Archive for Muscle Healing

BPC 157 as an effective therapy for muscle crush injury

This trial shows that BPC157 accelerates muscle healing and to restore full muscle function!

Surgery Today Journal
August 2008, Volume 38, Issue 8, pp 716-725

Gastric pentadecapeptide BPC 157 as an effective therapy for muscle crush injury in the rat
Purpose
Stable gastric pentadecapeptide BPC 157 accelerates the healing of a transected Achilles tendon and a transected quadriceps muscle. It may also be of clinical relevance as a systemic and local peptide treatment for crush injury of a major muscle, such as gastrocnemius muscle complex. BPC 157 is effective without a carrier, and it is presently undergoing trials for inflammatory bowel disease, and no toxicity has so far been reported.

Methods
In crushed rats (force delivered 0.727 Ns/cm2), BPC 157 was applied either intraperitoneally or locally, as a thin cream layer, immediately after injury (sacrifice at 2 h), and once a day for 14 days.

Results
BPC 157 improved muscle healing, macroscopically (less hematoma and edema, no post-injury leg contracture), microscopically, functionally, and also based on enzyme activity (creatine kinase, lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase).

 

Conclusion
BPC 157, at all investigated intervals, given locally or intraperitoneally, accelerated post-injury muscle healing and also helped to restore the full function.

 

Key words
BPC 157 Crush injury Peptide therapy Muscle regeneration Rat

Source for this article: http://link.springer.com/article/10.1007%2Fs00595-007-3706-2

 

Useful References:

