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
European Society of Gastrointestinal Endoscopy recommends needle-knife fistulotomy (NKF) as the preferred precut technique. However, there is little information on whether NKF performed at ...different times is associated with different success and adverse event rates. We compared the outcomes of 3 different timings of NKF. This was an observational study conducted at 4 institutions and this was a retrospective analysis of prospectively collected data. We included 330 consecutive patients submitted to NKF attempt for biliary access. Patients were divided into three groups: NKF as an initial procedure for biliary access (group A, n = 121); early NKF defined as after 5 min, 5 attempts, or 2 pancreatic passages (group B, n = 99); and late NKF: after at least 10 min of unsuccessful standard biliary cannulation (group C, n = 110). We assessed the success rate of biliary cannulation at initial ERCP, time to perform NKF until biliary cannulation, overall biliary cannulation rate (second ERCP when initial failure), adverse event rate, and predictors of post-ERCP pancreatitis (PEP). The initial cannulation rate was 98%, 91% and 94% for groups A, B and C respectively,
p
= 0.08, whereas overall biliary cannulation rate was 100%, 95% and 98%,
p
= 0.115. The adverse event rate/PEP was 4.1%/2.5%, 7.1%/4% and 10.9%/8.2%, for groups A, B and C respectively, (
p
= 0.197 and
p
= 0.190). Median time for creating the fistula was A = 4.0 min, B = 3.2 min, and C = 5.6 min,
p
< 000.1. Each additional minute spent attempting cannulation increased the odds ratio (OR) for PEP by 1.072, and patients with 3 or more risk factors for pancreatitis had a higher chance of PEP. In conclusion, the timing of NFK does not appear to influence success rates but late NFK is associated with a higher time to create a fistula and an increased risk of pancreatitis. Primary NFK is associated with a high rate of success and a low rate of PEP and deserves additional investigation.
Introduction: Malignant biliary obstruction drainage is essential, since jaundice is associated with morbidity and mortality. Endoscopic retrograde cholangiopancreatography (ERCP) is the recommended ...procedure for biliary drainage, with percutaneous biliary drainage being the classic alternative in cases of unsuccessful ERCP. Recently, endoscopic ultrasound-guided biliary drainage has been emerged as a new option, with EUS-guided choledochoduodenostomy (EUS-CDS) being considered an effective and safe method in the drainage of distal obstructions of the common bile duct. Aim: The aim of the study was to evaluate the efficacy and safety of EUS-CDS performed in patients with distal malignant biliary obstructions, after failed ERCP. Methods: Single-center retrospective cohort study between July 2017 and June 2022 including all consecutive patients submitted to EUS-CDS in our center. The primary outcomes were “technical success” and “clinical success,” defined as “resolution of jaundice or improvement in total serum bilirubin level above 50% at 7th day and above 75% at 30th day after the procedure.” Secondary outcomes were procedure-related adverse events, endoscopic reintervention, and survival time. Results: EUS-CDS was performed in 20 patients (65.0% male; median age 76 years). The most frequent etiology for the biliary obstruction was pancreatic adenocarcinoma (n = 17; 85.0%), and most patients presented at advanced stages of cancer (12/60% in stages III or IV). ERCP failure was mainly due to the presence of obstruction in the duodenal lumen (n = 11; 55.0%). Fully covered metallic stents were used in all patients, mostly HotAxios TM (n = 15; 75.0%). The technical success rate was 100%, and the clinical success rate was 89.5% (n = 17/19) at 7th day and 93.3% (n = 14/15) at 30th day. Four patients (20.0%) developed cholangitis within the first 30 days after the procedure; there were no late complications, and no patient died as a complication of the procedure. In 2 patients (10.0%), endoscopic reintervention was necessary due to stent migration, incidentally detected. Median survival was 93 days (minimum 5–maximum 751). Conclusion: EUS-CDS was effective in biliary decompression of malignant obstructions of the common bile duct, with high clinical success and a favorable safety profile.
There are many studies and therapeutic properties attributed to the flowers and leaves of the Cannabis species, but even with few pharmacological studies, Cannabis sativa L. (Cannabaceae) roots ...presents several therapeutic indications in folk medicine.
