BPC-157 in the digestive system. Cytoprotective effect of BPC-157 in disease conditions of the stomach, intestines, and liver.

Abstract:

The peptide BPC-157 acts directly on the digestive system, exhibiting therapeutic, regenerative, and preventive effects. Its broad spectrum of action is used, among others, in the treatment of gastric ulcer disease. 

Keywords: BPC 157; stomach stress; lower esophageal sphincter; pyloric sphincter; ulcer; analgesic; nonsteroidal anti-inflammatory drugs; reflux disease; gastric ulcer disease; blood vessels; psychogenic factor; toxic effect; stomach; small intestine; jejunum; duodenum; colon; inflammation; hydrochloric acid; stomach body; cell proliferation; antibiotics; cytoprotection; organoprotection; digestive system; celecoxib; mediator

List of abbreviations: BPC - Body Protection Compound; GERD - gastroesophageal reflux disease; NSAIDs - nonsteroidal anti-inflammatory drugs

Material and methods of research: The studies were conducted on laboratory animals, in this case albino rats, both males and females. Summarizing the findings regarding the action of BPC-157, we can state that they provide evidence that the stable gastric pentadecapeptide BPC-157 can participate, both peripherally and centrally, in solving intestinal and stomach problems. A particularly encouraging point is that BPC-157 has a very safe action profile, which has been confirmed in conducted studies.  

Digestive system

Structure of the digestive system

Let's briefly recall the structure of the digestive system as one of the most complex systems of our body. 

(Fig.1) The presented structure of the digestive tract will help us better understand and illustrate the effect of BPC-157 on individual organs of this system.

Figure 1. Overview diagram of the digestive system structure

Functions of the digestive system

The primary, well-known function of the digestive system is to obtain energy from food and absorb the necessary nutrients. The exact outline of the digestive system's functions is well known to everyone, so its presentation will typically be in the form of a reminder. The processes that initiate digestion occur in the oral cavity. The organs of the digestive system presented above allow for the assimilation and digestion of food, absorption of food components into the bloodstream, absorption of nutrients that have not entered the bloodstream, or the excretion of unnecessary components. The liver, as one of the most important glands, is responsible for the proper metabolism of carbohydrates, fats, and proteins in the body, and also stores reserves of vitamins A, D, and B12. Additionally, it has detoxifying functions by neutralizing toxins delivered with food. The pancreas is responsible for digestive functions, producing digestive enzymes. It is also responsible for controlling blood glucose levels and neutralizing stomach contents. All parts of the digestive system are important for the body to achieve health balance. Therefore, it is worth taking care of its proper functioning, among other things, by using the peptide BPC-157 as a cytoprotective and reparative agent for the organs of the digestive system.  

Digestive system diseases influenced by BPC-157 therapeutic treatment

Due to the complex structure of the digestive system, pathological conditions, i.e., diseases, often occur. There are many diseases of the digestive tract. Presented in table form are some of them, for which the peptide BPC-157 has a therapeutic effect. 

Therapeutic treatment with BPC-157 for selected digestive system diseases based on conducted studies

• Hyperemia of the digestive system/Gastric mucosal inflammation

A healthy gastric mucosa, depending on the degree of vascularization and distension, has a pink-red color. It is therefore obvious that when an intense red color is observed during an endoscopic examination, it indicates that the mucosa is hyperemic, pointing to a pathological condition. Such a diagnosis means that inflammation has developed in the gastric mucosa. The inflammation can be localized in several areas and may involve inflammation of the entire stomach, inflammation of the antral part, or inflammation of the gastric body. The most common cause of the disease is the presence of Helicobacter pylori bacteria, which directly affects the gastric glandular epithelium, leading to cell proliferation. As a result, an infiltrate consisting of lymphocytes, plasma cells, macrophages, and eosinophils forms. Treatment with a single antibiotic does not yield the desired results, so most often dual antibiotic therapy is implemented, along with drugs that reduce hydrochloric acid secretion.

a. BPC-157 Therapy

As studies have shown, the BPC-157 peptide reduces gastric acid secretion. In cases of gastric mucosal inflammation, nonsteroidal anti-inflammatory drugs should be avoided. If the stomach has already been damaged by these drugs, therapy with the BPC-157 peptide can be applied, which weakens the toxic effects of NSAIDs on its function. Additionally, acting preventively, when drinking strong beverages like tea or coffee daily, BPC-157 supports the stomach to prevent hyperemia caused by substances contained in them. Using the peptide in this disease state reduces hyperemia, and consequently, the inflammatory condition in the stomach is gradually eliminated. 

