| Cheng 2026 Sci Adv Intestinal inflammation models · Airway epithelium · Delivery and formulation | Animal Mouse colitis and acute lung injury models | Measured colonic accumulation and inflammatory endpoints; the conjugate reached 3.8-fold higher colonic accumulation than free KPV. | Prodrug conjugate, not free KPV. | Evidence grade C |
| Lee 2026 Cytotechnology Lipid and adipocyte models | In vitro Human HepG2 hepatocytes (oleic-acid lipid loading) | Measured lipid accumulation, FAS expression, ROS, ERK, AKT/mTORC1 and PPAR-gamma phosphorylation in oleic-acid-loaded HepG2 cells treated with KPV. | Single hepatoma cell line. | Evidence grade D |
| An 2026 Tissue Cell Lipid and adipocyte models | Animal 3T3-L1 preadipocytes; high-fat-diet mice (oral) | Measured Oil Red O staining (about 55% lower), triglyceride content (about 38% lower) and adipogenic markers in vitro, and body weight, adipose mass and plasma lipids in high-fat-diet mice. | Single laboratory; 2026 publication not yet independently replicated. | Evidence grade C |
| Bai 2026 Tissue Cell Vascular models | In vitro RAW264.7 macrophages (oxidised LDL) | Measured lipid accumulation, ROS, p38/NF-kappaB activation and NLRP3 inflammasome assembly in oxLDL-treated macrophages exposed to KPV. | Single murine cell line. | Evidence grade D |
| Sung 2025 Tissue Cell Skin and keratinocyte models | In vitro Human HaCaT keratinocytes and 3D skin model exposed to PM10 | Measured viability, ROS, ERK/p38 activation, apoptosis proteins, caspase-1 and IL-1 beta after PM10 exposure; KPV-treated cultures showed lower ROS and IL-1 beta and higher viability. | Cell line and reconstructed tissue only. | Evidence grade D |
| Zhang 2024 Front Pharmacol Intestinal inflammation models · Delivery and formulation | Animal Acute and chronic DSS colitis in mice; macrophages | Measured body weight, colon length, disease activity index, MPO, NO, ROS, TNF-alpha, IL-1 beta, IL-6 and tight-junction proteins; the co-assembled nanoparticles exceeded both the KPV-only and FK506-only groups. | Combination with an immunosuppressant; free-KPV arm was a comparator, not the focus. | Evidence grade C |
| Zhang 2024 Adv Healthc Mater Vascular models | Animal Mouse vascular calcification model; cells in vitro | Measured vascular calcification, inflammatory markers and autophagy in mice given KPV-rapamycin nanoparticles. | Combination with rapamycin; KPV contribution not isolated. | Evidence grade C |
| Zhao 2022 Acta Biomater Intestinal inflammation models · Delivery and formulation | Animal TNBS colitis in rats (intracolonic) | Measured mucosal adhesion, epithelial barrier recovery and gut flora composition in TNBS-treated rats given the hydrogel-bound KPV. | Formulation effect; rat model. | Evidence grade C |
| Sun 2021 ACS Biomater Sci Eng Intestinal inflammation models · Delivery and formulation | Animal TNBS colitis in rats (rectal) | Measured release kinetics, stability at 37 C, weight loss, disease activity index, colon length, MPO, TNF-alpha and IL-6 in TNBS-treated rats given the hydrogel formulation. | Formulation effect; rat model. | Evidence grade C |
| Shao 2021 Biomater Sci Tissue-repair models · Antimicrobial assays · Delivery and formulation | Animal Rat chemotherapy-induced oral mucositis; MRSA-infected gingival wounds | Measured food intake, body weight, gingival histology, CK10/PCNA, IL-1 beta, TNF-alpha and IL-10 in rats treated with the KPV-loaded hydrogel. | Carrier contains EGCG, which is itself antibacterial; effects are of the combination. | Evidence grade C |
