BPC-157

Bpc 157 Research

What is the research background of Bpc 157?

Bpc 157 is a peptide composed of 15 amino acids and is part of the sequence of the body protection compound (Bpc) discovered and isolated from human gastric juice. The following is the research background related to Bpc 157:

The Brain-Gut Axis and Bpc 157: 

Brain-gut interaction involves peptidergic growth factors. Among them, the stable gastric pentadecapeptide  Bpc 157 is an anti-ulcer peptidergic drug that is safe and effective in inflammatory bowel disease trials and is currently undergoing trials for multiple sclerosis. It naturally exists in human gastric juice^[1] . Bpc 157 may act as a new mediator of Robert cell protection, participating in maintaining the integrity of the gastrointestinal mucosa without toxic effects.

It has achieved success in treating gastrointestinal diseases, periodontitis, liver and pancreatic lesions, as well as the healing of various tissues and wounds. It also stimulates the Egr-1 gene, NAB2, FAK-paxillin, and JAK-2 pathways^[1] .When Bpc 157 is administered peripherally, corresponding beneficial central effects are initially observed, especially changes in serotonin release in certain areas of the brain (mainly the nigrostriatal region). Bpc 157 regulates the serotonergic and dopaminergic systems, having a beneficial effect on various behavioral disorders that occur due to specific stimulation/damage of the neurotransmitter system.

In addition, Bpc 157 has neuroprotective effects, such as protecting somatosensory neurons, promoting peripheral nerve regeneration, counteracting the progression process after traumatic brain injury, preventing axonal and neuronal necrosis, demyelination, and cyst formation in rats with spinal cord compression accompanied by caudal paralysis, and restoring caudal function^[1] .

The Role in Gastric Cell Protection and Organ Protection: 

Bpc 157 is of great significance as a possible mediator of Robert's gastric cell protection/adaptive cell protection and organ protection, as well as a new mediator of Selye's stress response. Bpc 157 protects gastric cells and maintains the integrity of the stomach against various harmful substances.

It can prevent the adverse effects of alcohol and non-steroidal anti-inflammatory drugs on the gastric epithelium and other epithelia (such as the skin, liver, pancreas, heart, and brain), and has potential applications in wound healing. In addition, Bpc 157 can also counteract gastric endothelial damage, protect other vascular endothelia, have a positive impact on blood vessels, rapidly reconstruct the integrity of blood flow, and counteract tumor cachexia, muscle wasting, and increased pro-inflammatory/cachectic cytokines^[2] .

The Therapeutic Role in Vascular Occlusion: 

In the study of superior mesenteric artery and vein occlusion in rats, Bpc 157 can rapidly activate collateral pathways, including the superior mesenteric vein-inferior anterior pancreaticoduodenal vein-superior anterior pancreaticoduodenal vein-pyloric vein-portal vein pathway, alternative pathways to the inferior vena cava through the middle colic vein and inferior mesenteric vein, as well as the inferior anterior pancreaticoduodenal artery and inferior mesenteric artery.

Bpc 157 can counteract superior sagittal sinus, portal vein, and inferior vena cava hypertension, aortic hypotension, progressive venous and arterial thrombosis in the peripheral and central areas, alleviate multi-organ lesions, lesions in the heart, lungs, liver, kidneys, gastrointestinal tract, especially in the brain, and oxidative stress in tissues ^[3].

The Role in Budd-Chiari Syndrome: In the study of the Budd-Chiari syndrome model (occlusion of the suprahepatic vena cava) in rats, Bpc 157 can rapidly form bypass pathways of the inferior vena cava-azygos vein (hemiazygos vein)-superior vena cava and portacaval shunt, counteract portal vein and inferior vena cava hypertension, aortic hypotension, and alleviate thrombosis, electrocardiogram disorders, and lesions in the liver and gastrointestinal tract. During ligation, the levels of nitric oxide and malondialdehyde in the liver remain within the normal healthy value range, and the increase in serum enzymes is also significantly reduced ^[4].

