Asthma is a chronic inflammatory disease that targeting lower airways, being characterized by bronchial smooth muscle hyper responsiveness and mucus hypersecretion. Asthma is considered the most ...common respiratory disease in the world, affecting approximately 235 million individuals. The main therapy sometimes fails to establish clinical improvement in patients, which leads to a constant search for new alternatives. Camphor is a transparent solid monoterpene with a strong aroma, which due to its high lipophilicity is insoluble in water. Nanostructured carrier systems have shown promise as a delivery system for lipophilic compounds such as monoterpenes. Therefore, the objective of this work was to evaluate the relaxant effect of nanoemulsified camphor (NEC), as well as the mechanism of action of that monoterpene, in isolated rat trachea. The results obtained demonstrated that NEC promote relaxation of the isolated rat trachea when smooth muscle contraction was induced by both carbachol (CCh) and KCl, presenting a pCE50 of 2.25 ± 0.27 and 3.30 ± 0.07, respectively. In the presence of dexamethasone (DEXA), tetraethylammonium (TEA), glibenclamide (GLIB), 1H-1,2,4-oxadiazole-4,3,-a-quinoxaline-1-one (ODQ) and ruthenium red (RR) there was a significant difference in at least one of the evaluated pharmacological parameters, such as concentration-response curves shape, Emax or pCE50.
As conclusion, NEC may be involved with β-adrenergic receptors, channels for K+ sensitive to ATP (KATP) or Channels for K+ opened by Ca2+ (KCa), increase in prostanoids and with receptor channel with transient potential (TRPv). In conclusion, β-adrenergic receptors, prostanoids, nitric oxide (NO), ATP-sensitive K+ channels (KATP), Ca2+-opened K+ channels (KCa), and transient receptor potential cation channel subfamily V (TRPV) are involved in the relaxing effect of NEC.
In addition, the mechanism of action of NEC may be involved with the signal transduction pathway Nitric Oxide/soluble guanylyl cyclase/cGMP/cGMP-activated protein kinase. NEC, therefore, demonstrates spasmolytic activity when presenting tracheal relaxation compared to CCh and KCl contracturants.
•Nanostructured carrier systems improve the water solubility for that monoterpenes.•Nanoemulsion loaded with camphor (NEC) allows the evaluation mechanism of action of insoluble compounds in in vitro studies.•Camphor has a relaxing effect on rat trachea.•The mechanism of action of camphor involves multiple cell signaling pathways and remains unknown.
Pain and inflammation are unpleasant experiences that usually occur as a result of tissue damage. Despite the number of existing analgesic drugs, side effects limit their use, stimulating the search ...for new therapeutic agents. In this sense, five hydrazone derivatives (H1, H2, H3, H4, and H5), with general structure R1R2C = NNR3R4, were synthesized with molecular modification strategies. In this paper, we describe the ability of hydrazone derivatives to attenuate nociceptive behavior and the inflammatory response in mice. Antinociceptive activity was evaluated through acetic acid-induced writhing and formalin-induced nociception tests. In both experimental models, the hydrazone with the greatest potency (H5) significantly (p < 0.05) reduced nociceptive behavior. Additionally, methods of acute and chronic inflammation induced by different chemicals (carrageenan and histamine) were performed to evaluate the anti-inflammatory effect of H5. Moreover, molecular docking analysis revealed that H5 can block the COX-2 enzyme, reducing arachidonic acid metabolism and consequently decreasing the production of prostaglandins, which are important inflammatory mediators. H5 also changes locomotor activity. In summary, H5 exhibited relevant antinociceptive and anti-inflammatory potential and acted on several targets, making it a candidate for a new multi-target oral anti-inflammatory drug.
Although the root of Cannabis sativa L. has been mentioned in some regions, such as the Vale do São Francisco, for its potential traditional medicinal use as an anti-inflammatory, anti-asthmatic, and ...against gastrointestinal diseases, it has received little exploration and discussion.
This study aimed to perform a chemical analysis of an aqueous extract of Cannabis sativa roots (AqECsR) and evaluate its pharmacological effects against uterine disorders, in vivo and ex vivo, in rodents.
The roots were provided by the Brazilian Federal Police, and the freeze-dried extract was used for the chemical analysis of the AqECsR by high performance liquid chromatography coupled with mass spectrometry (HPLC-MS). The sample was subsequently used in three doses for pharmacological assays (12.5, 25, and 50 mg/kg), which included the spasmolytic activity test and the primary dysmenorrhea test. The primary dysmenorrhea test aimed to verify the effect of AqECsR on induced abdominal contortions in female mice in vivo and to perform a morphometric analysis of the organs. Association tests at subtherapeutic doses of AqECsR with antidysmenorrheic drugs were also performed.
