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.
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.
Systemic arterial hypertension and heart failure are cardiovascular diseases that affect millions of individuals worldwide. They are characterized by a change in the autonomic nervous system balance, ...highlighted by an increase in sympathetic activity associated with a decrease in parasympathetic activity. Most therapeutic approaches seek to treat these diseases by medications that attenuate sympathetic activity. However, there is a growing number of studies demonstrating that the improvement of parasympathetic function, by means of pharmacological or electrical stimulation, can be an effective tool for the treatment of these cardiovascular diseases. Therefore, this review aims to describe the advances reported by experimental and clinical studies that addressed the potential of cholinergic stimulation to prevent autonomic and cardiovascular imbalance in hypertension and heart failure. Overall, the published data reviewed demonstrate that the use of central or peripheral acetylcholinesterase inhibitors is efficient to improve the autonomic imbalance and hemodynamic changes observed in heart failure and hypertension. Of note, the baroreflex and the vagus nerve activation have been shown to be safe and effective approaches to be used as an alternative treatment for these cardiovascular diseases. In conclusion, pharmacological and electrical stimulation of the parasympathetic nervous system has the potential to be used as a therapeutic tool for the treatment of hypertension and heart failure, deserving to be more explored in the clinical setting.
Anti-inflammatory molecules, such as rose oxide (RO), are likely to exert therapeutic effects in systemic arterial hypertension (SAH), a disease associated with abnormal immune responses. We aimed to ...investigate acute autonomic effects of RO on hemodynamic parameters of Wistar and spontaneously hypertensive rats (SHR).
Rats were anesthetized and femoral artery and veins were cannulated. Next day, blood pressure (BP) and heart rate (HR) were recorded. Acute effects of RO (1.25, 2.5, or 5.0 mg/kg; iv) on BP, HR, and variability of systolic arterial pressure (SAP) and pulse interval (PI) were assessed. The effects of RO were also investigated in SHR, which received atropine (2 mg/kg), propranolol (4 mg/kg), or hexamethonium (20 mg/kg) 15 min before receiving RO. Vasorelaxant effects of RO (10–10 to 10–4 M) on aortic rings of rats were also assessed.
In Wistar rats, none of the RO doses evoked significant changes in BP, HR, and variability of SAP and PI. On the other hand, in SHR, RO elicited reduction in mean arterial pressure (MAP), and prevented the increase in the low frequency power (LF) of the SAP spectra. Pretreatment with atropine or propranolol did not alter hypotension, but attenuated RO-induced bradycardia. Hexamethonium prevented RO-induced hypotension and bradycardia. RO exerted vasorelaxant effects on aortic rings with (Wistar and SHR) or without functional endothelium (SHR only).
Rose oxide, a monoterpene with anti-inflammatory properties, acts as an antihypertensive molecule due to its ability to acutely promote hypotension and bradycardia in spontaneously hypertensive rats.
Background and Aim
Simaba ferruginea
A.St.-Hil. Popularly known as “calunga,” is a typical Brazilian cerrado plant whose rhizomes are popular for treating diarrhea.
Aims
The aim of this study was to ...evaluate the spasmolytic activity and the antidiarrheal effect of the ethanolic extract obtained from
S. ferruginea
(Sf-EtOH).
Methods
Ileal segments (1–2 cm) from male Wistar rats were mounted in isolated organ baths and connected to a force transducer, and then to an amplifier which was connected to a computer (AVS Projetos/São Paulo-SP). After stabilization for 60 min, under tension (1 gf), two submaximal contractions were induced with KCl 40 mM or carbachol 10
−6
M on ileal segments. During the third tonic and sustained contraction, Sf-EtOH was added in cumulative concentrations to the organ bath. Incubations with L-NAME (10
−4
M), ODQ (10
−5
M), TEA
+
(5 or 1 mM), glibenclamide (10
−5
M), or apamine (100 nM) were prepared (
n
= 5), separately and used to verify the involvement of the nitric oxide synthase, guanylate cyclase, and potassium channels in the relaxing effect. The results were expressed as mean ± standard error of the mean and were statistically evaluated using one-way ANOVA followed by Bonferroni test, when necessary *
p
< 0.05.
