INTRODUCTION:

Ulcer in colon affects the rectum and colon. Inflammation of the body part is spoken as redness, and tenderness of the body part and sigmoid as proctosigmoiditis. Left-sided inflammatory bowel disease point out illness including the colon distal to the lienal flexure. Intensive inflammatory bowel disease alters the colon proximal to the lienal flexure and includes pan-colitis, wherever total colon is concerned³.

Ulcerative colitis or inflammatory bowel sickness could be a womb-to-tomb disease that's related to vital morbidity. It also can affect a person's social and psychological successfulness, significantly if poorly controlled. Typically, it's a relapsing–remitting pattern. Associate degree calculable five hundredth of individuals with colitis can have a minimum of one relapse per year¹. 80% of these are delicate to moderate and regarding 20%measure severe².

Approximately twenty-fifth of individuals with ulcerative inflammatory bowel disease possess single or additional event of intense severe colitis in their lifespan, along twenty-ninth colectomy rate. Though lethality scales have upgraded steadily ago thirty years, intense extreme inflammatory bowel disease still features a range of up to twenty³. Lethality is altered by the temporal order of interventions, as well as medical care and colectomy. The foremost recent UK audit incontestible associate degree overall GB national mortality of 0.8%³.

Current medical approaches target curing active sickness to deal with symptoms of urgency, a frequency of defaecation and body part trauma, and additionally to enhance the quality of life, and thenceforth to keep up remission. The long edges of achieving tissue layer healing stay unclear. The treatment chosen for active sickness is probably going to depend upon clinical severity, the extent of sickness and therefore the person's preference, and will embody the utilization of aminosalicylates, corticosteroids or biological medication.

This medication may be oral or topical (into the rectum), and corticosteroids could also be administered intravenously in the population with acute severe sickness. Surgery could also be thought-about as an emergency treatment for severe colitis that doesn't answer drug treatment. The population might also choose to possess elective surgery for unresponsive or often reversion sickness that's moving their quality of life.

Most patients receive maintenance medical care with aminosalicylates. There could also be variation within the doses of aminosalicylates and in whether or not a mixture of treatment routes is employed. Relating to immunological disorder medicinal drug or immunosuppressant, it seems that medicinal drug and immunosuppressant square measure more and more accustomed maintain remission in a population with frequently-relapsing colitis³.

Symptoms:

The first symptom is diarrhoea. Diarrhoea could commence gradually or quickly. Symptoms depend upon what quantity of the colon is affected. Abdominal pain and bloody diarrhoea are the common symptoms of inflammatory bowel disease⁴.

The following are also possible:

· weariness or temporary state

· Weight reduction

· anorexia

· Anaemia

· Exalted temporary state

· Significant loss of body fluid

· Longing to empty the bowels perpetually⁴.

Table:1 Types of ulcerative colitis with signs and symptoms:

TYPES

SIGNS AND SYMPTOMS

Ulcerative proctitis:

Inflammation in rectum⁵

Sometimes the mildest style of inflammation

· Rectal hurt

· Rectal pain

· An inability to manoeuvre the bowels

· Muscle spasm

· Lower abdominal pain

· Faecal urgency

· Blood or secretion passage per body part or mixed with stool

Proctosigmoiditis:

The lower end of the colon is affected^4,5. Proctosigmoiditis may be a style of inflammatory bowel disease that affects the colon. The colon connects the remainder of your colon, or gut, to the body part wherever stool in then expelled from the body⁴.

· Loose stool

· Abdominal pain

· Fever

· Weight loss

· Constipation

· Rectal spasm

Left-sided inflammation:

Inflammation includes the body, up the left aspect through the sigmoid and colon^4,5

· Bloody diarrhoea

· Abdominal cramping on the left aspect

· Weight loss

Pancolitis:

The full colon is affected^4,5

· Abdominal pain

· Abdominal cramps

· Fatigue

· Considerable weight loss

Fulminant inflammation:

A rare style of inflammation which will be grave. The total colon is affected⁴.

· Severe pain

· Severe diarrhoea, Which might result in dehydration and shock with sudden inflammation, there’s a risk of colon rupture and toxic colon.

Causes and Risk Factors:

The exact causes of ulcerative colitis aren't legendary. Ultimately, scientists believe that there’s quite one cause which the many various factors work along to cause the unwellness. Further, the cause of one specific individual with the unwellness can be completely different from another’s.

Genetics:

Although inflammatory bowel disease (IBD) is understood to "run in families", researchers note that it had been not as straightforward as being passed down from parent to kid. Quite a hundred genes are known as having a possible role. The most vital risk issue presently known for developing IBD has a relative world health organization conjointly has the unwellness. However, having the genes that are related to this disease doesn't perpetually mean an individual can develop the disease. There's another piece to the puzzle, and researchers assume that this can be wherever a spread of alternative potential triggers get play.

Environmental Triggers:

Genetics and therefore the system response might not be enough to clarify the event of inflammatory bowel disease. There is also one or additional conditions that can trigger IBD and many potential candidates which includes the following:

Smoking:

Ulcerative colitis is usually known as a “disease of non-smokers.” The unwellness is additional common among people who have quit smoking. It's not counselled that people are being smoking cigarettes or return to smoking when being diagnosed with inflammatory bowel disease. The result that smoking has on the body way outweighs any attainable profit it would have for inflammatory bowel disease.

