جستجوی مقالات مرتبط با کلیدواژه « Antagonist » در نشریات گروه « پزشکی »

Toxoplasma gondii is an obligate intracellular parasite. T. gondii leads to increased production of dopamine in the host's brain. It is possible that dopamine plays a role in the proliferation of T. gondii. In this study, the effect of dopamine on the proliferation of Toxoplasma tachyzoites in HFF-1 cells was investigated.

HFF-1 cells were cultured and treated with 500 nM dopamine. 4 × 105 tachyzoites were added to the cell wells. To investigate the role of receptors, first the confluensed cells were treated with dopamine. Dopamine D1 and D2 receptor antagonists (SCH-23390 and sulpiride, respectively), alone and in combination, were added to the culture medium at a concentration of 10 nM. The treated cells were infected with Tachyzoite. The amounts of tachyzoites were evaluated by microscopic counting and by RT-qPCR method.

Dopamine significantly (p < 0.05) increases proliferation of tachyzoites in HFF-1 cells. SCH-23390 significantly neutralized the effect of dopamine in treated cells (p < 0.05), while sulpiride could not avert the effect of dopamine. Moreover, combination of two antagonists, SCH-23390 and sulpiride, significantly reduced the proliferation of tachyzoites in HFF-1 cells (p < 0.05).

Our study showed that dopamine stimulates proliferation of tachyzoites in HFF-1 cell line. In addition, dopamine exerts its effect on parasite proliferation through D1 receptors. These results can help to design and develop effective drugs against Toxoplasma.

Muscle imbalance and its amount and extent among opposing muscle groups is one of the important risk factors in causing musculoskeletal injuries. The aim of the present study was to evaluate the extent and rate of strength imbalances among opposing muscle groups of elite athletes.

To conduct the present review, the search history was searched through electronic search engines over the past two decades (2000 to 2020) at PubMed and Google Scholar. The keywords "Muscle", "Imbalance", "Athletics", "Muscle Imbalance", "Muscle Strength", "Rate", " Elite" are used for the search, along with related synonyms. Also, to search for Persian articles, the Iranian Magazines Database (MAGIRAN), the University Jihad Scientific Database (SID), the Islamic World Science Citation Database (ISC), the Iranian Medical Sciences Information Database (IRANMEDEX) and the Iranian Medical Library (MEDLIB) were used. Selected articles were obtained by considering the inclusion and exclusion criteria of the research.

Considering the inclusion and exclusion criteria of the present study, 28 articles (including 26 English articles and 2 Persian articles) were selected. The findings showed that in the knee joint, the ratio of opposite muscle imbalance (agonist / antagonist), for hamstring muscles to quadriceps (H: Q) were 63.2% and 61.8% respectively. These values ​​in the hip joint for abductor to adductor muscles (ABD: ADD) were 89.2% and 75.4% respectively. Mean of these values ​​in the ankle joint for dorsiflexor to plantarflexor muscles (DR: PL) were 35.3% and 35.6% respectively. The mean these values for inverter to aviator (I: E) muscles were 83.5% and 77.8% respectively. These values ​​in the shoulder joint for flexor to extensor muscles (FL: EX) respectively; were 76.8% and 72.8%. For external to internal retinal muscles (ER: IR) respectively; were 63.8% and 70.5%. The mean of these values ​​in the elbow joint for extensor to flexor muscles (EX: FL) respectively; were 92.3% and 91.6%. The mean of these values ​​in the scapular joint for the scapular to proximal scapular muscles (RT: PR) respectively; were 88.1% and 77%.

The results showed that in the evaluation of muscle imbalance in different groups in the upper and lower limb of elite athletes, certain relative values can be considered as quantitative and reference values. This reference is used to find out if the differences in muscle strength are such that they are considered muscle imbalance. Also, in assessing muscle strength imbalance, application of the isokinetic assessment method with the technique of 60 degrees per second is more beneficial. To conduct future studies in the field of muscle imbalance assessment, researchers recommend that in addition to strength imbalance, other aspects of muscle imbalance such as muscle length, flexibility, joint range of motion, muscular endurance, and structural profile of elite athletes should be considered.

