BPC-157: Repairing Gastrointestinal and Joint Damage

By Cocer Peptides      15 days ago

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Overview of BPC-157

BPC-157 is a stable gastrointestinal pentapeptide initially discovered for its anti-ulcer properties. It remains stable in human gastric juice for over 24 hours, enabling it to continuously exert its effects in the gastrointestinal environment and laying the foundation for repairing gastrointestinal and joint damage. Its chemical structur

e is GEPPPGKPADDAGLV, with a molecular weight of 1419. This molecular structure enables it to interact with various biomolecules in the body, thereby exerting important physiological functions.

Figure 1 BPC-157 influences the proliferation and cell cycle distribution of HUVECs.

The Repairing Effects of BPC-157 on Gastrointestinal Damage

Protecting Gastric Cells and Maintaining Gastric Integrity

BPC-157 plays a key role in protecting gastric cells, effectively defending against the harmful effects of various drugs on the stomach. Substances such as alcohol and nonsteroidal anti-inflammatory drugs (NSAIDs) often cause damage to gastric cells and disrupt gastric integrity. BPC-157 can protect gastric cells from direct damage by these harmful substances through a series of complex physiological mechanisms. When exposed to alcohol stimulation, BPC-157 regulates metabolic pathways in gastric cells, enhances the cells' antioxidant defense system, and reduces oxidative damage caused by alcohol metabolites. For NSAID-induced gastric mucosal damage, BPC-157 influences intracellular signaling pathways to inhibit the release of inflammatory mediators, thereby mitigating the destructive effects of inflammatory responses on the gastric mucosa. This helps maintain the integrity of the gastric mucosa and ensure normal physiological functions of the stomach.

Figure 2 BPC-157 increased wound reepithelialization and collagen content of granulation tissue.

Stabilizing intestinal permeability

Abnormal increases in intestinal permeability are an important factor contributing to the development of many intestinal diseases. Gastrointestinal irritants, such as physical or mental stress, NSAID use, bile acid surfactant stimulation, and alcohol intake, can all lead to increased intestinal epithelial permeability, triggering leaky gut syndrome. BPC-157 can stabilize intestinal permeability by regulating tight junction proteins between intestinal epithelial cells, thereby enhancing intercellular connection strength. According to data, in animal models exposed to the aforementioned stress factors, the use of BPC-157 resulted in increased expression of tight junction proteins between intestinal epithelial cells, with more tightly arranged structures, thereby reducing intestinal permeability to large molecules. This effectively alleviated symptoms of leaky gut syndrome, reduced the risk of harmful substances entering the bloodstream from the intestines, and maintained the stability of the intestinal microenvironment.

Promoting gastrointestinal wound healing

Whether in the healing process of ulcers throughout the gastrointestinal tract or external fistulas (such as esophageal skin fistulas, gastric skin fistulas, duodenal skin fistulas, and colonic skin fistulas) and internal fistulas (such as colonic bladder fistulas and rectal vaginal fistulas) of the gastrointestinal tract, BPC-157 demonstrates significant promotional effects. BPC-157 promotes the proliferation and migration of fibroblasts, accelerates collagen synthesis and deposition, thereby providing the necessary matrix support for wound healing. It also regulates local inflammatory responses, attracts immune cells to the wound site to clear pathogens and necrotic tissue, and promotes angiogenesis, ensuring adequate nutrient and oxygen supply for wound healing. In gastrointestinal anastomosis surgery, when the anastomotic site faces healing difficulties due to factors such as NSAIDs, cystamine, or colectomy, BPC-157 can also play a positive role in promoting anastomotic healing and reducing the risk of complications such as anastomotic fistula.

Effects on pancreatic and gastrointestinal lesions

In a rat model of acute pancreatitis induced by bile duct ligation, BPC-157 demonstrated protective effects on the pancreas whether used as a preventive or therapeutic agent. Prophylactic administration of BPC-157 significantly reduced the severity of pancreatitis, decreased pancreatic necrosis, edema, and neutrophil infiltration, while increasing monocyte counts. In the treatment of severe acute pancreatitis that has already occurred, significant beneficial effects were also observed, with serum amylase levels being controlled. BPC-157 also has a positive impact on concurrent gastric and duodenal lesions, helping to maintain the integrity of the gastrointestinal mucosa and reduce inflammatory damage to the stomach and duodenum.

The Repairing Effects of BPC-157 on Joint Damage

Improvement of temporomandibular joint osteoarthritis

In a rat model of temporomandibular joint osteoarthritis, joint damage was induced surgically, such as unilateral condylar articular surface damage, lateral collateral ligament of the articular disc, and posterior disc attachment level incisions, to simulate the pathological process of osteoarthritis. Following surgery, BPC-157 was administered via intraperitoneal injection. At the 6-month follow-up assessment, the BPC-157 treatment group exhibited a significant increase in overall joint cartilage thickness compared to the control group. Specifically, this manifested as increased thickness in both the cartilage zone and joint zone, reduced cartilage cell aggregation, disappearance of vertical cartilage fissures, and preservation of normal cartilage layering. This suggests that BPC-157 can effectively alleviate the pathological changes of temporomandibular joint osteoarthritis and promote the repair and regeneration of articular cartilage. Its mechanism of action may be related to the interaction of BPC-157 with molecules such as collagen and proteoglycans associated with articular cartilage development. According to research, multiple motifs of BPC-157 are concentrated in collagen α-1 (I), collagen α-1 (IX), aggrecan, fibronectin precursor, chondroitin sulfate proteoglycan NG2 precursor, and chondroitin oligosaccharide precursor, which are crucial for maintaining the structure and function of joint cartilage. BPC-157 may promote the repair and reconstruction of joint cartilage by regulating the expression or activity of these molecules.