The data obtained by HPLC-MS suggested the presence of four substances: cannabisativine, anhydrocannabisativine, feruloyltyramine, and p-coumaroyltyramine. In the pharmacological assays, the AqECsR showed no spasmolytic effect. However, in the antidysmenorrheal activity test, AqECsR demonstrated a significant in vivo effect of reducing oxytocin-induced abdominal contortions. Morphometric analysis of the uterus showed no significant organ enlargement effect, and the association of AqECsR with subtherapeutic doses of three drugs used in antidysmenorrheal therapy (mefenamic acid, scopolamine, and nifedipine) showed an effect in reducing abdominal contortions.
In conclusion, AqECsR contains four chemical compounds and exhibits an antidysmenorrheic effect both alone and in association with drugs, reducing abdominal contortions in female mice without generating organ enlargement in the animals. Further studies are needed to prove the mechanism of action by which AqECsR promotes its effect on primary dysmenorrhea and to explore its associations.
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•Cannabisativine, anhydrocannabisativine, p-coumaroyltyramine and feruloyltyramine were identified in AqECsR.•AqECsR reduce abdominal contortions in a mouse model of primary dysmenorrhea.•Subtherapeutic doses of AqECsR associated with three antidysmenorrheal drugs showed a reduction in abdominal contortions.•Morphometric analysis of the uterus showed no significant organ enlargement effect.•AqECsR did not show spasmolytic activities.
Carvacrol is a phenolic constituent of essential oils that has antinociceptive, anti-inflammatory, and antioxidant activities.
This study aimed to evaluate the in vitro spasmolytic and in vivo ...anti-dysmenorrhea potential of a nanoemulsion-containing carvacrol (nanoCARV).
In isolated rat uterus, nanoCARV reduced spontaneous contractions (pEC50 = 3.91 ± 0.25) and relaxed preparations pre-contracted with oxytocin (pEC50 = 3.78 ± 0.2), carbachol (pEC50 = 4.15 ± 0.4), prostaglandin F2α (pEC50 = 3.00 ± 0.36), and KCl (pEC50 = 3.98 ± 0.32). The investigation of the mechanism of action revealed significant differences (p < 0.05) between the pEC50 values of nanoCARV in the absence or presence of aminophylline or tetraethylammonium. In a primary dysmenorrhea model, treatment with nanoCARV reduced the number of oxytocin-induced abdominal writhes.
These data indicate that the anti-dysmenorrhea effect of nanoCARV may be related to the relaxation of uterine smooth muscle, with participation of the cAMP signaling pathway and potassium channels.
The traditional use of the M. charantia L. plant to treat coughs, fever and expectoration is widely practiced in different cultures, but its effectiveness and safety still require scientific ...investigation. This study sought to perform a chemical analysis and evaluate the antitussive, expectorant and antipyretic effects of the ethanolic extract of M. charantia leaves (EEMc) in rats and mice. The EEMc was subjected to chemical analysis by HPLC-DAD, revealing the presence of the flavonoids astragalin and isoquercetin. Acute oral toxicity in mice did not result in deaths, although changes in liver weight and stool consistency were observed. EEMc demonstrated an antitussive effect at doses of 100 and 300 mg/kg in mice subjected to cough induction by citric acid nebulization. Furthermore, it showed expectorant activity at a dose of 300 mg/kg, assessed based on the elimination of the phenol red marker in bronchoalveolar lavage. In the evaluation of antipyretic activity in rats, fever induced by Saccharomyces cerevisiae was reduced at all doses tested during the first hour after treatment. This innovative study identified the presence of astragalin and isoquercetin in EEMc and indicated that the extract has antitussive, expectorant and antipyretic properties.
Abstract
SARS-CoV-2 and its different variants caused a “wave and wave” pandemic pattern. During the first wave we demonstrated that standardized Brazilian green propolis extract (EPP-AF®) reduces ...length of hospital stay in adult patients with COVID-19. Afterwards, we decided to evaluate the impact of EPP-AF in hospitalized patients during the third wave of the pandemic. BeeCovid2 was a randomized, double-blind, placebo-controlled clinical trial in hospitalized COVID-19 adult patients. Patients were allocated to receive an oral dose of 900 mg/day of EPP-AF® or placebo for 10 days. The primary outcome was length of hospital stay. Secondary outcomes included safety, secondary infection rate, duration of oxygen therapy dependency, acute kidney injury and need for intensive care. Patients were followed up for 28 days after admission. We enrolled 188 patients; 98 were assigned to the propolis group and 90 to the placebo group. The post-intervention length of hospital stay was of 6.5 ± 6.0 days in the propolis group versus 7.7 ± 7.1 days in the control group (95% CI − 0.74 − 1.94 to 0.42;
p
= 0.22). Propolis did not have significant impact on the need for oxygen supplementation or frequency of AKI. There was a significant difference in the incidence of secondary infection between groups, with 6.1% in the propolis group versus 18.9% in the control group (95% CI − 0.28 0.1–0.76,
p
= 0.01). The use of EPP-AF was considered safe and associated with a decrease in secondary infections. The drug was not associated with a significant reduction in length of hospital stay. ClinicalTrials.gov (NCT04800224).
