Chronic inflammation is linked with the generation and progression of various diseases such as cancer, diabetes and atherosclerosis, and anti-inflammatory drugs therefore have the potential to assist in the treatment of these conditions. Carica papaya is a tropical plant that is traditionally used in the treatment of various ailments including inflammatory conditions. A literature search was conducted by using the keywords "papaya", "anti-inflammatory and inflammation" and "immunomodulation and immune" along with cross-referencing. Both in vitro and in vivo investigation studies were included. This is a review of all studies published since 2000 on the anti-inflammatory activity of papaya extracts and their effects on various immune-inflammatory mediators. Studies on the anti-inflammatory activities of recognized phytochemicals present in papaya are also included. Although in vitro and in vivo studies have shown that papaya extracts and papaya-associated phytochemicals possess anti-inflammatory and immunomodulatory properties, clinical studies are lacking.

https://www.tandfonline.com/doi/pdf/10.3109/1547691X.2016.1149528

Anti-inflammatory and immunomodulatory properties of Carica papaya.

Immunomodulatory components of helminths offer great promise as an entirely new class of biologics for the treatment of inflammatory diseases. Here, we discuss the emerging themes in helminth-driven immunomodulation in the context of therapeutic drug discovery. We broadly define the approaches that are currently applied by researchers to identify these helminth molecules, highlighting key areas of potential exploitation that have been mostly neglected thus far, notably small molecules. Finally, we propose that the investigation of immunomodulatory compounds will enable the translation of current and future research efforts into potential treatments for autoimmune and allergic diseases, while at the same time yielding new insights into the molecular interface of host-parasite biology.

Identifying the immunomodulatory components of helminths.

Increased tumor necrosis factor (TNF)-alpha production by postburn splenic macrophages is well documented. Splenic macrophages are a heterogeneous population, and the effect of thermal injury on these subpopulations has not been documented. We examined the effects of scald injury on myeloid cells with the phenotype of red pulp, white pulp, and marginal zone monocyte/macrophages. We found that thermal injury greatly increased the number of splenocytes with the phenotype of white pulp monocytes. These cells were the major producers of TNF-alpha in the postburn spleen. Cells with the red pulp macrophage phenotype had an increased ability to make TNF-alpha after burn injury, but had only half the capacity to make TNF-alpha as did postburn monocytes. The postburn changes in TNF-alpha production correlated with an increased in vivo susceptibility to endotoxin. The increase in monocytes in the spleen from postburn days 1 to 10 correlated with an increasing ability of splenocytes to produce granulocyte colony-stimulating factor, monocyte chemoattractant protein 1, macrophage inflammatory protein 2, and macrophage inflammatory protein 1-alpha. These data suggest that the monocyte is a major source of inflammatory cytokines in the postburn spleen.

Postburn monocytes are the major producers of TNF-alpha in the heterogeneous splenic macrophage population.

Systemic inflammation enhances the risk and progression of Alzheimer’s disease (AD). Lipopolysaccharide (LPS), a potent pro-inflammatory endotoxin produced by the gut, is found in excess levels in AD where it associates with neurological hallmarks of pathology. Sex differences in susceptibility to inflammation and AD progression have been reported, but how this impacts on LPS responses remains under investigated. We previously reported in an APP/PS1 model of AD that systemic LPS administration rapidly altered hippocampal metabolism in males. Here, we used untargeted metabolomics to comprehensively identify hippocampal metabolic processes occurring at onset of systemic inflammation with LPS (100 µg/kg, i.v.) in APP/PS1 mice, at an early pathological stage, and investigated the sexual dimorphism in this response. Four hours after LPS administration, pathways regulating energy metabolism, immune and oxidative stress responses were simultaneously recruited in the hippocampi of 4.5-month-old mice with a more protective response in females despite their pro-inflammatory and pro-oxidant metabolic signature in the absence of immune stimulation. LPS induced comparable behavioural sickness responses in male and female wild-type and APP/PS1 mice and comparable activation of both the serotonin and nicotinamide pathways of tryptophan metabolism in their hippocampi. Elevations in N-methyl-2-pyridone-5-carboxamide, a major toxic metabolite of nicotinamide, correlated with behavioural sickness regardless of sex, as well as with the LPS-induced hypothermia seen in males. Males also exhibited a pro-inflammatory-like downregulation of pyruvate metabolism, exacerbated in APP/PS1 males, and methionine metabolism whereas females showed a greater cytokine response and anti-inflammatory-like downregulation of hippocampal methylglyoxal and methionine metabolism. Metabolic changes were not associated with morphological markers of immune cell activation suggesting that they constitute an early event in the development of LPS-induced neuroinflammation and AD exacerbation. These data suggest that the female hippocampus is more tolerant to acute systemic inflammation.

Sex-specific hippocampal metabolic signatures at the onset of systemic inflammation with lipopolysaccharide in the APPswe/PS1dE9 mouse model of Alzheimer's disease.

Canine babesiosis is a tick-borne disease with a worldwide distribution, caused by the haemoprotozoan parasites of the genus Babesia. One of the most prevalent complication is acute kidney injury, and an early diagnosis of altered kidney function remains a challenge for veterinary practice. The aim of this study was to assess the urine metabolic profile from dogs with babesiosis and different degree of kidney function using untargeted and targeted MS-based metabolomics approaches. In this study, 22 dogs naturally infected with Babesia canis and 12 healthy dogs were included. Untargeted metabolomics approach identified 601 features with a differential abundance between the healthy group and groups of dogs with babesiosis and different level of kidney function, with 27 of them identified as a match to known standards; while targeted approach identified 17 metabolites with significantly different concentrations between the groups. A pattern of significantly altered metabolites referring to the inflammatory host response, oxidative stress, and energy metabolism modulation in babesiosis was presented. Our findings have demonstrated that kidney dysfunction accompanying canine babesiosis was associated with changes in amino acid metabolism, energy metabolism, fatty acid metabolism, and biochemical pathways such as urea cycle and ammonia detoxication. These findings will enable the inclusion of urinary markers for the detection and monitoring of renal damage in babesiosis, as well as in other similar diseases.

/pdf/combined-untargeted-and-targeted-metabolomics-approaches-3s5an8t3x8.pdf

Combined Untargeted and Targeted Metabolomics Approaches Reveal Urinary Changes of Amino Acids and Energy Metabolism in Canine Babesiosis With Different Levels of Kidney Function.

M. Gallowitsch Puerta

Papers

Choline suppresses inflammatory responses

Galantamine improves survival in lethal endotoxemia