Isolation, Chemical Characterization, Evaluation of Analgesic and Anti-Inflammatory Activities of Triterpenoids from the Tubers of Raphionacme vignei E. A. Bruce (Apocynaceae)

Raphionacme vignei E. A. Bruce (Apocynaceae) is a plant of the traditional African pharmacopoeia, whose parts are used in the treatment of various pathologies. Water-soaked R. vignei tubers are edible. The objective of this study was to isolate triterpenoids from the acetonic extract of R. vignei tubers, evaluate the analgesic and anti-inflammatory activities of each molecule. The isolated compounds, characterized by NMR and mass spectrometry, is composed of six triterpenoids: beta-amyrin dodecanoate 1(DDQ1), lupeol dodecanoate 2(DDQ2), beta-amyrin acetate 3(DDQ3), lupeol acetate 4(DDQ4), luepol 5(DDQ5) and β-sitosterol 6(DDQ6). These molecules (DDQ2, DDQ3, DDQ4, DDQ5, DDQ6) are anti-inflammatory in carrageenan induced rat paw edema, with better anti-inflammatory power for DDQ2 and DDQ4, which would be related to the presence of acetate function and cycle E. DDQ2 and DDQ4 are also analgesic in acetic acid induced contortions and the removal test of rat tail on the heating plate. The analgesic action of DDQ2 and DDQ4, superior to that salicylic acetyl acid, identical to that morphine, suggests a central action of these two molecules. The potent analgesic effect of DDQ2 and DDQ4, could be attributed to the presence of cyclopentane and isoprene substitution in position 19 of the lupane family. DDQ2 and DDQ4 represent a potential for the synthesis of structural analogues with analgesic and/or anti-inflammatory properties.

EFFECTS OF NEW PIPERIDINE DERIVATIVES WITH SUBSTITUTIONS IN THE 1ST AND 4TH POSITIONS IN NALOXONE SENSITIVE ANALGESY

Background. Despite the wide arsenal of painkillers, pain relief is an urgent interdisciplinary problem that requires a search for new solutions. Purpose of the study. To establish the role of opioid receptors in the mechanism of the analgesic action of the piperidine derivatives AGV-22 and AGV-23. Material and methods. The studies were carried out on 96 white mice of both sexes weighing 30-40 g. The analgesic effect of the compounds was tested on models of thermal and chemical irritation with preliminary administration of the opioid receptor antagonist naloxone. Results. The pain reactions of mice with models of thermal and chemical stimulation in the AGV-22 / AGV-23 + naloxone and AGV-22 / AGV-23 groups were comparable. Conclusions. The mechanism of the analgesic action of the piperidine derivatives AGV-22 and AGV-23 is not associated with the activation of opioid receptors.

Cannabinoids and Neurogenesis: The Promised Solution for Neurodegeneration?

The concept of neurons as irreplaceable cells does not hold true today. Experiments and evidence of neurogenesis, also, in the adult brain give hope that some compounds or drugs can enhance this process, helping to reverse the outcomes of diseases or traumas that once were thought to be everlasting. Cannabinoids, both from natural and artificial origins, already proved to have several beneficial effects (e.g., anti-inflammatory, anti-oxidants and analgesic action), but also capacity to increase neuronal population, by replacing the cells that were lost and/or regenerate a damaged nerve cell. Neurogenesis is a process which is not highly represented in literature as neuroprotection, though it is as important as prevention of nervous system damage, because it can represent a possible solution when neuronal death is already present, such as in neurodegenerative diseases. The aim of this review is to resume the experimental evidence of phyto- and synthetic cannabinoids effects on neurogenesis, both in vitro and in vivo, in order to elucidate if they possess also neurogenetic and neurorepairing properties.

Charles and Emma Darwin: Under the ‘influence’ of chloroform anaesthesia

A number of Charles Darwin’s biographies record the administration of chloroform by Darwin to his wife Emma, during her labour and delivery of her eighth child, Leonard. This occurred on 15 January 1850, a little over two years after James Young Simpson in Edinburgh described the analgesic action of inhaled chloroform. An online search of more than 9000 items of Darwin’s correspondence at Cambridge University and other sources revealed that he was an active proponent and user of chloroform in midwifery, for euthanising animals he studied, as well as in botanical studies of carnivorous plants. He also discovered that the concurrent inhalation of chloroform, during its administration to his wife, alleviated his distressing anxiety which he suffered when present at her earlier confinements.

Biological Effects on μ-Receptors Affinity and Selectivity of Aryl Propenyl Chain Structural Modification on Diazatricyclodecane Derivatives

Opioid analgesics are clinically used to relieve severe pain in acute postoperative and cancer pain, and also in the long term in chronic pain. The analgesic action is mediated by μ-, δ-, and κ-receptors, but currently, with few exceptions for k-agonists, μ-agonists are the only ones used in therapy. Previously synthesized compounds with diazotricyclodecane cores (DTDs) have shown their effectiveness in binding opioid receptors. Fourteen novel diazatricyclodecanes belonging to the 9-propionyl-10-substituted-9,10-diazatricyclo[4.2.1.12,5]decane (compounds 20–23, 53, 57 and 59) and 2-propionyl-7-substituted-2,7-diazatricyclo[4.4.0.03,8]decane (compounds 24–27, 54, 58 and 60) series, respectively, have been synthesized and their ability to bind to the opioid μ-, δ- and κ-receptors was evaluated. Five of these derivatives, compounds 20, 21, 24, 26 and 53, showed μ-affinity in the nanomolar range with a negligible affinity towards δ- and κ-receptors and high μ-receptor selectivity. The synthesized compounds showed μ-receptor selectivity higher than those of previously reported methylarylcinnamyl analogs.