  • 1. Sikiric P, Petek M, Rucman R, Seiwerth S, Grabarevic Z, Rotkvic I, et al. A new gastric peptide BPC. An overview of stomach — organoprotection hypothesis and beneficial effect of BPC. J Physiol (Paris) 1993;87:313–327.
  • 2. Sikiric P, Seiwerth S, Brcic L, Blagaic AB, Zoricic I, Sever M, et al. Stable gastric pentadecapeptide BPC 157 in trials for inflammatory bowel disease (PL-10, PLD-116, PL 14736, Pliva, Croatia). Full and distended stomach, and vascular response. Inflammopharmacology 2006;14:214–221.
  • 4. Jelovac N, Sikiric P, Rucman R, Petek M, Marovic A, Perovic D, et al. Pentadecapeptide BPC 157 attenuates disturbances induced by neuroleptics: the effect on catalepsy and gastric ulcers in mice and rats. Eur J Pharmacol 1999;379:19–31.
  • 5. Sikiric P, Seiwerth S, Grabarevic Z, Rucman R, Petek M, Jagic V, et al. Beneficial effect of a novel pentadecapeptide BPC 157 on gastric lesions induced by restraint stress, ethanol, indomethacin, and capsaicin neurotoxicity. Dig Dis Sci 1996;41:1604–1614.
  • 6. Sikiric P, Seiwerth S, Grabarevic Z, Rucman R, Petek M, Jagic V, et al. The influence of a novel pentadecapeptide, BPC 157, on N(G)-nitro-L-arginine methylester and L-arginine effects on stomach mucosa integrity and blood pressure. Eur J Pharmacol 1997;332:23–33.
  • 7. Sikiric P, Seiwerth S, Mise S, Staresinic M, Bedekovic V, Zarkovic N, et al. Corticosteroid-impairment of healing and gastric pentadecapeptide BPC-157 creams in burned mice. Burns 2003;29:323–334.
  • 8. Veljaca M, Chan K, Guglietta A. Digestion of h-EGF, h-TGF alpha, and BPC-15 in human gastric juice. Gastroenterology 1995;108:761.
  • 12. Staresinic M, Petrovic I, Novinscak T, Jukic I, Pevec D, Suknaic S, et al. Effective therapy of transected quadriceps muscle in rat: Gastric pentadecapeptide BPC 157. J Orthop Res 2006;24:1109–1117.
  • 14. Krivic A, Anic T, Seiwerth S, Huljev D, Sikiric P. Achilles detachment in rat and stable gastric pentadecapeptide BPC 157: promoted tendon-to-bone healing and opposed corticosteroid aggravation. J Orthop Res 2006;24:982–989.
  • 15. Staresinic M, Sebecic B, Patrlj L, Jadrijevic S, Suknaic S, Perovic D, et al. Gastric pentadecapeptide BPC 157 accelerates healing of transected rat Achilles tendon and in vitro stimulates tendocytes growth. J Orthop Res 2003;21:976–983.
  • 16. Sebecic B, Nikolic V, Sikiric P, Seiwerth S, Sosa T, Patrlj L, et al. Osteogenic effect of a gastric pentadecapeptide, BPC-157, on the healing of segmental bone defect in rabbits: a comparison with bone marrow and autologous cortical bone implantation. Bone 1999;24:195–202.
  • 17. Bilic M, Bumber Z, Blagaic AB, Batelja L, Seiwerth S, Sikiric P. The stable gastric pentadecapeptide BPC 157, given locally, improves CO2 laser healing in mice. Burns 2005;31:310–315.
  • 18. ikus D, Sikiric P, Seiwerth S, Petricevic A, Aralica G, Druzijanic N, et al. Pentadecapeptide BPC 157 cream improves burn-wound healing and attenuates burn-gastric lesions in mice. Burns 2001;127:817–827
  • 19. Seiwerth S, Sikiric P, Grabarevic Z, Zoricic I, Hanzevacki M, Ljubanovic D, et al. BPC 157’s effect on healing. J Physiol (Paris) 1997;91:173–178.
  • 21. Xue XC, Wu YJ, Gao MT. Study of the protective effects of pentadecapeptide BPC 157 on wounds in small type pigs. Chin New Drugs J 2004;12:602–604.
  • 23. Gjurasin M, Miklic P, Buljat G, Perovic D, Jukic I, Sikiric P, et al. Selective healing effect of the gastric pentadecapeptide BPC 157 on injured part of the nerve in subtotal sciatic nerve transection. Dig Dis Sci 2003;48:1878.
  • 24. Vuksic T, Zoricic I, Brcic L, Sever M, Klicek R, Radic B, et al. Stable gastric pentadecapeptide BPC 157 in trials for inflammatory bowel disease (PL-10, PLD-116, Pliva, Croatia) heals ileoileal-anastomosis in rat. Surg Today 2007;37:768–777.
  • 34. Lovric-Bencic M, Sikiric P, Hanzevacki JS, Seiwerth S, Rogic D, Kusec V, et al. Doxorubicine-congestive heart failure-increased big endothelin-1 plasma concentration: reversal by amlodipine, losartan, and gastric pentadecapeptide BPC 157 in rat and mouse. J Pharmacol Sci 2004;95:19–26.
  • 35. Prkacin I, Separovic J, Aralica G, Perovic D, Gjurasin M, Lovric-Bencic M, et al. Portal hypertension and liver lesions in chronically alcohol drinking rats prevented and reversed by stable gastric pentadecapeptide BPC 157 (PL-10, PLD-116), and propranolol, but not ranitidine. J Physiol (Paris) 2001;95:315–324.
  • 37. Sikiric P, Separovic J, Anic T, Buljat G, Mikus D, Seiwerth S, et al. The effect of pentadecapeptide BPC 157, H2 blockers and sucralfate on new vessels and new granulation tissue formation. J Physiol (Paris) 1999;93:479–485.
  • 38. Veljaca M, Lesch CA, Sanchez B, Low J, Guglietta A. Protection of BPC-15 on TNBS-induced colitis in rats: possible mechanisms of action. Gastroenterology 1995;108:936.
  • 39. Veljaca M, Lesch CA, Pllana R, Sanchez B, Chan K, Guglietta A. BPC-15 reduces trinitrobenzene sulfonic acid-induced colonic damage in rats. J Pharmacol Exp Ther 1994;272:417–422.

BPC 157: The Healing Miracle Molecule

What is BPC 157?

The human body has a remarkable system of self-healing and damage repair. One of the important components of this system is a protein called Body Protection Compound (BPC) 157.