Nonsteroidal Anti-Inflammatory medication (NSAIDs):

This type of pain medication is usually used with care in individuals with ulcerative colitis as a result of it’s been shown to be related to flare-ups of the disease. Even in the population that don't have inflammatory bowel disease, NSAIDs has the potential to irritate within the canal. NSAIDs will cause harm to the internal organ mucous membrane of the abdomen, tiny viscus, and colon^8,9. NSAIDs may increase internal organ porosity by inhibiting cox, that reduces autocoid production.^8,9 Inhibition of prostaglandins has been concerned in IBD because of immunoregulatory effects, ten significantly through the inhibition of growth mortification issue and also the induction of medication cytokines like lymphokine (IL)

Antibiotics:

Antibiotics are shown to precipitate flare-ups of the unwellness for a few individuals. Some analysis has shown that antibiotics, particularly once taken for a protracted amount (such as thirty days) of your time or employed in kids, is related to a better risk of developing a style of IBD.

Contraceptive Pill:

It’s not legendary if the employment of the management of this pill is also a risk issue for developing inflammatory bowel disease, because the proof is conflicting. Oral contraceptive pills might increase the danger of developing IBD through the consequences of steroid hormone. Steroid hormone acts as an associate immune foil, significantly in relevance body substance immunity and also the proliferation of macrophages, whereas progestogen acts as associate immune-suppressor⁷. 17-beta estrogen might result in growth mortification issue secretion and CD16 expression by macrophages⁷. As an alternative, steroid hormone might play an infective role in IBD through a method of multifocal epithelial duct infarct because of its thrombogenic potential⁶.

Nutritional factors:

Many tries are created at associating the incidence of IBD with dietary excess or deficit of assorted foods¹¹. Indeed, a high intake of saturated fats and monosaccharides and a coffee intake of fibre are joined with a hyperbolic risk of CD development¹².

Monosaccharides and sweets:

Numerous studies have stressed the result of excessive consumption of dietary monosaccharides on IBD development. Russel et al¹³ emphasized the result of overwhelming cola-type drinks and chocolate on increasing IBD incidence. Their observation was confirmed by sakamoto et al¹⁴, World Health Organization incontestable a negative result of sweets and artificial sweeteners on the chance of developing each UC and CD. However, in 2014, chalet al¹⁵ bestowed results of an outsized prospective study of over 400000 men and girls that incontestable no association between total intake of carbohydrates, sugar or starch and incidence of UC or CD.

It ought to be stressed that milk sugar consumption doesn't increase the chance of IBD¹⁶.

Proteins and fats:

According to Reif et al¹⁶, An hyperbolic consumption of protein and fats could lead to a coffee degree of hyperbolic risk of IBD development. Similar authors conjointly incontestable that a high-fat diet, notably one made in cholester in and animal fats, could increase IBD incidence¹⁶. In their study, Ananthakrishnan et al¹⁷ confirmed the result associate high consumption of linolic acid, an unsaturated, polyunsaturated fatty acid carboxylic acid, on the chance of UC development had been additionally incontestible. This carboxylic acid may be a precursor of arachidonic acid, the metabolites of that exhibit pro-inflammatory properties¹⁸. AA consumption can also increase UC risk, whereas an increase in monounsaturated fatty acid, a monounsaturated carboxylic acid, may be a preventive factor¹⁹.

Fibre:

Fibre consumption exerts a protecting result in IBD development as a high fibre diet decreases the danger of developing IBD¹⁶. In line with Anathakrishnan et al²⁰, a diet with a fibre content of 24.3 g/d could decrease the danger of chrons disease development by 400^th. A very positive result was noted with fibre originating from fruit sources. In a study of 130 people below thirty years old time, Amre et al²¹ confirmed the role of dietary fibre consumption on the hindrance of CD.

Vitamins and minerals:

Vitamin D deficiency may be a common development in patients with IBD. As such, some authors regard this deficiency as a dietary issue that will increase the danger of IBD development²². Reif et al¹⁶ pointed to the protecting result of diets made in fluids, Mg and ascorbic acid on IBD risk; on the opposite hand, a retinol rich product could facilitate IBD development^16,20,21. It ought to be stressed that fruit and fruit juices consumption, visible of the fibre and ascorbic acid content, could represent a separate organic process issue that decreases the danger of developing IBD due to their anti-oxidative activity²³.

Alcohol:

Some studies have incontestable a protecting result of alcohol consumption with relevance UC development. Notwithstanding, this result is negated once drinking alcohol is combined with smoking²⁴. No vital variations were ascertained in CD development between people overwhelming alcohol a minimum of fourfold every week and teetotalers²⁵.

Stress:

Psychological stress has been recommended to play a job within the etiology and pathological process of IBD due to the chronic, relapsing, and remitting nature of this unwellness^26,27. Both chronic and acute stress will alter immune perform²⁶. Results from experimental studies are inconsistent, with findings supporting each positive ad null associations²⁶.

Diagnosis:

A doctor can raise concerning symptoms and case history, and take a look at to search out whether or not any shut relatives have had inflammatory bowel disease, IBD or colitis.

They will conjointly examine the patient for signs of anaemia and tenderness within the abdominal space.

