Therapeutic Efficacy of Stable Analogues of Vasoactive Intestinal Peptide against Pathogens

Campos‐Salinas, Jenny; Cavazzuti, Antonio; O’Valle, Francisco; Forte-Lago, Irene; Caro, Marta; Beverley, Stephen M.; Delgado, Mario; González‐Rey, Elena

doi:10.1074/jbc.m114.560573

Cited by 38 publications

(31 citation statements)

References 58 publications

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“…Experimental evidence accumulated over the last two decades has demonstrated beneficial effects of VIP in all stages of RA development through its anti-inflammatory and immunomodulatory abilities [131,158,199] (Figure 2). In addition, numerous studies have shown the direct antimicrobial activity of VIP against a wide range of bacteria [200], as well as its protective effect in polymicrobial sepsis [201]. Interestingly, VIP is able to counteract the effects of LPS from Porphyromonas gingivalis in monocytes, which is an oral bacterium related to increased risk of arthritis associated with periodontal disease [202,203].…”

Section: Vip In Rheumatoid Arthritismentioning

confidence: 99%

A Clinical Approach for the Use of VIP Axis in Inflammatory and Autoimmune Diseases

Martı́nez

Juarranz

Gutiérrez‐Cañas

et al. 2019

IJMS

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The neuroendocrine and immune systems are coordinated to maintain the homeostasis of the organism, generating bidirectional communication through shared mediators and receptors. Vasoactive intestinal peptide (VIP) is the paradigm of an endogenous neuropeptide produced by neurons and endocrine and immune cells, involved in the control of both innate and adaptive immune responses. Exogenous administration of VIP exerts therapeutic effects in models of autoimmune/inflammatory diseases mediated by G-protein-coupled receptors (VPAC1 and VPAC2). Currently, there are no curative therapies for inflammatory and autoimmune diseases, and patients present complex diagnostic, therapeutic, and prognostic problems in daily clinical practice due to their heterogeneous nature. This review focuses on the biology of VIP and VIP receptor signaling, as well as its protective effects as an immunomodulatory factor. Recent progress in improving the stability, selectivity, and effectiveness of VIP/receptors analogues and new routes of administration are highlighted, as well as important advances in their use as biomarkers, contributing to their potential application in precision medicine. On the 50th anniversary of VIP’s discovery, this review presents a spectrum of potential clinical benefits applied to inflammatory and autoimmune diseases.

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Section: Vip In Rheumatoid Arthritismentioning

confidence: 99%

A Clinical Approach for the Use of VIP Axis in Inflammatory and Autoimmune Diseases

Martı́nez

Juarranz

Gutiérrez‐Cañas

et al. 2019

IJMS

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“…Recent evidence indicated the beneficial effects of grape seed proanthocyanidins (GSPs) on the mammalian animals' gut as an effective antibiotic alternative [8]. GSPs are primarily known for their antioxidant activity.…”

Section: Introductionmentioning

confidence: 99%

Dietary grape seed proanthocyanidins (GSPs) improve weaned intestinal microbiota and mucosal barrier using a piglet model

et al. 2016

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Proanthocyanidins have been suggested as an effective antibiotic alternative, however their mechanisms are still unknown. The present study investigated the effects of grape seed proanthocyanidins on gut microbiota and mucosal barrier using a weaned piglet model in comparison with colistin. Piglets weaned at 28 day were randomly assigned to four groups treated with a control ration, or supplemented with 250 mg/kg proanthocyanidins, kitasamycin/colistin, or 250 mg/kg proanthocyanidins and half-dose antibiotics, respectively. On day 28, the gut chyme and tissue samples were collected to test intestinal microbiota and barrier function, respectively. Proanthocyanidins treated piglets had better growth performance and reduced diarrhea incidence ( P < 0.05), accompanied with decreased intestinal permeability and improved mucosal morphology. Gene sequencing analysis of 16S rRNA revealed that dietary proanthocyanidins improved the microbial diversity in ileal and colonic digesta, and the most abundant OTUs belong to Firmicutes and Bacteroidetes spp . Proanthocyanidins treatment decreased the abundance of Lactobacillaceae , and increased the abundance of Clostridiaceae in both ileal and colonic lumen, which suggests that proanthocyanidins treatment changed the bacterial composition and distribution. Administration of proanthocyanidins increased the concentration of propionic acid and butyric acid in the ileum and colon, which may activate the expression of GPR41. In addition, dietary proanthocyanidins improved the antioxidant indices in serum and intestinal mucosa, accompanied with increasing expression of barrier occludin. Our findings indicated that proanthocyanidins with half-dose colistin was equivalent to the antibiotic treatment and assisted weaned animals in resisting intestinal oxidative stress by increasing diversity and improving balance of gut microbes.

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“…In this regard, we further investigated the parasiticidal activity of this peptide in mice infected with T. equiperdum. Although a few studies have demonstrated the use of AMPs in animal models of infection by trypanosomatids (26,35,(41)(42)(43), to our knowledge, this is the first study assessing the therapeutic potential of eCATH1 in a T. equiperdum infection model. We found that eCATH1 at the highest dose of 10 mg/kg prolongs the life of infected mice.…”

Section: Discussionmentioning

confidence: 99%

Killing of Trypanozoon Parasites by the Equine Cathelicidin eCATH1

Cauchard

Reet

Büscher

et al. 2016

Antimicrob Agents Chemother

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h Trypanozoon parasites infect both humans, causing sleeping sickness, and animals, causing nagana, surra, and dourine. Control of nagana and surra depends to a great extent on chemotherapy. However, drug resistance to several of the front-line drugs is rising. Furthermore, there is no official treatment for dourine. Therefore, there is an urgent need to develop antiparasitic agents with novel modes of action. Host defense peptides have recently gained attention as promising candidates. We have previously reported that one such peptide, the equine antimicrobial peptide eCATH1, is highly active against equine Gram-positive and Gram-negative bacteria, without cytotoxicity against mammalian cells at bacteriolytic concentrations. In the present study, we show that eCATH1 exhibits an in vitro 50% inhibitory concentration (IC 50 ) of 9.5 M against Trypanosoma brucei brucei, Trypanosoma evansi, and Trypanosoma equiperdum. Its trypanocidal mechanism involves plasma membrane permeabilization and mitochondrial alteration based on the following data: (i) eCATH1 induces the rapid influx of the vital dye SYTOX Green; (ii) it rapidly disrupts mitochondrial membrane potential, as revealed by immunofluorescence microscopy using the fluorescent dye rhodamine 123; (iii) it severely damages the membrane and intracellular structures of the parasites as early as 15 min after exposure at 9.5 M and 5 min after exposure at higher concentrations (19 M), as evidenced by scanning and transmission electron microscopy. We also demonstrate that administration of eCATH1 at a dose of 10 mg/kg to T. equiperdum-infected mice delays mortality. Taken together, our findings suggest that eCATH1 is an interesting template for the development of novel therapeutic agents in the treatment of trypanosome infections.

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Therapeutic Efficacy of Stable Analogues of Vasoactive Intestinal Peptide against Pathogens

Cited by 38 publications

References 58 publications

A Clinical Approach for the Use of VIP Axis in Inflammatory and Autoimmune Diseases

A Clinical Approach for the Use of VIP Axis in Inflammatory and Autoimmune Diseases

Dietary grape seed proanthocyanidins (GSPs) improve weaned intestinal microbiota and mucosal barrier using a piglet model

Killing of Trypanozoon Parasites by the Equine Cathelicidin eCATH1

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