A Review on Herbal Plants used in The Management of Stomach Ulcer

A peptic ulcer, also known as a stomach ulcer, is characterized by extensive damage to the mucosa or lining of the stomach and duodenum that goes beyond the muscular mucosa, notably to the muscle layer, due to the environment's generation of gastric acid. The two most frequent etiological antecedents are chronic Helicobacter pylori (H. pylori) infection and the use of nonsteroidal anti-inflammatory drugs (NSAIDs), which naturally include acetylsalicylic acid (ASA). Less than 5% of cases of peptic ulcer PU are caused by particular, uncommon, and carefully considered coupled antecedents. Among these is gastronomy, or Zollinger-Ellison syndrome (ZES). (1)

Since excessive gastric acid secretion was thought to be the main cause of the gastric ulcer, the previous treatment concentrated on lowering stomach acid output with antacids, histamine, H2 receptor blockers, and proton pump inhibitors. The main culprit behind stomach ulcers, Helicobacter pylori, could not be eliminated by such medications, however. Antibiotics have the potential to eradicate Helicobacter pylori, but their long-term use can cause toxicity and the emergence of antibiotic resistance in bacteria. As a result, there is an urgent need for safe, effective, and reasonably priced anti-ulcer medications. Herbal remedies have naturally occurred active ingredients that could have anti -ulcer characteristics are a potentially effective new treatment option for stomach ulcers. (2)

There are four times as many peptic ulcers in the duodenum. Since around 4% of stomach ulcers are caused by metastases, many biopsies are required to rule out cancer.
Duodenal ulcers are often benign. Convex, resembling a colon polyp, concave, pit-like, or classic erosive ulcers are some possible ulcer shapes. The duodenum and pylori generally exhibit the convex form, whereas the right stomach usually exhibits the erosive concave form. Although the shapes of these convex growths vary, they are invariably higher than the surrounding tissues. These growths are distinguished by the mucosal tissues' persistent lack of surface breaches, and even at larger sizes, they first fail to distinguish themselves visually from nearby tissues. (3)

ANATOMY OF STOMACH:

The bottom portion of the rib cage covers the left hypochondrial area, which is where the stomach is primarily located. On the other hand, the upper umbilical and epigastric regions of the abdomen include the lower and distal portions of the stomach. The stomach is an organ that may expand. It can hold 1.5 litres on average in an adult. The stomach is roughly J-shaped, though some people may have a steer-horn stomach, in which case it lies transversely. Depending on the person's posture and how full their stomach is, the size, shape, and location of the stomach can change significantly. The stomach seems flattened when empty. It has two surfaces: the anterior and the posterior, which are separated by larger and smaller curvatures.

In the diagnostic interpretation of gastric diseases and their treatment, endoscopists, radiologists, and surgeons consider the notable physiological and histochemical variations among the stomach's regions. Projecting upward above the level of the heart opening is the stomach's fundus. It connects with the left diaphragm dome while lying to the left of the abdominal oesophagus. There is a noticeable notch called the angular notch (incisura angularis) two-thirds of the way from the cardiac orifice along the stomach's lesser curvature. The stomach's body stretches from the cardiac orifice to the angular notch. (4)

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PHYSIOLOGY OF STOMACH:

An organ's structure mostly determines the role it serves in the body, as is the case with the majority of physiological processes. The purpose of the stomach wall is to help create a temporary acidic environment that facilitates the breakdown of food into chyme, a semisolid mixture. The fundus, cardia, body, and pylorus are the four parts of the stomach organ. The stomach's inner surface is rotated to give the gastric mucosa more surface area, which permits the stomach to expand as food is consumed. The mucosal layer, submucosa, muscularis externa, and adventitia/serosa are the four distinct tissue layers that make up the stomach wall. The lamina propria, a layer of connective tissue, the muscularis mucosa, and the surface epithelium are the three additional layers that make up the stomach mucosal layer. (6)

PATHOPHYSIOLOGY OF STOMACH ULCER:

H pylori infection and long-term NSAID use are the main causes of PUD cases. Usually, the infection starts early in childhood and lasts for a few decades. The two primary modes of transmission for H pylori are fecal-oral and oral-oral. This bacterium is primarily seen in developed nations and is primarily spread by oral-oral transmission. Sharing utensils during meals appears to be the main way that infections spread across family members, particularly from an adult to a youngster. Contaminated water, which is frequently seen in nations with inadequate sanitation, is the source of fecal-oral transmission.