AN EXPERIMENTAL EVALUATION OF Andrographis macrobotrys Nees., A FOLK MEDICINAL PLANT FOR ANALGESIC ACTION IN WISTAR ALBINO RATS AND SWISS ALBINO MICE- IN VIVO STUDY

Background and objective: In India Medicinal plants have a wide range of uses in folk medical practice. An- drographis macrobotrys Nees. belongs to Acanthaceae family is found in South India and Srilanka. It is in folk use by tribes in Kerala to treat muscle pain, snakebite, fever, and jaundice. The present research work aims to evaluate test drugs for their analgesic action. Methods: The detailed review of the test drug and disease Pain has been carried out. An animal experimental study has been carried out to assess the analgesic activity of the drug by acetic acid- induced writhing movement in Swiss albino mice and Eddy’s hot plate method in Wistar albino rats. Results and conclusion: The test drug showed analgesic action with Swarasa of leaves and Kashaya of the whole plant. The drug was found to have both peripheral and central analgesic action. Keywords: Andrographis macrobotrys Nees., Acanthaceae, folk medicinal plant, Analgesic action

The Hydroethanolic Stem Bark Extract of Tieghemella heckelii (A.Chev.) Pierre ex Dubard (Sapotaceae) Produced N-Methyl-D-Aspartate (NMDA) Receptor-Dependent Analgesia and Attenuates Acute Inflammatory Pain via Disruption of Oxidative Stress

Background. Tieghemella heckelii stem bark is used in African traditional medicine to treat inflammatory pain conditions. However, these biological actions of the plant have not been proven. This study investigates the phytochemical composition and the mechanisms of analgesic and anti-inflammatory actions of the hydroethanolic stem bark extract of T. heckelii (THBE). Methods. Phytochemical composition of THBE was investigated using qualitative and quantitative phytochemical analyses. Anti-inflammatory activity was evaluated using the carrageenan-induced paw oedema assay. Analgesic activity was evaluated using hot plate and acetic acid-induced writhing assays. Mechanism of analgesic action was determined using pharmacological antagonist such as naloxone, atropine, flumazenil, nifedipine, or ketamine. Test agents were administered orally as follows: Tween 80 (5%) (control), diclofenac sodium (DS) 10/tramadol 9 mg/kg (standard), or THBE 10, 100, and 450 mg/kg. Glutathione peroxidase (GPx), superoxide dismutase (SOD), and lipid peroxidation levels were also measured. Results. THBE which contained 58.45% saponins, 229.04 ± 0.049 GAE mg/g phenolic compounds,and 0.482 ± 0.0028 QE mg/g flavonoids produced ( p < 0.5) anti-inflammatory effect of 56.22% and analgesia of 330 ± 72% and 50.4% in the hot plate and writhing assays, respectively, at 10 mg/kg and inhibited oxidative stress by GPx and SOD elevation in rats during inflammation. Ketamine significantly blocked the analgesia of THBE, indicating NMDA receptor-dependent analgesic action. Whereas, naloxone, atropine, nifedipine, and flumazenil could not antagonize the analgesic action of THBE. Conclusion. These results show that THBE produced potent anti-inflammatory effect via disruption of oxidative stress and also generated NMDA receptor-dependent analgesia.

The Effects of Ondansetron on the Analgesic Action of Intravenous Acetaminophen after Tonsillectomy in Children: A Triple-Blind Randomized Controlled Trial

Introduction. Severe pain, nausea, and vomiting after tonsillectomy surgery are among the issues that not only affect patient satisfaction but also may result in complications and delay patient discharge. This study was conducted to assess the effect of intravenous administration of ondansetron on the analgesic action of intravenous acetaminophen after tonsillectomy in children. Materials and methods. This randomized controlled trial was conducted on 53 children between the age of 3 and 12 years old who were referred to Besat Hospital Hamadan, Iran, for tonsillectomy. Patients were randomly assigned to two groups. The intervention group (I) received intravenous acetaminophen plus 0.1 mg/kg ondansetron intravenously while the control group (C) received intravenous acetaminophen plus 2 ml of normal saline intravenously. Postoperative pain severity was assessed using the Children’s Hospital Eastern Ontario Pain Scale (CHEOPS). Frequency of nausea, vomiting, and need for analgesic was assessed and recorded four times, at recovery unit, after 6, 12, and 24 hours postsurgery. Data analysis was performed at 95% confidence level using the statistical package for social sciences (SPSS) software version 21. Results. The number of patients in groups I and C was 27 and 26 patients, respectively. Mean pain score in I and C groups was 4.48 and 2.88 at recovery unit, 2.74 and 2.04 after 6 hours, 1.67 and 0.81 after 12 hours, and 0.67 and 0.20 after 24 hours postsurgery, respectively. Frequency of nausea at recovery unit was 23.1% in I group and 0.0% in group C ( p = 0.010 ) while the mean number of analgesic requirements in I and C groups was 1.07 and 0.56 times, respectively ( p = 0.027 ). Conclusions. Intravenous administration of 0.1 mg/kg ondansetron reduces the analgesic action of intravenous acetaminophen after tonsillectomy in 3 to 12-year-old children.