PEPITEM is an immune-modulatory peptide that effectively regulates inflammation and mitigates immune-mediated inflammatory diseases (IMIDs). Here, we identify two independently active tripeptide pharmacophores within PEPITEM and engineered peptidomimetics with enhanced pharmacodynamic properties. These peptidomimetics regulate T-cell trafficking in vitro and reduce T-cell, neutrophil and macrophage numbers in the inflamed peritoneal cavity in vivo. In a plaque psoriasis model, topical administration reduced disease severity, inflammation and immune cell infiltration, while regulating cytokine release in macrophages and fibroblasts, as well as keratinocyte proliferation. Th1 and Th17 cell abundance, along with their cytokines, was reduced in secondary lymphoid organs. This expanded functional repertoire of PEPITEM and its derivatives provides innovative tools for countering immune and stromal cell-induced pathology in IMIDs. Moreover, by identifying significantly smaller tripeptide pharmacophores of 14 amino acid PEPITEM, we may be able to deliver substantial financial advantages in synthesis and formulation. The order of magnitude increase in efficacy observed for some peptidomimetics may deliver agents with enhanced pharmacological characteristics compared to the parent PEPITEM sequence. Taken together with other reports on the efficacy of PEPITEM, this study paves the way for the development and translation of a novel class of anti-inflammatory agents which may have utility in a broad range of autoimmune and chronic inflammatory diseases.

The common bean (Phaseolus vulgaris L.) is one of the oldest food crops in the world. In this study, the ultra-high-performance liquid chromatography high-resolution mass spectrometry (UHPLC-MS/MS) technique was used to characterize the polar lipid composition and polyphenolic fraction of five bean varieties commonly consumed in Italy: Cannellino (PVCA), Controne (PVCO), Borlotti (PVBO), Stregoni (PVST), and Vellutina (PVVE). Lipid content represents a minor fraction of the whole metabolome in dry beans, and little is known about their polar lipids, which could be potentially bioactive components. Thirty-three compounds were detected through UHPLC-MS/MS, including oxylipins, phospholipids, N-acyl glycerolipids, and several fatty acids. The dichloromethane extracts were subjected to principal component analysis (PCA), with the results showing greater differentiation for the Borlotti variety. Moreover, 27 components belonging to different polyphenol classes, such as phenolic acids, flavonoids, catechins, anthocyanins and their glycosides, and some saponins, were identified in the hydroalcoholic seed extracts. In addition, the mineral content of the beans was determined. Considering the high number of compounds in the five apolar seed extracts, all samples were examined to determine their in vitro inhibitory activity against the enzyme cyclooxygenase-2 (COX-2), which is inducible in inflammatory cells and mediates inflammatory responses. Only PVCO showed the best inhibition of the COX-2 enzyme with an IC₅₀ = 31.15 ± 2.16 µg/mL. In light of these results, the potential anti-inflammatory properties of PVCO were evaluated in the LPS-stimulated murine macrophage cell line J774A.1. Herein, we demonstrate, for the first time, that PVCO at 30 µg/mL can significantly reduce the release of TNF-α, with a less significant anti-inflammatory effect being observed in terms of IL-6 release.

Background/Objectives: Benign prostatic hyperplasia (BPH) is one of the most common chronic diseases affecting the urinary tract that occurs mainly in men over 40 years of age. Among the natural therapies, proanthocyanidins (PACs), which can treat a wide range of immune-mediated inflammatory diseases (IMIDs), have been shown to play an important role in the treatment of pathologies concerning prostate health. In this regard, the present study aimed to evaluate the different bioactivities of a grape seed extract (GSE), rich in polymeric PACs, and its version processed under alkaline conditions (ATGSE), characterized by a higher content of oligomeric PACs, in an animal model of BPH induced by subcutaneous injection of testosterone (1 mg/mouse). Methods: These latter were divided into a control group (vehicle, olive oil), a BPH group (testosterone 1 mg/mouse), and four treatment groups treated with GSE (500 mg/kg) and ATGSE (125, 250, 500 mg/kg) by oral gavage. At the experimental endpoint (4 weeks), hematological and biochemical analyses of blood and tissues were performed. Results: Data showed that oral administration of ATGSE (250 mg/kg) was significantly more effective than GSE in reducing prostate (p ≤ 0.0001) and seminal vesicle (p ≤ 0.0001) weight. Moreover, ATGSE exhibited enhanced effectiveness in significantly reducing PSA levels (p ≤ 0.0001 vs. GSE) and the expression of key pro-inflammatory cyto-chemokines in prostate and seminal vesicles homogenates. Conclusions: These findings pave the way for the clinical application of ATGSE as a nutraceutical and/or functional food.

PEPITEM is an immune-modulatory peptide that effectively regulates inflammation and mitigates immune-mediated inflammatory diseases (IMIDs). Here we identify two independently active tripeptide pharmacophores within PEPITEM and engineered peptidomimetics with enhanced pharmacodynamic properties. These peptidomimetics regulate T-cell trafficking in vitro and reduce T-cell, neutrophil and macrophage numbers in the inflamed peritoneal cavity i n vivo . In a plaque psoriasis model, topical administration reduced disease severity, inflammation and immune cell infiltration, while regulating cytokine release in macrophages and fibroblasts, as well as keratinocyte proliferation. Th1 and Th17 cell abundance, along with their cytokines, was reduced in secondary lymphoid organs. This expanded functional repertoire of PEPITEM and its derivatives provides innovative tools for countering immune and stromal cell-induced pathology in IMIDs, paving the way for a novel class of anti-inflammatory agents.