Background Alzheimer’s disease (AD) is a neuropathology strongly associated with the activation of inflammatory pathways. Accordingly, inflammation resulting from obesity exacerbates learning and memory deficits in humans and in animal models of AD. Consequently, the long-term use of non-steroidal anti-inflammatory agents diminishes the risk for developing AD, but the side effects produced by these drugs limit their prophylactic use. Thus, plants natural products have become an excellent option for modern therapeutics. Malva parviflora is a plant well known for its anti-inflammatory properties. Methods The present study was aimed to determine the anti-inflammatory potential of M . parviflora leaf hydroalcoholic extract (MpHE) on AD pathology in lean and obese transgenic 5XFAD mice, a model of familial AD. The inflammatory response and Amyloid β (Aβ) plaque load in lean and obese 5XFAD mice untreated or treated with MpHE was evaluated by immunolocalization (Iba-1 and GFAP) and RT-qPCR (TNF) assays and thioflavin-S staining, respectively. Spatial learning memory was assessed by the Morris Water Maze behavioral test. Microglia phagocytosis capacity was analyzed in vivo and by ex vivo and in vitro assays, and its activation by morphological changes (phalloidin staining) and expression of CD86, Mgl1, and TREM-2 by RT-qPCR. The mechanism triggered by the MpHE was characterized in microglia primary cultures and ex vivo assays by immunoblot (PPAR-γ) and RT-qPCR (CD36) and in vivo by flow cytometry, using GW9662 (PPAR-γ inhibitor) and pioglitazone (PPAR-γ agonist). The presence of bioactive compounds in the MpHE was determined by HPLC. Results MpHE efficiently reduced astrogliosis, the presence of insoluble Aβ peptides in the hippocampus and spatial learning impairments, of both, lean, and obese 5XFAD mice. This was accompanied by microglial cells accumulation around Aβ plaques in the cortex and the hippocampus and decreased expression of M1 inflammatory markers. Consistent with the fact that the MpHE rescued microglia phagocytic capacity via a PPAR-γ/CD36-dependent mechanism, the MpHE possess oleanolic acid and scopoletin as active phytochemicals. Conclusions M . parviflora suppresses neuroinflammation by inhibiting microglia pro-inflammatory M1 phenotype and promoting microglia phagocytosis. Therefore, M . parviflora phytochemicals represent an alternative to prevent cognitive impairment associated with a metabolic disorder as well as an effective prophylactic candidate for AD progression. Electronic supplementary material The online version of this article (10.1186/s12974-019-1515-3) contains supplementary material, which is available to authorized users.

Alzheimer's disease (AD) is the most common form of senile dementia and is characterized by progressive cognitive impairment and neuronal degeneration. Microglial activation is an important pathologic hallmark of AD. During disease progression, microglial cells switch from an alternative or anti-inflammatory and neuroprotective profile (M2) to a classic or proinflammatory and neurotoxic profile (M1). Phenotypically, M1 microglia is characterized by the activation of inflammatory signaling pathways that cause increased expression of proinflammatory genes, including those coding for cytokines and chemokines. This microglia-mediated neuroinflammation contributes to neuronal cell death. Recent studies in microglial cells have shown that a group of plant-derived compounds, known as flavonoids, possess anti-inflammatory properties and therefore exert a neuroprotective effect through regulating microglia activation. Here, we discuss how flavonoids can promote the switch from an inflammatory M1 phenotype to an anti-inflammatory M2 phenotype in microglia and how this represents a valuable opportunity for the development of novel therapeutic strategies to blunt neuroinflammation and boost neuronal recovery in AD. We also review how

Inflammation plays a key role in carcinogenesis and metastasis. This process involves the inactivation of tumor suppressor molecules, yet the molecular mechanisms by which inflammation impairs tumor suppressors are not completely understood. In this study, we show that proinflammatory signals such as tumor necrosis factor (TNF) support lung cancer metastasis by reducing the levels of the tumor suppressor Merlin through regulation of miR-146a. Immunodeficient mice inoculated with A549 cells expressing high miR-146a levels and low Merlin protein levels exhibited reduced survival, which correlated with the number of metastatic nodes formed. Accordingly, restoring Merlin protein levels inhibited metastasis and increased survival of the mice. Consistent with these results, we found that elevated miR-146a expression levels correlated with low Merlin protein levels in human lung adenocarcinoma. Furthermore, human invasive and metastatic tumors showed higher TNF and miR-146a levels, but lower Merlin protein levels than noninvasive tumors. These findings indicate that upregulation of miR-146a by TNF in lung adenocarcinoma promotes Merlin protein inhibition and metastasis. Thus, we suggest that the ratio between miR-146a and Merlin protein levels could be a relevant molecular biomarker that can predict lung cancer progression and that the TNF/miR-146a/Merlin pathway is a promising new therapeutic target to inhibit lung adenocarcinoma progression.