KPV is the tail end of alpha-MSH, a hormone your pituitary gland naturally produces that's best known for controlling skin pigment, but also has a separate, surprisingly powerful job: turning down inflammation. Researchers discovered decades ago that you don't need the whole alpha-MSH molecule to get this calming effect - just this last three-letter piece does most of the work, without the pigment-related side effects of the full hormone. Since then, labs around the world have tested KPV in mouse and rat models of colitis, skin wounds, burns, lung inflammation, and infection, and in human cell dishes, consistently finding it dials down the same inflammatory alarm system (a signal called NF-kB) across very different tissues. It has never been tested in a human clinical trial, so everything known about it comes from animals and lab dishes.
How strong is the evidence?
Of the 40 papers on file, none are human clinical trials. The evidence is a large, repeated body of mouse and rat studies (mostly colitis models, plus wound healing, burns, and vascular disease), lab-dish experiments using human cell lines (skin, gut, and lung cells growing in a dish, not living patients), delivery-technology papers (nanoparticles, hydrogels, patches designed to carry KPV to the right tissue), and a handful of review articles that summarize this same animal and lab work. A few hits in the file are false matches where 'KPV' means something unrelated (a knee X-ray angle, a lab mouse genetic strain, a vinegar polysaccharide, an old polio paper) and were excluded from every conclusion below. What remains is a genuinely consistent story across more than a dozen independent labs and 25+ years - but consistent animal data is not the same as proof in people. No dose, safety profile, or benefit has been confirmed in a living human being.
Uses
What people use it for
Calming gut inflammation (colitis / IBD)
Animal / labThis is where KPV has been studied the most. In mouse and rat models of ulcerative colitis and Crohn's-like inflammation, giving KPV by mouth, rectally, or packaged in nanoparticles and hydrogels consistently reduced gut inflammation and helped the gut lining heal. This is the largest and most consistent cluster of evidence in the file, but it's all animal work - no human IBD trial of KPV exists.
Soothing irritated or pollution-damaged skin
Animal / labIn human skin cells grown in a dish, KPV protected against damage from air pollution particles, reducing cell death and inflammation. This is lab-dish work, not a test on real skin exposed to pollution in daily life.
Speeding up wound healing (skin, eyes, mouth)
Animal / labTopical KPV sped up corneal (eye surface) healing in rabbits, and KPV-loaded gels and patches improved healing of skin wounds in diabetic mice and mouth sores in rats after chemotherapy. All of this is animal-model work aimed at building better wound dressings, not tested in human patients yet.
Fighting bacteria and possibly viruses
Animal / labOlder lab studies found that KPV and its parent hormone can directly inhibit growth of Staph bacteria and Candida yeast, and reduce HIV replication in infected human immune cells in a dish. These are decades-old lab findings, not evidence it treats infections in a real person.
General inflammation control (burns, sepsis-like reactions, lung and blood vessel inflammation)
Animal / labAcross many different animal disease models - severe burns, endotoxin/sepsis-like reactions, airway inflammation, and even blood vessel calcification - KPV has repeatedly turned down the same inflammatory signaling pathway. It's a consistent pattern, but again, entirely from rodent studies and isolated cells.
Potential benefits
What it may help with
Reduces colitis symptoms and helps the gut lining heal (animal studies)
Animal / labAcross many independent labs, mice and rats given KPV - orally, rectally, or via nanoparticle and hydrogel delivery systems - showed less weight loss, less colon tissue damage, and lower inflammatory markers during induced colitis. One study found KPV even helped prevent colon tumors linked to chronic gut inflammation.
Protects skin cells from pollution and oxidative stress
Animal / labIn a 2025 lab study, human skin cells (keratinocytes) treated with KPV (at 50 micrograms/mL in the dish) were protected from fine air pollution particles, showing less cell death and lower levels of the inflammatory signal IL-1 beta. This was cell-dish research, not a real-world skin test.
Studies:40073467Speeds up wound and tissue repair
Animal / labTopical KPV helped rabbit corneas re-heal completely within 60 hours versus no healing in untreated eyes, and KPV-loaded dressings improved healing of diabetic skin wounds in mice and chemotherapy-related mouth sores in rats.
Blocks the core inflammation switch (NF-kB) in many tissues
Animal / labIn lung, skin, immune, and gut cells, KPV consistently blocks a molecular switch called NF-kB that turns on inflammation, and it dampened inflammatory chemical surges after burns and in sepsis-like reactions in rats.
Direct antimicrobial and antiviral action in lab tests
Animal / labKPV and its parent hormone slowed growth of Staph bacteria and Candida yeast, and reduced HIV replication in infected human immune cells growing in a dish. This is old, narrow lab data - not evidence it fights infections in real people.
Emerging signals in fatty liver and blood vessel calcification
Animal / labNewer lab studies suggest KPV may reduce fat buildup in liver cells and, when paired with another compound in a nanoparticle, may reduce calcium buildup in blood vessels in mice. These are early, single-study findings that need to be repeated before they mean much.
What to watch for
Side effects & risks
- Mild
No adverse effects reported in the animal and lab studies on file
Across the colitis, wound-healing, and delivery-system studies reviewed, researchers specifically noted that KPV and its nanoparticle/hydrogel carriers were non-toxic and well tolerated in mice and rats, with no cytotoxicity in the cell lines tested. That's a reassuring pattern, but it comes from short animal experiments, not long-term human use.
- Moderate
Human safety is simply unknown
Because no clinical trial has ever tested KPV in people, there is no data on allergic reactions, dosing side effects, long-term safety, or interactions with health conditions. Anyone using it is relying entirely on animal safety signals, not human evidence.
Dosing
Dosing — what studies used
There is no established human dose for KPV - it has never been tested in a clinical trial, so there is no medically approved amount, frequency, or duration to point to. Every dose below is what researchers used in a mouse, rat, rabbit, or cell-dish experiment, most of which also relied on special delivery systems (nanoparticles, hydrogels, patches) to get KPV to the right tissue and keep it stable, because the plain peptide breaks down quickly and barely absorbs on its own. Treat every number here as a research detail, never as a recommended dose for a person.
Corneal (eye surface) wound healing, rabbits
Animal study1, 5, or 10 mg/mL solution (30 microliters per drop)
Two drops, four times a day · 4 days, starting right after the corneal injury · Topical eye drops
The only protocol in the file with a fully specified amount, frequency, and duration. All doses tested fully re-healed the cornea; none of this was tested in humans.
Colitis models (ulcerative colitis / IBD), mice
Animal studyNot specified in the published abstract - KPV was added directly to drinking water or given orally
Continuous, throughout the colitis-induction period · Length of the colitis model (typically 1-2 weeks) · Oral (drinking water)
Foundational studies showing oral KPV reduces colitis severity in mice, but the exact concentration used isn't given in the abstract text available here.
Colitis models, rectal delivery via hydrogel carriers (rats)
Animal studyConcentration not detailed in the abstracts - KPV was loaded into a self-crosslinking or double-network hydrogel and delivered directly into the colon, rather than as a plain solution
Varies by study · Varies by study (days to about 2 weeks in most colitis models) · Rectal (into the colon)
These studies focus more on the delivery technology (getting KPV to stick to inflamed gut tissue and stay stable) than on establishing a specific dose.
Colitis models, oral delivery via colon-targeted nanoparticles (mice)
Animal studyConcentration not stated in plain terms - KPV was packed into nanoparticles wrapped in a polysaccharide or hyaluronic-acid coating; one study reported the nanoparticle packaging let KPV work at a concentration about 12,000 times lower than free KPV
Varies by study · Varies by study (typically the length of the colitis model) · Oral (nanoparticles engineered to release KPV once they reach the colon)
These are swallowed nanoparticle systems built to carry KPV safely through the gut and release it at the inflamed colon - not rectal treatments. The focus is the delivery technology rather than a set dose.
Because KPV breaks down fast and doesn't absorb well on its own, almost every serious study pairs it with a delivery technology (nanoparticles, hydrogels, skin patches, iontophoresis). That tells you researchers see it as a promising active ingredient but not yet a ready-to-use drug - the packaging problem hasn't been solved for human use.
These figures describe what researchers used in studies. They are not a recommendation or a prescription.
Mechanism
How it works
Your body makes a hormone called alpha-MSH that does a lot of jobs, including controlling skin color. KPV is just the last three building blocks (amino acids) of that hormone, snipped off - and it turns out this tiny piece keeps the hormone's anti-inflammatory power without touching pigment at all. Inside cells, KPV blocks a molecule called NF-kB, which acts like a master alarm switch that turns on inflammation genes. By keeping that alarm switched off, KPV reduces the release of inflammatory chemicals (like TNF-alpha and IL-1 beta) that cause swelling, tissue damage, and pain. In the gut, KPV also gets pulled into cells by a specific transporter (called PepT1) that is turned up during gut inflammation, which may explain why it seems to concentrate right where it's needed most. Interestingly, researchers found KPV doesn't need the same receptors the full hormone uses - it seems to work through a separate, still not fully mapped route, which is part of why it's studied as its own ingredient rather than just a piece of alpha-MSH.
Who should avoid it
- Anyone expecting a proven treatment - KPV has never been tested in a human clinical trial for any condition, including IBD or skin healing
- Pregnant or breastfeeding people - there is no safety data at all
- Children - no safety data exists
- People with active infections or cancer - some lab studies show KPV affects immune signaling and cell survival pathways; how this plays out in a person with an active illness is unknown
- Anyone relying on an unregulated online product - since it's not an approved medicine, purity, actual dose, and contamination of any product sold as 'KPV' cannot be verified
Interactions to know
- No drug-interaction studies exist in humans - KPV has never been tested alongside common medications, supplements, or other peptides in a real person.
