Inflammaging and Brain: Curcumin and Its Beneficial Potential as Regulator of Microglia Activation

Inflammaging is a term used to describe the tight relationship between low-grade chronic inflammation and aging that occurs during physiological aging in the absence of evident infection. This condition has been linked to a broad spectrum of age-related disorders in various organs including the brain. Inflammaging represents a highly significant risk factor for the development and progression of age-related conditions, including neurodegenerative diseases which are characterized by the progressive dysfunction and degeneration of neurons in the brain and peripheral nervous system. Curcumin is a widely studied polyphenol isolated from Curcuma longa with a variety of pharmacologic properties. It is well-known for its healing properties and has been extensively used in Asian medicine to treat a variety of illness conditions. The number of studies that suggest beneficial effects of curcumin on brain pathologies and age-related diseases is increasing. Curcumin is able to inhibit the formation of reactive-oxygen species and other pro-inflammatory mediators that are believed to play a pivotal role in many age-related diseases. Curcumin has been recently proposed as a potential useful remedy against neurodegenerative disorders and brain ageing. In light of this, our current review aims to discuss the potential positive effects of Curcumin on the possibility to control inflammaging emphasizing the possible modulation of inflammaging processes in neurodegenerative diseases

Beneficial Effects of Spirulina Consumption on Brain Health

Spirulina is a microscopic, filamentous cyanobacterium that grows in alkaline water bodies. It is extensively utilized as a nutraceutical food supplement all over the world due to its high levels of functional compounds, such as phycocyanins, phenols and polysaccharides, with anti-inflammatory, antioxidant, immunomodulating properties both in vivo and in vitro. Several scientific publications have suggested its positive effects in various pathologies such as cardiovascular diseases, hypercholesterolemia, hyperglycemia, obesity, hypertension, tumors and inflammatory diseases. Lately, different studies have demonstrated the neuroprotective role of Spirulina on the development of the neural system, senility and a number of pathological conditions, including neurological and neurodegenerative diseases. This review focuses on the role of Spirulina in the brain, highlighting how it exerts its beneficial anti-inflammatory and antioxidant effects, acting on glial cell activation, and in the prevention and/or progression of neurodegenerative diseases, in particular Parkinson's disease, Alzheimer's disease and Multiple Sclerosis; due to these properties, Spirulina could be considered a potential natural drug

Evidence for endogenous retroviruses in human chemokine receptor gene introns: possible evolutionary inferences and biological roles

The human chemokine receptor (CKR) genes CCR2, CCR6, CCR7, CCR9, CCR10, CXCR4, and CXCR5 harbor one or two introns. CCR7, CCR9, CCR10, and CXCR5 introns, (but not CCR2, CCR6, and CXCR4 introns) encompass retrovirus-like inserts with the characteristics of SINEs (short interspersed nuclear elements) up to 300 nucleotides (nt) long. Other characteristic elements of the retroviral genome, such as long terminal repeats and gag, pol, and env genes, are lacking. The inserts likely derived from one (or more) of the following retroviruses: XA34 (NCBI GenBank Nucleotides, U29659), HERV-P-T47D (AF087913), ERV FTD (U27241), HERV-K (Y17832), HML6p (U86698), HERV-H/env60 (AJ289710), XA38 (U37066). Virus-like inserts are remarkably homogeneous in all CKR introns, with nt identities of about 80%. Percentages of nt identities between the CKR inserts and the corresponding viral sequences are also about 80%. With reference to the CKR sequence, the viral sequence aligns in some instances Plus/Plus (XA34, HML6p, HERV-H/env60, and XA38) and in other instances Plus/Minus (HERV-P-T47D, ERV FTD, and HERV-K). Some aspects of the evolution of retroviruses and CKRs as well as hypotheses on the biological significance of the SINE inserts are discussed

Expression of UDP-glucuronosyltransferase 1A6 isoform in Caco-2 cells stimulated with lipopolysaccharide

Glucuronidation is an important metabolic process of detoxification in all vertebrates. The reaction is catalyzed by a multigene family of UDP-glucuronosyltransferases (UGTs) able to convert many xenobiotics and endobiotics (hydrophobic substances) to inactive, water-soluble glucuronides. The UGTs play a protective role, facilitating the elimination of potentially toxic metabolites via urine, bile and feces; therefore, impairment of UGTs may have important toxicological consequences. The regulation of UGTs during bacterial infection or inflammation is not well described. In this study, we investigated the in vitro effect of lipopolysaccharide (LPS) on the expression of the UGT1A6 isoform in human colon carcinoma Caco-2 cells. Results demonstrated a significant down-regulation of UGT1A6 expression, both in terms of mRNA and protein levels, and a reduced UGT activity after LPS exposure of cell cultures, suggesting a role for endotoxins on UGT regulation mechanisms