BPC 157 is a peptide made up of 15 amino acids; and is produced by the body in the acidic environment of the stomach. The peptide is well-known for its ability to heal, repair and regenerate. Studies suggest that BPC 157 is useful in the treatment of ulcers in the digestive tract as well as management of inflammatory bowel disease (IBD), a group of inflammatory disorders of the digestive tract. BPC 157 also facilitates wound healing of various tissues, including skin, muscle, bone, ligament, and tendon.

BPC 157 in the Digestive Tract

Given that BPC 157 is present in the juices of the stomach, we would expect it to be involved in functioning of the digestive tract. And this is indeed the case. In fact, BPC 157 is also called “stable gastric pentadecapeptide”as it remains stable in human gastric juices for at least 24 hours.

BPC 157 has several functions in the digestive tract. It preserves the integrity of the stomach lining, improves digestion, and facilitates healing throughout the digestive tract. It is particularly helpful in [1] [2]:

  1. Inflammatory bowel disease; such as Ulcerative Colitis, Crohn’s Disease and Esophagitis
  2. Fistula and intestinal anastomosis (the latter is a process where a section of an intestine is cut and removed. The two ends are then surgically connected.)
  3. Reversing short bowel syndrome
  4. Protecting the gastro-intestinal tract from NSAID overuse

Much of the healing capacity of BPC 157 comes from its ability to:

  • Protect the endothelium – inner lining of blood vessels and the lymphatic system known as the endothelium,
  • Play an important role in the formation of new blood vessels – a process known as angiogenesis.

BPC 157 as an Anti-ulcer Agent

BPC 157 is a cytoprotective agent; meaning it can limit the damage to gastric mucosa by agents that trigger ulcer formations. Most importantly, it doesn’t prevent gastric acid secretion but strengthens the protection for gastric mucosa.

NSAID’s or non-steroidal anti-inflammatory drugs are commonly used to relieve pain and inflammation. Overuse of NSAIDs is known to cause ulcers and even bleeding in the digestive tract. BPC 157 possesses the ability to heal these ulcers and a study published in 2013 noted that BPC 157 has clear antidote activity against NSAIDS side effects; and that the “variety of the beneficial effects portrayed by BPC 157 may well be a foundation for establishing BPC 157 as a NSAIDs antidote since no other single agent has portrayed a similar array of effects.” [3]

In addition, BPC 157 can heal lesions in the liver developed due to overuse of alcohol. These lesions can lead to liver tissue damage. Thus, BPC 157 can protect the liver from further deteriorating.

BPC 157 in Inflammatory Bowel Disease

BPC 157 shows great potential in reducing the symptoms of advanced inflammatory bowel disease (IBD). The peptide combines its anti-inflammatory and healing properties to manage the following conditions:

  • Crohn’s disease: chronic inflammation affecting the digestive tract. It causes abdominal pain, diarrhea, and poor absorption of nutrients leading to fatigue and malnutrition.
  • Ulcerative colitis: formation of ulcers and open sores in the colon
  • Esophagitis: inflammation of the esophagus (food pipe) making it extremely painful and difficult swallow.

BPC 157 in Wound Healing

Wound healing is a complex process involving a sequential, cascade of events; which are critical for maintaining the integrity of the body.

BPC 157 holds tremendous potential in wound healing of many tissues such as skin, muscle, bone, ligaments, and tendons. It reduces inflammation at the wound site and allows faster healing of bone ligaments, damaged muscle, Achilles tendons and skin wounds [4] [5].

There are three major processes by which BPC 157 plays a vital role in wound healing; angiogenesis, granulation tissue formation, and production of collagen. All of these mechanisms are central to any healing process occurring within the body.

Angiogenesis is a process where new blood vessels are formed around the site of injury. It allows new blood vessels to send oxygen, nutrients, and inflammatory cells to the healing and regenerating tissues. BPC 157 increases the expression of vascular endothelial growth factor (VEGF) that promotes angiogenesis [6].

A quick primer on VEGF

VEGF is a protein that signals the growth of new blood vessels when a tissue is damaged. It is a very important process that serves to reinstate the blood supply; and with it oxygen and nutrition, to the tissues at the time of reduced blood circulation. In other words, during an injury, the growth factor triggers the sprouting of new blood vessels – an action that increases the influx of nutrients to the damaged tissue.