Results
Sf-EtOH promotes relaxation on rat isolated ileum pre-contracted with CCh and KCl in a concentration-dependent manner. Sf-EtOH also inhibited ileum contractions against cumulative concentrations of carbachol (CCh), KCl, and CaCl
2
, shifting the curves to the right in a non-parallel manner with an
E
max
reduction. In the presence of potassium channel blockers, Sf-EtOH shifted the curves to the right with a reduction of
E
max
, suggesting the involvement of BK
Ca
, K
ATP
, and SK
Ca
in its spasmolytic effect. In the presence of L-NAME or ODQ, the relaxation curves were shifted to the right, suggesting the involvement of this pathway in Sf-EtOH spasmolytic effect.
Conclusions
Sf-EtOH acts in a concentration-dependent manner, involving the positive modulation of K
+
channels and NO pathway.
Mart. & Zucc. (Combretaceae) is a plant commonly found in the regions of the Brazilian cerrado, popularly used for the treatment of gastrointestinal disorders. There are no reports in the literature ...on the use of
for the treatment of the cardiovascular system conditions. Nevertheless, plants of the same genus, such as
(Roxb.) Wight & Arn and
Engler & Diels, present cardioprotective, hypotensive and vasodilatating effects. In light of this, the aim of the study was to investigate the effect of the ethanolic extract (Tf-EE) and of its aqueous (Tf-AQF), hexanic (Tf-HEXF) and hydroethanolic (Tf-HAF) partition fractions obtained from the stem bark of
Mart. & Zucc. The effects of the extract and partition fractions of
were evaluated on isometric tensions in the thoracic aorta rings of Wistar rats (250-300 g). Tf-EE, Tf-HEXF and Tf-HAF presented a concentration-dependent vasorelaxant effect, and Tf-AQF presented a vasorelaxant effect that was more potent in the presence of endothelium. The relaxation curves of the aorta promoted by the fraction investigated were attenuated in the presence of the following pharmacological tools: L-NAME, ODQ or PTIO. The vasorelaxant effect of the aorta promoted by Tf-AQF was attenuated in the presence of TEA and 4-AP. Tf-EE induced a concentration-dependent and endothelium-independent vasorelaxation. Tf-HAF and Tf-HEXF presented concentration-dependent and vascular-endothelium-independent vasorelaxation, but did not obtain 100% of relaxation. On the other hand, Tf-AQF presented concentration-dependent vasorelaxation that was more potent in aorta rings with vascular endothelium. The relaxant mechanism induced by the Tf-AQF involves the NO/sGC/cGMP pathway and channels Kv.
BPP-BrachyNH
2
is a proline-rich oligopeptide (PRO) firstly identified in skin secretion of the frog
Brachycephalus ephippium
, which possess in vitro inhibitory activity of angiotensin-I converting ...enzyme (ACE) and endothelium-dependent vasorelaxant activity. Considering its potential application in the treatment of cardiovascular diseases, the present work assessed the toxicological profile of the BPP-BrachyNH
2
. The in silico toxicity prediction was performed from the best model obtained through the optimization of the FASTA query peptide. This prediction study revealed that BPP-BrachyNH
2
induced high predicted LD
50
values for both humans and rats, and then is well-tolerated in the recommended range. The MTT assay was applied for the in vitro cytotoxic evaluation in murine macrophages. In this assay, a decrease of cell viability was not observed. The in vivo acute toxicological study was performed after the intraperitoneal administration of BPP-BrachyNH
2
at doses of 5 and 50 mg/kg. After intraperitoneal administration, no death, alterations in behavioral parameters or weight gain curve was observed, as well as none in the serum biochemical parameters, and gross pathological and histopathological analyses. These observations demonstrates an acceptable safety profile for BPP-BrachyNH
2
, leading towards further studies focused on investigation of pharmacological and therapeutical applications for this peptide.
