Cyclodextrin-complexed Ocimum basilicum leaves essential oil increases fos protein expression in the central nervous system and produce an antihyperalgesic effect in animal models for fibromyalgia

O. basilicum leaves produce essential oils (LEO) rich in monoterpenes. The short half-life and water insolubility are limitations for LEO medical uses. β-Cyclodextrin (β-CD) has been employed to improve the pharmacological properties of LEO. We assessed the antihyperalgesic profile of LEO, isolated or complexed in β-CD (LEO/β-CD), on an animal model for fibromyalgia. Behavioral tests: mice were treated every day with either LEO/β-CD (25, 50 or 100 mg/kg, p.o.), LEO (25 mg/kg, p.o.), tramadol (TRM 4 mg/kg, i.p.) or vehicle (saline), and 60 min after treatment behavioral parameters were assessed. Therefore, mice were evaluated for mechanical hyperalgesia (von Frey), motor coordination (Rota-rod) and muscle strength (Grip Strength Metter) in a mice fibromyalgia model. After 27 days, we evaluated the central nervous system (CNS) pathways involved in the effect induced by experimental drugs through immunofluorescence protocol to Fos protein. The differential scanning analysis (DSC), thermogravimetry/derivate thermogravimetry (TG/DTG) and infrared absorption spectroscopy (FTIR) curves indicated that the products prepared were able to incorporate the LEO efficiently. Oral treatment with LEO or LEO-βCD, at all doses tested, produced a significant reduction of mechanical hyperalgesia and we were able to significantly increase Fos protein expression. Together, our results provide evidence that LEO, isolated or complexed with β-CD, produces analgesic effects on chronic non-inflammatory pain as fibromyalgia

Abarema cochliacarpos extract decreases the inflammatory process and skeletal muscle injury induced by bothrops leucurus venom

Snakebites are a public health problem, especially in tropical countries.However, treatment with antivenomhas limited effectiveness against venoms’ local effects. Here, we investigated the ability of Abarema cochliacarpos hydroethanolic extract (EAc) to protect mice against injection of Bothrops leucurus venom. Swiss mice received perimuscular venom injection and were subsequently treated orally with EAc in different doses. Treatment with EAc 100, 200, and 400mg/kg reduced the edema induced by B. leucurus in 1%, 13%, and 39%, respectively. Although lower doses showed no antihypernociceptive effect in the Von Frey test, the higher dose significantly reduced hyperalgesia induced by the venom. Antimyotoxic activity of EAc was also observed by microscopy assessment, with treated muscles presenting preserved structures, decreased edema, and inflammatory infiltrate as compared to untreated ones. Finally, on the rotarod test, the treated mice showed better motor function, once muscle fibers were preserved and there were less edema and pain. Treated mice could stand four times more time on the rotating rod than untreated ones. Our results have shown that EAc presented relevant activities against injection of B. leucurus venom in mice, suggesting that it can be considered as an adjuvant in the treatment of envenomation

Antioxidant activity and mechanisms of action of natural compounds isolated from lichens : a systematic review

Chronic diseases such as cancer, diabetes, neurodegenerative and cardiovascular diseases are characterized by an enhanced state of oxidative stress, which may result from the overproduction of reactive species and/or a decrease in antioxidant defenses. The search for new chemical entities with antioxidant profile is still thus an emerging field on ongoing interest. Due to the lack of reviews concerning the antioxidant activity of lichen-derived natural compounds, we performed a review of the antioxidant potential and mechanisms of action of natural compounds isolated from lichens. The search terms “lichens”, “antioxidants” and “antioxidant response elements” were used to retrieve articles in LILACS, PubMed and Web of Science published until February 2014. From a total of 319 articles surveyed, 32 met the established inclusion and exclusion criteria. It was observed that the most common isolated compound studied was usnic acid, cited in 14 out of the 32 articles. The most often described antioxidant assays for the study of in vitro antioxidant activity were mainly DPPH, LPO and SOD. The most suggested mechanisms of action were scavenging of reactive species, enzymatic activation and inhibition of iNOS. Thus, compounds isolated from lichens are possible candidates for the management of oxidative stress, and may be useful in the treatment of chronic diseases

Antioxidant activity and mechanisms of action of natural compounds isolated from lichens : a systematic review

Chronic diseases such as cancer, diabetes, neurodegenerative and cardiovascular diseases are characterized by an enhanced state of oxidative stress, which may result from the overproduction of reactive species and/or a decrease in antioxidant defenses. The search for new chemical entities with antioxidant profile is still thus an emerging field on ongoing interest. Due to the lack of reviews concerning the antioxidant activity of lichen-derived natural compounds, we performed a review of the antioxidant potential and mechanisms of action of natural compounds isolated from lichens. The search terms “lichens”, “antioxidants” and “antioxidant response elements” were used to retrieve articles in LILACS, PubMed and Web of Science published until February 2014. From a total of 319 articles surveyed, 32 met the established inclusion and exclusion criteria. It was observed that the most common isolated compound studied was usnic acid, cited in 14 out of the 32 articles. The most often described antioxidant assays for the study of in vitro antioxidant activity were mainly DPPH, LPO and SOD. The most suggested mechanisms of action were scavenging of reactive species, enzymatic activation and inhibition of iNOS. Thus, compounds isolated from lichens are possible candidates for the management of oxidative stress, and may be useful in the treatment of chronic diseases

Molecular modeling of BPP-BrachyNH₂ and human ACE and <i>in silico</i> docking studies.

<p>(A) Theoretical model of BPP-BrachyNH₂ showing the structure with lower energy system; (B) theoretical model of ACE showing the structure with lower energy system; (C) Docking between BPP-BrachyNH₂/ACE; (D) binary complex relationship with zoom in and detailed interactions; and (E) interactions between the substrate and the catalytic triad His³⁸³, His³⁸⁷ and Glu⁴¹¹, indicating a probable block of the catalytic activity.</p

Sequencing of the proline-rich peptides (PROs) from the skin secretion of <i>B</i>. <i>ephippium</i>.

<p>(A) Mass spectra of BPP-Brachy, [M+H]⁺ = 907.37 and (B) BPP-BrachyNH₂, [M+H]⁺ = 906.36 acquired in an UltraFlex III MALDI-TOF/TOF operating under LIFT™ mode for MS/MS experiments. The observed fragments allowed complete assignment of the major y and b ion series. The peptide sequence using one-letter code following the y and b series orientation is shown on the top part of the spectra.</p

The inhibitory effect of BPP-BrachyNH₂ and captopril on rat serum ACE activity.

<p>Residual enzymatic activities are plotted against the corresponding inhibitor concentrations. IC₅₀ values were calculated from nonlinear regression analysis of obtained data using GraphPad 5.0 software (GraphPad Prism, San Diego, CA).</p

Vasodilator effect of BPP-BrachyNH₂ and captopril (10⁻⁹–3 × 10⁻⁵ M) on rat thoracic aorta.

<p>Aortic rings were pre-contracted with phenylephrine (3 × 10⁻⁷ M) and then cumulatively incubated with BPP-BrachyNH₂ (A) or captopril (B). Effect of L-NAME (100 μM) on BPP-BrachyNH₂-induced vasodilator effect (C). Respective comparisons among E_max (D) values were plotted. The results were expressed as means ± SEM (n = 6). Non-paired Student’s t test. ^**<i>p</i> < 0.01 and ^***<i>p</i> < 0.001 versus endothelium-intact (E+) preparations.</p