- Anti-inflammatory or immune-suppressing drugs (steroids, biologics for IBD, etc.) - since KPV works on some of the same inflammation pathways, combining them is completely unstudied and could theoretically add up in ways that aren't understood.
- Other melanocortin-related products (like melanotan compounds) - because KPV comes from the same hormone family, stacking it with other melanocortin-pathway products has not been studied together.
The papers that matter most
Key studies
One of the foundational efficacy papers: KPV treatment led to faster weight recovery and less colon inflammation in two different mouse colitis models, and even rescued mice lacking a working pigment receptor - suggesting the effect doesn't depend on that receptor.
Melanocortin-derived tripeptide KPV has anti-inflammatory potential in murine models of inflammatory bowel disease
Showed KPV gets pulled into gut and immune cells through a specific transporter (PepT1) that's turned up during inflammation, and that oral KPV reduced colitis in two separate mouse models - a key mechanistic explanation for why oral dosing might work.
PepT1-mediated tripeptide KPV uptake reduces intestinal inflammation
Found that KPV reduces inflammation through a different route than the main pigment hormone receptors, instead working by blocking IL-1 beta activity - explaining why KPV calms inflammation without the pigmentation effects of full alpha-MSH.
Dissection of the anti-inflammatory effect of the core and C-terminal (KPV) alpha-melanocyte-stimulating hormone peptides
Summarizes two decades of animal evidence showing KPV calms inflammation in skin, gut, eyes, lungs, and joints, while flagging that its exact signaling mechanism was still not fully understood at the time.
Terminal signal: anti-inflammatory effects of alpha-melanocyte-stimulating hormone related peptides beyond the pharmacophore
A recent, more mechanistically detailed study showing KPV protects human skin cells from air-pollution particle damage by blocking oxidative stress and the same NF-kB inflammation switch - reinforcing the core mechanism in a modern skin-relevant model.
Lysine-Proline-Valine peptide mitigates fine dust-induced keratinocyte apoptosis and inflammation by regulating oxidative stress and modulating the MAPK/NF-kB pathway
A cutting-edge 2026 delivery study showing a specially engineered oral version of KPV reached inflamed colon tissue far better than plain KPV, and also helped in a mouse lung-injury model - suggesting future formulations may make KPV far more usable, though still animal-only.
Inflammation-triggered self-immolative conjugates enable oral peptide delivery by overcoming gastrointestinal barriers
Bottom line
KPV has one of the more consistent preclinical stories in the peptide world - more than a dozen independent labs, over 25 years, keep finding the same anti-inflammatory effect in gut, skin, lung, and other tissues. But 'consistent in animals' is not the same as 'proven in people': there is not a single published human clinical trial of KPV, no established human dose, and no confirmed real-world safety data. It's a genuinely interesting research compound worth watching, not a validated treatment.
Research papers
Studies we have on file for KPV. Tap a title to open it on PubMed. Labels like “animal” or “human trial” are rough guides.
40 papers
Lysine-Proline-Valine peptide mitigates fine dust-induced keratinocyte apoptosis and inflammation by regulating oxidative stress and modulating the MAPK/NF-κB pathway.
Airborne particulate matter (PM) poses a major environmental risk that impairs skin health by triggering oxidative stress, inflammation, and cell death. In this study, we investigated the protective effects of Lysine-Proline-Valine (KPV)-an endogenous peptide derived from α-melanocyte-stimulating hormone-against oxidative damage and inflammation induced by fine PM (PM10) in human HaCaT keratinocytes. Our results show that PM10 markedly suppresses HaCaT cell proliferation via cytotoxic effects and induces a pro-inflammatory response by increasing IL-1β secretion. Notably, treatment with 50 μg/mL of KPV restored cell viability and reduced IL-1β secretion disrupted by PM10 exposure. To counteract PM10-induced cell death, KPV inhibited reactive oxygen species (ROS) production, which is responsible for activating extracellular signal-regulated kinase and p38 mitogen-activated protein kinase. Additionally, KPV decreased the expression of apoptosis-related proteins (Bax, Bcl-2, and cleaved caspase-3) and IL-1β through suppression of the redox-sensitive transcription factor nuclear, factor-kappa B in PM10-treated HaCaT cells. Against PM10-induced inflammation, KPV effectively blocked ROS-mediated caspase-1 activation, reducing IL-1β secretion. In a three-dimensional (3D) skin model, KPV treatment effectively attenuated the inflammatory cell death induced by PM10. Collectively, these findings suggest that KPV protects keratinocytes by mitigating PM10-induced pyroptosis and holds potential as a therapeutic agent for preventing environmental pollutant-related skin damage, with promising applications in functional cosmetics and skin-protective treatments.
The neuroimmunomodulatory peptide alpha-MSH.
Alpha-melanocyte-stimulating hormone (alpha-MSH), a neuroimmunomodulatory peptide of ancient origin, is known to be involved in the control of host responses. In inflammatory cells, in the periphery and within the central nervous system, alpha-MSH modulates the production and action of proinflammatory cytokines. This broad influence occurs via endogenous alpha-MSH (melanocortin) receptors. The key to this anti-inflammatory influence is inhibition of NF-kappa B. Indeed alpha-MSH inhibits activation of this nuclear factor through preservation of I kappa B alpha, which binds to NF-kappa B and prevents its migration to the nucleus. Cells transfected with alpha-MSH plasmid vector are resistant to challenge with bacterial lipopolysaccharide. The peptide also act on central melanocortin receptors to modulate inflammation in the periphery. In brief, alpha-MSH and certain of its fragments such as alpha-MSH [11-13] KPV modulate inflammation via three general actions: direct actions on peripheral host cells; actions on inflammatory cells within the brain to modulate local reactions; and descending neural anti-inflammatory pathways that control inflammation in peripheral tissues.
Vimentin is required for tumor progression and metastasis in a mouse model of non-small cell lung cancer.
Vimentin is highly expressed in metastatic cancers, and its expression correlates with poor patient prognoses. However, no causal in vivo studies linking vimentin and non-small cell lung cancer (NSCLC) progression existed until now. We use three complementary in vivo models to show that vimentin is required for the progression of NSCLC. First, we crossed LSL-KrasG12D; Tp53fl/fl mice (KPV+/+) with vimentin knockout mice (KPV-/-) to demonstrate that KPV-/- mice have attenuated tumor growth and improved survival compared with KPV+/+ mice. Next, we therapeutically treated KPV+/+ mice with withaferin A (WFA), an agent that disrupts vimentin intermediate filaments (IFs). We show that WFA suppresses tumor growth and reduces tumor burden in the lung. Finally, luciferase-expressing KPV+/+, KPV-/-, or KPVY117L cells were implanted into the flanks of athymic mice to track cancer metastasis to the lung. In KPVY117L cells, vimentin forms oligomers called unit-length filaments but cannot assemble into mature vimentin IFs. KPV-/- and KPVY117L cells fail to metastasize, suggesting that cell-autonomous metastasis requires mature vimentin IFs. Integrative metabolomic and transcriptomic analysis reveals that KPV-/- cells upregulate genes associated with ferroptosis, an iron-dependent form of regulated cell death. KPV-/- cells have reduced glutathione peroxidase 4 (GPX4) levels, resulting in the accumulation of toxic lipid peroxides and increased ferroptosis. Together, our results demonstrate that vimentin is required for rapid tumor growth, metastasis, and protection from ferroptosis in NSCLC.
NLRP3 autophagic degradation disruption in melanocytes contributes to vitiligo development.
NLRP3 functions as a critical intracellular danger sensor for inflammasome activation, playing a crucial role in autoimmune diseases. Vitiligo progression has been linked to NLRP3, yet its specific involvement in melanocytes of vitiligo remains poorly understood. In this study, we demonstrate that NLRP3 expression is significantly upregulated in the melanocytes of vitiligo patients and melanoma-Treg-induced vitiligo mouse model. Genetic knockout of NLRP3 effectively alleviates vitiligo progression in these mice. Our mechanistic investigations reveal that the downregulation of the E3 ligase β-TrCP1 in vitiligo melanocytes decreases K27-linked ubiquitination levels of NLRP3, which in turn weakens its interaction with the autophagy receptor NDP52. This disruption impairs the selective autophagic degradation of NLRP3, leading to hyperactivation of inflammation and pyroptosis in melanocytes, thereby accelerating vitiligo pathogenesis. Notably, melanocyte-specific knockdown of NLRP3 using lysine-proline-valine (KPV)-modified deformable liposomes (KPV-Lipos) carrying Nlrp3 shRNA significantly alleviates vitiligo development. This study elucidates the mechanism by which autophagy dysfunction mediated excessive NLRP3 inflammasome activation in melanocytes contributes to vitiligo pathogenesis, highlighting potential therapeutic strategies targeting these pathways for the treatment of vitiligo and other pigment-related skin diseases. Overview of disrupted NLRP3 autophagic degradation in vitiligo melanocytes. In healthy melanocytes, NLRP3 expression is upregulated when subjected to oxidative stress, along with an increase in the E3 ligase β-TrCP1, which enhances the K27-linked ubiquitination of NLRP3 and further strengthens its binding to the autophagy receptor protein NDP52, thus effectively suppressing the excessive inflammatory response. Whereas in the melanocytes of vitiligo patients, decreased expression of β-TrCP1 leads to downregulation of K27-linked ubiquitination in NLRP3, thus inhibiting its autophagic degradation. The persistent activation of NLRP3 in vitiligo melanocytes promotes the cleavage of pro-IL-1β and GSDMD. GSDMD-N subsequently forms pores on the cell membrane, which causes the release of IL-1β and results in melanocyte pyroptosis. In our study, we utilize KPV-Lipos with Nlrp3 shRNA to precisely knockdown NLRP3 expression in melanocytes and effectively alleviate vitiligo development, which provide a potentially promising strategy for the treatment of vitiligo. MC, melanocytes.