Viral sequence integration into introns of chemokine receptor genes

Viral DNA sequences are able to integrate into the non-coding DNA sections of the genome of human cells which have been infected, either spontaneously or experimentally. We have made a data-base search for integration events of non-endogenous viruses into the introns of chemokine receptor sequences. A BLAST search of all viral DNA sequences, using the intronic sequences as "Query," returned several significant alignments. However, due to the high reiteration rate of the non-coding sequences in the human genome, it became necessary to re-examine the individual alignments to verify whether the virus-flanking intronic sequence was really located in a chemokine receptor intron. We found only one unquestionable event of viral insertion of a section of a long terminal repeat of the murine leukemia virus within the first intron of the CC chemokine receptor 7 gene. Possible biological effects of such an insertion are discussed. Further experimental or clinical research could demonstrate the occurrence of other intronic viral insertions in human chemokine receptor genes

IL-10 plays a pivotal role in anti-inflammatory effects of resveratrol in activated microglia cells

The development of agents that can modulate microglial activation has been suggested as one potential strategy for the treatment or prevention of neurodegenerative diseases. Among these agents, resveratrol, with its anti-inflammatory action, has been described to have neuroprotective effects. In this paper we demonstrate that in LPS-stimulated microglia resveratrol pretreatment reduced, in a dose-dependent manner, pro-inflammatory cytokines IL-1β, TNF-α and IL-6 mRNA expression and increased the release of anti-inflammatory interleukin (IL)-10. Moreover, resveratrol pretreatment up-regulated the phosphorylated forms of JAK1 and STAT3, as well as suppressor of cytokine signaling (SOCS)3 protein expression in LPS activated cells, demonstrating that the JAK-STAT signaling pathway is involved in the anti-inflammatory effect exerted by resveratrol. By supplementing the cultures with an IL-10 neutralizing antibody (IL-10NA) we obtained the opposite effect. Taken together, these data allow us to conclude that the LPS-induced pro-inflammatory response in microglial cells can be markedly reduced by resveratrol, through IL-10 dependent up-regulation of SOCS3, requiring the JAK-STAT signaling pathway

Canine leishmaniasis in Southern Italy: a role for nitric oxide released from activated macrophages in asymptomatic infection?

<p>Abstract</p> <p>Background</p> <p>Human and canine leishmaniasis (CanL) by <it>Leishmania infantum </it>is endemic in Italy, with a high percentage of infected asymptomatic animals. However, the immune response mechanisms underlying the clinical presentation of CanL have not been fully investigated. Among leishmanicidal molecules produced by activated macrophages, nitric oxide (NO) produced by an inducible NO synthase seems to play an important protective role, but no conclusive data are available. Therefore, NO released by cultured macrophages from dogs with natural <it>Leishmania </it>infection living in an endemic area for CanL was evaluated.</p> <p>Methods</p> <p>On the basis of one year's clinical and laboratory follow-up, 22 dogs infected by <it>Leishmania infantum </it>were identified and grouped as: asymptomatic dogs (n = 13) and dogs with symptoms of leishmaniasis (n = 9). Each animal was bled twice at 4-month intervals and macrophage and lymphocyte cultures were obtained from peripheral blood mononuclear cells. Supernatants of <it>L. infantum</it>-infected macrophage cultures, with or without addition of autologous lymphocytes, were assayed for NO production by Griess reaction for nitrites.</p> <p>Results</p> <p>In the first months of the infection the levels of NO in supernatants of <it>Leishmania</it>-infected macrophages were higher in symptomatic than in asymptomatic dogs, but they were significantly increased in the latter group eight months after the diagnosis of infection. Furthermore, NO release significantly decreased in the presence of autologous lymphocytes in both groups of animals.</p> <p>Conclusion</p> <p>These results suggest that NO may be involved in the long-term protection of dogs against natural <it>Leishmania </it>infection and in the clinical presentation of canine leishmaniasis in the Mediterranean area.</p