The 2019 coronavirus disease (COVID-19) pandemic continues to spread and affects large numbers of people with unprecedented impacts. Experimental evidence has already been obtained for use of the ...standardized extract of Brazilian green propolis (EPP-AF) against viral targets, and clinical rationality has been demonstrated for testing this extract as an adjunct to treatment in patients affected by COVID-19. The BeeCovid2 study aims to assess whether EPP-AF has an impact on the improvement of patients hospitalized with COVID-19 by reducing the length of hospital stay.
BeeCovid2 is a randomized, double-blinded, placebo-controlled clinical study being conducted in Brazil to provide further evidence on the effectiveness of standardized green propolis extract as an adjunctive treatment for adults hospitalized with COVID-19. Hospitalized patients over 18 years of age with a confirmed diagnosis of COVID-19 and up to 14 days of symptoms were included. Patients under mechanical ventilation at randomization, pregnant women, cancer patients, transplanted or using immunosuppression, HIV patients, patients who used propolis in the last 30 days, bacterial or fungal infection at randomization, impossibility of using medication orally or enterally, and advanced chronic diseases (e.g., advanced heart failure, severe liver disease, and end-stage chronic kidney disease). Enrolled patients are randomized at a 1:1 ratio to receive placebo or standardized propolis extract (900 mg/day) for 10 days. The study treatments are administered in a double-blinded manner, and patients are followed for 28 days. The primary outcome is the difference in length of hospital stay in days between groups. Secondary outcomes include the need for mechanical ventilation, the rate of secondary infection, rate of acute kidney injury, the need for renal replacement therapy, the requirement for vasoactive drugs, the use of an intra-aortic balloon pump (IABP), and the use of extracorporeal membrane oxygenation (ECMO).
This trial is very useful and will provide more data on the effectiveness of using the standardized Brazilian green propolis extract as an adjunctive treatment in association with standard care in adults hospitalized with moderate to severe acute COVID-19.
ClinicalTrials.gov NCT04800224 . Registered on March 16, 2021.
The species Lippia origanoides Kunth, popularly known as “salva-de-marajó”, is used in Brazilian traditional “quilombola” communities to treat menstrual cramps and uterine inflammation.
Evaluate the ...spasmolytic activity of Lippia origanoides essential oil (LOO) on experimental models of uterine conditions related to menstrual cramps and investigate its mechanism of action.
Virgin rat-isolated uterus was mounted in the organ bath apparatus to evaluate the spasmolytic effect of LOO on basal tonus and contractions induced by carbachol, KCl, or oxytocin. We used pharmacological agents to verify the relaxation mechanism of LOO. The evaluation of uterine contractility in virgin rats, after treatment with LOO for three consecutive days, was carried out by the construction of a concentration-response curve with oxytocin or carbachol. The primary dysmenorrhea animal model was replicated with an injection of estradiol cypionate in female mice for three consecutive days, followed by intraperitoneal application of oxytocin.
LOO relaxed the rat uterus precontracted with 10−2 IU/mL oxytocin (logEC50 = 1.98 ± 0.07), 1 μM carbachol (logEC50 = 1.42 ± 0.07) or 60 mM KCl (logEC50 = 1.53 ± 0.05). It was also able relax uterus on spontaneous contractions (logEC50 = 0.41 ± 0.05). Preincubation with glibenclamide, propranolol, phentolamine or L-NAME in contractions induced by carbachol did not alter significantly the relaxing effect of LOO. However, in the presence of 4-aminopyridine, CsCl or tetraethylammonium there was a reduction of LOO potency, whereas the blockers methylene blue, ODQ, aminophylline and heparin potentiated the LOO relaxing effect. Preincubation with LOO in a Ca2+ free medium at concentrations of 27 μg/mL or 81 μg/mL reduced the contraction induced by carbachol. The administration of LOO for 3 days did not alter uterus contractility. The treatment with LOO at 30 or 100 mg/kg intraperitoneally, or 100 mg/kg orally, inhibited writhing in female mice. The association of LOO at 10 mg/kg with nifedipine or mefenamic acid potentiated writhing inhibition in mice.
The essential oil of L. origanoides has tocolytic activity in rat isolated uterus pre-contracted with KCl, oxytocin, or carbachol. This effect is possibly related to the opening of potassium channels (Kir, KV, and KCa), cAMP increase, and diminution of intracellular Ca2+. This relaxant effect, probably, contributed to reduce the number of writhings in an animal model of dysmenorrhea being potentiated by nifedipine or mefenamic acid. Taken together, the results here presented indicate that this species has a pharmacological potential for the treatment of primary dysmenorrhea, supporting its use in folk medicine.
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•Lippia origanoides essential oil (LOO) has spasmolytic effect in isolated rat uterus.•The spasmolytic effect of LOO was dependent on the K+ channels, cAMP increasing, and reduction of Ca2+i.•Lippia origanoides essential oil presented anti-dysmenorrhea activity in mice.•Nifedipine and mefenamic acid potentiated the anti-dysmenorrhea activity of LOO.
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