PepT1-mediated tripeptide KPV uptake reduces intestinal inflammation.
KPV is a tripeptide (Lys-Pro-Val), which possesses anti-inflammatory properties; however, its mechanisms of action still remain unknown. PepT1 is a di/tripeptide transporter normally expressed in the small intestine and induced in colon during inflammatory bowel disease (IBD). The aim of this study was to 1) investigate whether the KPV anti-inflammatory effect is PepT1-mediated in intestinal epithelian and immune cells, and 2) examine the anti-inflammatory effects in two models of mice colitis. Human intestinal epithelial cells Caco2-BBE, HT29-Cl.19A, and human T cells (Jurkat) were stimulated with pro-inflammatory cytokines in the present or absence of KPV. KPV anti-inflammatory effect was assessed using a NF-kappaB luciferase gene reporter, Western blot, real-time RT-PCR and ELISA. Uptake experiments were performed using cold KPV as a competitor for PepT1 radiolabelled substrate or using [(3)H]KPV to determine kinetic characteristics of KPV uptake. Anti-inflammatory effect of KPV was also investigated in DSS- and TNBS-induced colitis in mice. KPV was added to drinking water and inflammation was assessed at the histologic level and by proinflammatory cytokine mRNA expression. Nanomolar concentrations of KPV inhibit the activation of NF-kappaB and MAP kinase inflammatory signaling pathways, and reduce pro-inflammatory cytokine secretion. We found that KPV acts via PepT1 expressed in immune and intestinal epithelial cells. Furthermore, oral administration of KPV reduces the incidence of DSS- and TNBS-induced colitis indicated by a decrease in pro-inflammatory cytokine expression. This study indicates tht KPV is transported into cells by PepT1 and might be a new therapeutic agent for IBD.
New insights into the functions of alpha-MSH and related peptides in the immune system.
There is a substantial body of evidence that the tridecapeptide alpha-melanocyte-stimulating hormone (alpha-MSH) functions as a mediator of immunity and inflammation. The immunomodulating capacity of alpha-MSH is primarily because of its effects on melanocortin receptor (MC-1R)-expressing monocytes, macrophages, and dendritic cells (DCs). alpha-MSH down-regulates the production of proinflammatory and immunomodulating cytokines (IL-1, IL-6, TNF-alpha, IL-2, IFN-gamma, IL-4, IL-13) as well as the expression of costimulatory molecules (CD86, CD40, ICAM-1) on antigen-presenting DCs. In contrast, the production of the cytokine synthesis inhibitor IL-10 is up-regulated by alpha-MSH. At the molecular level, these effects of alpha-MSH are mediated via the inhibition of the activation of transcription factors such as NFkappaB. Not only alpha-MSH but also its C-terminal tripeptide (alpha-MSH 11-13, KPV) was able to bind to MC-1R and to modulate the function of APCs. In vivo, using a mouse model of contact hypersensitivity (CHS) systemic and topical application of alpha-MSH or KPV inhibited the sensitization and the elicitation phase of CHS and was able to induce hapten-specific tolerance. To investigate the underlying mechanisms of tolerance induction, we have performed in vivo transfer experiments. Treatment of naive mice with bone marrow-derived immature haptenized and alpha-MSH-pulsed DCs resulted in a significant inhibition of CHS. Furthermore, tolerance induction was found to be mediated by the generation of CTLA4(+) and IL-10-producing T lymphocytes. The potent capacity of alpha-MSH to modulate the function of antigen-presenting cells (APCs) has been further supported in another experimental approach. In vitro, by activating APCs, alpha-MSH has been shown to modulate IgE production by IL-4 and anti-CD40 stimulated B lymphocytes. Moreover, in a murine model of allergic airway inflammation, systemic treatment with alpha-MSH resulted in a significant reduction of allergen-specific IgE production, eosinophil influx, and IL-4 production. These effects were mediated via IL-10 production, because IL-10 knockout mice were resistant to alpha-MSH treatment. Therefore, therapeutic application of alpha-MSH or related peptides (KPVs) as well as alpha-MSH/KPV-pulsed DCs may be a useful approach for the treatment of inflammatory, autoimmune, and allergic diseases in the future.
A KPV-binding double-network hydrogel restores gut mucosal barrier in an inflamed colon.
Ulcerative colitis (UC) usually occurs in the superficial mucosa of the colorectum. Here, a double-network hydrogel (PMSP) was constructed from maleimided γ-polyglutamic acid and thiolated γ-polyglutamic acid through crosslinking of thiol-maleimide and self-oxidized thiols. PMSP with a negative charge specifically adhered to the inflamed mucosa with positively charged proteins rather than to the healthy mucosa. PMSP exhibited good mechanical strength with storage modulus (G') of 17.6 Pa and a linear viscoelastic region (LVR) of 107.2% strain. Moreover, PMSP showed a stronger bio-adhesive force toward the inflamed tissue-mimicking substrate than toward its healthy counterpart. In vivo imaging confirmed that PMSP specifically adhered to the inflamed colonic mucosa of rats with TNBS-induced UC. KPV (Lys-Pro-Val) as a model drug was easily captured by PMSP through electrostatic interactions, thus retaining its bioactivity for a longer time under high temperature conditions. Moreover, the alleviating effect of KPV on rats with TNBS-induced colitis was significantly improved by PMSP after intracolonic administration. The epithelial barrier of the colon also effectively recovered following PMSP-KPV treatment. PMSP-KPV also modulated the gut flora, markedly augmenting the abundance of beneficial microorganisms in gut homeostasis. The mechanism by which PMSP-KPV induces a therapeutic effect may be associated with the inhibition of oxidative stress. Conclusively, the PMSP hydrogel seems to be a promising rectal delivery system for the therapy of UC. STATEMENT OF SIGNIFICANCE: Ulcerative colitis (UC) is a chronic and relapsing disease of the gastrointestinal tract. A key therapeutic approach to treat UC is to repair the mucosal barriers. Here, a double-network hydrogel (PMSP) was constructed from maleimided and thiolated γ-polyglutamic acid through crosslinking of thiol-maleimide and self-oxidized thiols. The negatively charged PMSP specifically adhered to the inflamed colon rather than its healthy counterpart and was retained for a longer time. KPV as a model drug was easily captured by PMSP, which provided better stability to KPV when exposed to high temperature of 50 °C. The epithelial mucosal barrier of the colon was effectively recovered by the rectal administration of PMSP-KPV to rats with TNBS-induced UC. Moreover, PMSP-KPV modulated the gut flora of colitic rats, markedly augmenting the abundance of beneficial microorganisms. Conclusively, PMSP seems to be a promising rectal delivery system for UC therapy.
The neuropeptide alpha-MSH in host defense.
The presence of the ancient peptide alpha-melanocyte-stimulating hormone (alpha-MSH) in barrier organs such as gut and skin suggests that this potent anti-inflammatory molecule may be a component of the innate host defense. In tests of antimicrobial activities, alpha-MSH and its fragment KPV showed inhibitory influences against the gram-positive bacterium Staphylococcus aureus and the yeast Candida albicans. Anti-tumor necrosis factor and antimicrobial effects of alpha-MSH suggest that the peptide might likewise reduce replication of human immunodeficiency virus (HIV). Treatment with alpha-MSH reduced HIV replication in chronically and acutely infected human monocytes. At the molecular level, alpha-MSH inhibited activation of the transcription factor NF-kappa B known to enhance HIV expression. alpha-MSH that combines antipyretic, anti-inflammatory, and antimicrobial effects could be useful in the treatment of disorders in which infection and inflammation coexist.
Peptide Receptor-Targeted Fluorescent Probe: Visualization and Discrimination between Chronic and Acute Ulcerative Colitis.
The inflammatory activity of ulcerative colitis plays an important role in the medical treatment. However, accurate and real-time monitoring of the colitis activity with noninvasive bioimaging method is still challenging, especially in distinguishing between chronic and acute colitis. As a good receptor, the oligopeptide transporter (PepT1) is overexpressed in the colonic epithelial cells of chronic ulcerative colitis, which can deliver tripeptide KPV (Lys-Pro-Val, the C-terminal sequence of α-MSH) into cytosol in the intestine. Herein, we report a PepT1 peptide receptor-targeted fluorescent probe, dicyanomethylene-4H-pyran (DCM)-KPV, with the strategy of conjugating the KPV into the DCM chromophore. The diagnostic fluorescent probe bestows a specific receptor-targeted interaction with PepT1 through the KPV moiety, possessing several beneficial characteristics, such as efficient long emission, low photobleaching, negligible cytotoxicity, and high cytocompatibility in living cells. We build the overexpressed PepT1 on the cytomembrane of ulcerative colitis model Caco-2 cell as the efficient receptor to accumulate the targeted tripeptide KPV in the cytoplasm and nucleus. With the co-localization of DCM-KPV and the DNA-specific fluorophore, DAPI, the specifically long emission from chromophore DCM and efficient receptor-targeted peptide KPV, the fluorescent probe of DCM-KPV makes a breakthrough to the direct noninvasive observation of the accumulation in colon inflammation regions via intestinal mucosa, even successfully distinguishing the chronic, acute ulcerative colitis and normal groups. Compared with the traditional unenhanced magnetic resonance imaging and hematoxylin and eosin (H&E) staining, we make full use of exploiting the specific target-receptor interaction between the tripeptide unit, KPV, and the oligopeptide transporter, PepT1, for sensing selectivity. The desirable diagnostic ability of DCM-KPV can guarantee the real-time tracking and visualization of the role of intracellular KPV on ulcerative colitis, which provides an alternative to replace the time-consuming and tissue sampling-invasive H&E staining diagnosis.
alpha-Melanocyte-stimulating hormone, MSH 11-13 KPV and adrenocorticotropic hormone signalling in human keratinocyte cells.
alpha-MSH signals by binding to the melanocortin-1 receptor (MC-1R) and elevating cyclic AMP in several different cells. The anti-inflammatory properties of this peptide are also believed to be cyclic AMP dependent. The carboxyl terminal tripeptides of alpha-MSH (KPV / KP-D-V) are the smallest minimal sequences reported to prevent inflammation but it is not known if they operate via MC-1R or cyclic AMP. The aim of this study was to examine the intracellular signalling of key MSH and ACTH peptides in human keratinotocytes. No elevation in cyclic AMP was detected in either HaCaT or normal human keratinocytes in response to alpha-MSH, KPV or ACTH peptides. Rapid and acute intracellular calcium, however, were observed in HaCaT keratinocytes in response to alpha-MSH (10(-15)-10(-7) M), KPV (10(-15)-10(-7) M), KP-D-V (10(-15)-10(-7) M) and ACTH (10(-15)-10(-7) M), but only in the presence of PIA, an adenosine agonist that inhibits the cyclic AMP pathway. Normal keratinocytes responded to all the above peptides but in addition responded to ACTH 1-17 (10(-13)-10(-7) M) in contrast to the HaCaT keratinocytes. Stable transfection of Chinese hamster ovary cells with the MC-1 receptor showed that alpha-MSH and the KPV peptides elevated intracellular calcium.