The helical (spiral) gram-negative bacterium H pylori causes harm to host cells by colonizing the surface of stomach epithelial cells and causing an adverse inflammatory response. Numerous bacterial virulence factors that contribute to the pathophysiology of PUD have been identified. Three pathogenic pathways can be distinguished in H pylori infection: immune evasion, illness induction, and colonization. (7)

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CAUSES OF STOMACH ULCER:

Ulcer disease is thought to be primarily caused by excess acid. Therefore, neutralizing and controlling stomach acid secretion is the main focus of treatment. According to Franceschi et al. (2014), acid is still thought to have a key role in the development of ulcers. The primary cause of ulcer illness nowadays is thought to be a stomach infection caused by a bacteria known as "Helicobacter pyloricus" (H. pylori). The use of long-term anti-inflammatory medications, sometimes known as NSAIDs (anti-inflammatory drugs), such as aspirin, is another significant cause of ulcers. Additionally, smoking contributes significantly to the development of ulcers and the failure of ulcer therapy.
The bacteria Pylori is quite prevalent. Globally, these bacteria infect around one billion individuals. According to estimates, 50% of Americans over 60 have H. pylori infections (Parsonnet et al. 1996). More than 80% of individuals with stomach and duodenal ulcers have an H. pylori infection, which often lasts for years and causes ulcers in 10% to 15% of those infected. However, the exact process by which H. pylori causes ulcers is still unknown. It has been amply demonstrated that using antibiotics to eradicate these germs stops ulcers from returning. NSAIDs are medications used to treat painful inflammatory diseases and arthritis, according to Brewer et al. (2010). NSAIDs alter the composition of stomach mucus, which may make it easier for pepsin to break it down.

Examples of medications in this class include aspirin, ibuprofen (Motrin), naproxen (Naprosyn), and etodolac (Lodine). Prostagladins play a crucial role in preventing gut lining injury. Corrosive acids. Overproduction of prostaglandins is crucial for the protection of the stomach mucosa. By interfering with prostaglandins in the stomach, NSAIDs lead to ulcers. (9)

CLINICAL SYMPTOMS:

Patients with NSAID-induced PUD often report experiencing regurgitation and heartburn. The main cause of this is gastroesophageal reflux brought on by PUD-induced erosions. Patients could also exhibit bleeding symptoms. Alarming symptoms including melena and hematemesis are linked to the bleeding, which is a major PUD consequence. Anorexia may be one of the symptoms of a PUD patient.

This weight loss worry is often linked to postprandial discomfort. Anemia, which is usually caused by GIB or iron deficiency, may also be to blame. Although PUD is usually associated with recurring ulcers caused by NSAID misuse, it can occasionally result in serious, potentially fatal effects like bleeding and perforations. (10)

DIAGNOSIS:

Numerous techniques are available to identify H. pylori infection. Due to its trophic status for gastric epithelium, the organism is mainly found in the stomach, where it produces the distinctive and easily identifiable histologic pattern of acute-on-chronic inflammation. The most accurate method of detecting organisms is immunohistochemistry utilizing antibodies specific to H. pylori. Usually, organisms are abundant and may be identified using specialized stains. There are numerous more tests available, from molecular testing with next-generation sequencing to serologic assays for anti-H. pylori IgG antibodies. While some tests can be performed noninvasively, others need an endoscopy to take a sample of the stomach contents. Non-invasive testing is usually preferable.

One of the current requirements for using IgG serology is having a very high pretest chance of an H. pylori-related condition, like an active duodenal ulcer. If serology is performed without a very high pretest probability, it is advised that, depending on the presentation, a urea breath test (UBT), stool antigen test, or endoscopy be performed to confirm the presence of an active infection prior to beginning therapy. The UBT and stool antigen test are non-invasive methods for detecting active infection. (11)

COMPLICATIONS OF STOMACH ULCER:

The outcomes of PUD (adenocarcinoma and MALT lymphoma) included persistent symptoms, bleeding, perforation, penetration, limitation of the stomach outlet, and gastric cancer. In 15 to 20% of cases, bleeding is the most common outcome. The majority of acute upper gastrointestinal bleeding (40–60%) is brought on by PUD. Upper gastrointestinal bleeding must be assessed and treated immediately since it is an emergency. When inspecting a bleeding patient, alerting a GI expert early on can aid in the coordination of severely ill patients' care. To categorize risks, Glasgow-Blatchford and Rockall ratings were employed. For treatment, proper resuscitation using intravenous fluid and blood products is necessary to maintain the target hemoglobin level above 7.