Aim of the study: This study aimed to evaluate the anti-inflammatory and spasmolytic effects as well as the toxicological profile of the aqueous extract of Cannabis sativa roots (CsAqEx) in mice.
We assessed the anti-inflammatory effect with carrageenan-induced leukocyte migration assay, and carrageenan and histamine-induced paw edema methods; The spasmolytic effect was assessed through in vitro assays with isolated mice trachea. To assess motor coordination and mobility, mice went through the rotarod and open field tests, respectively. For the single-dose toxicity study, we administered CsAqEx at the dose of 1000 mg/kg by gavage. In a repeated dose toxicity study, animals received CsAqEx at doses of 25 mg or 100 mg/kg for 28 days.
The CsAqEx inhibited the migration of leukocytes at the doses of 25, 50, and 100 mg/kg. The CsAqEx showed anti-inflammatory activity after the intraplantar injection of carrageenan, presenting a reduction in edema formation at all tested doses (12.5, 25, 50 and 100 mg/kg). The dose of 12.5 mg/kg of CsAqEx prevented edema formation after intraplantar injection of histamine. In an organ bath, 729 μg/mL of CsAqEx did not promote spasmolytic effect on isolated mice tracheal rings contracted by carbachol (CCh) or potassium chloride (KCl). We did not observe clinical signs of toxicity in the animals after acute treatment with CsAqEx, which suggested that the median lethal dose (LD50) is greater than 1000 mg/kg. Repeated dose exposure to the CsAqEx did not produce significant changes in hematological, biochemical, or organ histology parameters.
The results suggest that the anti-inflammatory effect of CsAqEx is related to the reduction of vascular extravasation and migration of inflammatory cells, without effects on the central nervous system. Moreover, there was no spasmolytic effect on airway smooth muscle and no toxicity was observed on mice.
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•Cannabissativine is the main component of aqueous extract of Cannabis sativa roots (CsAqEx).•The CsAqEx roots present anti-inflammatory activity in mice models of inflammation.•However, it showed no spasmolytic effect on mice isolated trachea.•The CsAqEx did not change motor coordination and locomotor activity in mice.•The CsAqEx did not present toxic effects.
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.
This article describes the phytochemical study of Cannabis sativa roots from northeastern Brazil. The dried plant material was pulverized and subjected to exhaustive maceration with ethanol at room ...temperature, obtaining the crude ethanolic extract (Cs‐EEBR). The volatile compounds were analyzed by gas chromatography coupled with mass spectrometry (GC/MS), which allowed to identify 22 compounds by comparing the linear retention index (LRI), the similarity index (SI) and the fragmentation pattern of the constituents with the literature. By this technique the major compounds identified were: friedelan‐3‐one and β‐sitosterol. In addition, two fractions were obtained from Cs‐EEBR by classical column chromatography and preparative thin layer chromatography. These fractions were analyzed by NMR and IR and together with the mass spectrometry data allowed to identify the compounds: epifriedelanol, friedelan‐3‐one, β‐sitosterol and stigmasterol. The study contributed to the phytochemical knowledge of Cannabis sativa, specifically the roots, as there are few reports on the chemical constituents of this part of the plant.
Many studies are performed with the aerial parts of Cannabis sativa L. (Cannabaceae). However, roots remain poorly studied, despite citations in the scientific literature. The C. sativa roots are ...indicated for the treatment of pain, inflammation, fever, among other health problems.
Aim of the study: This study aimed to evaluate the antinociceptive, antipyretic, antiasthmatic, and spasmolytic activities of C. sativa roots in experimental models using mice and rats.
The chemical composition of the aqueous extract of C. sativa roots (AECsR) was evaluated by LC-MS. The antinociceptive activity was assessed in mice by the induction of writhing with acetic acid, paw licking with formalin, and reactivity in the hot plate test. Fever was induced by the administration of a suspension of Saccharomyces cerevisiae in young rats. The asthmatic activity was performed with ovalbumin (OVA)-immunized mice with cellular and histological analysis. Finally, the spasmolytic activity was performed using mice isolated trachea. For in vivo studies, the doses were 12.5, 25, or 50 mg/kg whereas for in vitro, the concentration of AECsR was 729 μg/mL.