Dissection of the anti-inflammatory effect of the core and C-terminal (KPV) alpha-melanocyte-stimulating hormone peptides.
In this study, we analyzed the anti-inflammatory effects of alpha-melanocyte stimulating hormone (MSH)11-13 (KPV) in comparison with other MSH peptides in a model of crystal-induced peritonitis. Systemic treatment of mice with KPV, alpha-MSH, the core melanocortin peptide His-Phe-Arg-Trp, and the melanocontin receptor 3/4 agonist Ac-Nle4-c[Asp5,d-Phe7,Lys10]NH2 ACTH4-10 (MTII) but not the selective MC1-R agonist H-Ser-Ser-Ile-Ile-Ser-His-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2 (MS05) resulted in a significant reduction in accumulation of polymorphonuclear leukocyte in the peritoneal cavity. The antimigratory effect of KPV was not blocked by the MC3/4-R antagonist Ac-Nle4-c[Asp5,d-2Nal7,Lys10]NH2 ACTH4-10 (SHU9119). In vitro, macrophage activation, determined as release of KC and interleukin (IL)-1beta was inhibited by alpha-MSH and MTII but not by KPV. Furthermore, macrophage activation by MTII led to an increase in cAMP accumulation, which was attenuated by SHU9119, whereas KPV failed to increase cAMP. The anti-inflammatory properties of KPV were also evident in IL-1beta-induced peritonitis inflammation and in mice with a nonfunctional MC1-R (recessive yellow e/e mice). In conclusion, these data highlight that the C-terminal MSH peptide KPV exhibits an anti-inflammatory effect that is clearly different from that of the core MSH peptides. KPV is unlikely to mediate its effects through melanocortin receptors but is more likely to act through inhibition of IL-1beta functions.
Transdermal Iontophoretic Delivery of Lysine-Proline-Valine (KPV) Peptide Across Microporated Human Skin.
Lysine-proline-valine (KPV) is a C-terminal peptide fragment of α-melanocyte stimulating hormone with potent anti-inflammatory properties. Present study investigates various transdermal enhancement strategies such as iontophoresis (ITP), microneedles (MN), and their combination (ITP + MN) on KPV delivery across dermatomed human skin. KPV attains a positive charge at pH less than 7.0, thus anodal ITP was used. The influence of current strength, KPV concentration, and duration of current application on the KPV delivery was investigated. At defined ITP parameters, the influence of MN on KPV delivery (ITP + MN) across skin was also determined. KPV permeation was less than detectable levels (limit of detection, 0.01 μg/mL) by simple passive diffusion. However, KPV permeation was increased to 4.4 μg/cm2/h by MN treatment. Furthermore, ITP and ITP + MN increased the permeation rate by 8 and 35 fold, respectively, as compared to MN alone. The skin retention levels of KPV by MN, ITP, and ITP + MN were increased by 5, 10, and 10 fold, respectively, as compared to passive diffusion. Confocal studies indicate that fluorescein isothiocyanate-labeled KPV migrated through the stratum corneum, along the microchannels and into the lower epidermal tissue because the fluorescence was observed beyond the depth of 100 μm.
Inflammation-triggered self-immolative conjugates enable oral peptide delivery by overcoming gastrointestinal barriers.
Oral delivery of peptide therapeutics remains challenging due to gastrointestinal (GI) degradation and poor intestinal absorption. Here, we propose a self-immolative peptide prodrug conjugate (SIPPC) platform for inflammation-targeted oral delivery, integrating a hydrophilic polyethylene glycol segment, a reactive oxygen species (ROS)-responsive hydrophobic self-immolative module, and a hydrolyzable scaffold, which collectively enable spontaneous assembly into micelle-like nanoparticles. Using three anti-inflammatory peptides (KPV, Ac-QAW, and IRW), we demonstrated that the engineered conjugates exhibit remarkable GI stability, efficient mucus penetration, and ROS-responsive release at inflamed sites. In colitis mice, the KPV-based conjugate (proKPV) achieved a 3.8-fold greater colonic accumulation than free KPV, with enhanced efficacy even at a 20-fold lower dose. Beyond therapeutic effects in the colitis model, oral proKPV substantially accumulated in inflamed lungs and exhibited potent anti-inflammatory efficacy in mice with acute lung injury. Ac-QAW and IRW-based conjugates exhibited comparable benefits, underscoring SIPPC as a transformative paradigm for oral peptide therapeutics, offering substantial promise for clinical translation in inflammatory disorders.
Drug-loaded nanoparticles targeted to the colon with polysaccharide hydrogel reduce colitis in a mouse model.
One of the challenges to treating inflammatory bowel disease (IBD) is to target the site of inflammation. We engineered nanoparticles (NPs) to deliver an anti-inflammatory tripeptide Lys-Pro-Val (KPV) to the colon and assessed its therapeutic efficacy in a mouse model of colitis. NPs were synthesized by double-emulsion/solvent evaporation. KPV was loaded into the NPs during the first emulsion of the synthesis process. To target KPV to the colon, loaded NPs (NP-KPV) were encapsulated into a polysaccharide gel containing 2 polymers: alginate and chitosan. The effect of KPV-loaded NPs on inflammatory parameters was determined in vitro as well as in the dextran sodium sulfate-induced colitis mouse model. NPs (400 nm) did not affect cell viability or barrier functions. A swelling degree study showed that alginate-chitosan hydrogel containing dextran-fluorescein isothiocyanate-labeled NPs collapsed in the colon. Once delivered, NPs quickly released KPV on or within the closed area of colonocytes. The inflammatory responses to lipopolysaccharide were reduced in Caco2-BBE (brush border enterocyte) cells exposed to NP-KPV compared with those exposed to NPs alone, in a dose-dependent fashion. Mice given dextran sodium sulfate (DSS) followed by NP-KPV were protected against inflammatory and histologic parameters, compared with mice given only DSS. Nanoparticles are a versatile drug delivery system that can overcome physiologic barriers and target anti-inflammatory agents such as the peptide KPV to inflamed areas. By using NPs, KPV can be delivered at a concentration that is 12,000-fold lower than that of KPV in free solution, but with similar therapeutic efficacy. Administration of encapsulated drug-loaded NPs is a novel therapeutic approach for IBD.
Antimicrobial effects of alpha-MSH peptides.
The presence of the ancient anti-inflammatory peptide alpha-melanocyte-stimulating hormone [alpha-MSH (1-13), SYSMEHFRWGKPV] in barrier organs such as gut and skin suggests a role in the nonspecific (innate) host defense. alpha-MSH and and its carboxy-terminal tripeptide (11-13, KPV) were determined to have antimicrobial influences against two major and representative pathogens: Staphylococcus aureus and Candida albicans. alpha-MSH peptides significantly inhibited S. aureus colony formation and reversed the enhancing effect of urokinase on colony formation. Antimicrobial effects occurred over a broad range of concentrations including the physiological (picomolar) range. Small concentrations of alpha-MSH peptides likewise reduced viability and germ tube formation of the yeast C. albicans. Antimicrobial influences of alpha-MSH peptides could be mediated by their capacity to increase cellular cAMP. Indeed, this messenger was significantly augmented in peptide-treated yeast and the potent adenylyl cyclase inhibitor dideoxyadenosine (ddAdo) partly reversed the killing activity of alpha-MSH peptides. Reduced killing of pathogens is a detrimental consequence of therapy with anti-inflammatory drugs. Because alpha-MSH has potent anti-inflammatory effects we determined influences of alpha-MSH on C. albicans and S. aureus killing by human neutrophils. alpha-MSH peptides did not reduce killing but rather enhanced it, likely as a consequence of the direct antimicrobial activity. alpha-MSH peptides that combine antipyretic, anti-inflammatory, and antimicrobial effects could be useful in treatment of disorders in which infection and inflammation coexist.
Structural and immunological feature of rhamnogalacturonan I-rich polysaccharide from Korean persimmon vinegar.
The crude polysaccharide (KPV-0) isolated from Korean persimmon vinegar was fractionated using gel filtration chromatography to enhance the immunostimulatory activity and to identify the structural features of active fraction. Among three fractions, KPV-I obtained in a void volume, demonstrated the potent production of macrophage-stimulating mediators, including tumor necrosis factor-α, interleukin (IL)-6, IL-12, and nitric oxide. KPV-I showed a combined single peak with high molecular weight of 55,000Da by high performance size exclusion chromatography. Component sugar analysis revealed that KPV-I contained mainly of arabinose, mannose, galactose, rhamnose and galacturonic acid. Single radial gel diffusion assay using β-glucosyl Yariv reagent showed that KPV-I contained arabinogalactan protein with 13.7%. Methylation analysis indicated that KPV-I contained 21 kinds of neutral glycosidic linkages, which seemed to be composed three kinds of polysaccharide; that is a rhamnogalacturonan-I (65-70%) derived from persimmon as a raw material, a mannan (20-25%) derived from fermentation-associated microorganisms, and a linear glucans (less than 10%). In conclusion, polysaccharide isolated from persimmon vinegar could augment the macrophage stimulation, and a large amounts of RG-I polysaccharide derived from persimmon is likely a crucial role in expression of the activity in persimmon vinegar.