BPC 157 exerts a particularly effective role in tendon healing. Muscles have a remarkable process of healing; owing to a highly-evolved system of blood vessels and also stem cells. However, tendons lack this blood vessel network and as a result there is a reduced flow of oxygen and nutrients to the recuperating tendon. This leads to impaired healing.

BPC 157, by up-regulating VEGF, triggers an adequate and controlled angiogenic response that allows tendons to heal faster. Controlled angiogenesis is important, as prolonged instances interferes in healing, eventually leading to chronic tendon disease.

BPC 157 achieves effective muscle and tendon healing by regulating certain underlying complex processes, “In tendon and muscle healing its functional, biomechanical, and pathohistological beneficial effect is accompanied by angiogenic action. BPC 157 may directly protect endothelium, influence the NO-system, counteract the effect of both NOS-inhibitor and NO-precursor as well as over expression of endothelin.”

The anti-inflammatory properties of BPC 157 further contribute to its healing benefits. The peptide decreases the concentration of inflammatory mediators in the injured or damaged tissues – promoting the wound healing process and allowing the tissue to heal faster.

BPC Influences the NO system

BPC 157 interacts with, and modulates the nitric oxide (NO) system; an important property responsible for many of its wound healing and tissue repair outcomes.

NO is a gas naturally produced by the body and is implicated in many aspects of repair, healing and regeneration processes – involving angiogenesis, inflammation, cell proliferation, matrix deposition, and remodeling to name a few. Nitric oxide plays a particularly important role in mediating a number of inflammatory responses and promoting angiogenesis (growth of new blood vessels).

Furthermore, a study showed that the protein’s ability to influence the NO system may be helpful in many conditions [7]:

  1. Protects the gastric mucosa following alcoholic lesions
  2. Alcohol intoxication and withdrawal
  3. Cardiovascular problems, including chronic heart failure, irregular heart beat and elevated blood pressure in the arteries of the lungs
  4. Changes in blood potassium levels that can lead to dysfunction of the cell membranes
  5. Complications with fistula healing; both of colon and esophagus.

BPC 157 is safe with no side effects

BPC 157 is naturally produced by the body in small amounts. There are no reported side effects associated with its use. With no Lethal Dose 1 achieved for BPC 157, it enjoys quite a high safety profile. Lethal Dose 1 of any substance is the dose at which 1 % of the test population is killed.

BPC 157 Benefits in a Nutshell

Miraculous healing protein

  1. Anti-ulcer and provides protection to the gastric mucosa
  2. Provides relief in inflammatory bowel disease; including Ulcerative Colitis and Crohn’s Disease
  3. Promotes healing in intestinal surgery and fistula
  4. Promotes faster healing of damaged muscle and tendons.
  5. Improved healing of superficial cuts, skin wounds and abrasions

 

References:

  1. Cesarec V, Becejac T, Misic M, Djakovic Z, Olujic D, Drmic D, Brcic L, Rokotov DS, Seiwerth S, Sikiric P. Pentadecapeptide BPC 157 and the esophagocutaneous fistula healing therapy. European Journal of Pharmacology. 2013
  2. Stable gastric pentadecapeptide BPC 157: novel therapy in gastrointestinal tract.  Current Pharmaceutical Design. 2011
  3. P Sikiric et al. Toxicity by NSAIDs. Counteraction by stable gastric pentadecapeptide BPC 157. Current Pharmaceutical Design. 2013
  4. Chang CH, Tsai WC, Hsu YH, Pang JH. BPC 157 enhances the growth hormone receptor expression in tendon fibroblasts. Molecules. 2014
  5. Krivic, A., Anic, T., Seiwerth, S., Huljev, D. and Sikiric, P. Achilles Detachment in Rat and Stable Gastric Pentadecapeptide BPC 157: Promoted Tendon-to-Bone Healing and Opposed Corticosteroid Aggravation. . J. Orthop. 2006
  6. L. Brcic et al. Modulatory Effect Of Gastric Pentadecapeptide Bpc 157 On Angiogenesis In Muscle And Tendon Healing. Journal of Physiology And Pharmacology 2009
  7. P Sikiric et al. Stable gastric pentadecapeptide BPC 157-NO-system relation. Current Pharmaceutical Design. 2014