: The monoterpene (−)‐borneol is present in essential oils of several medicinal plants. The aim of this study was to evaluate (−)‐borneol effects on rat thoracic aorta artery rings. The cumulative ...addition of (−)‐borneol (10−9–3 × 10−4 M) on a phenylephrine‐induced pre‐contraction (10−6 M) promoted a vasorelaxant effect in a concentration‐dependent manner and independent of vascular endothelium. A similar effect was obtained on KCl‐induced pre‐contractions (80 mM). (−)‐Borneol (10−5–3 × 10−4 M) inhibited contractions induced by cumulative addition of CaCl2 (10−6–3 × 10−2 M) in depolarizing medium without Ca2+ in a concentration‐dependent manner. On S‐(−) Bay K 8644‐induced pre‐contractions (10−7 M), (−)‐borneol did not induce significant changes compared with KCl‐induced pre‐contractions. In a Ca2+‐free medium, (−)‐borneol (10−5, 10−4 or 10−3 M) interfered in calcium mobilization from phenylephrine (10−6 M)‐ or caffeine (20 mM)‐sensitive intracellular stores. The involvement of K+ channels was evaluated by tetraethylammonium (3 mM), 4‐aminopyridine (1 mM) and glibenclamide (10−5 M) pre‐treatment, and (−)‐borneol‐induced vasorelaxation was markedly attenuated. Thus, this vasorelaxant effect can probably be attributed to calcium influx blockade through voltage‐operated calcium channels (CaVL), calcium mobilization from intracellular stores and potassium channels activation.
Many plants produce (−)‐linalool, a plant‐derived monoterpene alcohol, including members of the Lamiaceae (mints) and Lauraceae family (laurels, cinnamon, rosewood). The anti‐inflammatory and ...analgesic effects of (−)‐linalool have been widely suggested for various studies. Poor chemical stability and short half‐life restrain the clinical applications of some essential oil and monoterpenes, including (−)‐linalool. However, β‐cyclodextrin (β‐CD) has been used to increase solubility and stability of lipophilic compounds and also to improve the pharmacological effects. In this study, the antinociceptive effect of (−)‐linalool and (−)‐linalool/β‐CD was examined using the acetic acid writhing reflex, formalin and hotplate tests in rodents. (−)‐Linalool and (−)‐linalool/β‐CD demonstrated strong antinociceptive activity in all the chemical‐ and heat‐induced mice models (p < 0.01 or p < 0.001). These findings imply the involvement of both peripheral and central antinociceptive mechanisms. In peritonitis induced by carrageenan, isolated monoterpene or β‐CD complex also reduced total leucocyte migration and TNF‐α levels in peritoneal fluid. The inclusion complexes, (−)‐linalool/β‐CD, revealed that the antinociceptive effect was significantly (p < 0.01) improved when compared with (−)‐linalool alone. Such results were unlikely to be provoked by any motor abnormality. Together, our results suggest that β‐CD might represent an important tool for improvement of analgesic and anti‐inflammatory profiles of (−)‐linalool and other water‐insoluble compounds, such as lipophilic monoterpenes or essential oils.
We describe the antinociceptive and anti-inflammatory properties of citronellol (CT) in rodents. CT, a monoterpene alcohol, is a naturally occurring monoterpene compound prevalent in essential oils ...of various aromatic plant species, such as Cymbopogon citratus. In mice, when evaluated against acetic-acid-induced abdominal writhing, CT (25, 50 and 100 mg/kg, i.p.) reduced (P < 0.001) the amount of writhing compared to the control group. In the formalin test, CT also significantly inhibited both the early (neurogenic pain) and the late (inflammatory pain) phases of formalin-induced licking (P < 0.001). When assessed in a thermal model of pain, CT (100 mg/kg, i.p.) caused a significant increase (P < 0.05) in the latency response on the hot-plate test. Such results were unlikely to be caused by motor abnormality. The anti-inflammatory activity of CT was investigated through carrageenan-induced pleurisy in mice. Pretreatment with CT was able to inhibit both neutrophil infiltration and the increase in TNF-α level in the exudates from carrageenan-induced pleurisy. In in vitro experiments, CT (1 and 100 μg/ml) also decreased nitric oxide production by LPS-stimulated macrophage. Together, these results indicate that CT is effective as an analgesic compound in various pain models, with its action probably mediated by the inhibition of peripheral mediators as well as central inhibitory mechanisms that could be related to its strong antioxidant effect observed in vitro.
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