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Kpv2.0
KPV – Forschung
Überwiegend Mechanismus / Beobachtung
6 begutachtete Studien
Was die Evidenz sagt
Überwiegend Mechanismus / Beobachtung
Die meisten Studien zu KPV sind mechanistisch oder beobachtend statt RCTs, die einen klinischen Effekt messen — betrachte die Ergebnisse als vorläufig.
Die meiste Evidenz stammt aus gemischt-qualitativen Studien, veröffentlicht 2008–2019.
Basierend auf 6 Studien
Konfidenz
Geringe Konfidenz
Nach Outcome
InflammationEin entzündungshemmendes α-MSH-Fragment, das die NF-κB-/MAP-Kinase-Signalübertragung hemmt und Darmentzündungen bei Mäusen/Ratten reduziert; keine abgeschlossenen Humanstudien und unbekannte Dosis/Applikationsart/Sicherheit beim Menschen. · Nicht belegt (keine Humandaten)
Überwiegend Mechanismus / Beobachtung5 Studien
Digestive healthReduzierte Darmentzündung und beschleunigte Schleimhautheilung in Nagetiermodellen der Kolitis über PepT1-vermittelte Aufnahme an entzündeten Stellen; ausschließlich präklinisch. · Nicht belegt (keine Humandaten)
Überwiegend Mechanismus / Beobachtung5 Studien
Wound & ulcer healing
Zu wenige bewertete Studien2 Studien
Ältere Forschungsbasis
Neueste Studie von 2019
200820132019
1Tierstudie2008
Nanomolar concentrations of KPV inhibit the activation of NF-kappaB and MAP kinase inflammatory signaling pathways, and reduce pro-inflammatory cytokine secretion.
Dalmasso G, Charrier-Hisamuddin L, Nguyen HT, Yan Y, Sitaraman S, Merlin D. · Gastroenterology (2008)
Core mechanism study: nanomolar KPV inhibited NF-κB and MAP-kinase signalling and reduced pro-inflammatory cytokine secretion in human intestinal epithelial and T cells
Showed KPV acts via the PepT1 transporter expressed in both immune and intestinal epithelial cells
Oral KPV in drinking water reduced the incidence of DSS- and TNBS-induced colitis in mice, with lower pro-inflammatory cytokine mRNA
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.
Kannengiesser K, Maaser C, Heidemann J, Luegering A, Ross M, Brzoska T, et al. · Inflamm Bowel Dis (2008)
Tested α-MSH(11-13) / KPV in two IBD models: DSS colitis and CD45RB-high transfer colitis
In mice with a non-functional melanocortin-1 receptor, KPV still rescued animals from DSS-colitis death — anti-inflammatory effect partly MC1R-independent
Mice given dextran sodium sulfate (DSS) followed by NP-KPV were protected against inflammatory and histologic parameters, compared with mice given only DSS.
Laroui H, Dalmasso G, Nguyen HT, Yan Y, Sitaraman SV, Merlin D. · Gastroenterology (2010)
Engineered nanoparticles loaded with KPV and encapsulated in an alginate-chitosan hydrogel to target the inflamed colon in a DSS-colitis mouse model
NP-KPV protected mice against inflammatory and histologic colitis parameters versus DSS alone
KPV could be delivered at a concentration ~12,000-fold lower than free KPV with similar therapeutic efficacy via targeted nanoparticles
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.
Xiao B, Xu Z, Viennois E, Zhang Y, Zhang Z, Zhang M, et al. · Mol Ther (2017)
Loaded KPV into hyaluronic-acid-functionalized polymeric nanoparticles targeting colonic epithelial cells and macrophages
HA-KPV-NPs accelerated mucosal healing and alleviated inflammation, downregulating TNF-α in a mouse colitis model
Nanoparticles appeared non-toxic and biocompatible with intestinal cells
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.
Viennois E, Ingersoll SA, Ayyadurai S, Zhao Y, Wang L, Zhang M, et al. · Cell Mol Gastroenterol Hepatol (2016)
Studied the PepT1 transporter in colitis-associated cancer (AOM/DSS) and the therapeutic effect of PepT1-transported KPV
KPV prevented carcinogenesis in wild-type mice but had no effect in PepT1-knockout mice, mechanistically tying the benefit to the transporter
Human colonic biopsies showed increased PepT1 expression in colorectal cancer, suggesting a target
Truncated α-MSH peptides such as Lys-Pro-Val (KPV)... have been found to possess anti-inflammatory effects but to lack the pigment-inducing activity of α-MSH... promising future candidates for the treatment of cutaneous wounds and skin ulcers.
Böhm M, Luger T. · Exp Dermatol (2019)
Review of melanocortin peptides for cutaneous wound healing, highlighting truncated α-MSH peptides such as KPV
Notes KPV possesses anti-inflammatory effects but lacks α-MSH's pigment-inducing activity, proposing it as a candidate for cutaneous wounds and skin ulcers
Frames the supporting data as in silico, in vitro, ex vivo, and animal models — explicitly hypothesis-stage