The Potential Therapeutic Role in COVID-19: 

COVID-19 is regarded as a thrombotic and vascular disease mainly targeting systemic endothelial cells, which can cause central vascular dysfunction, leading to complications and multi-organ failure. Bpc 157 is a peptide that has anti-inflammatory, cytoprotective, and endothelial protective effects in different organ systems of different species. It can activate endothelial nitric oxide synthase, which is related to nitric oxide release, tissue repair, and vascular regulation properties, improve vascular integrity and immune response, reduce the pro-inflammatory state, and reduce the severity of the disease. Therefore, it is crucial to discuss its potential as a preventive and supplementary treatment method^[5] (Deek S A, 2022).

What is the specific mechanism of action of Bpc 157 in the brain-gut axis?

The brain-gut axis is a complex two-way communication system involving the interaction between the nervous system and the gastrointestinal tract, and Bpc 157 plays an important role in it, mainly in three aspects: First, as a cytoprotective mediator, Bpc 157 can participate in maintaining the integrity of the gastrointestinal mucosa. As a new mediator of Robert cell protection without toxic effects, it maintains the normal physiological function of the gastrointestinal tract by protecting gastrointestinal cells, thereby affecting the balance of the brain-gut axis. Second, it regulates the neurotransmitter system. Bpc 157 can regulate the serotonergic and dopaminergic systems. When Bpc 157 is administered peripherally, the release of serotonin in specific brain areas (mainly the nigrostriatal region) will change, producing beneficial central effects. Moreover, it can beneficially affect various behavioral disorders that occur due to specific stimulation/damage of the neurotransmitter system. For example, it regulates the serotonergic and dopaminergic systems to improve behavioral problems caused by abnormal neurotransmitter systems. Third, it has neuroprotective effects. Bpc 157 can protect somatosensory neurons, promote neuron survival and functional recovery in case of nerve injury, promote peripheral nerve regeneration, and restore nerve conduction function, reducing traumatic brain injury. For example, in the case of spinal cord compression in rats accompanied by caudal paralysis, axonal and neuronal necrosis, demyelination, and cyst formation, Bpc 157 can salvage caudal function and reduce the damage to organs such as the nervous system and gastrointestinal tract caused by drug overdose or encephalopathy, protecting the normal functions of the body^[1].

What is the specific mechanism of Bpc 157 in treating central nervous system diseases?

Bpc 157 has shown multiple potential mechanisms in treating central nervous system diseases. In the model of cerebral ischemic stroke, Bpc 157 effectively counteracts the stroke induced by bilateral common carotid artery clamping by protecting neurons and supporting specific gene expression. It can address the persistent damage to brain neurons in rats, while improving disturbed memory, motor, and coordination abilities. It has a direct protective effect on the neuronal damage caused by ischemic stroke and also supports the expression of specific genes in the hippocampal tissue. It may promote the survival and functional recovery of neurons by regulating the expression of specific genes^[6] .

Examples of successful administration mechanisms for the delivery of BPC 157; all routes, local and systemic, have been reported to have positive healing outcomes

Source:PubMed^[7]

For schizophrenia, Bpc 157 regulates the relationship between the nitric oxide system and the dopamine system and counteracts various abnormalities of the dopamine system, thereby improving the symptoms of schizophrenia. It can address the complex relationship between the nitric oxide system and amphetamine, apomorphine, MK-801, and chronic methylphenidate administration, indicating that it may improve the symptoms of schizophrenia by regulating the functions of the nitric oxide system and the dopamine system. It can also counteract various abnormalities of the dopamine system, including dopamine receptor blockade, the development of receptor hypersensitivity, receptor activation, excessive release, nigrostriatal damage, and vesicular depletion, etc. It has a wide range of regulatory effects on the dopamine system and helps to restore the functional balance of the dopamine system in schizophrenia patients^[6] .

In addition, as a new type of cytoprotective mediator, Bpc 157 regulates the serotonergic and dopaminergic systems, has a beneficial effect on behavioral disorders, and through its neuroprotective effect, protects somatosensory neurons, promotes peripheral nerve regeneration, counteracts the progression of traumatic brain injury, and restores caudal function. It may act as a new type of cytoprotective mediator, participate in maintaining the integrity of the gastrointestinal mucosa, and have an indirect therapeutic effect on central nervous system diseases. It can also regulate the serotonergic and dopaminergic systems, have a beneficial effect on various behavioral disorders that occur due to specific (excessive) stimulation/damage of the neurotransmitter system, and at the same time have neuroprotective effects, such as protecting somatosensory neurons, promoting peripheral nerve regeneration, counteracting the progression of traumatic brain injury, counteracting axonal and neuronal necrosis, demyelination, and cyst formation in rats with spinal cord compression, and restoring caudal function^[1] .

