O papel da melatonina na redução das citocinas IL-6 e IL-17 na menopausa

A menopausa é um processo biológico que ocorre em mulheres, em que os ovários cessam seu funcionamento pela falta de óvulos. Esse estágio da vida pode ocorrer dos 35 até 60 anos, podendo trazer sintomas desconfortáveis e doenças, piorando a qualidade de vida da mulher. O cessar da ovulação tem como consequência a redução da produção do estradiol que causa alteração no sistema imunológico predispondo a doenças infecciosas e inflamatórias. Tal predisposição pode aumentar os níveis de os mediadores inflamatórios IL-6 e IL-17 no organismo feminino. A melatonina é um hormônio produzido pela glândula pineal durante o período noturno, sendo depurada na presença de luz. Este hormônio regula o ciclo circadiano e é imunomodulador. Essa imunomodulação da melatonina atua na sintetização e inibição de alguns mediadores inflamatórios. Este trabalho tem como objetivo identificar se o tratamento de melatonina pode reduzir a quantidade de mediadores inflamatórios em mulheres na menopausa. Esta análise foi realizada por meio de uma revisão com artigos pesquisados nas bases de dados Pubmed, Scielo, Sciencedirect e RBAC pelas palavras-chave: melatonin, menopause, inflammatory mediator, inflammatory modulation, publicado nos últimos 15 anos. A partir das análises dos artigos foi identificado que a melatonina influencia na redução dos mediadores inflamatórios, podendo auxiliar na melhora da qualidade de vida das mulheres que estão ou que vão entrar na menopausa. Porém, é necessário a busca de protocolos de uso de melatonina, com previsão de doses de uso e verificação dos efeitos no organismo.

The extract of Acanthopanacis Cortex relieves the depression-like behavior and modulates IL-17 signaling in chronic mild stress-induced depressive mice

Background: Acanthopanacis Cortex (AC) is a valuable Chinese herbal medicine in Eleutherococcus Maxim., which has the effects of immune inflammatory modulation, anti-stress, anti-fatigue, sedation and analgesia. The functions of herbs from Eleutherococcus Maxim. involve neuroactivity, anti-fatigue, anti-stress and immune inflammatory modulation, and the peripheral functions of which are consistent with AC. However, the central nervous system function of AC has not been clearly illustrated. Since immune inflammatory modulation plays a critical role in the treatment of depression. In this study, we investigated the effect of AC against depression through immune inflammatory modulation.Methods: Chronic mild stress (CMS)-induced depressive mice were used to evaluate the effect of AC against depression. Behavior study and detection of neurotransmitters, neurotrophic factors and pro-inflammatory cytokines were carried out in the study. Interleukin-17 (IL-17) signaling cascade was involved to further study the underlying mechanism of AC against depression.Results: AC had a beneficial effect on CMS-induced depressive mice, including improvement in depressive behavior and modulation of the levels of neurotransmitters, neurotrophic factors and pro-inflammatory cytokines. Moreover, AC was able to suppress IL-17-midiated signaling cascade and thereby alleviating neuroinflammation and depression.Conclusions: Our results revealed that AC showed great effects on anti-depression through immune inflammatory modulation. These findings provide an insight into anti-depression therapy, which will be useful for the development of clinical application of AC.

Exosome and Melatonin Additively Attenuates Inflammation by Transferring miR-34a, miR-124, and miR-135b

The positive effects of mesenchymal stem cells (MSCs) are primarily activated through molecular secretions known as paracrine activity, which regulates the function of various cell types including immune cells. Accumulating evidence shows that exosomes of soluble factors released from MSCs are potential alternative agents for stem cell-based therapy, although the exact underlying mechanism has not been elucidated. The purpose of this study was to evaluate the potential effects of exosomes produced by adipose-derived MSCs and to examine the changes in anti-inflammatory genes in concurrence with the polarization of M2 macrophages in cellular models ex vivo. Isolated exosomes were used to investigate the inflammatory modulation in pro-inflammatory cytokine-treated fibroblasts and THP-1 cells. The anti-inflammatory mRNA expression associated with M2 macrophages was significantly upregulated after exosome treatment in an interferon gamma and tumor necrosis factor alpha-treated inflammatory environment. Furthermore, melatonin-stimulated exosomes exerted superior anti-inflammatory modulation via exosomal miRNAs miR-34a, miR-124, and miR-135b, compared with exosomes. Our results indicate that melatonin-stimulated exosomes originating from adipose-derived MSCs are safe and efficient tools for regenerative medicine to treat inflammatory diseases.