From the LC-MS data, we identified p-coumaroyltyramine, feruloyltyramine canabissativine in AECsR. The extract promoted a reduction of writhing in all tested doses (12.5, 25, or 50 mg/kg). Similarly, it reduced the pain in the formalin test at doses of 12.5 and 50 mg/kg (first phase) and 12.5 and 25 mg/kg (second phase). In the hot plate test, the doses of 12.5, 25, and 50 mg/kg promoted antinociceptive effect at different times, and the lowest dose maintained its action in the analyzes performed at 60, 90, and 120 min after administration. The anti-inflammatory activity of AECsR was observed in the mouse model of asthma, reducing the total leukocyte count in the bronchoalveolar fluid (BALF) at a dose of 25 mg/kg, as well as reducing eosinophilia in all tested doses (12.5, 25, and 50 mg/kg). Histological analysis of lungs stained with H&E and PAS showed a reduction in the number of inflammatory cells in the perivascular and peribronchial region, as well as reduced mucus production.
The results suggest that AECsR promotes pain control, either by a central or inflammatory mechanism, and has antiasthmatic activity. However, there was no antipyretic or spasmolytic effect.
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•p-coumaroyltyramine, feruloyltyramine, and cannabissativine were identified in C. sativa roots.•C. sativa roots have antinociceptive and anti-inflammatory activities.•C. sativa roots showed antiasthmatic activity.•C. sativa roots did not show antipyretic and spasmolytic activities.
Schinus terebinthifolia Raddi is a plant broadly used in folk medicine and the use of its leaf extract as an antitumor agent has been reported.
To evaluate the antitumor potential and the toxicity of ...saline extract (SE) and lectin (SteLL) from S. terebinthifolia leaves in sarcoma 180-bearing mice.
Cytotoxicity to sarcoma 180 cells was tested in vitro, and antitumor assay was performed using Swiss female mice. The treatments (0.15 M NaCl, negative control; methotrexate 1.5 mg/kg, positive control; SE 100 mg/kg; SteLL 1 and 5 mg/kg) by intraperitoneal injections started on the 8th day after tumor inoculation and lasted 7 days. It was analyzed: tumor weight; number and gauge of tumor vessels; hematological and biochemical parameters; histopathological changes; and occurrence of micronuclei in bone marrow cells.
SE and SteLL showed IC50 values (concentrations that reduced cell viability to 50%) of 301.65 and 8.30 μg/mL, respectively. The lectin was able to induce apoptosis. Treatments with the extract and lectin caused a 57.6–73.6% reduction in tumor weight, which was not significantly different from the reduction in the methotrexate group. Tumors of animals treated with SteLL at 5 mg/kg showed reduced number of secondary vessels while the gauge was lower in all treated groups. In the groups treated with SteLL, tumors showed reduced and slightly vascularized parenchyma, with necrosis in the center and at the periphery. No alterations in the blood levels of urea, creatine, and glucose were detected while serum AST level was moderately increased in the SE group. Histopathological analysis revealed vacuolization and steatosis in the liver of animals treated with the extract and lectin. In addition, the treatments with SE and SteLL resulted in the reduction of filtration space and alterations in tubular architecture in kidneys. In respect to hematological parameters, it was only detected increase in the number of monocytes in SE group. The extract and lectin did not induce the formation of micronuclei in the bone marrow cells.
SE and SteLL had antitumor effect against sarcoma 180 without inducing hematological changes and genotoxic effects in mice; however, some degree of hepatic and renal toxicity was observed, suggesting the evaluation of drug delivery strategies in the future.
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After multidisciplinary evaluation of the patient conditions, given the patient frailty it was decided to treat the condition using an endoscopic approach – laser lithotripsy assisted by ...cholangioscopy.Fig. 2. The data regarding this case are not publicly available due to containing information that could compromise the privacy of the patient but are available from M.M. (corresponding author e-mail) upon reasonable request. Conflict of Interest Statement Authors declare no conflict of interests for this article.
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