Self-Cross-Linked Hydrogel of Cysteamine-Grafted γ-Polyglutamic Acid Stabilized Tripeptide KPV for Alleviating TNBS-Induced Ulcerative Colitis in Rats.
KPV (Lys-Pro-Val), which is a tripeptide derived from α-MSH (α-melanocyte-stimulating hormone), has an anti-inflammatory effect on colitis. However, KPV solution is very unstable when rectally administered, compromising its therapeutic efficacy. Herein, cysteamine-grafted γ-polyglutamic acid (SH-PGA) was synthesized by conjugating cysteamine with the carboxyl groups of γ-PGA. The synthesized SH-PGA has the thiol grafting amount of 4.5 ± 0.3 mmol/g. Without the use of the cross-linker, the SH-PGA hydrogel with 4% of the polymer was formed by self-cross-linking of thiol groups. Moreover, the formation of the SH-PGA hydrogel was not affected by KPV. The KPV/SH-PGA hydrogel presented higher elastic modulus (G') than the corresponding viscous modulus (G″) at 0.01-10 Hz, exhibiting good mechanical stability. The KPV/SH-PGA hydrogel presented a shear-thinning behavior, which was helpful for rectal administration. Only 30% of KPV was released from the KPV/SH-PGA hydrogel within 20 min, followed by a sustained-release behavior. Importantly, the stability of KPV in the SH-PGA hydrogel was obviously enhanced, which was presented by detecting its anti-inflammatory activity and promoting cell migration potential after 2 h of exposure to 37 °C. The enhanced therapeutic effect of the KPV/SH-PGA hydrogel on colitis was confirmed on 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced ulcerative colitis rats. The colitis symptoms including body weight loss and the disease activity index score were obviously attenuated by rectally administering the KPV/SH-PGA hydrogel. Besides, the KPV/SH-PGA hydrogel treatment prevented the colon shortening of TNBS-infused rats and decreased the colonic myeloperoxidase level. The morphology of the colon including the epithelial barrier, crypt, and intact goblet cells was recovered after KPV/SH-PGA hydrogel treatment. Besides, the KPV/SH-PGA hydrogel decreased the expression of proinflammatory cytokines such as tumor necrosis factor α and interleukin 6. Collectively, the KPV/SH-PGA hydrogel may provide a promising strategy for the treatment of ulcerative colitis.
Effects of the COOH-terminal tripeptide alpha-MSH(11-13) on corneal epithelial wound healing: role of nitric oxide.
It is known that alpha-melanocyte stimulating hormone (alpha-MSH) may exert anti-inflammatory effects and facilitate reparative processes in different tissues. The effective message sequence of alpha-MSH resides in the COOH-terminal tripeptide alpha-MSH(11-13). This study was undertaken to investigate the effects of topical administration of the COOH-terminal tripeptide sequence of alpha-MSH (alpha-MSH(11-13), KPV) on corneal epithelial wound healing in rabbits and the possible role of nitric oxide (NO) in these effects. The whole corneal epithelium was denuded in both eyes by mechanical abrasion. The area of the corneal epithelial defect was stained with fluorescein, photographed, and then measured before the treatment and every 12 h by a computerized software. The mean epithelial wound area and the mean percent of epithelial defect remaining at each follow-up control were compared between experimental groups. Rabbits were topically treated with KPV 1, 5 or 10 mg/ml (30 microl), two drops four times in a day, for 4 days, starting immediately after corneal abrasion, while control animals received topical phosphate-buffered saline as vehicle. In order to study the role of NO in corneal repair processes, the NO donor, sodium nitroprusside (SP, 10 mg/ml, 30 microl) was administered in both eyes, two drops four times in a day, for 4 days. The effects of KPV or SP were challenged by pre-treatment with the nitric oxide synthase inhibitor, N omega-nitro-L-arginine methyl ester (L-NAME, 10 mg/ml, 30 microl) 30 min prior to KPV or SP instillation. The mean percent epithelial defect remaining each time was significantly smaller in animals treated with KPV or SP in comparison to controls. Sixty hours later, eight out of eight (100%) corneas treated with KPV or SP were completely re-epithelized (P<0.05) while none of the corneas treated with placebo were re-epithelized. Pre-treatment with L-NAME inhibited the facilitating effect of KPV on corneal epithelial wound healing process and totally prevented the effect of SP. Rabbit corneal epithelial cells (RCE) in culture were exposed for 1, 6 and 24 h to different KPV concentrations (0.1, 1 and 10 microM) in medium containing 15% foetal bovine serum (FBS). Cell viability was stimulated by 1 and 10 microM concentrations of the substance. Thus, KPV may facilitate corneal epithelial wound healing in rabbits with a mechanism that may involve NO disposition in corneal tissue. However, it is not known whether this mechanism is likely to depend on a direct stimulating repairing activity shared by the entire molecule of alpha-MSH.
Terminal signal: anti-inflammatory effects of α-melanocyte-stimulating hormone related peptides beyond the pharmacophore.
During the last two decades a significant number of investigations has established the fact that α-Melanocyte-stimulating hormone (α-MSH) is a potent anti-inflammatory mediator. The anti-inflammatory effects of α-MSH can be elicited via melanocortin receptors (MC-Rs) broadly expressed in a number of tissues ranging from the central nervous system to cells of the immune system and on resident somatic cells of peripheral tissues. α-MSH affects various pathways regulating inflammatory responses such as NF-κB activation, expression of adhesion molecules, inflammatory cytokines, chemokine receptors, T-cell proliferation and activity and inflammatory cell migration. In vivo α-MSH has been shown to be anti-inflammatory as well in animal models of fever, irritant and allergic contact dermatitis, cutaneous vasculitis, fibrosis, in ocular, gastrointestinal, brain and allergic airway inflammation and arthritis. A broad range of effects of α-MSH exerted beyond the field of inflammation, its pigmentory capacity being only the most visible aspect, has been one of the major impediments limiting the use of α-MSH in human inflammatory disorders. Interestingly KPV, C-terminal tripeptide of α-MSH, which lacks the entire sequence motif required for binding to any of the known MC-Rs, retains almost all of the anti-inflammatory capacity of the full hormone, but in its activities display a lack of any pigmentory action. While the exact signaling mechanism utilized by KPV and related peptides currently is unknown it has been demonstrated already that significant similarities between anti-inflammatory signaling of α-MSH and those short peptides exist. These α-MSH related tripeptides thus may be useful alternatives for anti-inflammatory peptide therapy. KdPT, a derivative of KPV corresponding to IL-1β(193-195), currently is emerging as another tripeptide with potent anti-inflammatory effects. A more limited spectrum of biologic activities, potentially advantageous physicochemical, pharmacokinetic and pharmacodynamic properties as well as the expectation of low costs for pharmaceutical production make these agents interesting candidates for the treatment of immune-mediated inflammatory skin and bowel diseases, allergic asthma and arthritis.
Orally Targeted Delivery of Tripeptide KPV via Hyaluronic Acid-Functionalized Nanoparticles Efficiently Alleviates Ulcerative Colitis.
Overcoming adverse effects and selectively delivering drug to target cells are two major challenges in the treatment of ulcerative colitis (UC). Lysine-proline-valine (KPV), a naturally occurring tripeptide, has been shown to attenuate the inflammatory responses of colonic cells. Here, we loaded KPV into hyaluronic acid (HA)-functionalized polymeric nanoparticles (NPs). The resultant HA-KPV-NPs had a desirable particle size (∼272.3 nm) and a slightly negative zeta potential (∼-5.3 mV). These NPs successfully mediated the targeted delivery of KPV to key UC therapy-related cells (colonic epithelial cells and macrophages). In addition, these KPV-loaded NPs appear to be nontoxic and biocompatible with intestinal cells. Intriguingly, we found that HA-KPV-NPs exert combined effects against UC by both accelerating mucosal healing and alleviating inflammation. Oral administration of HA-KPV-NPs encapsulated in a hydrogel (chitosan/alginate) exhibited a much stronger capacity to prevent mucosa damage and downregulate TNF-α, thus they showed a much better therapeutic efficacy against UC in a mouse model, compared with a KPV-NP/hydrogel system. These results collectively demonstrate that our HA-KPV-NP/hydrogel system has the capacity to release HA-KPV-NPs in the colonic lumen and that these NPs subsequently penetrate into colitis tissues and enable KPV to be internalized into target cells, thereby alleviating UC.
KPV and RAPA Self-Assembled into Carrier-Free Nanodrugs for Vascular Calcification Therapy.
Cardiovascular disease (CVD) is a leading cause of death globally, and vascular calcification (VC) is an important independent risk factor for predicting CVD. Currently, there are no established therapeutic strategies for the treatment of VC. Although recognized combination therapies of nanomedicines can provide effective strategies for disease treatment, the clinical application of nanomedicines is limited because of their complex preparation processes, low drug loading rates, and unpredictable safety risks. Thus, developing a simple, efficient, and safe nanodrug to simultaneously regulate inflammation and autophagy may be a promising strategy for treating VC. Herein, an anti-inflammatory peptide (lysine-proline-valine peptides, KPV) and the autophagy activator rapamycin (RAPA) are self-assembled to form new carrier-free spherical nanoparticles (NPs), which shows good stability and biosafety. In vivo and in vitro, KPV-RAPA NPs significantly inhibit VC in mice compared to the other treatment groups. Mechanistically, KPV-RAPA NPs inhibit inflammatory responses and activated autophagy. Therefore, this study indicates that the new carrier-free KPV-RAPA NPs have great potential as therapeutic agents for VC combination therapy, which can promote the development of nanodrugs for VC.
