Alcoholic monoterpenes found in essential oil of aromatic spices reduce allergic inflammation by the modulation of inflammatory cytokines

<p>Allergic inflammation is a response of the body against pathogens by cytokine release and leucocyte recruitment. Recently, there was an increase in morbimortality associated with allergic inflammation, especially asthma. The treatment has many adverse effects, requiring the search for new therapies. Monoterpenes are natural products with anti-inflammatory activity demonstrated in several studies and can be an option to inflammation management. Thus, we investigated the effects of citronellol, α-terpineol and carvacrol on allergic inflammation. The model of asthma was established by OVA induction in male Swiss mice. The monoterpenes were administered (25, 50 or 100 mg/kg, i.p.) 1 h before induction. After 24hs, the animals were sacrificed to leucocytes and TNF-α quantification. Monoterpenes significantly decrease leucocyte migration and TNF-α levels, possibly by modulation of COX, PGE₂ and H1 receptor, as demonstrated by molecular docking. These findings indicate that alcoholic monoterpenes can be an alternative for treatment of allergic inflammation and asthma.</p

Toxicological evaluation <i>in silico</i> and <i>in vivo</i> of secondary metabolites of <i>Cissampelos sympodialis</i> in <i>Mus musculus</i> mice following inhalation

<p>The ethanolic extract of the leaves of <i>Cissampelos sympodialis</i> showed great pharmacological potential, with inflammatory and immunomodulatory activities, however, it showed some toxicological effects. Therefore, this study aims to verify the toxicological potential of alkaloids of the genus <i>Cissampelos</i> through <i>in silico</i> methodologies, to develop a method in LC-MS/MS verifying the presence of alkaloids in the infusion and to evaluate the toxicity of the infusion of the leaves of <i>C. sympodialis</i> when inhaled by Swiss mice. Results <i>in silico</i> showed that alkaloid 93 presented high toxicological potential along with the products of its metabolism. LC-MS/MS results showed that the infusion of the leaves of this plant contained the alkaloids warifteine and methylwarifteine. Finally, the <i>in vivo</i> toxicological analysis of the <i>C. sympodialis</i> infusion showed results, both in biochemistry, organ weights and histological analysis, that the infusion of <i>C. sympodialis</i> leaves presents a low toxicity.</p

Morphological changes in <i>D. rerio</i> during the 48 hours of exposure to piplartine.

<p><b>A</b>) Leakage of the ocular pigment caused by 1.8 ppm piplartine, <b>B</b>) tissue alterations on the head and mouth caused by 1.6 µg/ml piplartine, <b>C</b>) exophthalmia and hemorrhage caused by 1.4 µg/ml piplartine and D) control group.</p

Mortality of <i>B. glabrata</i> adults exposed to methanolic extracts of different organs of <i>Piper tuberculatum</i>.

<p>n = 30 adult snails.</p><p>Values were obtained at the end of the 7^th day of observation.</p

Toxicity of piplartine and niclosamide to the freshwater microcrustacean <i>D. similis</i> and the fish <i>D. rerio</i>.

<p>Data are presented as EC₅₀ or LC₅₀ (µg/ml) with the respective 95% confidence limits in brackets.</p><p>Toxicity classification: Cat. 1 - acute toxicity ≤1.00 µg/ml; Cat. 2 - acute toxicity >1.00 but ≤10.0 µg/ml; Cat. 3 - acute toxicity >10.0 but <100 µg/ml <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0002251#pntd.0002251-Abiquim1" target="_blank">[28]</a>.</p

Calculated (squares) and predicted (circles) PLS data.

<p>These data were generated from ESIMS data, versus measured and autoscaled LC₅₀ values of <i>P. tuberculatum</i> extracts for <i>B. glabrata</i>.</p

<i>B. glabrata</i> embryos exposed to piplartine at the blastula stage.

<p><b>A</b>) Immediately following exposure to 1.2 µg/ml piplartine, <b>B</b>) during the 7 day observation period after exposure to 1.0 µg/ml piplartine (1- dead, 2 - normal, 3 – malformed).</p

LC₅₀ and LC₉₀ for <i>B. glabrata</i> embryos and adults exposed to piplartine.

<p>[ ] 95% confidence interval.</p><p>nc – not calculated.</p

Mortality of <i>B. glabrata</i> adults and embryos exposed to amides (20 µg/ml).

<p>n = 10 snails for the adult stage; total embryo number for the other stages.</p><p>0^* = negative control (1% DMSO).</p><p>Values were obtained at the end of the 7^th day of observation.</p