What are the Studies Related to Bpc 157?

As a Potential Treatment for COVID-19: 

In late 2019, coronavirus disease 2019 (COVID-19) triggered a large-scale pandemic worldwide. Research suggests that COVID-19 is largely a thrombotic and vascular disease targeting systemic endothelial cells, which can lead to the disruption of central vascular function ^[5]. Patients with COVID-19 may develop multi-organ failure such as acute respiratory distress syndrome, cardiovascular complications, liver injury, and nerve injury. Based on animal model data, researchers have discussed the role of Bpc 157 as a novel drug in improving the clinical management of COVID-19. Bpc 157 is a peptide that exhibits anti-inflammatory, cytoprotective, and endothelial protective effects in different organ systems of different species. Bpc 157 activates endothelial nitric oxide synthase (eNOS), which is related to nitric oxide (NO) release, tissue repair, and vascular regulation properties, and can improve vascular integrity and immune response, reduce the pro-inflammatory state, and reduce the severity of the disease. Therefore, it is of great significance to discuss its potential as a preventive and adjuvant treatment method.

Accelerating the Healing of Musculoskeletal Soft Tissue: 

A review has been conducted on the role of Bpc 157 in the treatment of soft tissue injuries^[7] .Currently, all experiments studying Bpc 157 have shown that for various types of injuries (including traumatic and systemic injuries and a variety of soft tissue injuries), Bpc 157 has a consistent positive and rapid healing effect. However, to date, most of the studies have been conducted on small rodent models, and the efficacy of Bpc 157 has not been confirmed in humans. Nevertheless, Bpc 157 clearly has great potential and is expected to become a treatment method for the conservative treatment of low-vascular and low-cellular soft tissue (such as tendons and ligaments) injuries or as an adjuvant for recovery after further development. In addition, the skeletal muscle injury model shows that Bpc 157 not only has a beneficial effect on injuries caused by direct trauma but also on systemic injuries including hyperkalemia and hypermagnesemia.

Improving Motor Function after Spinal Cord Injury: 

Researchers have used a well-designed rat model to demonstrate that the stable gastric pentadecapeptide Bpc 157 can improve spinal cord injury^[8] . Previous studies have shown that Bpc 157 can counteract the consequences of peripheral (sciatic nerve) nerve transection/anastomosis and improve nerve healing, brain trauma, and various encephalopathies. Bpc 157 has been used as an anti-ulcer peptide in inflammatory bowel disease trials and multiple sclerosis trials. In one study, rats received a single intraperitoneal injection of Bpc 157 (200 or 2μg/kg) or normal saline (5ml/kg) after spinal cord injury. All injured rats showed continuous improvement after Bpc 157 treatment, with significantly better clinical tail motor function and no self-mutilation behavior; the spasm problem was solved on the 15th day; under the microscope (starting from the 7th day), the vacuoles and axonal loss in the white matter, edema in the gray matter, and loss of motor neurons in Bpc 157 rats, as well as the reduction in the number of large myelinated axons in the rat caudal nerve, were largely counteracted. Electromyogram recordings showed a significant decrease in motor unit potentials in the tail muscles. In addition, researchers also conducted another experiment. Bpc 157 was administered 4 days after spinal cord injury, and Bpc 157 (10μg/kg, 0.16μg/mL, 12ml/rat/day) was given through drinking water for 4 weeks, while the control group received only drinking water. The results showed that the rats treated with Bpc 157 showed great improvement and continued to recover until complete recovery.