These include:

· Blood tests

· Stool test

· X-ray

· Barium irrigation

· Sigmoidoscopy, during which a versatile tube with a camera at the top is inserted through the anus into the rectum

· Colonoscopy, wherever a protracted, versatile viewing tube with a camera at the top is inserted through the anus and therefore the rectum

· CT scan of the abdomen or pelvis.

Fig: 1 Mild²⁸

Fig: 2 Moderate²⁸

Fig:3 Severe²⁸

Mild:

· Less than four stools daily, with or without blood

· No systemic disturbance

· Normal erythrocyte sedimentation rate and C reactive protein values

Moderate:

· Four to six stools a day with minimal systemic disturbance

· Coarsely granular

· Friable

Severe:

· More than six stools a day containing blood (fever, tachycardia, anemia, or hypoalbuminemia)

· Frank ulceration

· Spontaneously haemorrhage

CLINICAL TREATMENT FOR COLITIS:

Ulcerative colitis treatment typically involves each of two drugs or surgery.

Many classes of medications are also active in treating IBD. Medication relays on the severity of the illness. The medication that works well for few individuals might not work for others. Therefore it should take time to search out drugs that help you. Additionally, some medication has serious aspect effects observance for these is needed²⁹.

Anti-inflammatory medication:

Anti-inflammatory medications usually abide the primary step within the treatment of IBD. They include

5-aminosalicylates:

Samples of this sort of medication embrace sulfasalazine (Azulfidine), mesalamine (Asacol HD, Delzicol, others), balsalazide (colazal) and olsalazine (Dipentum). Taken either oral or as an enema depends on the position of our colon that is affected.

Corticosteroids:

These medication, that embrace prednisone and hydrocortisone, are usually reserved for controlled to severe Inflammatory bowel disease that does not answer alternative treatment, because of the adverse effects, they’re not typically given long run²⁹.

Immune system suppressors:

These medication additionally decreases inflammation by suppressing the immune system response that starts the process of inflammation. For a few individuals, a mix of the medication works higher than one drug alone. Such as:

Azathioprine and mercaptopurine:.

These are the fore most wide used immunosuppressants for treatment of IBD. Needs regular checkup with your doctor to avoid side effects

Cyclosporine (Gengraf, Neoral, Sandimmune). This is often for those who haven't responded well to alternative medications. Cyclosporine has the potential for serious aspect effects and isn't for long-term use.

Infliximab (Remicade), adalimumab (Humaria) and golimumab (Simponi). These medication is known as tumor necrosis factor (TNF) inhibitors work by neutralizing protein synthesized by your immune system

Vedolizumab:

This medication was newly proven for the treatment of inflammatory bowel disease for those who cannot tolerate alternative treatments. It works by interference inflammatory cells from going to the location of the inflammation.

Other medications:

Antibiotics:

Individuals with IBD run fevers can seemingly take antibiotics to assist forestall or management infection.

Anti-diarrheal medications:

For serious symptom, loperamide (Imodium) is also effectual. Use anti-diarrheal medications with nice caution because they may lead to the risk of toxic megacolon (enlarged colon).

Pain relievers:

Gentle pain- acetaminophen (Tylenol, others) is prescribed. Nonsteroidal anti-inflammatory drug (Advil, Mortin IB, others), Aleve (Aleve), might worsen symptoms and boost the severity of unwellness.

Surgery:

Surgery will usually eliminate inflammatory bowel disease. However, that sometimes means that separating your entire colon and body part.

In most cases, this involves a method known as ileal pouch-anal conjunction. This method eliminates the necessity to wear a bag to gather stool. Physician constructs a pouch from the top of the intestine. The pouch is then hooked up on to orifice, permitting to expel waste comparatively ordinarily. In certain situation, a pouch isn’t attainable. Instead, surgeons produce a permanent gap in your abdomen (ileal stoma) through that stool is passed for assortment in associate hooked up bag²⁹

Table:2 Herbal drugs for ulcerative colitis:

