BPC-157 is the term used to refer to a pentadecapeptide, a protein with 15 amino acids. BPC is an acronym for 'Body Protection Compounds' and refers to "peptides comprising 8-15 amino acids residues with a molecular weight of 900-1,600 daltons" according to the patent for BPC-157, although another study claims that BPC refers to a gastroprotective protein used to isolate BPC-157. This particular sequence does not share homology with other known gastric peptides, with at least one study noting that this sequence did not register in the Protein BLAST database (as of 2016). There are a few studies in which this peptide is also referred to as PL 14736, PL-10, and Bepecin. This entry will use the acronym BPC-157 exclusively.
BPC-157 is a peptide consisting of 15 amino acids. While they are 'natural' compounds, this particular sequence is not known to occur in nature and is derived from another protein.
BPC-157 is freely soluble in water of normal pH value. The pentadecapeptide sequence is Gly-Glu-Pro-Pro-Pro-Gly-Lys-Pro-Ala-Asp-Asp-Ala-Gly-Leu-Val and is stated to be quite stable relative to other peptides by not degrading in stomach acid (ex vivo) for at least 24 hours. It has been shown to be moderately stable in plasma ex vivo, with 36% of the intact peptide remaining after 60 minutes.
When researchers tested BPC-157 in a CAM assay (chick embryo), it seemed to be capable of increasing the process of angiogenesis (blood vessel production) by 129+/-7% and 152+/-14% when administered in doses of 0.01 μg and 0.1 μg, respectively. This effect was later confirmed in HUVECs, where concentrations of 0.1 μg/mL and 1 μg/mL increased the formation of perfect tubes by 119+/-9% and 147+/-7% over 24 hours of incubation (with 1 μg/mL being determined to be the optimal concentration in HUVECs). This observation was confirmed in rats given limb damage as well. After a week of treatment with BPC-157, there appeared to be more blood vessels in the damaged limb than control.
An increase in VEGFR2 expression was noted in the rats with an injured limb given BPC-157 compared to control, which was thought to underlie the increase in blood vessel production. When tested further, researchers discovered that VEGF-A is wholly unaffected at the concentration of 1 μg/mL, while VEGFR2 increased in a time-dependent manner within the cell and then proceeded to activate the VEGFR2-Akt-eNOS pathway (a pathway important to angiogenesis). When dynasore, a VEGFR2 inhibitor, was introduced, the entire pathway was no longer activated and tube formation no longer occurred in vitro.
BPC-157 appears to activate a protein known as VEGFR2 and internalizes it within a cell, which then activates a particular pathway (VEGFR2-Akt-eNOS) that is important in blood vessel production and repair.
BPC-157 has also been found to stimulate the mRNA of the growth factor EGR-1 in intestinal cells (Caco-2) at 10-100 μM, with most efficacy at 50 μM. A related protein, mRNA NAB2, was also increased shortly after. Both of these effects parallel the effects of PDGF-BB (an endogenous growth factor) although they require much higher concentrations. EGF-1 protein content also appeared to be increased.
The growth factor EGF-1 may also be related to the observed benefits of BCP-157.
When incubated in plasma ex vivo, it appears that a large amount of the peptide detected is registered as 'metabolites' (79+/-2%) of the parent compound within 60 minutes, although it then seems to stabilize, with the remaining intact peptide remaining for up to 240 minutes.
There does appear to be some degradation of BPC-157 in plasma, although what remains after this degradation is currently not known. The effects of orally ingested BPC-157 are also currently unknown.
It has been mentioned indirectly by the author of many BPC-157 studies that no known binding to dopamine receptors has been found, though there is no citation provided for this particular claim.
When administered at 10 ng/kg or 10 μg/kg, BPC-157 administered at the same time as amphetamine found that only the higher dose was able to attenuate some observable effects of the amphetamine (rat behaviours such as compulsive sniffing, licking, and gnawing). Administering the BPC-157 an hour after amphetamine also showed some benefits. When rats were previously given haloperidol (which makes rats subsequently more sensitive to the effects of amphetamine) coadministration of BPC-157 appeared to mitigate the expected haloperidol-induced sensitivity. This apparently antagonistic effect may also apply chronically, meaning a single dose of BPC-157 (10 μg/kg I.P; 10 ng/kg ineffective) given before chronic amphetamine administration seemed to attenuate the behavioral effects of amphetamine in rats throughout the observation period.
There appear to be some influence of BPC-157 on dopaminergic systems, where it limits the efficacy of dopamine agonists. It is not currently known how this occurs.
BPC-157 has been investigated for its involvement in the serotonergic system due to its involvement in gut health, with researchers suggesting a possible brain-gut axis due to the effects of BPC-157 in both of these areas. In regard to a connection between the brain and intestines, serotonin is a likely player due to its high prevalence in the intestines.
Researchers found that rats given 10 μg/kg (subcutaneous injection) of BPC-157 acutely experience increased serotonin synthesis after 40 minutes in several brain regions, including the substantia nigra reticulata and medial anterior olfactory nucleus while simultaneously experiencing a decrease in the hypothalamus, hippocampus (ventral and dorsal), amd the thalamus (dorsal but not ventral). When this dose was given for one week, the increase in serotonin synthesis in the substantia nigra persisted (occurring in both the reticulata and compacta) while the decreases in serotonin synthesis seen with a single dose no longer persisted.
There appears to be some interactions between BPC-157 and serotonin in the brain, but the underlying mechanisms are unknown.
