Background: CCL-11 (eotaxin) is a chemokine with an important role in allergic conditions. Recent evidence indicates that CCL-11 plays a role in brain disorders as well. This paper reviews the associations between CCL-11 and aging, neurodegenerative, neuroinflammatory and neuropsychiatric disorders. Methods: Electronic databases were searched for original articles examining CCL-11 in neuropsychiatric disorders. Results: CCL-11 is rapidly transported from the blood to the brain through the blood-brain barrier. Age-related increases in CCL-11 are associated with cognitive impairments in executive functions and episodic and semantic memory, and therefore, this chemokine has been described as an “Endogenous Cognition Deteriorating Chemokine” (ECDC) or “Accelerated Brain-Aging Chemokine” (ABAC). In schizophrenia, increased CCL-11 is not only associated with impairments in cognitive functions, but also with key symptoms including formal thought disorders. Some patients with mood disorders and premenstrual syndrome show increased plasma CCL-11 levels. In diseases of old age, CCL-11 is associated with lowered neurogenesis and neurodegenerative processes, and as a consequence, increased CCL-11 increases risk towards Alzheimer’s disease. Polymorphisms in the CCL-11 gene are associated with stroke. Increased CCL-11 also plays a role in neuroinflammatory disease including multiple sclerosis. In animal models, neutralization of CCL-11 may protect against nigrostriatal neurodegeneration. Increased production of CCL-11 may be attenuated by glucocorticoids, minocycline, resveratrol and anti-CCL11 antibodies. Conclusions: Increased CCL-11 production during inflammatory conditions may play a role in human disease including age-related cognitive decline, schizophrenia, mood disorders and neurodegenerative disorders. Increased CCL-11 production is a new drug target in the treatment and prevention of those disorders.

The aim of this study was to evaluate the effects of fucoidan isolated from C. crinita on histamine-induced paw inflammation in rats, and on the serum levels of TNF-α, IL-1β, IL-6, and IL-10 in rats during systemic inflammation response. The levels of TNF-α in a model of acute peritonitis in rats were also investigated. The isolated crude fucoidan was identified as a sulfated xylogalactofucan with high, medium, and low molecular weight fractions and a content of fucose of 39.74%, xylose of 20.75%, and galactose of 15.51%. Fucoidan from C. crinita showed better anti-inflammatory effects in the rat paw edema model, and this effect was present during all stages of the experiment. When compared to controls, a commercial fucoidan from F. vesiculosus, the results also displayed anti-inflammatory activity on the 60th, 90th, and 120th minute of the experiment. A significant decrease in serum levels of IL-1β in rats treated with both doses of C. crinita fucoidan was observed in comparison to controls, whereas TNF-α concentrations were reduced only in the group treated with fucoidan from C. crinita at the dose of 25 mg/kg bw. In the model of carrageenan-induced peritonitis, we observed a tendency of decrease in the levels of the pro-inflammatory cytokine TNF-α in peritoneal fluid after a single dose of C. crinita fucoidan, but this did not reach the statistical significance margin. Single doses of C. crinita fucoidan did not alter serum levels of the anti-inflammatory cytokine IL-10 in animals with lipopolysaccharide-induced systemic inflammation.

Alginates are anionic polysaccharides present in the cell walls of brown seaweeds. Various biological activities of alginate and its derivatives have been described. In this study, we assessed the potential of alginate obtained from Ericaria crinita (formerly Cystoseira crinita) to scavenge free radicals and function as a ferric ion reductor. The anti-inflammatory effect on the serum levels of TNF-α, IL-1β, IL-6, and IL-10 of rats with LPS-induced systemic inflammation after 14 days of treatment was also examined. Ericaria crinita alginate showed antioxidant activities of IC₅₀ = 505 µg/mL (DPPH) and OD₇₀₀ > 2 (ferric reducing power). A significant decrease in serum levels of IL-1β was observed only in animals treated with the polysaccharide at a dose of 100 mg/kg bw. Both doses of E. crinita alginate (25 and 100 mg/kg bw) significantly reduced the serum concentrations of pro-inflammatory cytokines TNF-α and IL-6, but no statistical significance was observed in the levels of the anti-inflammatory cytokine IL-10. Our findings show the potential of E. crinita alginate to act as an antioxidant and anti-inflammatory agent. It is likely that the exhibited antioxidant ability of the polysaccharide contributes to its antiphlogistic effects. More in-depth studies are needed to fully understand the specific mechanisms and the molecular pathways involved in these activities.

The aim of this study was to identify the chemical composition and sequential structure of alginate isolated from C. crinita harvested in the Bulgarian Black Sea, as well as its effects in histamine-induced paw inflammation in rats. The serum levels of TNF-α, IL-1β, IL-6, and IL-10 in rats with systemic inflammation, and the levels of TNF-α in a model of acute peritonitis in rats were also investigated. The structural characterization of the polysaccharide was obtained by FTIR, SEC-MALS, and ¹H NMR. The extracted alginate had an M/G ratio of 1.018, a molecular weight of 7.31 × 10⁴ g/mol, and a polydispersity index of 1.38. C. crinita alginate in doses of 25 and 100 mg/kg showed well-defined anti-inflammatory activity in the model of paw edema. A significant decrease in serum levels of IL-1β was observed only in animals treated with C. crinita alginate in a dose of 25 mg/kg bw. The concentrations of TNF-α and IL-6 in serum were significantly reduced in rats treated with both doses of the polysaccharide, but no statistical significance was observed in the levels of the anti-inflammatory cytokine IL-10. A single dose of alginate did not significantly alter the levels of the pro-inflammatory cytokine TNF-α in the peritoneal fluid of rats with a model of peritonitis.

Fucoidans are sulfated polysaccharides detected mainly in the cell walls of brown seaweeds. Here, we examined the effects of single doses of fucoidan derived from Ericaria crinita (formerly Cystoseira crinita) on carrageenan-induced paw inflammation in rats. The serum levels of TNF-α, IL-1β, IL-6, and IL-10 of rats with LPS-induced systemic inflammation after 14 days of treatment were also evaluated. Subchronic treatment with fucoidan from E. crinita attenuated the inflammation during the late phase of the degraded carrageenan-induced paw edema (3rd to 5th hour after carrageenan injection) with peak activity at the 3rd hour after the application. Both doses of fucoidan from E. crinita (25 and 50 mg/kg bw) significantly decreased the levels of all tested pro-inflammatory cytokines (IL-1β, TNF-α, and IL-6) in the serum of rats with a model of system inflammation but had no effect on the anti-inflammatory cytokine IL-10. The results showed that the repeated application of fucoidan has a more prominent effect on the levels of some pro-inflammatory cytokines in serum in comparison to a single dose of the sulfated polysaccharide. This reveals the potential of E. crinita fucoidan as an anti-inflammatory agent. Furthermore, E. crinita fucoidan exhibited in vitro antioxidant capacity, determined by 2,2-diphenyl-1-picryl-hydrazyl radical scavenging and ferric reducing antioxidant power assays as follows: IC₅₀ = 412 µg/mL and 118.72 μM Trolox equivalent/g, respectively.