BPC 157 as Potential Support for COVID-19The emergence of coronavirus disease (COVID-19) in China at the end of 2019 has caused a large global outbreak. COVID-19 is largely seen as a thrombotic and vascular disease targeting endothelial cells (ECs) throughout the body that can provoke the breakdown of central vascular functions (See Figure 1 below). This explains the complications and multi-organ failure seen in COVID-19 patients including acute respiratory distress syndrome, cardiovascular complications, liver damage, and neurological damage.
Figure 1: SARS-CoV-2 Infection Pathway
Acknowledging the comorbidities and potential organ injuries throughout the course of COVID-19 is therefore crucial in the clinical management of patients. Here we discuss BPC 157 (see Figure 2 below), based primarily on animal model data, as a novel agent that can improve the clinical management of COVID-19.
BPC 157 is a peptide that has demonstrated anti-inflammatory, cytoprotective, and endothelial-protective effects in different organ systems in different species. BPC 157 activated endothelial nitric oxide synthase (eNOS) is associated with nitric oxide (NO) release, tissue repair and angio-modulatory properties which can lead to improved vascular integrity and immune response, reduced proinflammatory profile, and reduced critical levels of the disease. As a result, discussion of its use as a potential prophylactic and complementary treatment is critical.
Figure 2: BPC 157 Molecule
Researchers hypothesize BPC 157 to be a promising treatment for COVID-19 patients. Plausibly, BPC 157 may offer improved COVID-19 outcomes by mitigating cytokine derailment and subsequent multi-organ failure based on its anti-inflammatory, cytoprotective, and endothelium-protecting effects (e.g., through BPC 157-eNOS interactions). Furthermore, BPC 157 applications may obstruct viral replication, improve clinical and biochemical parameters, attenuate organ damage from the systemic alterations, provoked from SARS-CoV-2. Support for such a hypothesis is explained in further detail below.
a. BPC as an eNOS Promoter
Severe cases of COVID-19 patients can lead to the loss of eNOS activity or eNOS uncoupling by adverse regulation of redox switches in eNOS and it's up-/down-stream signaling molecules. Endothelial integrity and cellular defense requires eNOS function and its ability to generate NO.
NO deficiency is indicative of injured vessels; ultimately related to hypertension and thrombus formation frequently seen in severe COVID-19 patients. In practice, NO has shown to be clinically effective in the treatment of congenital heart disease, mitral valvular disease combined with pulmonary hypertension and in orthotopic cardiac transplantation patients. Notably, eNOS function and activity in the endothelium is not the sole mechanism essential for vascular integrity and homeostasis. Nonetheless, this signaling pathway represents an attractive target for pharmacological therapy of COVID-19 and various cardiovascular diseases.
BPC 157 has been shown to interact with eNOS, NO system, and counteract the adverse effect of L-NAME and L-arginine. In addition, BPC applications have directly shown to modulate the vasomotor tone of an isolated aorta in a concentration and NO-dependent manner via the activation Src-Cav-1-eNOS pathway in rats.
Thus, it is plausible BPC 157-eNOS/NO interactions may be an early treatment by lowering viral burden and attenuating platelet-endothelial dysfunction and associated thrombosis.
b. BPC 157 Cardioprotective Applications in Animal Studies
BPC 157 endothelial protective and cytoprotective effects have led to its investigation as an angio-modulatory agent in animal models. BPC-157 has shown to do the following in recent studies:
• Prevent and resolve inferior cava vein hypertension
• Reduced the duration of arrhythmias during hypoxia and reoxygenation
• Counteracted right heart failure by acute thrombotic coronary occlusion
• Prevent pulmonary interstitial edema
• Reduced lymphocyte count and capillary congestion
• Counteract lung lesions
The list goes on and on! This is extremely notable. As these outcomes mimic the outcomes seen with acute respiratory distress syndrome evoked from SARS-Cov-2.