Structural modification of the tripeptide KPV by reductive "glycoalkylation" of the lysine residue.
Peptides that exhibit enzymatic or hormonal activities are regulatory factors and desirable therapeutic drugs because of their high target specificity and minimal side effects. Unfortunately, these drugs are susceptible to enzymatic degradation, leading to their rapid elimination and thereby demanding frequent dosage. Structurally modified forms of some peptide drugs have shown enhanced pharmacokinetics, improving their oral bioavailability. Here, we discuss a novel glycomimetic approach to modify lysine residues in peptides. In a model system, the ε-amine of Ts-Lys-OMe was reductively alkylated with a glucose derivative to afford a dihydroxylated piperidine in place of the amine. A similar modification was applied to H-KPV-NH2, a tripeptide derived from the α-melanocyte stimulating hormone (α-MSH) reported to have antimicrobial and anti-inflammatory properties. Antimicrobial assays, under a variety of conditions, showed no activity for Ac-KPV-NH2 or the α- or ε-glycoalkylated analogs. Glycoalkylated peptides did, however, show stability toward proteolytic enzymes.
Host defense peptides as a new drug lead to a strategy for inflammatory bowel disease.
Inflammatory bowel diseases (IBDs) are chronic disorders affecting the gastrointestinal tract, causing severe inflammation and tissue damage. Current treatments often have adverse effects, underscoring the need for alternatives. This article is a short review of host defense peptides (HDPs), which have emerged as promising candidates for IBDs because of their antimicrobial and immunomodulatory properties. The HDPs cited include cathelicidins [e.g. LL-37-Tα1, lipid transfer protein (LTP), C-L, KR-12], defensins [e.g. human alpha defensin 5 (HD-5), human beta-defensin 2 (hBD2)], cecropins (e.g. CC34), microcins [e.g. microcin J25 (MccJ25)], brevinins (e.g. chensinin-1), proline-rich antimicrobial peptides (PrAMPs) (e.g. abaecin), type V peptides [e.g. vasopressin-neurophysin (VP-NP)], and alpha-melanocyte-stimulating hormone (α-MSH) (e.g. KPV). HDPs have immunoregulatory mechanisms, downregulating the nuclear factor kappa B (NF-κB) pathway, modulating cytokine release, and restoring homeostasis. The data suggest that HDPs have therapeutic potential for IBDs, offering a way to reduce side effects, and we focus on this issue here.
Melanocortin-derived tripeptide KPV has anti-inflammatory potential in murine models of inflammatory bowel disease.
Despite some progress in recent years, the options for treating inflammatory bowel disease (IBD) are still dissatisfying, and surgery rates are still high. The anti-inflammatory effects of melanocortin peptides such as alpha-melanocyte-stimulating hormone (alpha-MSH) have been described recently in, for example, dextran sodium sulfate (DSS) colitis in mice. The aim of this study was to investigate the therapeutic potential of the melanocortin-derived tripeptide alpha-MSH(11-13) (KPV) and its mode of action in 2 models of intestinal inflammation. The anti-inflammatory activity of KPV was analyzed in 2 well-described models of IBD: DSS colitis, and CD45RB(hi) transfer colitis. Furthermore, animals expressing a nonfunctional melanocortin-1 receptor (MC1Re/e) received DSS for induction of colitis and were treated with KPV. The course of inflammation was monitored by weight loss and histological changes in the colon as well as by myeloperoxidase (MPO) activity. In the DSS-colitis model, treatment with KPV led to earlier recovery and significantly stronger regain of body weight. Histologically, inflammatory infiltrates were significantly reduced in KPV-treated mice, which was confirmed by the significant reduction of MPO activity in colonic tissue after KPV treatment. Supporting these findings, KPV treatment of transfer colitis led to recovery, regain of body weight, and reduced inflammatory changes histologically. In MC1Re/e mice, KPV treatment rescued all animals in the treatment group from death during DSS colitis. The melanocortin-derived tripeptide KPV showed significant anti-inflammatory effects in 2 murine models of colitis. These effects seem to be at least partially independent of MC1R signaling. In conclusion, our data suggest KPV as an interesting therapeutic option for the treatment of IBD.
Stability-indicating HPLC assay for lysine-proline-valine (KPV) in aqueous solutions and skin homogenates.
A simple, sensitive and stability-indicating high-performance liquid chromatographic (HPLC) assay method was developed and validated for a bioactive peptide, lysine-proline-valine (KPV) in aqueous solutions and skin homogenates. Chromatographic separation was achieved on a reversed phase Phenomenex C18 column (4.6 × 250 mm, packed with 5 µm silica particles) with a gradient mobile phase consisting of 0.1% trifluoroacetic acid (TFA) in water (A) and 0.1% TFA in acetonitrile (B). The proposed HPLC method was validated with respect to accuracy, precision, linearity, repeatability, limit of detection (LOD) and limit of quantitation (LOQ). The calibration curve was linear with a correlation coefficient (r) of 0.9999. Relative standard deviation values of accuracy and precision experiments were <2. The LOD and LOQ of KPV were 0.01 and 0.25 µg/mL, respectively. Under stress conditions (acid, alkali and hydrogen peroxide) KPV yielded lys-pro-diketopiperazine as major degradation product, which was identified by flow injection MS analysis. The developed HPLC method was found to be efficient in separating the active peptide from its degradation products generated under various stress conditions. Also, the validated method was able to separate KPV from other peaks arising from endogenous components of the skin homogenate.
Inhibitory effects of the peptide (CKPV)2 on endotoxin-induced host reactions.
alpha-Melanocyte stimulating hormone (alpha-MSH) is an endogenous peptide that has remarkable anti-inflammatory and antimicrobial effects. These activities have been traced to the C-terminal tripeptide Lys-Pro-Val (KPV). A dimer composed of two KPV sequences connected with a Cys-Cys linker, (CKPV)2, is currently under clinical investigation for antimicrobial use. The present research was designed to evaluate effects of (CKPV)(2) on endotoxin-induced host reactions in vitro and in vivo. Effects of (CKPV)2, KPV, and [Nle4-dPhe7]-alpha-MSH (NDP-alpha-MSH) on tumor necrosis factor alpha (TNF-alpha) production were determined: 1) in human peripheral blood mononuclear cells (PBMC) stimulated with lipopolysaccharide (LPS) in vitro, and 2) in rats injected with LPS i.v. and sacrificed at 1 h. In additional experiments, dialysis peritonitis was induced in rats by adding LPS to dialysis fluid. Net ultrafiltrate was calculated and concentrations of nitrite (NO2-) and TNF-alpha were measured in blood and peritoneal fluid at 7 h. (CKPV)2 inhibited TNF-alpha production by LPS-stimulated human PBMC. This small peptide was as effective as NDP-alpha-MSH and more potent than KPV. Similar effectiveness was observed in vivo: 1 h after LPS injection, the large increase in circulating TNF-alpha was markedly reduced by (CKPV)2 treatment. In LPS-induced peritonitis, (CKPV)2 restored net ultrafiltrate to control values and significantly inhibited concentrations of TNF-alpha and NO2- both in plasma and in dialysate. The remarkable capacity of (CKPV)2 to inhibit endotoxin-induced host reactions suggests that it may be useful in treatment of inflammatory disorders.
In situ mucoadhesive hydrogel capturing tripeptide KPV: the anti-inflammatory, antibacterial and repairing effect on chemotherapy-induced oral mucositis.
The self-healing of chemotherapy-induced oral mucositis is difficult in practice because of both local bacterial infection and severe inflammation. Herein, in situ mucoadhesive hydrogels (PPP_E) were successfully prepared by using temperature-sensitive PLGA-PEG-PLGA (PPP) as a matrix and epigallocatechin-3-gallate (EGCG) with inherent antibacterial activity as an adhesion enhancer. A series of PPP_E precursor solutions with various EGCG concentrations (1%, 2% and 5%) were prepared by fixing the PPP concentration at 25%. EGCG slightly decreased the sol-gel transition temperature and shortened the sol-gel transition time of the PPP hydrogel. Moreover, the incorporation of EGCG could significantly increase the tissue adhesion properties of the PPP hydrogel at 37 °C. PPP_2%E displayed a suitable gelation temperature (36.2 °C), gelation time (100 s) and storage modulus (48 Pa). Tripeptide KPV as a model drug was easily dissolved in cold PPP_2%E precursor solution to prepare KPV@PPP_2%E hydrogel. The anti-inflammatory activity and promotion of cell migration potential by KPV in PPP-2% E hydrogel were well maintained. Moreover, KPV@PPP_2%E exhibited strong antibacterial efficacy against S. aureus. PPP_2%E precursor solution rapidly transformed to a hydrogel and adhered to the wound surface for 7 hours when administrated to the gingival mucosa of rats. Treatment with KPV@PPP_2%E hydrogel greatly improved the food intake and body weight recovery of rats with chemotherapy-induced oral mucositis. Moreover, the tissue morphology of the ulcerated gingiva after application of KPV@PPP_E hydrogel was also well repaired by promoting CK10 and PCNA expression. In addition, the inflammatory cytokines including IL-1β and TNF-α were significantly inhibited by KPV@PPP_2%E hydrogel while IL-10 was up-regulated. KPV@PPP_2%E hydrogel also had an anti-bacterial effect on MRSA-infected gingival ulcer wounds, which resulted in the obvious inhibition of infiltration by inflammatory cells into submucosal tissues. Conclusively, KPV@PPP_E may be a promising practical application for cancer patients with chemotherapy-induced oral mucositis.