HERBS	FAMILY	CHEMICAL CONSTITUENTS	ACTIVITY	OTHER USES
Apple	Rosaceae	Flavonoids, phytochemicals as well as quercetin glycosides, catechin, procyanidin, cyanidin-3-galactoside, chlorogenic acid and phloridzin.³¹	Administration of apple polyphenols decreased the transcription and macromolecule levels of cyclooxygenase, TNF- α, calpain still as tissue transglutaminase.³²	Cancer, vas diseases, asthma and polygenic disorder.³⁰
Bilberry	Ericaceae	Flavanoids like hyperoside, isoquercitrin, quercitrin, anthocyanins	Bilberry preparation diminished the full dressing score and also the microscopic anatomy.³⁵(but a rise in sickness activity was discovered once we stop intake of bilberry, useful effects of bilberries is seen only when taken frequently.)	Ocular disorders increase visual modality, used in the treatment of cataracts, diabetic retinopathy and devolution.^33,34
Black raspberry	Rose family	Anthocyanin, quercetin, cyanidins, gallic acid, pelargonidin, kaempferol and salicylic acid	Raspberry bush crumb displayed higher upkeep of body mass and decrement in colonic shortening and ulceration.³⁷ They shrunk levels of plasma autocoid E2 (PGE2), and also suppressed the tissue levels of cyclooxygenase and key pro-inflammatory cytokines like TNF-α and IL-1β.³⁷	Anti-oxidant, anti-inflammatory, weight loss, anti-cancer³⁶
Cocoa	Malvaceae	epicatechin, procyanidin B2, catechin, and procyanidin B1	This impact was confirmed by minimization in inflammation, WBC infiltration within the membrane due to declining in producing NO, COX-2, phospho-STAT-3 (pSTAT-3), pSTAT1α, and NF-κB p65.³⁸	Improve blood flow to the heart, brain, reduce blood pressure, prevent blood clots and fight cell damage
Bael	Rutaceae	tannins, some essential oils like caryophyllene, Citral, sterols, and triterpenoids, flavonoids like rutin and coumarins, as well asaegeline, marmesin, phlobatannins, flavon-3-old, leucoanthocyanins, and anthocyanins^39,40	Intake of the Bael fruit juice lead to a major decline in illness activity index, megascopic score and microscopic scores.⁴¹	Control cholesterol, reduce skin rashes, purify the blood, increase breast milk, control diabetes
Green tea	Theaceae	The active compounds of tea area unit the catechins proanthocyanidins, flavonols (kaempferol, quercetin, and myricetin within the sort of glycosides), gallic acids, and theanine⁴²	Experiments conjointly discovered that GrTP interfered with inflammatory bowel disease and irritation linked colon cancer in male ICR mice⁴³	Brain function, weight loss cancer positive impact on pressure level, hypoglycemic agent resistance, inflammation, and aerophilic stress in patients with obesity-related high blood pressure
Grapes	Vitaceae	epicatechin gallate; procyanidin dimers, trimers, catechin, gallic acid; procyanidin pentamers, hexamers, and heptamers and their gallates; resveratrol; phenolics; flavonoids; and anthocyanins⁴⁴	Polyphenols from grape seed are capable in diminishing TNBS- and DSS-induced inflammatory bowel disease in rodents.	anti-inflammatory drug, anti-ageing, potent inhibitor, prevent damage in liver, heart, kidney and has anti-cancer properties⁴⁴
Olive oil	oleaceae	Oleic acid, squalene and phenolic constituents such as hydroxytyrosol, tyrosol, and oleuropein,	The active constituent hydroxytyrosol is capable of decreasing the DSS-induced harm⁴⁵. Intake of food rich virgin vegetable oil (EVOO) considerably reduced the DSS-induced mortality by nearly five hundredths, attenuated the clinical and histologic signs of harm⁴⁵	Moisturizes skin has anti-aging properties, prevent breast cancer, treat depression, weight loss, eliminate kidney stones
Indian gooseberry	Grossulariaceae	ellagic acid, chebulinic acid, , emblicanin-A, emblicanin-B, punigluconin, ellagitannin, trigalloyl aldohexose, chebulagic acid, corilagin, quercetin, kaempferol 3-O-α-l (6” methyl) rhamnopyranoside, and kaempferol 3-O-α-l (6” ethyl) rhamnopyranoside.[84]	The methanolic extract was potent in ameliorative the severity of carboxylic acid acid-induced rubor in rats. It decreased colon weight/length quantitative relation, and megascopic scores for inflammation, additionally to suck dehydrogenase (LDH), indicating that amla protected against the inflammogen and possessed cytoprotective effects.⁴⁶	Neuroprotective antifungal, antiviral, radicalscavenging, anti-mutagenic, medication, cardioprotective, gastroprotective, hepatoprotective, nephroprotective and antitumor properties.
Garlic	Amaryllidaceae	Aliin, allicin, ajoene, trisulfide, S-allyl cysteine, vinyl dithiins	Rats fed garlic orally for four weeks and three days throughout carboxylic acid for four weeks and three days throughout carboxylic acid induced redness displayed a big decrease in colon weight. Garlic intake returned the degree of GSH and inhibitor enzymes with a concomitant reduction in lipid peroxidation treated inflammation teams.⁵⁰	Antiviral, bactericide, fungicide, to suppress a common cough,⁴⁷ treat epithelial duct disorders⁴⁸, cardio-protective agent.^49,50
Ginger	Zingiberaceae	10-gingerol, 8-gingerol, 6-gingerol, and 6-shogaol, with 6-gingerol⁵¹	Ginger extract ameliorated the carboxylic acid–induced dropsical inflammation within the colon by considerably attenuating the extent and severity of lump, necrosis, and inflammatory cell infiltration within the mucous membrane⁽⁵³⁾ were additionally shrivelled. Administering ginger restored the degree of GSH, enzyme (CAT), and SOD⁽⁵³⁾	treat cold, head pain, vomiting, dysentery cure inflammatory disease, rheumatological conditions, muscular discomfort, and acts as a flatulence reliever⁽⁵²⁾
Saffron	Iridaceae	Crocin, carotenoids such as lycopene, zeaxanthin,picrocrocin^54,55,56,57	Intake of crocetin to mice for eight days considerably ameliorated 2,4,6-Trinitrobenzenesulfonic acid-induced UC⁽⁵⁸⁾crocetintaken animals had decreasedlooseness of the bowels and disruption of colonic design.	Treat Alzheimer, depression, menstrual discomfort,
Malabar tamarind	Clusiaceae	Citric acid lactone, ascorbic acid, tartaric acid, garcinol, cyanidin	The extract blocked TNBS-induced inflammation in rats by preventing animal tissue harm, decreasing the activity of MPO, decreasing the expression of Cox-2 and iNOS, reducing colonic PGE2 and IL-1β levels, and reducing vegetative cell polymer harm.⁽⁶⁰⁾	Weight loss, joint pain, treating hypolipidemic, anti-adipogenic, appetite suppressor effect^(59,60), severe diarrhoea
Fenugreek	Leguminosae	Flavanoids, alkaloids, coumarins, vitamins and saponins	It suppresses TNF-induced NF-κB activation as determined by polymer binding, activation of IκBa enzyme, IκBa phosphorylation, IκBa degradation, p65 phosphorylation, and p65 nuclear translocation through Akt⁽⁶²⁾inhibition. It additionally down-regulated TNF-induced expression of NF-κB–regulated factor in cell proliferation (cyclin D1, COX-2, c-myc) and anti-apoptosis (IAP1, Bcl-2, Bcl-XL, Bfl-1/A1, TRAF1, and cFLIP).⁽⁶²⁾	labour induction, aiding digestion, and as a general tonic to enhance metabolism treatment of cardiovascular disease, cataract, inflammation, thyroid pathology, malaria, lipoidaemia.⁽⁶¹⁾
Turmeric	Zingiberaceae	Curcumin, demethoxycurcum-in, bisdemethoxy curcumin, cyclocurcumin, dihydro curcumin⁽⁶³⁾	Once administered orally or systemically, either as a prophylactic or curative agent, curcumin improved the survival rate, and shriveled the wasting and discomfort induced by numerous ulcerogenslike DSS^{(65,66,67,68,69)}, dinitrobenzene acid (DNB)⁽⁷⁰⁾, dinitrochlorobenzene (DNCB)⁽⁷¹⁾, TNBS^(72,73),ethanoic acid, and additionally in genetically susceptible IL-10-knockout^(74,75) and mdr1a-/- mice.^(76,77)	Hay fever, depression, high cholesterol, osteoarthritis, itching cytoprotective effect⁽⁶⁴⁾