Counteracting Spinal Instability: 

To induce spinal instability in rats, researchers focused on bilateral facetectomy and explored the possible therapeutic benefits of the stable gastric pentadecapeptide Bpc 157 in drinking water^[9] .In previous studies, Bpc 157 has been shown to improve spinal cord injury, peripheral nerve injury, brain trauma, and various encephalopathies. In this study, rats received complete bilateral L3-L4 facetectomy, and after the operation, they were given Bpc 157 (10ng/kg, 0.16ng/mL, 12ml/rat/day) or only drinking water. Radiological evaluations were performed at week 1 and week 8. The results showed that at week 1, no obvious deformity was observed in the rats of the control group and the Bpc 157 group in any plane, the intervertebral disc space seemed to be unaffected, the neural foramen at the surgical level was slightly widened, and the rats in the Bpc 157 drinking group had a higher overall bone density. At week 8, no obvious deformity was observed in the rats of both groups in any plane, the intervertebral disc space was unaffected, the neural foramen at the surgical level was slightly widened, the rats in the Bpc 157 group had significantly higher bone density, and there was a lack of a large amount of callus formation in a random pattern visible in the control group. In addition, the rats in the control group showed obvious motor impairment immediately after injury induction, while the rats in the Bpc 157 drinking group completely counteracted this motor impairment.

In conclusion, the core value of Bpc 157 lies in its endogenous and multi-system regulatory characteristics, providing innovative solutions for refractory inflammation, tissue defects, and neuropsychiatric diseases. In the field of sports trauma, it can accelerate the repair and regeneration of tissues such as muscles, tendons, and ligaments, shorten the recovery time, and has a good therapeutic effect on acute trauma. In the treatment of burns, Bpc 157 can significantly enhance the biological functions of endothelial cells such as proliferation, migration, and tubule formation, thus accelerating the repair of burn wounds. In addition, it has a protective effect on the gastrointestinal tract, can promote the healing of gastrointestinal ulcers, and prevent and alleviate gastrointestinal diseases. Bpc 157 also shows potential in neuroprotection, protecting the nervous system through mechanisms such as reducing the inflammatory response and inhibiting apoptosis. It also has a protective effect on human organs such as the pancreas, liver, and heart, demonstrating its wide range of biological effects as a multifunctional peptide.

Relevant Citations

[1] Sikiric P, Seiwerth S, Rucman R, et al. Brain-gut Axis and Pentadecapeptide BPC 157: Theoretical and Practical Implications[J]. Current Neuropharmacology, 2016,14(8):857-865.DOI:10.2174/1570159X13666160502153022.

[2] Sikiric P, Hahm K, Blagaic A B, et al. Stable Gastric Pentadecapeptide BPC 157, Robert's Stomach Cytoprotection/Adaptive Cytoprotection/Organoprotection, and Selye's Stress Coping Response: Progress, Achievements, and the Future[J]. Gut and Liver, 2020,14(2):153-167.DOI:10.5009/gnl18490.

[3] Knezevic M, Gojkovic S, Krezic I, et al. Occluded Superior Mesenteric Artery and Vein. Therapy with the Stable Gastric Pentadecapeptide BPC 157[J]. Biomedicines, 2021,9(7).DOI:10.3390/biomedicines9070792.

[4] Gojkovic S, Krezic I, Vrdoljak B, et al. Pentadecapeptide BPC 157 resolves suprahepatic occlusion of the inferior caval vein, Budd-Chiari syndrome model in rats.[J]. World Journal of Gastrointestinal Pathophysiology, 2020,11(1):1-19.DOI:10.4291/wjgp.v11.i1.1.

[5] Deek S A. BPC 157 as Potential Treatment for COVID-19[J]. Medical Hypotheses, 2022,158.DOI:10.1016/j.mehy.2021.110736.

[6] Vukojevic J, Milavic M, Perovic D, et al. Pentadecapeptide BPC 157 and the central nervous system[J]. Neural Regeneration Research, 2022,17(3):482.DOI:10.4103/1673-5374.320969.

[7] Gwyer D, Wragg N M, Wilson S L. Gastric pentadecapeptide body protection compound BPC 157 and its role in accelerating musculoskeletal soft tissue healing[J]. Cell and Tissue Research, 2019,377(2):153-159.DOI:10.1007/s00441-019-03016-8.

[8] Perovic D, Krezic I, Dokuzovic S, et al. Stable Gastric Pentadecapeptide BPC 157 Recovers Motor Function After Rat Spinal Cord Injury[J]. Faseb Journal, 2019,33.https://doi.org/10.1096/fasebj.2019.33.1_supplement.822.5.

[9] Dokuzovic S, Bebek I, Perovic D, et al. Spinal Instability in Rats Counteracted by Pentadecapeptide BPC 157[J]. Faseb Journal, 2019,33.https://doi.org/10.1096/fasebj.2019.33.1_supplement.822.3.