| Songok 2018 PLoS One Chemistry and analysis · Antimicrobial assays | In vitro Bacterial cultures; protease stability | Reported a lysine glycoalkylation method; Ac-KPV-NH2 and its analogues showed no antimicrobial activity, while the modified peptides resisted proteolytic enzymes. | Negative antimicrobial result conflicts with earlier reports under different conditions. | Evidence grade D |
| Xiao 2017 Mol Ther Intestinal inflammation models · Delivery and formulation | Animal Colonic epithelial cells and macrophages; mouse colitis model | Measured mucosal damage and TNF-alpha; the HA-functionalised nanoparticle/hydrogel system outperformed a non-targeted KPV nanoparticle system. | Formulation effect; mouse model. | Evidence grade C |
| Pawar 2017 J Pharm Sci Skin and keratinocyte models · Delivery and formulation | Ex vivo Dermatomed human skin (in vitro permeation) | Measured transdermal permeation; passive permeation was below the 0.01 ug/mL detection limit, microneedles gave 4.4 ug/cm2/h, and iontophoresis plus microneedles gave 35-fold more than microneedles alone. | Excised skin; no biological endpoint. | Evidence grade D |
| Viennois 2016 Cell Mol Gastroenterol Hepatol Intestinal inflammation models · Tumour-model research | Animal AOM/DSS colitis-associated tumour model in WT, hPepT1-transgenic and PepT1-KO mice; human colonic biopsies | Measured tumour number and size in a chemically induced colitis-associated tumour model; tumour burden tracked PepT1 expression, and KPV reduced tumorigenesis in wild-type but not PepT1-knockout mice. | Mouse model; the human biopsies measured PepT1 expression only, with no KPV exposure. | Evidence grade C |
| Pawar 2015 Biomed Chromatogr Chemistry and analysis | Analytical Aqueous solutions and skin homogenates | Validated a reversed-phase HPLC assay (LOD 0.01 ug/mL, LOQ 0.25 ug/mL); under acid, alkali and peroxide stress KPV degraded mainly to lys-pro-diketopiperazine. | Analytical method paper. | Evidence grade D |
| Schaible 2013 PLoS One Neuroinflammation models | Animal Mouse controlled cortical impact (traumatic brain injury model) | Measured secondary lesion volume, microglial activation and neuronal apoptosis; lesion volume and apoptosis markers were lower, while TNF-alpha and IL-1 beta expression did not change. | Single time-point administration; mixed inflammatory readouts. | Evidence grade C |
| Land 2012 Int J Physiol Pathophysiol Pharmacol Airway epithelium | In vitro Human bronchial epithelial cells 16HBE14o- (TNF-alpha, RSV) | Measured NF-kappaB reporter activity, MMP-9, IL-8 and eotaxin; KPV reduced them and the study linked this to inhibition of p65RelA nuclear import at the importin-alpha3 site. | Single immortalised cell line; single-author study. | Evidence grade D |
| Singh 2011 Antimicrob Agents Chemother Antimicrobial assays | In vitro Methicillin-sensitive and -resistant S. aureus | Measured bacterial killing and membrane depolarisation; the C-terminal fragments killed more than 90% of cells at micromolar concentrations. | Culture assays only. | Evidence grade D |
| Laroui 2010 Gastroenterology Intestinal inflammation models · Delivery and formulation | Animal Caco2-BBE cells; DSS colitis in mice | Measured epithelial inflammatory responses and colitis parameters; nanoparticle-delivered KPV gave similar effects at a concentration reported as 12,000-fold lower than free KPV solution. | Formulation effect, not free KPV; mouse model. | Evidence grade C |
| Dalmasso 2008 Gastroenterology Intestinal inflammation models | Animal Caco2-BBE, HT29-Cl.19A and Jurkat cells; DSS and TNBS colitis models in mice | Measured PepT1-mediated uptake, NF-kappaB and MAP kinase activation, and colonic cytokine mRNA; nanomolar KPV reduced these readouts and the two chemically induced colitis models showed lower inflammation scores. | Chemically induced mouse models; cytokine and histology endpoints only. | Evidence grade C |