Some dietary tips could facilitate relieve symptoms

Tips include:

· Having little food, often, for instance, 5 to 6 little meals each day.

· Consuming lots of fluid, particularly water, to stop dehydration.

· Alkaloid and alcohol will increase diarrhoea so avoid them.

· Avoiding sodas, as it increases gas.

· Keeping a food dairy, and nothing that foods build symptoms worse

The United Kingdom’s National Health Service (NHS) recommends that, throughout an occurrence, briefly following a low-fibre diet could facilitate. This includes refined foods, like rice, lean, meat or fish, eggs and steamed vegetables.

CONCLUSION:

Ulcer in the colon is a chronic medical condition which will need patient to require medicament life long to limit worsening, decreases, a possibility of colorectal cancer. Though patients in the first phase, typically having 70% of their recommended medicament. Herbal drugs remedies can treat a good vary of intense and persistent ulcers. Physicians must address their patients information related to this type of regimen and supply proper knowledge regarding usage. These herbal medicaments have typically been put out to test in ancient times and have also been discovered to be helpful in a novel and existing ways that are thereby leading to a new path for the treatment. Thus, herbal Drugs is one among the good medical systems of the world.

REFERENCE:

1. Truelove SC et al . Cortisone in ulcerative colitis; final report on a therapeutic trial. BMJ. 1955; 2(4947):1041-1048.

2. Travis S et al. European evidence based Consensus on the management of ulcerative colitis: Current management. Journal of Crohns and Colitis. 2008; 2(1):24-62

3. www.spg.pt/wp-content/uploads/2015/11/2013-UC-management.pdf

4. https://www.medicalnewstoday.com/articles/163772.php

5. Sagar Garud and Mark A Peppercorn. Ulcerative colitis: Current Treatment Strategies and Future Prospects. Therapeutic advances in Gastroenterology. 2009 (3): 505-521.

6. Cornish JA, et al. The risk of oral contraceptives in the etiology of inflammatory bowel disease: a meta-analysis. Am J Gastroenterol. 2008;103:2394–2400.

7. Cutolo M, Capellino S, Sulli A, et al. Estrogens and autoimmune diseases. Ann N Y Acad Sci. 2006;1089:538–547.

8. Felder JB, Korelitz BI, Rajapakse R, Schwarz S, Horatagis AP, Gleim G. Effects of nonsteroidal anti-inflammatory drugs on inflammatory bowel disease: a case-control study. Am J Gastroenterol. 2000;95:1949–1954.

9. Cipolla G, Crema F, Sacco S, Moro E, de Ponti F, Frigo G. Nonsteroidal anti-inflammatory drugs and inflammatory bowel disease: current perspectives. Pharmacol Res. 2002;46:1–6.

10. Berg DJ, Zhang J, Weinstock JV, et al. Rapid development of colitis in NSAID-treated IL-10-deficient mice. Gastroenterology. 2002;123:1527–1542.

