KPV

Effects measured: KPV (taken up via the PepT1 transporter) reduced colitis severity: colonic MPO activity fell roughly 50% in DSS and roughly 30% in TNBS, body-weight loss was significantly reduced by day 8, colon shortening was prevented, and pro-inflammatory cytokine mRNA (IL-6, IL-12, IL-1beta, IFN-gamma) was decreased. In cells, KPV cut NF-kB luciferase activity by roughly 35-50%, slowed IkB-alpha degradation, strongly reduced ERK/JNK/p38 MAP kinase phosphorylation, and lowered IL-8 mRNA by roughly 35%.

Side effects: KPV alone (without colitis induction) had no effect on basal MPO or other inflammatory parameters; no adverse effects or toxicity were reported in this study.

Sources: Dalmasso G, et al. PepT1-mediated tripeptide KPV uptake reduces intestinal inflammation. Gastroenterology. 2008;134(1):166-178.

Effects measured: KPV produced significant anti-inflammatory effects in both colitis models: significantly stronger body-weight regain in DSS-treated mice, significantly reduced inflammatory infiltrates on histology, and reduced colonic MPO activity. In MC1Re/e mice (lacking a functional melanocortin-1 receptor), KPV rescued all treated animals from death during DSS colitis, indicating effects at least partly independent of MC1R signalling.

Side effects: No adverse events reported in this study.

Sources: Kannengiesser K, et al. Melanocortin-derived tripeptide KPV has anti-inflammatory potential in murine models of inflammatory bowel disease. Inflamm Bowel Dis. 2008;14(3):324-331.

Effects measured: HA-KPV-NP-treated mice had the smallest maximal body-weight loss and best weight recovery among DSS groups, markedly lower colonic MPO activity, reduced spleen weight, preserved colon length, and lower colonic TNF-alpha mRNA versus DSS controls. In vitro, the nanoparticles produced dose-dependent wound-healing recovery of epithelial layers and sustained suppression of TNF-alpha mRNA out to 72-96 hours.

Side effects: Nanoparticles were described as non-toxic and biocompatible; no cytotoxicity was seen in cell tests and no adverse events were reported in the mice.

Sources: Xiao B, et al. Orally Targeted Delivery of Tripeptide KPV via Hyaluronic Acid-Functionalized Nanoparticles Efficiently Alleviates Ulcerative Colitis. Mol Ther. 2017;25(7):1628-1640.

Effects measured: Versus vehicle, KPV reduced lesion volume from 27.7 to 21.0 mm3 (about 24% smaller, p=0.016) and cut apoptotic neurons from about 55 to 26 cells per region (about 52% fewer, p=0.002), and reduced microglial activation (p=0.033). TNF-alpha and IL-1beta showed only non-significant downward trends, and the neurological score did not differ significantly (p=0.139).

Side effects: No serious adverse events reported; one treatment-group animal was euthanized before injection due to persistent post-injury seizures, all other animals survived the observation period.

Sources: Schaible EV, et al. Single Administration of Tripeptide alpha-MSH(11-13) Attenuates Brain Damage by Reduced Inflammation and Apoptosis after Experimental Traumatic Brain Injury in Mice. PLoS One. 2013;8(8):e71056.

Effects measured: proKPV reached about 3.8-fold higher colonic accumulation than free KPV. Free KPV at 1 mg/kg showed no benefit, whereas proKPV (most effective at 2.5 mg/kg) attenuated body-weight loss, lowered the disease activity index, prevented colon shortening, restored the colonic epithelium and mucus layer, and significantly suppressed colonic TNF-alpha, IL-1beta, IL-6, MPO, ROS and MDA.

Side effects: No apparent systemic toxicity; normal blood counts and organ histology after 7 days, and low cytotoxicity at concentrations up to 1000 micrograms/mL in cell tests.

Sources: Cheng J, et al. Inflammation-triggered self-immolative conjugates enable oral peptide delivery by overcoming gastrointestinal barriers. Sci Adv. 2026;12(2):eaea2989.