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.
Valeriana edulis ssp. procera, commonly known as "valeriana mexicana", is widely used in Mexican traditional medicine for the treatment of insomnia and anxiety. To evaluate the hypnotic effect and safety of 450 mg of Valeriana edulis standardized hydroalcoholic extract in patients with insomnia, a double-blind, cross-over, controlled study was carried out. Valeriana officinalis extract, at the same doses, was used as a positive control. In a sleep laboratory, polysomnographic (PSG) recordings were performed for analyzing the quantity and architecture of sleep as well as evaluating morning sleepiness, memory quotient, and side effects. The experimental procedures were conducted on four consecutive nights of 8 h each. Twenty patients were admitted. Based on the PSG results, V. edulis reduced the number of awaking episodes while both treatments increased the rapid eye movement (REM) sleep; this last parameter was better improved by V. officinalis extract. Other PSG data did not achieve outstanding statistical differences, but the clinical tendency with both treatments was to increase the sleep efficiency index. These Valeriana extracts produced beneficial effects on sleep architecture because they diminished the time of stages 1 and 2 in non-REM sleep while they increased delta sleep. Validated clinical tests showed that both species reduced notoriously the morning sleepiness, that was further improved by V. officinalis extract, and did not affect anterograde memory. In only three cases were slight side effects observed, one due to the experimental extract. Chemical analysis of the hydroalcoholic extract of V. edulis indicated that this extract contains 0.26 % of dihydroisovaltrate as the main valepotriate, and that it does not contain valerenic acid. In general, the results support the hypnotic effect and safety of acute treatment of Valeriana edulis and Valeriana officinalis on patients suffering insomnia.
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