b. Conducted experimental studies

Study 1

Material

The study was conducted on male albino rats using anesthetics to explore the therapeutic potential of the BPC-157 peptide in cases of gastric mucosal inflammation. Study procedure During the study, the appropriate temperature was maintained between 20-24 °C, with relative humidity of 40-70% and fluorescent lighting for 12 hours a day. The rats were deeply anesthetized intraperitoneally using thiopental and diazepam. The superior mesenteric vein and artery were ligated in the rats. After 30 minutes, the digestive organs were removed, resulting in decapitation. Changes occurring in the digestive system organs after administration of the BPC-157 peptide to the damaged organs were observed. Observations were made using a camera connected to a microscope. Disorders in the digestive tract were assessed in several categories on a scale from 0 to 4, where 0 indicated no bleeding in the digestive tract and the maximum score of 4 indicated intense bleeding in the area.

Results

After 30 minutes from the ligation of the arteries, significant changes are noticeable in the digestive tract, including hemorrhagic hyperemic areas in the stomach and duodenum, jejunum, cecum, ascending colon, and rectum. Observing the microscopic image, symptoms such as stomach hyperemia, hyperemia of the small intestine mucosa, rectum, and perirectal vascular plexus were minimized after administration of the BPC-157 peptide. 

Conclusions

The pathological condition known as hyperemia of the digestive system/gastric mucosal inflammation was minimized using BPC-157 peptide therapy. The observed reduction in organ hyperemia suggests that this peptide has a regenerative effect on the gastric mucosa.  

• Gastric ulcer disease

A stomach ulcer in medical terms means a defect in the stomach wall, involving the mucosa, muscular layer, and submucosal tissue. The first stage of ulcer formation is the development of an "erosion" on the stomach surface. These are relatively small changes that the mucosa can handle thanks to its regenerative abilities. Unfortunately, in cases where this does not happen and the symptom is untreated or unnoticed, it grows, penetrates deeper into the stomach, damaging its subsequent layers and blood vessels. The most common cause of the disease is the presence of Helicobacter pylori bacteria, as well as an inappropriate diet, smoking, or stress as a psychogenic factor that can trigger it.

a. BPC-157 Therapy

Through the use of BPC-157, a significant reduction in the number of stomach ulcers or their complete elimination is observed with its systematic and prolonged use. As previously mentioned, BPC-157 weakens the toxic effect of NSAIDs on the stomach, which also eliminates the formation of erosions or ulcers in the stomach. Used prophylactically, it creates a protective barrier that acts protectively even in the presence of factors leading to peptic ulcer disease.

b. Conducted experimental studies

Study 2

Material

The study was conducted on male rats weighing from 200g to 240g.

Course of the study

Each subject was given saline, mannitol, and amotidine as caloric control, excipient control, and positive control. The animals underwent a 24-hour fast with access to water, then were administered the BPC-157 peptide. Ulceration was induced by injection of indomethacin, followed by formaldehyde administration to the stomach. An incision was made on the stomach surface with stretching, where the size of the ulcers was measured. 

Results

Administration of the BPC-157 peptide in the presence of the painkiller indomethacin shows its protective effect on the stomach and prevention of ulcers caused by this drug. 

Conclusions

Peptic ulcer disease, which can be caused by Helicobacter pylori bacteria, stress, NSAIDs, or excessive secretion of HCl and pepsin in the presence of the BPC-157 peptide, is minimized and individual ulcers are completely eliminated.  

• Lower esophageal sphincter inflammation/gastroesophageal reflux disease

Gastroesophageal reflux disease (GERD) occurs as a result of pathological regurgitation of stomach contents into the esophagus. The people most at risk for this condition are those with abnormal lower esophageal sphincter function, gastric emptying disorders, or obesity. The cause of reflux is abnormalities in esophageal contractions, as its proper function relies on a rapid contraction to move food directly to the stomach without backflow. Treatment of reflux is based on administering antacids, locally protective drugs, changing eating habits, and in extreme cases, surgical treatment is considered. a.BPC-157 Therapy The BPC-157 peptide acts to regulate pressure in the esophagus. This concerns the lower esophageal sphincter and the pyloric sphincter, through which it can be used both prophylactically and as a drug acting directly on reflux symptoms, eliminating its course and symptoms.

b. Conducted experimental studies

Study 3

Material

Study conducted on albino female rats to explore the therapeutic potential of BPC-157 peptide in esophageal reflux. 