Immunization against poliomyelitis: risk/benefit/cost in a changing context.
Benefit/risk factors in immunization against poliomyelitis are examined from the viewpoint of the relative risk and efficacy of killed and live poliovirus vaccines in the currently changing contexts of poliomyelitis prevalence in developed and developing countries. Risk factors include virus of vaccine origin gaining access to the CNS, and failure of the vaccine to immunize. Data are presented to illustrate the degree to which the respective risks occur in developed and developing countries. The ultimate elimination of risk by eradication of wild and vaccine virus from the population is discussed.
Biomimetic Melanosomes Promote Orientation-Selective Delivery and Melanocyte Pigmentation in the H2O2-Induced Vitiligo Mouse Model.
Extremely limited drug retention and depigmentation represent the greatest barriers against vitiligo treatment advancement. Here, inspired by biological melanosomes, the primary melanin transporter, we developed biomimetic melanosomes to combat reactive oxygen species (ROS)-mediated melanocyte damage and depigmentation. Briefly, methylprednisolone (MPS) and melanin-mimicking polydopamine (PDA) were encapsulated inside lysine-proline-valine (KPV)-modified deformable liposomes (KPV-Lipos). Owing to their phospholipid bilayer flexibility and the specific affinity for melanocortin 1 receptor (MC1R), KPV-Lipos exhibited 1.43-fold greater skin deposition than traditional liposomes. The binding of KPV and its receptor also contributed to activating the cAMP-tyrosinase (TYR) signaling pathway, improving the endogenous melanin content. In addition, PDA mimicked melanosomes as it effectively increased the exogenous melanin content and scavenged ROS. Meanwhile, MPS inhibited inflammatory cytokine secretion, limiting the depigmented area. Ultimately, the biomimetic melanosomes affected the skin color of mice with H2O2-induced vitiligo. These melanosomes show potential as a universal platform for the self-supply of melanin by self-driven melanin synthesis with exogenous supplementation. Furthermore, this study offers ideas for the production of artificial packed melanosome substitutes for melanocyte-related diseases.
Inhibition of cellular and systemic inflammation cues in human bronchial epithelial cells by melanocortin-related peptides: mechanism of KPV action and a role for MC3R agonists.
Chemokine signaling from airway epithelium regulates macrophage recruitment to the lung in inflammatory diseases such as asthma. This study investigates the mechanism by which the α-melanocyte stimulating hormone-derived tripeptide, KPV, and the agonist of the dominant melanocortin receptor in airway epithelium (MC3R), γ-melanocyte stimulating hormone (γ-MSH), suppress inflammation in immortalised human bronchial airway epithelium. TNFα and rhino syncitial virus (RSV)-evoked nuclear factor-κB (NFκB) signaling was measured in immortalised human bronchial epithelial cells (16HBE14o-) in response to KPV and γMSH. Cellular and systemic inflammatory signaling was measured by NFκB reporter gene and chemokine (IL8, eotaxin) secretion, respectively. KPV and γMSH evoked a dose-dependent inhibition of NFκB, matrix metalloproteinase-9 activity, IL8 and eotaxin secretion. The KPV effect was associated with its nuclear import, IκBα stabilisation and suppressed nuclear translocation of YFP-tagged p65RelA. Competition assays revealed an interaction between KPV and the Imp-α3 binding site on p65RelA which may involve blockade of the importin-α armadillo domain 7 and 8. In contrast, the γMSH anti-inflammatory effect required MC3R whose apical expression occurred in epithelium distributed along the length of the respiratory tree in vivo. KPV and γMSH respectively suppress NFκB signalling in airway epithelium by: i) inhibition of p65RelA nuclear import and, ii) epithelial MC3R activation. Melanocortin peptides therefore provide a robust mechanism for targeting airway inflammation in lung disease.
[Measurements and analyses of full length weight bearing X ray radiographs of bilateral lower extremities in patients with knee osteoarthritis].
To reveal the characteristics of anatomical and mechanical axes in lower extremities by analyzing full length weight bearing X ray radiographsin patients with knee osteoarthritis(OA). From June 2015 to May 2016, the lower extremity CTA was performed for 20 patients with vascular diseases, and these patients without OA were assigned to the normal group. There were 7 males and 13 females, ranging in age from 24 to 72 years old with an average age of 63.2 years old. The weight bearing full length X ray radiographs of the lower extremities were taken for 53 patients with knee OA, and these patients were assigned to the OA group. There were 10 males and 43 females, ranging in age from 52 to 80 years old with an average age of 64.7 years old. The osteoarthritis group were divided into two groups:varus knee group and valgus knee group. The femoral shaft double condyle angle(F), tibial shaft plateau angle(T), joint gap angle(JS), femoral tibial angle(FT), hip knee ankle angle(HKA), knee physiological valgus angle(KPV), and femoral offset were measured. The SPSS 21.0 was used to analyze the statistical data. The mean F were (79.9±2.3)° and (81.4±3.5)°, T were (93.8±3.7)° and (94.6±2.7)°, JS were (1.7±1.0)° and (2.1±2.5)°, FT were (175.4±4.0)° and (178.1±6.3)°, HKA were (181.4±4.1)° and (184.3±6.9)°, KPV were (6.0±1.0)° and (6.2±1.5)°, offset were (38.5±6.5) mm and (38.1±9.2) mm in the normal and OA group respectively. There was a significant difference in the KPV between varus knee and valgus knee groups(t=2.956, P=0.005), and the greater mean KPV was found in varus knee. Positive correlations were found between KPV and age(r=0.241, P=0.016), as well as between KPV and offset (r=0.946, P=0.000). The average KPV in patients with knee OA was 6.2° in the present study, and the KPVs were also positively correlated with the patients' ages and the femoral offsets. The average KPV in the varus knee was greater than that of the valgus knee, and the difference was about 1°. The changes of mechanical parameters of lower limb may be one of the risks for developing knee OA. Analyzing the full length weight bearing X ray radiographs of the lower extremities preoperatively will be helpful to determine a individualized osteotomy method for patients.
Lysine-proline-valine peptide attenuates hepatic lipid accumulation through ROS-dependent regulation of the PPARγ pathway in HepG2 cells.
Hepatocellular steatosis, an early stage within the non-alcoholic fatty liver disease (NAFLD) spectrum, is characterized by excessive lipid accumulation and oxidative stress in hepatocytes. This study examined the protective role of Lysine-Proline-Valine (KPV), an endogenous tripeptide derived from α-melanocyte-stimulating hormone, against oleic acid (OA)-induced oxidative damage and lipid accumulation in hepatic epithelial HepG2 cells. OA treatment markedly enhanced hepatic lipid deposition by upregulation of fatty acid synthase (FAS) expression. Treatment with KPV (100 µg/mL) significantly attenuated OA-induced lipid accumulation and suppressed FAS expression without inducing cytotoxicity. Mechanistic analysis revealed that KPV reduced reactive oxygen species generation, thereby preventing activation of extracellular signal-regulated kinase. KPV also downregulated AKT phosphorylation, leading to inhibition of mTORC1 phosphorylation under hepatic steatosis conditions. Furthermore, KPV regulated the phosphorylation of peroxisome proliferator-activated receptor gamma, a key transcription factor in de novo lipogenesis, thereby normalizing FAS expression. These findings suggest that KPV acts as an effective antioxidant regulator of lipogenic signaling and may hold potential as a therapeutic candidate for attenuating hepatocellular steatosis. The online version contains supplementary material available at 10.1007/s10616-026-00967-z.
A nanoparticle platform for combined mucosal healing and immunomodulation in inflammatory bowel disease treatment.
Current treatments for inflammatory bowel disease (IBD) treatment consist of anti-inflammatory products. In this study, we sought to induce the physiological secretion of glucagon-like peptide 2, a peptide with intestinal growth-promoting activity, via nanoparticles while simultaneously providing with immunomodulation by tailoring the nanoparticle surface. To this end, we developed hybrid lipid hyaluronate-KPV conjugated nanoparticles loaded with teduglutide for combination therapy in IBD. The nanocarriers induced (or did not induce) immunosuppression depending on the presence (or absence) of a hyaluronan-KPV functionalization. This strategy holds promise as a nanoparticle platform for combined mucosal healing and immunomodulation in IBD treatment.
Alpha-melanocyte-stimulating hormone peptides inhibit HIV-1 expression in chronically infected promonocytic U1 cells and in acutely infected monocytes.
The purpose of the present research was to determine if alpha-melanocyte-stimulating hormone (alpha-MSH) and its C-terminal tripeptide [alpha-MSH (11-13), KPV] alter HIV expression in infected cells. The results indicate that chronically HIV-1-infected promonocytic U1 cells produce alpha-MSH and that immunoneutralization of the endogenous peptide enhances HIV expression. Because U1 cells express the alpha-MSH receptor 1 (MC1R), an autocrine-inhibitory circuit based on the peptide and its receptor likely occurs in these cells. To determine effects of pharmacological concentrations of alpha-MSH peptides on HIV expression, we measured p24 antigen release by TNF-alpha-stimulated U1 cells exposed to a wide range of concentrations of synthetic alpha-MSH and KPV. Viral expression was reduced by both peptides. KPV also effectively reduced HIV replication in acutely infected monocyte-derived macrophages (MDM). The basis of the peptide influence on viral replication is at the transcriptional level; KPV inhibited activation of NF-kappaB that is known to enhance viral expression. Endogenous alpha-MSH likely contributes to natural defense against HIV. However, greater concentrations of synthetic peptide are much more effective in reducing HIV expression in infected cells.
Downregulation of glucocorticoid receptors of liver cytosols and the role of the inflammatory cytokines in pathological stress in scalded rats.