BPC-157 appears to have protective effects on brain tissue when administered to rats (either in drinking water or injections) alongside the toxin cuprizone by reducing the amount of damaged cells in numerous brain regions, including the hippocampus. Cuprizone is a toxin used to mimic the damages seen in multiple sclerosis and potentially schizophrenia.
Oral ingestion of BPC-157 at an estimated 10 μg/kg (0.16 μg/mL in water) was similarly effective as injections of 10 ng/kg and 10 μg/kg although cuprizone is known to be a toxin that can induce neuronal damage (specifically demyelination) without necessarily reaching the brain.
Orally ingested BPC-157 has shown neuroprotective effects in rats given neurotoxins. The precise mechanism of how it exerts these effects is unknown but may be intestinal.
In female rats subject to a forced swim test (Porsolt's swim test), BPC-157 (intraperitoneal administration) at the doses of both 10 ng/kg and 10 μg/kg seem to perform to a statistically equal degree to the active controls of both imipramine (15 mg and 30 mg) and nialamide (30 mg and 40 mg), all of which outperformed the control group. BPC-157 also appeared effective in assisting these rats in a model of chronic unpredictable stress similar to 30 mg of imipramine.
At concentrations of 2 μg/mL in tendon fibroblasts which were then explanted, BPC-157 cells appeared to grow faster than fibroblasts not treated with BPC-157 within two days, reaching a significantly larger amount after one week. This effect was associated with both increased oxidative resistance to hydrogen peroxide and a concentration-dependent increase in the proteins FAK and paxillin not seen in control. F-actin formation, important for the spreading process of tendon fibroblasts, also appeared to be greatly increased with BPC-157 relative to control and are related to the actions of the aforementioned proteins (FAK and paxillin).
This study also found that ex vivo tendon fibroblasts in isolation were unaffected by BPC-157, only those explanted into rats, an effect also noted elsewhere when cultured tendocytes were unaffected by BPC-157 alone. However, the growth inhibitory effect of 4-hydroxynonenal (HNE) was negated by BPC-157 in these cells.
BPC-157 appears to allow tendon fibroblasts to grow and spread faster, although this effect may not persist in the fibroblasts alone, suggesting other cells may be required for this effect or BPC-157 may work by negating suppressing factors.
Researchers have observed benefits when putting BPC-157 on a sponge during surgery, where it appeared to improve the rate of collagen reformation, initially outperforming platelet-growth factor after four days but eventually being equipotent after eight days. Benefits have been seen in rats given intraperitoneal injections after an Achilles heel injury, where the rate of injury healing was visually confirmed with smaller cut size and depth.
Some evidence suggests that BPC-157 can assist tendon regenesis after surgical damage.
The protective effects of BPC-157 on ulcers has been found to be prevented in rats by coadministration of haloperidol (Alpha-1A and Dopamine receptor antagonist), phentolamine (Alpha adrenergic antagonist, nonselective), and clonidine (Alpha-2A adrenergic antagonist, similar to agmatine) but was not affected by prazosin, domperidone, or yohimbine.
The anti-ulcer actions of BPC-157 in the stomach may be related to the dopamine and adrenaline systems.
When it comes to inflammation, BPC-157 has shown benefit in rats against the toxins trinitrobenzene sulfonic acid (TNBS) and cysteamine, where both biomarkers of inflammation and visual markers of damage were reduced when BPC-157 was administered alongside the toxins. BPC-157 is not unique in this regard, as other active controls like ranitidine and omeprazole have shown efficacy in the same model of intestinal inflammation, though it was mentioned in a review by the authors that BPC-157 may be more practical due to proven benefits in other complications of intestinal disease: anastomosis healing, short bowel syndrome, and fistulas.
An anastomosis is a connection between two things that are not normally connected, with a fistula being an abnormal type commonly seen during intestinal diseases. Numerous studies have shown BPC-157 injections in rats having a mending property on anastomosis in numerous body regions, including aortic and esophagogastic. In studies assessing the intestines, benefits have been shown to colovesical, rectovaginal, colon-colon, and ileoileal fistulas. This particular benefit may be related to nitric oxide signaling (potentially the VEGFR2-Akt-eNOS pathway BPC-157 influences) since L-NAME, a nitric oxide synthase inhibitor, worsens anastomosis healing in a manner ameliorated by BPC-157.
Studies assessing BPC-157 in experimental models of short bowel syndrome also find benefit, with injections of BPC-157 ameliorating this state even when the state is worsened with the addition of L-NAME and diclofenac.
Most BPC-157 studies on intestinal damage use rats that undergo surgical-induced damage for experimental purposes. BPC-157 appears to have very potent protective effects in rats by mitigating damage to the tissue and structural abnormalities caused by the damage.
Most notably, a benefit for anastomosis healing (esophagogastric) has been found in rats given BPC-157 in drinking water (approximately 10 ng/kg or 10 μg/kg daily) without an injection, with no significant difference in efficacy between the two doses and statistically similar efficacy to injections of 10 ng/kg and 10 μg/kg.
It is possible, based on limited evidence, that BPC-157 may be orally active in the alimentary canal (the pathway between the mouth and anus).
One study in rats using the toxin MPTP (which induces damage similar to what is seen in Parkinson's Disease in rodents), administration of BPC-157 intraperitoneally appeared to mitigate some of the damage caused by MPTP.
In rodents given cuprizone (to induce damage similar to what is seen in multiple sclerosis) those given BPC-157 alongside the cuprizone (0.16 ng/mL or 0.16 μg/mL in drinking water over four days or 10 ng/kg or 10 μg/kg intragastrically on the final day) seemed to exhibit significantly less brain damage and clinical abnormalities from the cuprizone than did control rats not given BPC-157.