| Kannengiesser 2008 Inflamm Bowel Dis Intestinal inflammation models | Animal DSS colitis and CD45RB(hi) transfer colitis in mice; MC1R e/e mice | Measured weight recovery, histological infiltrates and colonic myeloperoxidase; KPV-treated mice showed faster weight regain, fewer infiltrates and lower MPO, including MC1R-deficient mice. | Mouse models only; group sizes not in abstract. | Evidence grade C |
| Charnley 2008 Peptides Antimicrobial assays | In vitro S. aureus and E. coli cultures | Measured bacterial growth; the acetylated, amidated tripeptides were antibacterial and so was a lysine-free variant, identifying an X-Pro-D/L-Val motif. | Capped analogues; culture assays only. | Evidence grade D |
| Bonfiglio 2006 Exp Eye Res Tissue-repair models | Animal Rabbit corneal epithelial abrasion; rabbit corneal epithelial cells | Measured corneal re-epithelialisation; 8 of 8 KPV-treated corneas were re-epithelialised at 60 h vs none of the controls, and an NOS inhibitor blocked the effect. | Small animal sample; single tissue model. | Evidence grade C |
| Elliott 2004 J Invest Dermatol Skin and keratinocyte models | In vitro Human HaCaT and normal human keratinocytes | Measured cAMP and intracellular calcium; no cAMP rise was detected, while rapid calcium responses occurred only when the cAMP pathway was inhibited. | Signalling readouts only; no inflammatory endpoint. | Evidence grade D |
| Getting 2003 J Pharmacol Exp Ther Systemic inflammation and fever models | Animal Mouse (urate crystal and IL-1 beta peritonitis; MC1R e/e mice) plus macrophages in vitro | Measured neutrophil accumulation in peritonitis models; KPV reduced it, the MC3/4 antagonist SHU9119 did not block it, KPV did not raise cAMP, and the effect persisted in MC1R-deficient mice. | Peritonitis models; mechanism inferred by exclusion. | Evidence grade C |
| Muceniece 2003 Peptides Systemic inflammation and fever models | In vitro RAW 264.7 macrophages; B16-F1 cells; MCR-expressing insect cells | Measured melanocortin-receptor binding, cAMP and nitric oxide; the tripeptides did not bind MCRs or raise cAMP but dose-dependently inhibited stimulated NO production. | Cell assays; includes non-native cyclic analogues. | Evidence grade D |
| Mandrika 2001 Biochem Pharmacol Systemic inflammation and fever models | In vitro RAW 264.7 macrophages (LPS/IFN-gamma) | Measured nitric oxide output and NF-kappaB nuclear translocation; the tripeptide inhibited both, and the study examined MC1 receptor binding, which FDA later cited as evidence KPV does not displace alpha-MSH. | Single murine cell line. | Evidence grade D |
| Haddad 2001 Biochem J Airway epithelium | In vitro Fetal alveolar type II epithelial cells (LPS) | Measured nuclear localisation of NF-kappaB subunits p50, p65 and c-Rel; the D-proline analogue suppressed it dose-dependently. | D-proline analogue, not native KPV; fetal cell model. | Evidence grade D |
| Cutuli 2000 J Leukoc Biol Antimicrobial assays | In vitro Staphylococcus aureus and Candida albicans cultures | Measured colony formation of S. aureus and viability/germ-tube formation of C. albicans; alpha-MSH peptides including KPV reduced both across a broad concentration range. | Culture assays; later work (PMID 29953505) found no activity for Ac-KPV-NH2 under its conditions. | Evidence grade D |
| Haycock 2000 J Biol Chem Skin and keratinocyte models | In vitro Human HaCaT keratinocytes and HBL melanoma cells | Measured glutathione peroxidase activity and intracellular peroxide; MSH 11-13 inhibited the stimulated activity at 10-100-fold higher concentrations than alpha-MSH. | Cell lines; biphasic dose-response. | Evidence grade D |