Activated charcoal can be given within four hours of ingestion to treat a NOAC overdose. Idarucizumab with hemodialysis can be used to treat life-threatening bleeding caused by dabigatran. The use of anticoagulants and antiplatelet medications can resume if hemostasis has been achieved. The timing is determined by the speed with which anticoagulation must be restored. Due to the increased risk of acute thrombosis following the implantation of a drug-eluting stent, patients receiving dual antiplatelet therapy should refrain from discontinuing both drugs patients who immediately begin taking aspirin after reaching hemostasis (within 1-3 or 7 days). Low molecular weight heparin cross-linking is recommended for patients with mechanical mitral valves or other thrombotic disorders since their warfarin levels are below therapeutic ranges. (12)

TREATMENT:

• First line treatment:
  Before choosing an H. pylori treatment plan, it is important to learn about the patient's past use of antibiotics. A PPI and two antibiotics are administered to patients with an H. pylori infection for the first 10–14 days of treatment. In the first line of treatment, amoxicillin, clarithromycin, and metronidazole are the preferred antibiotics. Clarithromycin-based therapy is safe and effective, but it's crucial that the patient hasn't already been exposed to clarithromycin or other medications in the macrolide class. It is likely that prior antibiotic exposure may contribute to treatment failure. According to Lee et al., the success rate of clarithromycin-based triple therapy was 90%; however, it is currently only 70–80%.
• Second-line treatment:
  If the initial treatment is unsuccessful, a second-line therapy is given. In this therapy levofloxacin, amoxicillin and PPI triple regimen is used. It has been claimed that 84% of patients were cured after 10 days of treatment. Quadruple therapy with bismuth is also employed as a second-line treatment. Gisbert et al. documented adverse effects, including metallic taste, nausea, vomiting, diarrhea, and stomach discomfort, in patients receiving second-line medication. Antibiotic resistance and other adverse effects can result from a lengthy second-line treatment course and an early treatment termination, according to Vakil et al. The Maastricht V/Florence consensus report recommends either a fluoroquinolone-containing triple or quadruple therapy or a colloidal bismuth pectin-containing quadruple therapy if first-line treatment with clarithromycin is ineffective.
• Third line Treatment:
  Infection with H. pylori is treated with this rescue treatment. When the first two treatments have not worked or when resistance to the first treatment has grown, third-line therapy is utilized. Treatment based on rifabutin is the third line. PPI, levofloxacin, amoxicillin, and rifabutin are the prescribed medications. This therapy has a 75–90% eradication rate. Widespread usage of rifabutin, a derivative of rifampicin, may lead to medication resistance in tuberculosis patients. Rifabutin can cause a severe but uncommon myelotoxicity that seems to be dose-dependent. Only when all other antibiotics have failed to eradicate H. pylori can rifabutin be administered as a "rescue" intervention. With gyrA mutations, H. pylori is more effectively combated by the novel quinolone derivative sitafloxacin. (13)

MANAGEMENT:

• Ineffective Medical Care
  Seventy-seven out of 135 patients (57%) who were started on a medication regimen and had conservative treatment using diet, antacids, and histamine blockers failed to successfully resolve their ulcer's symptoms or heal it. Nine (12%) of these 77 patients had Type III ulcers without a duodenal ulcer, six (8%) had Type III ulcers in conjunction with a known duodenal ulcer, eight (10%) had Type II ulcers, and 54 (70%) had Type I ulcers. For the 77 patients in the study who are still alive, have not undergone surgery, and have not yet been deemed "cured" on ongoing medication regimens, the average length of therapy is currently 29 months, and this number is rising. The average ulcer size upon diagnosis for this group of 77 patients whose ulcers did not go away with medication was 1.7 cm. Of these 77 patients, 40 have had their ulcer disease treated surgically. The average ulcer size in this group was 1.78 cm. Surgical Treatment goes into more detail about these 40 individuals. The 37 surviving patients are still receiving medical care and still exhibit symptoms. In this cohort, the average ulcer size under medical care is 1.54 cm. Some of these individuals have received medical care for up to 12 years, with an average of 31 months.
• The first surgical treatment
  Due to several ulcer-related issues, 28 patients had their stomach ulcers surgically treated within a month of the onset of symptoms without first considering a trial of more conservative methods. They were operated on without a scheduled medical treatment trial because they were bleeding (20 patients), in excruciating pain (21 patients), had extremely large ulcers (10 patients), or had perforations (5 individuals). Out of these 28 individuals, 19 (67.8%) had Type I ulcers, five had Type II ulcers, and four (14%) had Type III ulcers that were not duodenal ulcers. For this group, the average ulcer size was 2.2 cm. The largest measured 7 by 8 cm. The section on surgical treatment includes this category and goes into greater information about it.

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ROLE OF HERBAL & NATURAL MEDICINE USED FOR ULCER PREVENTION: