KPV

Overall Health Benefits of KPV

• Treats a Wide Array of Inflammatory Conditions [2-24]
• Improves Wound Healing [25-30]
• Improves Skin Health [31-45]
• Strengthens the Immune System [25, 26, 46-73]
• Protects Against Nerve Damage [74-97]
• Protects Against Stroke [98-111]

What is KPV?

KPV is a tripeptide (Lysine-Proline-Valine) that possesses potent anti-inflammatory properties. It’s a C-terminal tripeptide of α-MSH (alpha-Melanocyte-stimulating hormone). Peptides like KPV often act as hormones and relay information from one tissue through the blood to another via biological messengers. Whether given orally or in the form of injections, the KPV tripeptide has the potential to treat immune-mediated inflammatory conditions such as dermatitis, bowel diseases, allergic asthma, and arthritis.

How KPV Works?

KPV exerts its anti-inflammatory function inside cells, where it inactivates inflammatory pathways. KPV enters the cell and interacts directly with inflammatory signalling molecules inside the cell. It enters the nucleus of the cell and, once there, can inhibit the interaction of inflammatory substances and molecules. In addition to its anti‐inflammatory effect, KPV also has antimicrobial effects against pathogens such as S. aureus and C. albicans.

Chemical Structure of KPV

Research on KPV

Treats a Wide Array of Inflammatory Conditions

Interestingly, KPV appears to only have an effect in the setting of inflammation and it has almost no effect in normal tissue. The main reason for this is that KPV enters the cells using a transporter that is unregulated in case of inflammation. This suggests that the peptide may serve as an effective or preventive medication in inflammatory conditions. If taken regularly, KPV will be available when necessary and the body can simply excrete it if inflammation and other symptoms are not present. Another amazing advantage of KPV is that, unlike alpha-Melanocyte-stimulating hormone, it does not cause skin pigmentation. [1] Moreover, KPV retains most of the anti-inflammatory properties of alpha-Melanocyte-stimulating hormone but without unpleasant side effects. Another appealing aspect of KPV is that it can be administered via different routes – oral, intravenous (through the veins), subcutaneous (between the muscle and fat), and transdermal (into the dermis of the skin). This allows KPV to be administered in different body areas with a higher level of safety and efficacy.

An overwhelming body of clinical evidence suggests that KPV exerts its strong anti-inflammatory properties through various important mechanisms:

1. In a mice model of colitis (colon inflammation), oral administration of KPV (added to drinking water) inhibited the activation of NF-κB and MAP kinase inflammatory signaling pathways and reduced pro-inflammatory cytokine secretion. [2]
2. A 2001 study published in Biochem Pharmacology found that KPV exerts its anti-inflammatory activities through inhibition of NF-kappaB translocation and activation of MC(1) receptor/cAMP. [3-4]
3. In an animal model of colitis, KPV significantly reduced intestinal inflammation. [5-6]
4. As a C-terminal tripeptide of α-MSH, KPV fights inflammation by inhibiting tumor necrosis factor-α stimulated NF-κB activity and suppressing antigen-induced lymphocyte proliferation. [7-8]
5. A study published in the Journal of Federation of American Societies for Experimental Biology found that KPV suppresses inflammation through modulation of physiological responses in host defense. [9]
6. A 2003 study published in the Journal of Pharmacology and Experimental Therapeutics found that KPV exhibits its anti-inflammatory effect through inhibition of IL-1beta functions. [10]
7. A 2006 study published in the Basic & Clinical Pharmacology & Toxicology found that KPV fights inflammation by stimulating cAMP generation in a concentration-dependent way. [11]
8. One study found that KPV combats inflammation by significantly inhibiting NF-kappaB-luciferase activity. [12]
9. A 2010 study published in Advances in Experimental Medicine and Biology reported that KPV has significant similarities to the anti-inflammatory signaling of α-MSH. [13]
10. Several studies have shown a significant reduction of pro‐inflammatory substances such as IL1 β, IL6, TNFα, IL8, Groα, and interferon γ (IFNγ) following KPV treatment. [14-15]
11. A cell study found that KPV produced antibodies against the inflammatory IL10. [16]
12. Studies also show that KPV reduces inflammation through inhibition of inflammatory cell adhesion and transmigration. [17-18]
13. In murine models of colitis, KPV treatment showed significant anti-inflammatory effects which suggest that it can be an important therapeutic option in treating inflammatory bowel disease. [19]
14. In a mice model of ulcerative colitis, oral administration of KPV loaded into hyaluronic acid (HA)-functionalized polymeric nanoparticles (NPs) was effective in alleviating intestinal inflammation. [20]
15. In mice, topical administration of KPV in chemotherapy-induced oral mucositis resulted in improved healing due to its anti-inflammatory and antibacterial properties. [21]
16. In an imiquimod-induced psoriasis mouse model, the application of a gel containing alpha-MSH resulted in a reduction in psoriasis-associated inflammation. [22]
17. Studies reported that most of the anti-inflammatory activities of alpha-MSH can be attributed to its C-terminal tripeptide KPV. [23-24]

Improves Wound Healing

The potent anti-inflammatory properties of KPV may play a role in speeding up the wound healing process. In addition, since KPV does not cause skin pigmentation, this makes it a good candidate for improving wound healing while avoiding unpleasant skin changes. Another mechanism that is thought to contribute to faster wound healing is the immune-boosting effects of KPV, which helps lower the risk of infection during the regeneration process.

The beneficial effects of KPV on wound healing are backed by a number of studies:

1. Studies found that alpha-MSH peptides can speed up wound healing by enhancing the antimicrobial activity of human neutrophils and through their antifungal effects. [25-26]
2. In young adult mice with two circular through-and-through holes (6.5 mm diameter), the injection of 1 mg/kg of α-MSH reduced the scar area and improved the organization of the collagen fibers. [27]
3. In rats with liver injury caused by surgery, a single intravenous injection of α-MSH increased the replication of liver cells. [28]
4. In rats that had undergone heart transplantation, α-MSH preserved heart function and prolonged the survival of tissue graft. [29]
5. In rats with acute bleomycin-induced lung injury, α-MSH peptide treatment reduced inflammation and prevented alterations in genes involved in lung fluid homeostasis. [30]

Improves Skin Health

The anti-inflammatory effects of KPV make it an ideal treatment for various inflammatory skin conditions. Furthermore, the immune-boosting effects as well as antimicrobial and antifungal properties of this peptide may play a role in improving skin health.

Evidence suggests that KPV has the potential to treat unpleasant skin conditions:

1. In mice with experimental contact dermatitis, KPV suppressed the skin inflammatory response. [31-34]
2. In human subjects, the application of KPV cream reduced nickel‐induced contact eczema. [35]
3. KPV also suppresses antigen-induced lymphocyte proliferation in humans, resulting in healthier and smoother skin. [36]
4. A 2012 study published in the Journal of Allergy and Clinical Immunology found that KPV acts as a natural anti-allergic basophil-response modifier. [37]
5. A study published in the Archives of Dermatological Research reported that KPV regulates interleukin-10 production by human keratinocytes (skin cells), a mechanism that prevents skin inflammation. [38]
6. In mice, application of KPV on the skin suppressed contact hypersensitivity responses. [39]
7. Several studies also found that KPV is capable of suppressing the production of intercellular adhesion molecule-1 (ICAM-1) induced by pro-inflammatory stimuli such as TNF-α, IFN-γ, or LPS in the skin. [40-45]

Strengthens the Immune System

Aside from its potent anti-inflammatory properties, studies show that KPV may help boost immune function by positively affecting the production of immune system cells and other mechanisms:

1. Studies found that alpha-MSH peptides can enhance the antimicrobial activity of human neutrophils and can help fight fungi such as Cryptococcus neoformans. [25-26]
2. As a C-terminal tripeptide of α-MSH, studies found that KPV has potent antipyretic activity (lowers body temperature) in experimental fever. [46-55]
3. Studies show that KPV prevents fever by targeting the hypothalamus, the brain region that controls temperature, and by reducing pyrogens (substances that cause fever). [56-62]
4. A 2007 study published in Gene Therapy found that KPV treatment was associated with a high frequency of CD4+CD25+ regulatory T cells. [63]
5. In rats, KPV injections twice daily significantly reduced the clinical and histological signs of adjuvant-induced arthritis. [64]
6. In animal models of human autoimmune inflammatory eye diseases such as uveitis or retinitis, KPV significantly reduced symptoms and inflammatory substances. [65-69]
7. In an animal model of experimentally induced acute pancreatitis, KPV treatment reduced pancreas islet cell apoptosis (programmed cell death. [70-72]
8. In rabbits with fever induced by intravenous administration of leukocytic pyrogen, central (0.5-2.0 mg) and peripheral (2-200 mg) administration of KPV reduced fever. [73]

Protects Against Nerve Damage

As a C-terminal tripeptide of α-MSH, KPV exerts protective effects against various forms of nerve damage, suggesting that it can help combat the effect of aging and other medical conditions on nerve health:

1. In neonatal rats with nerve injury, KPV effectively induced sciatic nerve regeneration. [74-75]
2. A cell study found that KPV stimulated the growth of the long threadlike part of a nerve cell called an axon. [76]
3. In a rat model of spinal cord injury, application of α-MSH cream shortly after trauma in high doses induced nerve protection. [77]
4. In cultured rat brain cells, treatment with 10 nM α-MSH protected against cisplatin-induced neurotoxicity. [78-79]
5. A cell study also found that α-MSHprotects against nerve damage by blocking signals involved in programmed cell death. [80 -81]
6. Studies found that α-MSH protects nerve cells against ultraviolet radiation-induced apoptosis and DNA damage. [82-83]
7. Studies show that α-MSH may help protect nerve cells through its anti-scarring properties. [84-91]
8. In rats, local delivery of α-MSHcan increase postlesional repair of nerve. [92-93]
9. Rat studies also show that α-MSH treatment can significantly improve the neurological and electrophysiological function of the damaged spinal cord. [94-97]

Protects Against Stroke

Because KPV and α-MSH share similar properties, they may exert the same beneficial effects. There’s increasing evidence that supports that these peptides may be a therapeutic option in stroke:

1. α-MSH (1 mg/kg) was shown to improve the recovery of animals with stroke, especially when given before and during the 20-minute ischemia (reduced blood flow to the brain). [98]
2. When given before the start of the ischemia and again 1 hour after reperfusion (restoration of blood flow), α-MSH prevents further occlusion and inflammation of the artery. [99]
3. Several studies suggest that α-MSH exerts its protective mechanism against ischemic brain damage by reducing the brain levels of pro-inflammatory cytokines. [100-104]
4. A 2003 study published in the European Journal of Pharmacology reported that subcutaneous injection of α-MSH appears to significantly reduce the size of infarct (dead tissue caused by reduced blood flow). [105]
5. Several studies also found that α-MSH can help protect against heart and kidney problems associated with stroke. [106-111]

Associated Side Effects of KPV

KPV side effects are very uncommon. There have been some side effects associated with the use of this drug wherein the patient had one of the issues listed below at some point while being on KPV. However, these side effects weren’t confirmed to be associated with the treatment and could have been a coincidence and not related to the use of KPV. Despite this, it was listed as a side effect associated with KPV even though these associated side effects are very uncommon.

Side effects associated with KPV may include the following:

• Diarrhea
• Headache
• Nausea
• Vomiting

References

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