Course of the study

Rats with inflammation of the lower esophageal sphincter and duodenum were studied. BPC-157 was administered at a dose of 10 μg/kg. In the control trial, rats were given saline at a dose of 5.0 ml/kg. A catheter implantation procedure into the stomach through the esophagus was performed under deep anesthesia. BPC-157, ranitidine, or 0.9% NaCl were administered directly into the rat's stomach. After a few minutes, manometric assessment was conducted using a water manometer connected to the catheter drainage port.

Results

In rats after the procedure, reduced pressure was observed in the sphincters. Daily treatment with BPC-157 peptide after the procedure maintained sphincter pressure at normal levels, which corresponded to a reduction in esophagitis. Additionally, confluent hemorrhagic and yellowish lesions that appear in advanced esophagitis were reduced to a minimum. BPC-157 consistently restores the reduced pressure of both the lower esophageal sphincter and the pyloric sphincter.

Figure 2. BPC-157 peptide therapy allowing the minimization of esophagitis symptoms

Conclusions

The disease condition known as esophagitis was minimized using BPC-157 peptide therapy.  

• Leaky gut syndrome

Leaky gut syndrome is characterized, as the name suggests, by damage and lack of tightness in the intestinal mucosa. This phenomenon causes harmful microorganisms, parasites, or undigested chains of complex proteins to enter the bloodstream. The symptoms most commonly occurring in this condition are severe abdominal pain, diarrhea, and constipation. The cause of leaky gut syndrome is an inappropriate diet, stress, or excessive physical exertion. Treatment involves eliminating toxins from the body, using prebiotics and probiotics to balance the microflora, and reducing intestinal inflammation.

a. BPC-157 Therapy

BPC-157 acts as a membrane stabilizer, counteracting leaky gut syndrome through its action on molecular pathways. Due to its mode of action, it leads to increased permeability of capillaries. Using BPC-157 helps maintain the integrity of the intestinal mucosa.  

BPC-157 therapy in stomach stress pathology

Psychosomatic disorders are conditions in which a psychological aspect influences the physical state. Stress affects our entire body, and in the case of the digestive system, it can lead to serious dysfunctions. A person subjected to continuous stress factors is exposed to disease states such as pain in the esophagus or abdominal cavity as well as problems with appetite. Just as stress disorders affect our body, poor condition of digestive organs can lead to increased feelings of exhaustion, stress, insomnia, or anxiety. Psychological factors influence and play a role in the etiopathogenesis and treatment of digestive system diseases such as irritable bowel syndrome, reflux disease, or functional dyspepsia. Additionally, psychosomatic diseases currently include stomach neurosis, habitual vomiting, psychogenic constipation, as well as peptic ulcer disease of the stomach and duodenum, which does not arise only from chemical, infectious, or traumatic factors but also from prolonged stress stimuli. Somatic symptoms of anxiety related to the digestive tract activity include, among others, dry mouth, burning in the esophagus, heartburn, excessive salivation, nausea and vomiting, spastic states of the esophagus, stomach, and intestines, a feeling of discomfort in the abdominal cavity, diarrhea, functional motility disorders, swallowing problems, lack of appetite, and sometimes excessive appetite and obesity.

As known from the previous article (https://synthagenlabs.com/dzialanie-neuroprotekcyjne-i-przeciwdepresyjne-bpc-157-wplyw-bpc-157-na-prace-mozgu/) BPC-157 also acts protectively on our nervous system, which is why its effect on the digestive system is doubly important. Thanks to consistent and systematic use of BPC-157, symptoms of stress, burnout, depressive or anxiety states are reduced. This phenomenon occurs both when it has a basis related to the digestive system and only with symptoms from the nervous system. The BPC-157 peptide allows avoiding stress caused by digestive system disease and since this is a linked reaction, it also allows eliminating disease states in the digestive tract caused by a stressogenic factor. (Fig.3)

Figure 3. Consistent and systematic use of BPC-157 allows for the elimination of stomach ulcers caused by stress factors (stomach stress)

 