11. Baumgart DC, Sandborn WJ. Crohn’s disease. Lancet. 2012;380:1590–1605.

12. Basson A. Nutrition management in the adult patient with Crohn’s disease. S Afr J Clin Nutr. 2012;25:164–172.

13. Russel MG, Engels LG, Muris JW, Limonard CB, Volovics A, Brummer RJ, Stockbrügger RW. Modern life’ in the epidemiology of inflammatory bowel disease: a case-control study with special emphasis on nutritional factors. Eur J Gastroenterol Hepatol. 1998;10:243–249. [

14. Sakamoto N, et al. Dietary risk factors for inflammatory bowel disease: a multicenter case-control study in Japan. Inflamm Bowel Dis. 2005;11:154–163.

15. Chan SS, Luben R, et al. Carbohydrate intake in the etiology of Crohn’s disease and ulcerative colitis. Inflamm Bowel Dis. 2014;20:2013–2021.

16. Reif S, Klein I, Lubin F, et al. Pre-illness dietary factors in inflammatory bowel disease. Gut. 1997;40:754–760.

17. Ananthakrishnan AN, Khalili H, Konijeti GG, et al. Long-term intake of dietary fat and risk of ulcerative colitis and Crohn’s disease. Gut. 2014;63:776–784.

18. Tjonneland A, Overvad K, Bergmann MM, et al. Linoleic acid, a dietary n-6 polyunsaturated fatty acid, and the aetiology of ulcerative colitis: a nested case-control study within a European prospective cohort study. Gut. 2009;58:1606–1611.

19. de Silva PS, Luben R, Shrestha SS, Khaw KT, Hart AR. Dietary arachidonic and oleic acid intake in ulcerative colitis etiology: a prospective cohort study using 7-day food diaries. Eur J Gastroenterol Hepatol. 2014;26:11–18.

20. Ananthakrishnan AN, Khalili H, Konijeti GG, Higuchi LM, de Silva P, Korzenik JR, Fuchs CS, Willett WC, Richter JM, Chan AT. A prospective study of long-term intake of dietary fiber and risk of Crohn’s disease and ulcerative colitis. Gastroenterology. 2013;145:970–977.

21. Amre DK, D’Souza S, Morgan K, Seidman G, Lambrette P, Grimard G, Israel D, Mack D, Ghadirian P, Deslandres C, et al. Imbalances in dietary consumption of fatty acids, vegetables, and fruits are associated with risk for Crohn’s disease in children. Am J Gastroenterol. 2007;102:2016–2025.

22. Zhang YZ, Li YY. Inflammatory bowel disease: pathogenesis. World J Gastroenterol. 2014;20:91–99.

23. Rossi T, Gallo C, Bassani B, Canali S, Albini A, Bruno A. Drink your prevention: beverages with cancer preventive phytochemicals. Pol Arch Med Wewn. 2014;124:713–722.

24. El-Tawil AM. Epidemiology and inflammatory bowel diseases. World J Gastroenterol. 2013;19:1505–1507.

25. Han DY, Fraser AG, Dryland P, Ferguson LR. Environmental factors in the development of chronic inflammation: a case-control study on risk factors for Crohn‘s disease within New Zealand. Mutat Res. 2010;690:116–122.

26. Mawdsley JE, Rampton DS. Psychological stress in IBD: new insights into pathogenic and therapeutic implications. Gut. 2005;54:1481–1491.

27. Lerebours E, Gower-Rousseau C, Merle V, et al. Stressful life events as a risk factor for inflammatory bowel disease onset: A population-based case-control study. Am J Gastroenterol. 2007;102:122–131.

28. Taro Osada, Atsushi Arakawa, Naoto Sakamoto, HiroyaUeyama, Tomoyoshi Shibuya, Tatsuo Ogihara, Takashi Yao, and Sumio Watanabe. Autofluorescence imaging endoscopy for identification and assessment of inflammatory ulcerative colitis, 2011;17(46):5110-6.

29. https://www.mayoclinic.org/diseases-conditions/ulcerative-colitis/diagnosis-treatment/drc-20353331

30. Hyson DA. A comprehensive review of apples and apple components and their relationship to human health. AdvNutr 2011;2:408‑20.

31. Boyer J, Liu RH. Apple phytochemicals and their health benefits. Nutr J 2004;3:5.

32. D’Argenio G, Mazzone G, Tuccillo C, Ribecco MT, Graziani G, Gravina AG, et al. Apple polyphenols extract (APE) improves colon damage in a rat model of colitis. Dig Liver Dis 2012;44:555‑62.

33. Ulbricht C, Basch E, Basch S, Bent S, Boon H, Burke D, et al. An evidence‑based systematic review of bilberry (Vacciniummyrtillus) by the Natural Standard Research Collaboration. J Diet Suppl 2009;6:162‑200.

34. Canter PH, Ernst E. Anthocyanosides of Vacciniummyrtillus (bilberry) for night vision‑A systematic review of placebo‑controlled trials. SurvOphthalmol 2004;49:38‑50.

35. Biedermann L, Mwinyi J, Scharl M, Frei P, Zeitz J, Kullak‑Ublick GA, et al. Bilberry ingestion improves disease activity in mild to moderate ulcerative colitis ‑ An open pilot study. J Crohns Colitis 2013;7:271‑9.