The compiled findings suggest BPC 157, in animal models, is an effective therapy for disturbances in the cardiovascular system that are commonly seen in COVID-19 patients. This includes venous thromboembolism and coagulopathy from inflammatory and vascular disturbances, myocardial damage, arrhythmias, and pulmonary embolisms and may enhance the therapy for acute respiratory distress syndrome.
c. BPC 157 Lung and Liver Application
Liver damage is associated with outcomes in COVID-19 patients. Data from several observational studies illustrate the association between comorbid chronic liver disease, acute liver injury, and inflammation and outcomes of hospitalized COVID-19 patients.
BPC-157 aids in favorable liver outcomes by resolving gastrointestinal lesions, bile duct ligation, liver lesions, and hepatic encephalopathy in rodent models. It has also been shown to rapidly activate the portacaval shunt, normalize arterial and disturbed blood pressure, counteract formation of blood clots and cardiac rhythm changes, and counteract gastrointestinal mucosal lesions and lung lesions.
Furthermore, in rats subjected to congestive heart failure, 4 week administration of BPC 157 counteracted raised serum liver enzyme values ALT, AST, ALP, LDH, CK in ug dosage of BPC 157 in rats. Likewise, in research investigating BPC 157 on liver lesions, BPC 157 counteracted increased liver enzymes AST, ALT, ALP, and GGT and total bilirubin as well as decreased IL-6, TNF-α, IL-1β levels in liver tissue.
In summary, BPC 157 has shown to reign in inflammatory cytokines and promote function in both the lung and liver in animal models, and may recover damage from inflammation and cytokine release in these organs provoked from COVID-19.
d. BPC 157 Neuroprotective Applications in Animal Models
COVID-19 can cause profound molecular changes induced by inflammation in the brain. More specifically, induced significant cytokine and chemokine production, infiltration of peripheral immune cells, edema, increased blood–brain barrier (BBB) permeability and breakdown. This leads to neurological complications frequently seen in COVID-19 patients include encephalopathies, strokes, peripheral nerve damage.
BPC has demonstrated beneficial effects on the central nervous system, which is a system in the body with established vulnerability to SARS-CoV-2 onset. BPC 157 has shown to do the following in relation to its neuroprotective applications:
• Acts through different vasoactive pathways and systems that promote hippocampal neuron survival and growth that have demonstrated bidirectional effects on the gut-brain axis
• Reduce both immediate and delayed damage induced by brain trauma counteracted brain lesions from cuprizone
• Counteract brain encephalopathies from alcohol usage (acute and chronic), NSAIDs, and insulin overdose
• Decreased NF-κB, Nos2 gene expression and decreased pro-inflammatory gene Cox-2 in intestinal, liver and brain lesions in rats
Together these findings suggest BPC 157 applications may relieve the neuroinflammatory and cerebrovascular complications from COVID-19 such as encephalopathies, strokes, peripheral nerve damage, inflammation of the brain. These mechanisms are considered therapeutic targets in the management and treatment of patients with COVID-19.
BPC 157 proposes many potential effects to treat a range of conditions. Notably, BPC 157 eNOS interactions represent an attractive therapeutic target that has not yet been pharmacologically employed in COVID-19 patients. Furthermore, BPC 157 plays a role in several biological gene expressions and has demonstrated pleiotropic immunomodulatory properties that have proven extensive beneficial effects in animal models, resolving both localized and systemic damage of soft tissues.
BPC 157 has persistently exhibited anti-arrhythmic, endothelial protective and anti-inflammatory effects and has shown to prevent and reverse thrombosis formation, maintain platelet function, alleviate peripheral vascular occlusion disturbances in animal models. All attributing factors to COVID-19 outcomes. In animal models, BPC 157 has improved liver enzyme profile and disturbances, lung disturbances, cardiovascular disturbances, cerebrovascular disturbances and promoted homeostasis among neurotransmitter systems. As a result, BPC 157 poses as a necessary candidate in need of extensive investigation in preventing severe COVID-19.