Cytoprotective action of BPC-157

The concept of cytoprotection

By the concept of cytoprotection, we understand the ability, in this case of a substance, to protect the body's cells from undesirable and damaging effects of various factors. The protective effect acting on the cell is based on inhibiting oxidative stress, apoptosis, or functioning metabolism at the lowest possible energy level in case of deficiency. Protective effect of BPC-157 on the stomach BPC-157 is characterized by beneficial action, both in protecting the stomach and in protecting all organs of the digestive system.

stomach cytoprotection → organoprotection of the entire digestive tract

Cytoprotection, concerning the entire digestive system, includes changes of even the most complex nature, e.g., in cases of internal and external fistulas or severe colitis. BPC-157 also acts as a free radical eliminator, counteracts damage caused by them, normalizes and measures NO and MDA levels in tissues during ischemia and reperfusion. Through the presence of VEGFR 2 receptors as a growth factor, growth hormone receptors, VEGFR2-AKT-eNOS, ERK ½, FAK-paxillin, FoxO3a, p-AKT, p-mTOR, and p-GSK-3β pathways, and characteristic loops, the level of pro-inflammatory cytokines is reduced, thereby exhibiting protective effects in the event of inflammation throughout the digestive system.

Protection against the adverse effects of NSAIDs using BPC-157 therapy

The concept of NSAIDs

Nonsteroidal anti-inflammatory drugs (NSAIDs) are one of the most commonly used groups of drugs, available over the counter and with a broad spectrum of action such as anti-inflammatory, antipyretic, and analgesic effects. Due to their availability and frequent use by people, their side effects are often noticeable, which frequently lead to digestive system disorders. 

The impact of NSAIDs on the risk of digestive tract damage

The toxic effect of NSAIDs affects the entire digestive system. NSAIDs, having the ability to inhibit the synthesis of gastroprotective prostaglandins, exhibit gastrototoxic action. Prostaglandins are essential for the proper functioning of the digestive system. The process of inhibiting prostaglandin synthesis occurs through constitutive cyclooxygenase, also known as COX-1. The free submucosal blood flow and carbohydrate synthesis are inhibited, leading to disturbances in the digestive system. Additionally, NSAIDs easily penetrate epithelial cells because they are weak organic acids that do not dissociate in the acidic environment of the stomach. The consequence of penetrating epithelial cells is the initiation of the ionization process where NSAIDs do not dissolve in fats, thus remaining present in these cells. As a result of the so-called ion trap, damage to epithelial cells is increased. The reduction of gastric juice volume by NSAIDs, without reducing hydrogen ions, leads to the formation of inflammatory foci, which subsequently develops into gastric ulcer disease. The action of nonsteroidal anti-inflammatory drugs in the digestive tract can also cause, among others, enteropathy, perforations, strictures, or lead to exacerbation or recurrence of digestive system diseases. It is worth mentioning that most pathological changes caused by NSAIDs occur in the lower part of the digestive tract. Before starting the use of NSAIDs, one should familiarize themselves with their toxic effects on the digestive system, the consequences in case of symptom occurrence, and how to alleviate or prevent them. The therapeutic profile regarding the prevention and treatment of symptoms is demonstrated by the peptide BPC-157. 

a. BPC-157 Therapy

As is known, drugs from the NSAID group act cytotoxically on the digestive system. Agents preventing cytotoxic effects are called cytoprotective agents, among which is BPC-157. The cytoprotective action of BPC-157 may indicate that it becomes its new mediator, participating in both the cyto-protective response and the adaptive cyto-protective response, acting against exogenous and endogenous irritating factors. BPC-157 is stable in gastric juice and, by combining regenerative processes, shows a wide range of treatment for the effects of NSAID therapy. If the use of NSAIDs can lead to peptic ulcer disease, it is not surprising that BPC-157, by eliminating their cytotoxic effect, will protect the stomach from their formation, even in the case of simultaneous use as well as regeneration after therapy with drugs from the NSAID group. The VEGF growth factor has a significant influence on the regenerative action profile of BPC-157. BPC-157, being a stimulator of VEGFR, promotes angiogenesis. Angiogenesis induced by BPC-157 creates new blood vessels from existing vessels. Thanks to the occurrence of angiogenesis, the peptide BPC-157 finds its application in the healing process of stomach ulcers caused by NSAID therapy as well as in the regeneration of the digestive system after their use. 

b. Conducted experimental studies

Study 4

Material

The study was conducted on male albino rats, examining the effect of the BPC-157 peptide compared to the action of the amino acid L-arginine, in the presence of celecoxib, a drug belonging to selective cyclooxygenase-2 (COX-2) inhibitors, which is part of the NSAID group. 