Preliminary experiments indicated that target cells were resistant to glucocorticoid (GC) after pathological stress. This study was designed to investigate the alterations in plasma corticosterone level and GC receptor (GR) of liver cytosols, to assess the relative inflammatory cytokines contribution to GC resistant, and to observe the action of alpha-melanocyte-stimulating hormone (alpha-MSH) on the potential implications of glucocorticord regulatory effects in burned rats. Male Wistar rats (weight range, 180-200g) received a 35% total body surface area immersion scald and were randomly divided to receive either tumor necrosis factor alpha (TNFalpha), interleukin-1beta (IL-1beta), polyclonal antibody (pAb), alpha-MSH, Ac-D-Lys-L-Pro-D-Val (KPV peptide), or saline (control). The binding capacity (Rt) of the steroid-binding sites was measured by radioligand binding assay, using [3H]dexamethasone as the ligand. We examined plasma levels of IL-1beta, TNFalpha, IL-10, and corticosterone following scald challenge in rats. The Rt of GR (208.45+/-30.78fmol/mg of protein) in hepatic cytosol in rats, 12h later the scald was significantly lower than that (306.71+/-27.96fmol/mg of protein) of the control group (P<0.01). The injections of anti-rat TNFalpha (257.80+/-12.82fmol/mg of protein), IL-1beta antibody (254.46+/-21.21fmol/mg of protein), alpha-melanocyte-stimulating hormone (278.32+/-7.76fmol/mg of protein) and KPV peptide (263.46+/-17.46fmol/mg of protein) might prevent the Rt of GR from decreasing in hepatic cytosols of rats with scald, respectively (all of P<0.05) in vivo. Scald-induced robust increases in plasma IL-1beta (214.08+/-27.25pg/ml), TNFalpha (111.18+/-23.97pg/ml), IL-10 (177.50+/-15.79pg/ml) and corticosterone (2680+/-443.23ng/ml) levels after 12h. The administration of TNFalpha, IL-1beta pAb, alpha-MSH and KPV might attenuate these increases. These studies suggest that pro-inflammatory cytokines are involved in downregulation of GRs and thus alpha-MSH and KPV might increase the level of GR in rats with immersion scald.
The Melanocortin System in Inflammatory Bowel Diseases: Insights into Its Mechanisms and Therapeutic Potentials.
The melanocortin system is a complex set of molecular mediators and receptors involved in many physiological and homeostatic processes. These include the regulation of melanogenesis, steroidogenesis, neuromodulation and the modulation of inflammatory processes. In the latter context, the system has assumed importance in conditions of chronic digestive inflammation, such as inflammatory bowel diseases (IBD), in which numerous experiences have been accumulated in mouse models of colitis. Indeed, information on how such a system can counteract colitis inflammation and intervene in the complex cytokine imbalance in the intestinal microenvironment affected by chronic inflammatory damage has emerged. This review summarises the evidence acquired so far and highlights that molecules interfering with the melanocortin system could represent new drugs for treating IBD.
Skin-adaptive film dressing with smart-release of growth factors accelerated diabetic wound healing.
The general treatment of diabetic wound was use of wound dressings to absorb excess exudate. However, traditional wound dressings neither mimic the skin-like properties nor easily be withdrawn from the wound. Herein, the skin-adaptive three-layered films (AGB) dressing has been designed by alternatively depositing phenylboronic acid-grafted γ-PGA (PBA-PGA) and polyvinyl alcohol (PVA). The thickness of AGB film was only 479 μm and its flexibility was obviously strengthen by the boronic ester cross-linking. Besides, the dry AGB film was conveniently adhered to the fresh wound, where its adhesive force reached to 1267 ± 330 mN. Moreover, the adhered AGB film was easily peeled without any second damage after hydration. An anti-inflammatory tripeptide (KPV) and epidermal growth factor (EGF) as biologic factors were respectively encapsulated in the bottom layer and the middle-top two layers of AGB film. KPV was firstly released within 3 day and EGF was subsequently released in a glucose-responsive manner. AGB film containing KPV and EGF (K-E-AGB) could significantly improve the repair rate of full-thickness skin wound on diabetic mice. The mechanism of wound healing was associated with inflammatory inhibition, angiogenesis and collagen deposition. Collectively, skin-adaptive film may be a promising dressing as delivery of biologic factors for the chronic wound.
Critical role of PepT1 in promoting colitis-associated cancer and therapeutic benefits of the anti-inflammatory PepT1-mediated tripeptide KPV in a murine model.
The human intestinal peptide transporter 1, hPepT1, is expressed in the small intestine at low levels in the healthy colon and upregulated during inflammatory bowel disease. hPepT1 plays a role in mouse colitis and human studies have demonstrated that chronic intestinal inflammation leads to colorectal cancer (colitis-associated cancer; CAC). Hence, we assessed here the role of PepT1 in CAC. Mice with hPepT1 overexpression in intestinal epithelial cells (TG) or PepT1 (PepT1-KO) deletion were used and CAC was induced by AOM/DSS. TG mice had larger tumor sizes, increased tumor burdens, and increased intestinal inflammation compared to WT mice. Conversely, tumor number and size and intestinal inflammation were significantly decreased in PepT1-KO mice. Proliferating crypt cells were increased in TG mice and decreased in PepT1-KO mice. Analysis of human colonic biopsies revealed an increased expression of PepT1 in patients with colorectal cancer, suggesting that PepT1 might be targeted for the treatment of CAC. The use of an anti-inflammatory tripeptide KPV (Lys-Pro-Val) transported by PepT1 was able to prevent carcinogenesis in WT mice. When administered to PepT1-KO mice, KPV did not trigger any of the inhibitory effect on tumorigenesis observed in WT mice. The observations that pepT1 was highly expressed in human colorectal tumor and that its overexpression and deletion in mice increased and decreased colitis associated tumorigenesis, respectively, suggest that PepT1 is a potential therapeutic target for the treatment of colitis associated tumorigenesis.
Exploring the Role of Tripeptides in Wound Healing and Skin Regeneration: A Comprehensive Review.
Wound healing is a complex and dynamic process that requires the coordination of cellular, molecular, and physiological events to restore tissue integrity. Despite notable advances in treatment strategies, optimizing healing outcomes, particularly in chronic wounds, remains a major challenge. Emerging evidence highlights the therapeutic promise of peptides, especially tripeptides, in accelerating tissue repair through diverse mechanisms. These short peptides regulate key processes such as cell migration, proliferation, and differentiation, while also modulating inflammation, promoting angiogenesis, and facilitating extracellular matrix (ECM) remodeling. This review, covering studies published between 2016 and 2025, explores the role of tripeptides in enhancing wound repair, emphasizing their biological functions, mechanisms of action, and therapeutic applications. Recent findings demonstrate that tripeptides can stimulate fibroblast migration, enhance collagen deposition, and support angiogenesis. In addition, they exhibit antimicrobial and anti-inflammatory properties, making them valuable candidates for both acute and chronic wound management. GHK-based formulations, including nanoparticle conjugates, hydrogels, and clinical derivatives such as TriHex and TriHex 2.0, enhance fibroblast migration, ECM remodeling, collagen and elastin synthesis, and wound closure while providing antimicrobial activity. KdPT mitigates hyperglycemia-induced oxidative stress and restores keratinocyte function, whereas KPV-loaded hydrogels reduce inflammation, promote tissue regeneration, and combat MRSA infections. Additionally, lipotripeptides (DICAMs) inhibit and disrupt bacterial biofilms, and GPE supports neuroprotection and regeneration through ERK and PI3K/Akt signaling activation. Beyond wound repair, this review also discusses comparative physicochemical properties and wound healing applications of tripeptides versus larger peptides, factors influencing their performance, strategies for combination with biomaterial scaffolds, and emerging applications in fields such as cancer and cosmetics. Collectively, tripeptides represent a promising class of multifunctional bioactive molecules in wound care, offering novel avenues for targeted tissue regeneration. Future research should focus on improving their stability, bioavailability, and delivery systems to fully harness their clinical potential in regenerative medicine.
[Changes in aldosterone binding activity of kidney cytosol after stress in rats and the regulation].
To observe the changes in aldosterone binding activity of kidney cytosols after pathological stress in rats and the regulation, binding capacity (Rt) and apparent dissociation constant (Kd) of aldosterone binding activity of kidney cytosols in normal, low-degree or heavy-degree scalded rats were measured by radioligand binding assay using [3H]aldosterone as the ligand. Changes in Rt and Kd of aldosterone binding activity were observed after injection of anti-rat TNF alpha and IL-1 beta antibodies, alpha-melanocyte-stimulating hormone (alpha-MSH) and KPV peptide (Ac-D-Lys-L-Pro-D-Val). The results indicated that there were two types of aldosterone binding activities in kidney cytosol with different Rt and Kd, and the Rt of heavy-degree scalded rats (Rt1: 22.4 +/- 5.4 fmol/mg pro, Rt2: 196.3 +/- 32.5 fmol/mg pro) was lower than that of the control group (Rt1: 41.6 +/- 7.2 fmol/mg pro, Rt2: 317.6 +/- 70.0 fmol/mg pro) (P < 0.01; P < 0.01); while the Rt of low-degree scalded rats (Rt1: 41.4 +/- 5.0 fmol/mg pro, Rt2: 314.8 +/- 45.7 fmol/mg pro) was not significantly different from that of the control group (P > 0.05; P > 0.05). Injection of anti-rat TNF alpha and IL-1 beta antibodies, alpha-MSH and KPV prevented Rt of aldosterone binding activity from decrease in kidney cytosol of rats with heavy-degree scald. These findings suggest that aldosterone binding activity may be down-regulated in heavy-degree scalded rats, but it may be reversed by injection of anti-rat TNF alpha and IL-1 beta antibodies, alpha-MSH and KPV.
Quick links (PubMed)
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