| Barcellini 2000 J Leukoc Biol Systemic inflammation and fever models | In vitro Human promonocytic U1 cells; monocyte-derived macrophages | Measured HIV-1 p24 release and NF-kappaB activation in infected cells; KPV reduced viral expression and NF-kappaB activation. | Cell culture only. | Evidence grade D |
| Galimberti 1999 Biochem Biophys Res Commun Neuroinflammation models | In vitro Murine microglia (beta-amyloid + IFN-gamma) | Measured nitrite, TNF-alpha and iNOS/TNF-alpha mRNA in stimulated microglia; both alpha-MSH and the tripeptide reduced them. | Cell line only. | Evidence grade D |
| Delgado 1998 J Leukoc Biol Neuroinflammation models | In vitro Murine microglial cell line N9 (LPS + IFN-gamma) | Measured TNF-alpha, IL-6 and nitric oxide output from stimulated microglia; melanocortin peptides including the tripeptide reduced them concentration-dependently. | Single immortalised cell line. | Evidence grade D |
| Catania 1998 Peptides Systemic inflammation and fever models | Ex vivo Whole blood from people with HIV, stimulated with LPS | Measured IL-1 and TNF-alpha production in donated blood samples; melanocortins including the tripeptide reduced both concentration-dependently. | Ex vivo blood samples; no peptide was given to any person. | Evidence grade D |
| Hiltz 1992 Cytokine Systemic inflammation and fever models | Animal Mouse (cytokine-induced ear and paw inflammation) | Measured inflammation induced by IL-1 beta, IL-6, TNF-alpha, LTB4, PAF and IL-8; the analogue inhibited the cytokine-driven responses but not LTB4, PAF or IL-8. | D-valine analogue, not native KPV. | Evidence grade C |
| Uehara 1992 Eur J Pharmacol Systemic inflammation and fever models | Animal Rodent IL-1-induced anorexia model, intracerebroventricular (species not given in abstract) | Measured food intake after central IL-1; the tripeptide blocked IL-1-induced anorexia at the higher of two doses only. | Central administration; two doses only. | Evidence grade C |
| Hiltz 1991 Peptides Skin and keratinocyte models | Animal Mouse (picryl chloride ear swelling) | Compared stereochemical analogues; L-Pro12 was required for activity and D-Val13 substitution increased activity about four-fold over the parent tripeptide. | Analogues, not native KPV; bell-shaped dose-response complicates interpretation. | Evidence grade C |
| Hiltz 1990 Peptides Skin and keratinocyte models · Systemic inflammation and fever models | Animal Mouse (paw edema; contact sensitivity) | Measured paw edema and contact-sensitivity responses in mice; MSH peptides including the tripeptide reduced both. | Abstract does not separate tripeptide results from the full hormone in detail. | Evidence grade C |
| Hiltz 1989 FASEB J Skin and keratinocyte models · Systemic inflammation and fever models | Animal Mouse (picryl chloride ear swelling) | Measured irritant-induced ear swelling in mice; the tripeptide reduced swelling in a dose-related fashion. | Single irritant model; sample size not in abstract. | Evidence grade C |
| Deeter 1988 Peptides Systemic inflammation and fever models | Animal Rabbit (IL-1 fever), intracerebroventricular | Compared fever reduction by alpha-MSH fragments (11-13, 10-13, 8-13); all reduced fever dose-dependently and none matched alpha-MSH(1-13). | Acetylated, amidated analogue rather than native KPV; central administration only. | Evidence grade C |
| Richards 1984 Peptides Systemic inflammation and fever models | Animal Rabbit (leukocytic-pyrogen fever) | Measured body-temperature response to pyrogen in rabbits given the tripeptide centrally or peripherally; the tripeptide reduced fever with lower potency than full-length alpha-MSH. | 1984 study; sample size not stated in the abstract; potency lower than the parent hormone. | Evidence grade C |