Course of the study

Celecoxib at a dose of 1g/kg was administered intraperitoneally, then very quickly BPC-157 peptide was administered at doses of 10 μg/kg, 10 ng/kg, and 1 ng/kg, and L-arginine at a dose of 100 mg/kg. A control trial was also created in the study, where saline was administered intraperitoneally. The severity of injuries was assessed immediately after euthanasia. Stomach tissues were subjected to routine microscopic analysis to assess the effect of the peptide and amino acid on gastric changes in the presence of a nonsteroidal anti-inflammatory drug.

Results

Celecoxib, as a strong NSAID, caused serious changes in the stomach, including histopathological images showing mucosal defects in the intestine and stomach ulcers. After 48 hours from drug administration, these changes were aggravated. In samples where L-arginine was administered, these changes were weakened. An even more beneficial effect was shown by the administration of the BPC-157 peptide, which, given directly after celecoxib, completely alleviated the changes caused by celecoxib, both after 24 hours and after 48 hours. This study is an example of BPC-157's action in the presence of only one drug from the NSAID group, but its effect with other drugs from this group consistently shows the same beneficial and desired effect.

BPC-157 significantly alleviated liver damage caused by celecoxib, which induced the injury. Marked steatosis of microvesicles and macrovesicles in the liver, dilated sinusoids, and focal liver necrosis were observed.

Conclusions

BPC-157 acts directly on the digestive system, minimizing the effects of therapy with NSAID drugs and, in some cases, completely eliminating them.  

Aid in recovery after surgeries and operations

BPC-157, leading to the activation of the Src–caveolin-1–eNOS pathway and the activation of the VEGFR2–Akt–eNOS signaling pathway, exhibits regenerative effects, finding application in convalescence after procedures and surgeries within the digestive system. The expression of the protein associated with the ZO-1 junction prevents the increase of pressure in the abdominal cavity, which eliminates the occurrence of leaky gut syndrome, a very important aspect in the postoperative state. Additionally, BPC-157, by inhibiting the mRNA expression of inflammatory mediators (iNOS, IL-6, IFNγ, and TNF-α), minimizes the risk of unwanted inflammatory conditions during postoperative recovery.

Study 5

Material

The study was conducted on male albino rats to assess the degree of postoperative recovery with BPC-157 therapy. Study procedure The rats were deeply anesthetized intraperitoneally using thiopental and diazepam, then a gastroesophageal anastomosis was performed at the apex of the forestomach and the distal part of the incision and esophagus. BPC-157 was administered orally in drinking water at doses of 10 μg/kg, 10 ng/kg, 0.16 μg/ml, 0.16 ng/ml, and 12 ml daily. For comparison, L-arginine was also administered to better demonstrate the beneficial effects of BPC-157 through a comparative method.

Results

Rats undergoing gastroenteric anastomosis surgery without any drugs were exposed to a very severe postoperative condition, where pathological changes on the surface of such a small stomach were not large. However, changes were noticeable in the esophagus where severe inflammation occurred. The anastomoses were also weakened, resulting in water loss in the body and subsequently weight loss. Such pathological changes led to death. After administration of the BPC-157 peptide, changes in the stomach and inflammatory changes in the esophagus were weakened, and the anastomoses were strengthened. Additionally, pressure in the esophagus at the site of the anastomosis and the pyloric sphincter increased. Survival increased to such a level that fatal outcomes were avoided.  

Conclusions

BPC-157, demonstrating a broad spectrum of action, also acts regeneratively after undergone procedures and surgeries of the digestive tract, promoting faster convalescence. 

Summary

Proper functioning of the digestive system is essential for quality of life. The presented broad spectrum of BPC-157's effects on our digestive system allows it to be classified as a substance with therapeutic, regenerative, and preventive properties. Systematic use of the peptide will enable the full recovery of the digestive system's functionality, whose diseases or ulcers effectively reduce our comfort of functioning. A significant number of studies show that BPC-157 administered orally (via capsules or dissolving the substance in water) exhibits equally effective action on our digestive system as injection administration. It can be confidently stated that BPC-157 in the form of a stable salt is a new precursor in the treatment of digestive system disorders.  

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