Figure 3 BPC-157 promoted the expression of VEGF-a in wounded skin tissues.

Repair of knee joint injuries

Knee joint pain is a common clinical symptom caused by various factors, such as osteoarthritis, meniscus tears, tendon disorders, ligament tears, or sprains. A retrospective study observed 17 patients with knee joint pain, with 16 patients undergoing follow-up. Among these patients, 12 received intra-articular injections of BPC-157 alone, with 11 (91.6%) experiencing significant improvement in knee pain; the remaining 4 patients received combined injections of BPC-157 and thymosin-β4, with 75% of these patients experiencing significant pain relief. Overall, 87.5% of patients experienced relief of knee pain after using BPC-157 or its combination with thymosin-β4. This indicates that BPC-157 has good efficacy in alleviating various types of knee pain. Further analysis suggests that BPC-157 has the potential to repair tears and promote cartilage generation, which may be an important reason for its efficacy in alleviating knee pain. During the repair process of joint injuries, BPC-157 may promote the proliferation and differentiation of chondrocytes, increase the synthesis of cartilage matrix, thereby repairing damaged cartilage tissue. Additionally, it may also exert a reparative effect on damaged ligaments, tendons, and other tissues, improving joint stability and alleviating pain caused by joint instability.

Repair of tendon-muscle junction injuries

After the tendon of the right quadriceps muscle in rats was separated from the muscle, treatment with BPC-157 demonstrated significant therapeutic effects. From a macroscopic assessment, the control group exhibited a large defect between the quadriceps tendon and muscle that continued to progress, resulting in failed healing. In contrast, rats treated with BPC-157 showed ongoing healing, with the defect being significantly smaller from the outset, ultimately leading to the basic restoration of the tendon-muscle connection. Microscopic examination revealed that the control group exhibited tendon edema, moderate lymphocytic infiltration, and granulation tissue formation by the second week post-surgery, whereas the BPC-157 treatment group showed only mild lymphocytic infiltration, no granulation tissue formation, and good restoration of the tendon-muscle connection structure. Biomechanical assessment showed that muscle strength recovery was poor in the control group, while the BPC-157 treatment group achieved complete recovery. This indicates that BPC-157 not only has therapeutic effects on injured muscles and tendons but also exhibits specific reparative and therapeutic effects on damage to the tendon-muscle junction, aiding in the restoration of normal connection and function between muscles and tendons and ensuring normal joint mobility.

Potential and Prospects of BPC-157 in Clinical Applications

Treatment of Gastrointestinal Diseases

Given BPC-157's protective effects on gastric cells, stabilization of intestinal permeability, promotion of gastrointestinal wound healing, and positive influence on pancreatic and gastric-duodenal lesions, it holds significant potential in the treatment of various gastrointestinal diseases. In the treatment of gastric ulcers and duodenal ulcers, BPC-157 can accelerate ulcer healing and reduce the risk of recurrence. For inflammatory bowel diseases such as ulcerative colitis, BPC-157 may improve intestinal mucosal barrier function by regulating intestinal immune and inflammatory responses, alleviate symptoms, and promote disease remission. Following gastrointestinal surgery, the use of BPC-157 may help promote anastomotic healing, reduce the incidence of complications, and accelerate the patient's recovery process.

Treatment of joint diseases

In the field of joint diseases, BPC-157's reparative effects on temporomandibular joint osteoarthritis and knee injuries provide new insights into its potential application in the treatment of osteoarthritis and sports injuries. For osteoarthritis patients, BPC-157 may serve as a potential disease-modifying drug, not only alleviating pain symptoms but also slowing down cartilage degeneration, promoting cartilage repair, and improving joint function. In the treatment of sports injuries, such as tendon and ligament injuries in the knee and ankle joints commonly seen in athletes, BPC-157 can accelerate the repair of damaged tissues, shorten rehabilitation time, and enhance the recovery speed of athletes' athletic performance.

Conclusion

As a bioactive peptide with multiple repair functions, BPC-157 demonstrates certain efficacy in the fields of gastrointestinal and joint injury repair.

Sources

[1] Lee E, Padgett B J. Intra-Articular Injection of BPC 157 for Multiple Types of Knee Pain.[J]. Alternative Therapies in Health and Medicine, 2021,27 4:8-13.DOI:https://api.semanticscholar.org/CorpusID:236516759.

[2] Sikiric P, Drmic D, Sever M, et al. Fistulas Healing. Stable Gastric Pentadecapeptide BPC 157 Therapy[J]. Current Pharmaceutical Design, 2020,26(25):2991-3000.DOI:10.2174/1381612826666200424180139.

[3] Sikiric P, Hahm K B, 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.

[4] Huang T, Zhang K, Sun L, et al. Body protective compound-157 enhances alkali-burn wound healing in vivo and  promotes proliferation, migration, and angiogenesis in vitro[J]. Drug Des Devel Ther, 2015,9:2485-2499.DOI:10.2147/DDDT.S82030.

[5] Kokic N, Sikiric P, Seiwerth S, et al. Pentadecapeptide BPC-157 and rat temporomandibular joint osteoarthrosis[M]. 2001.https://www.researchgate.net/publication/266736896_Pentadecapeptide_BPC-157_and_rat_temporomandibular_joint_osteoarthrosis.

[6] Sikirić P, Seiwerth S, Grabarević Z, et al. Salutary and prophylactic effect of pentadecapeptide BPC 157 on acute  pancreatitis and concomitant gastroduodenal lesions in rats[J]. Digestive Diseases and Sciences, 1996,41(7):1518-1526.DOI:10.1007/BF02088582.

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