36. Wang LS, Kuo CT, Cho SJ, Seguin C, Siddiqui J, Stoner K, et al. Black raspberry‑derived anthocyanins demethylate tumor suppressor genes through the inhibition of DNMT1 and DNMT3B in colon cancer cells. Nutr Cancer 2013;65:118‑25.

37. Montrose DC, Horelik NA, Madigan JP, Stoner GD, Wang LS, Bruno RS, et al. Anti‑inflammatory effects of freeze‑dried black raspberry powder in ulcerative colitis. Carcinogenesis 2011;32:343‑50

38. Andujar I, Recio MC, Giner RM, Cienfuegos‑Jovellanos E, Laghi S, Muguerza B, et al. Inhibition of ulcerative colitis in mice after oral administration of a polyphenol‑enriched cocoa extract is mediated by the inhibition of STAT1 and STAT3 phosphorylation in colon cells. J Agric Food Chem 2011;59:6474‑83.

39. Maity P, Hansda D, Bandyopadhyay U, Mishra DK. Biological activities of crude extracts and chemical constituents of Bael, Aegle marmelos (L.) Corr. Indian J ExpBiol 2009;47:849‑61

40. Baliga MS, Bhat HP, Pereira MM, Mathias N, Venkatesh P. Radioprotective effects of Aegle marmelos (L.) Correa (Bael): A concise review. J Altern Complement Med 2010;16:1109‑16

41. Behera JP, Mohanty B, Ramani YR, Rath B, Pradhan S. Effect of aqueous extract of Aegle marmelos unripe fruit on inflammatory bowel disease. Indian J Pharmacol 2012;44:614‑8.

42. Balentine DA, Wiseman SA, Bouwens LC. The chemistry of tea flavonoids. Crit Rev Food SciNutr 1997;37:693‑704.

43. Kim M, Murakami A, Miyamoto S, Tanaka T, Ohigashi H. The modifying effects of green tea polyphenols on acute colitis and inflammation‑associated colon carcinogenesis in male ICR mice. Biofactors 2010;36:43‑51.

44. Pezzuto JM. Grapes and human health: A perspective. J Agric Food Chem 2008;56:6777‑84.

45. Sanchez‑Fidalgo S, Sanchez de Ibarguen L, Cardeno A, Alarcon de la Lastra C. Influence of extra virgin olive oil diet enriched with hydroxytyrosol in a chronic DSS colitis model. Eur J Nutr 2012;51:497‑506.

46. Deshmukh CD, Veeresh B, Pawar AT. Protective effect of Emblica Officinalis fruit extract on acetic acid induced colitis in rats. Journal of Herbal Medicine and Toxicology 2010;4:83‑87

47. Harris JC, Cottrell SL, Plummer S, Lloyd D. Antimicrobial properties of Allium sativum (garlic). ApplMicrobiolBiotechnol 2001;57:282‑6.

48. Filocamo A, Nueno‑Palop C, Bisignano C, Mandalari G, Narbad A. Effect of garlic powder on the growth of commensal bacteria from the gastrointestinal tract. Phytomedicine 2012;19:707‑11.

49. Mukherjee S, Lekli I, Goswami S, Das DK. Freshly crushed garlic is a superior cardioprotective agent than processed garlic. J Agric Food Chem 2009;57:7137‑44.

50. Harisa GE, Abo‑Salem OM, El‑Sayed el SM, Taha EI, El‑Halawany N. L‑arginine augments the antioxidant effect of garlic against acetic acid‑ induced ulcerative colitis in rats. Pak J Pharm Sci 2009;22:373‑80.

51. Brahmbhatt M, Gundala SR, Asif G, Shamsi SA, Aneja R. Ginger phytochemicals exhibit synergy to inhibit prostate cancer cell proliferation. Nutr Cancer 2013;65:263‑72.

52. Baliga MS, Haniadka R, Pereira MM, D’Souza JJ, Pallaty PL, Bhat HP, et al. Update on the chemopreventive effects of ginger and its phytochemicals. Crit Rev Food SciNutr 2011;51:499‑523.

53. El‑Abhar HS, Hammad LN, Gawad HS. Modulating effect of ginger extract on rats with ulcerative colitis. J Ethnopharmacol 2008;118:367‑72.

54. Srivastava R, Ahmed H, Dixit RK, Dharamveer, Saraf SA. Crocus sativus L.: A comprehensive review. Pharmacogn Rev 2010;4:200‑8.

55. Abdullaev FI. Cancer chemopreventive and tumoricidal properties of saffron (Crocus sativus L.). ExpBiol Med (Maywood) 2002;227:20‑5.

56. Kamalipour M, Akhondzadeh S. Cardiovascular effects of saffron: An evidence‑based review. J Tehran Heart Cent 2011;6:59‑61.

57. Schmidt M, Betti G, Hensel A. Saffron in phytotherapy: Pharmacology and clinical uses. Wien Med Wochenschr 2007;157:315‑9.

58. Kazi HA, Qian Z. Crocetin reduces TNBS‑induced experimental colitis in mice by downregulation of NFkB. Saudi J Gastroenterol 2009;15:181‑7.

59. Mahendran P, Devi CS. Effect of Garcinia cambogia extract on lipids and lipoprotein composition in dexamethasone administered rats. Indian J PhysiolPharmacol 2001;45:345‑50.

