around five millimeters (0.20 in) in diameter, dark red when fully mature, and, like all drupes, contains a single seed. Peppercorns, and also the fine-grained pepper derived from grinding them, may be described simply as pepper or more precisely as black pepper (cooked and dried unripe fruit), green pepper (dried unripe fruit) and white pepper (dried ripe seeds).

The word "pepper" is ultimately derived from the Dravidian word for long pepper, pippali. Ancient Greek and Latin turned pippali into the Latin piper that was utilized by the Romans to refer each to black pepper and long pepper, because the Romans mistakenly believed that each of those spices were derived from identical plant. The English word for pepper springs from the Old English pipor. The Latin word is also the source of Italian pepe, Dutch peper, German Pfeffer, French poivre, and other similar forms. In the sixteenth century, pepper started referring to the unrelated New World chili pepper as well. "Pepper" was used in a figurative sense to mean "spirit" or "energy" at least as far back as the 1840s; in the early 20th century, this was shortened to pep.The pepper plant may be a perennial woody tracheophyte growing up to four metres (13 ft) tall on supporting trees, poles, or trellises. It is a spreading tracheophyte, rooting readily where trailing stems touch the ground. The leave s area unit alternate, entire, five to ten cm long and three to six cm across.

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Figure: 4 Leaves & Fruit of Black Pepper

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Figure:6 Pepper before ripening And after ripening

And after ripening

The fruit of the black pepper is named a stone fruit and once dried it's a pepper. The flowers are small, produced on pendulous spikes 4 to 8 cm long at the leaf nodes, the spikes lengthening up to 7 to 15 cm as the fruit matures.

Pepper can be grown in soil that is neither too dry nor susceptible to flooding, moist, well-drained and rich inorganic matter (the vines do not do too well over an altitude of 3000 ft above sea level). The plants are propagated by cuttings about 40 to 50 centimetres long, tied up to neighbouring trees or climbing frames at distances of about two metres apart; trees with rough bark are favoured over those with sleek bark, because the pepper plants climb rough bark additional promptly. Competing plants are cleared away, going solely ample trees to produce shade and allow free ventilation. The roots are coated in leaf mulch and manure, and therefore the shoots are cut doubly a year. On dry soils the young plant s need watering each different day throughout the time of year for the primary 3 years. The plants bear fruit from the fourth or fifth year, and generally still bear fruit for seven years. The cuttings are sometimes cultivars, elect each for yield and quality of fruit.

A single stem can bear twenty to thirty mature spikes. The harvest begins as presently mutually or 2 fruits at the bottom of the spikes begin to show red, and before the fruit is totally mature, and still hard; if allowed to ripen fully, the fruit lose pungency, and ultimately fall off and are lost. The spikes are collected and spread out to dry in the sun and then the peppercorns are stripped off the spikes.

Black pepper is native to south Asian nation, and is extensively cultivated there in tropical regions. Currently Vietnam is that the world's largest producer and businessperson of pepper, producing 34% of the world's Piper nigrum crop as of 2008.

Dried ground pepper has been used since antiquity for each its flavour and as a drugs. Black pepper is the world's most traded spice. It is one in every of the foremost common spices additional to European cooking and its descendants. The spiciness of black pepper is because of the chemical piperin. It is present within the industrialised world, typically paired with flavoring.

Taxonomy:

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Binomial name: Piper nigrum

Medical Uses:

1. Black Pepper (or perhaps long pepper) was believed to cure illness such as constipation, diarrhea, earache, gangrene, heart disease, hernia, hoarseness, indigestion, insect bites, insomnia, joint pain, liver problems, lung unwellness, oral abscesses, sunbu rn, tooth decay, and toothaches.
2. Pepper contains small amounts of safrole, a mildly carcinogenic compound [40]. Also, it is eliminated from the diet of patients having abdominal surgery and ulcers because of its irritating effect upon the intestines [41] being replaced by what is referred to as a bland diet.
3. However, extracts from black pepper have been found to have antioxidant properties [42] and anti-carcinogenic effects, especially when compared to chili [43].
4. Piperine present in black pepper a cts as a thermogenic compound. Piperine enhances the thermogenesis of lipid and accelerates [44] energy metabolism in the body and also increases the serotonin and beta -endorphin production in the brain.
5. Piperine and other components from black pepper may also be helpful in treating vitiligo [45] although when combined with radiation should be staggered due to the effect of light on the compound [46].
6. Piperine has anti-inflammatory, antinociceptive, and antiarthritic effects in an arthritis animal model. Histological staining showed that piperin considerably reduced the inflammatory space within the ankle joint joints.

About plant family: Apiaceae:

The apiaceae (or Umbelliferae), commonly known as carrot, Umbelliferae family, is a group of mostly aromatic plants with hollow stems. The family is giant, with over three,700 species spread across 434 genera; it is the sixteenth largest family of flowering plants.

Most Umbelliferae are annual, biennial or perennial herbs (frequently with the leaves collective toward the base), although a minority are shrubs or trees. Their leaves are of variable size and alternately organized, or alternate with the upper leaves becoming nearly opposite. In some taxa the feel is leathered, fleshy, or perhaps rigid, however perpetually with stomata. They are petiolate or simple and a lot of or less protective cover, the blade sometimes cleft and compound, but entire in some genera. Most commonly crushing leaves emits a marked smell, aromatic to foetid, but absent in some members. The flowers area unit nearly perpetually collective in terminal umbels, simple or compound, typically inflorescence cymes, seldom in heads.

The Umbelliferae was initial represented by John Lindley in 1836. The name com es from the sort genus Apium, which was originally used by Pliny the Elder circa 50 AD for a celery -like plant. The alternative name for the family, Umbelliferae, derives from the inflorescence being generally in the form of a compound umbel. The family wa s one amongst the primary to be recognized as a definite cluster in Jacques Daleschamps’ 1586 Historia generalis plantarum. With Robert Morison’s 1672 Plantarum umbelilliferarum distribution nova it became the first group of plants for which a systematic study was published.

About Plant:

Asafoetida (Ferula assafoetida), (also known as devil's dung, stinking gum, asant, food of the gods, giant fennel, Jowani badian, hing and ting) is the dried latex (gum oleoresin) exuded from the living underground stem or faucet root of many species of Ferula, which is a perennial herb (1 to 1.5 m high). The species is native to Asian country Mountains and area unit foreign to Bharat. Asafoetida encompasses a pungent, unpleasant smell once raw, however in done dishes, it delivers a sleek flavor, cherish leeks.

Description of Plant:

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