60. dos Reis SB, de Oliveira CC, Acedo SC, Miranda DD, Ribeiro ML, Pedrazzoli J, Jr., et al. Attenuation of colitis injury in rats using Garcinia cambogia extract. Phytother Res 2009;23:324‑9.

61. Basch E, Ulbricht C, Kuo G, Szapary P, Smith M. Therapeutic applications of fenugreek. Altern Med Rev 2003;8:20‑7.

62. Shishodia S, Aggarwal BB. Diosgenin inhibits osteoclastogenesis, invasion, and proliferation through the downregulation of Akt, I kappa B kinase activation and NF‑kappa B‑regulated gene expression. Oncogene 2006;25:1463‑73

63. Kumar A, Prakash A, Dogra S. Protective effect of curcumin (Curcuma longa) against D‑galactose‑induced senescence in mice. J Asian Nat Prod Res 2011;13:42‑55.

64. Barzegar A, Moosavi‑Movahedi AA. Intracellular ROS protection efficiency and free radical‑scavenging activity of curcumin. PLoS One 2011;6:e26012

65. Arafa HM, Hemeida RA, El‑Bahrawy AI, Hamada FM. Prophylactic role of curcumin in dextran sulfate sodium (DSS)‑induced ulcerative colitis murine model. Food ChemToxicol 2009;47:1311‑7.

66. Deguchi Y, Andoh A, Inatomi O, Yagi Y, Bamba S, Araki Y, et al. Curcumin prevents the development of dextran sulfate Sodium (DSS)‑induced experimental colitis. Dig Dis Sci 2007;52:2993‑8.

67. Yadav VR, Suresh S, Devi K, Yadav S. Effect of cyclodextrin complexation of curcumin on its solubility and antiangiogenic and anti‑inflammatory activity in rat colitis model. AAPS PharmSciTech 2009;10:752‑62.

68. Yadav VR, Suresh S, Devi K, Yadav S. Novel formulation of solid lipid microparticles of curcumin for anti‑angiogenic and anti‑inflammatory activity for optimization of therapy of inflammatory bowel disease. J Pharm Pharmacol 2009;61:311‑21.

69. Liu L, Liu YL, Liu GX, Chen X, Yang K, Yang YX, et al. Curcumin ameliorates dextran sulfate sodium‑induced experimental colitis mice by downregulation of NFkB. Saudi J Gastroenterol 2009;15:181‑7. YX, et al. Curcumin ameliorates dextran sulfate sodium‑induced experimental colitis by blocking STAT3 signaling pathway. IntImmunopharmacol 2013;17:314‑20.

70. Salh B, Assi K, Templeman V, Parhar K, Owen D, Gomez‑Munoz A, et al. Curcumin attenuates DNB‑induced murine colitis. Am J Physiol Gastrointest Liver Physiol 2003;285:G235‑43.

71. Venkataranganna MV, Rafiq M, Gopumadhavan S, Peer G, Babu UV, Mitra SK. NCB‑02 (standardized Curcumin preparation) protects dinitrochlorobenzene‑ induced colitis through down‑regulation of NFkappa‑B and iNOS. World J Gastroenterol 2007;13:1103‑7.

72. Camacho‑Barquero L, Villegas I, Sanchez‑Calvo JM, Talero E, Sanchez‑Fidalgo S, Motilva V, et al. Curcumin, a Curcuma longa constituent, acts on MAPK p38 pathway modulating COX‑2 and iNOS expression in chronic experimental colitis. IntImmunopharmacol 2007;7:333‑42.

73. Jiang H, Deng CS, Zhang M, Xia J. Curcumin‑attenuated trinitrobenzenesulphonic acid induces chronic colitis by inhibiting expression of cyclooxygenase‑2. World J Gastroenterol 2006;12:3848‑53.

74. Larmonier CB, Uno JK, Lee KM, Karrasch T, Laubitz D, Thurston R, et al. Limited effects of dietary curcumin on Th‑1 driven colitis in IL‑10 deficient mice suggest an IL‑10‑dependent mechanism of protection. Am J Physiol Gastrointest Liver Physiol 2008;295:G1079‑91.

75. Ung VY, Foshaug RR, MacFarlane SM, Churchill TA, Doyle JS, Sydora BC, et al. Oral administration of curcumin emulsified in carboxymethyl cellulose has a potent anti‑inflammatory effect in the IL‑10 gene‑deficient mouse model of IBD. Dig Dis Sci 2010;55:1272‑7.

76. Baliga MS, Joseph N, Venkataranganna MV, Saxena A, Ponemone V, Fayad R. Curcumin, an active component of turmeric in the prevention and treatment of ulcerative colitis: Preclinical and clinical observations. Food Funct 2012;3:1109‑17.

77. Nones K, Dommels YE, Martell S, Butts C, McNabb WC, Park ZA, et al. The effects of dietary curcumin and rutin on colonic inflammation and gene expression in multidrug resistance gene‑deficient (mdr1a‑/‑) mice, a model of inflammatory bowel diseases. Br J Nutr 2009;101:169‑81.

Received on 04.10.2018 Modified on 25.10.2018

Research J. Pharm. and Tech. 2019; 12(3): 1409-1417.

DOI: 10.5958/0974-360X.2019.00235.X