Herbal plants are an important source of novel chemical drugs with therapeutic effects. Lavender is one of the most important herbal plants in the world that has many applications in the pharmaceutical and cosmetic industries. Its fresh and dried flowers are also used for cooking or making herbal tea. The lavender essential oil is known to have sedative, anti-flatulent, antidepressant, anti-inflammatory, analgesic, anti-convulsant, anti-parasitic, antioxidant, antimicrobial, cardioprotective, and anti-schistosoma properties and be mast cell degranulation inhibitor and imrpoves digestive disorders. It is used by aromatherapists as the holistic relaxant. Herbal components have been used for prevention and threatment of several diseases such as Alzheimer’s disease that is the most common age-related dementia in the word. The important characteristics of this disease include amyloid-β (Aβ) plaque, hyperphosphorylated tau, neuroinflammation, oxidative stress, and finally neuronal cell death. One of the most important enzymes involving in the conversion of glutamate to glutamine is glutamine synthetase. Its dysfunction leads to overactivation of N‑methyl‑D‑aspartate receptor (NMDAR) resulting in neuronal injury, activation of the mentioned enzymes, hyperphosphorylation of tau protein, cell death, and alzheimer’s disease. NMDAR is a glutamate receptor and ion channel that plays important role in brain physiology and pathology, and has strong therapeutic potential in different pathologic conditions such as NMDAR receptor overactivation. Among the most promising NMDAR-targeting drugs are allosteric inhibitors of GluN2B-containing receptors. One of the important roles of lavender essential oil may be in inhibiting the production of oxygen reactive species (ROS) due to its antioxidant activity. It can activate several signaling cascade associated with hyperphosphorylated tau protein. The present study aims to determine the chemical compounds of extracted lavender essential oil (Lavandula angustifolia Miller) and assess the effect of their antagonists on NMDA receptors in the brain using Gas chromatography mass spectrometry (GC-MS) and computational approaches.

Flowering inflorescences of lavender plant were harvested at full flowering stage from a cultivated farm and were dried in natural conditions for two weeks prior to the essential oil extraction. For the extraction of essential oil, the dried inflorescences (50 g) were distilled by hydro-distillation method for 3 hours using a one-liter full-glass Clevenger apparatus and the procedure proposed by European Pharmacopoeia for determining the oil content (v/w%) with three replications. To find the active constituents of lavender essential oil, a GC-MS was used. The GC-MS was done using an HP-5972 mass spectrometer with electron impact ionization (70eV) coupled with the HP-5890 series II gas chromatograph. Compounds were identified by calculating their retention index relative to n-alkanes (C9-C18) and the data for authentic compounds available in the literature and in our data bank, and also by matching their mass spectrum fragmentation patterns with corresponding data stored in the mass spectra library of the GC-MS data system. Crystal structure of GluN2B receptor was retrieved from Protein Databank (5EWJ.pdb). PyRx 0.8 virtual screening software in AutoDock Vina was used to perform molecular docking studies on the antagonist compounds of NMDAR in lavender. Twenty components that showed the highest frequency during the experiments were selected for molecular docking studies. Input coordinates for these 20 compounds were obtained from the PubChem website. In order to evaluate the binding affinity of these components (as ligands) with the amino terminal domains of the NMDAR subunit gluN2B, the scoring function (kcal/mol) in AutoDock was applied. The coordinates of the grid box were 24.45´29.90´37.61 Å, and the grid center had a dimension of 24.953´1.872´38.007 Å (x, y and z). Discovery studio v.16.1.0 software was used to prepare two-dimensional diagrams of docking model to show different interactions between NMDAR and ligands. In order to evaluate the results of docking, we used the NMDAR antagonist ifenprodil as a control. The interaction between GluN2B and ifenprodil was assessed using Discovery studio. The results of docking were compared with the residues in the active sites of ifenprodil to find the common residues and the best antagonist. Moreover, 20 lead compounds of phytochemicals were used for pharmacokinetic analysis in accordance with Lipinski’s rule of five.

The essential oil obtained from the lavender inflorescence was yellow-green and its yield was 1.37% (v/w). The 41 compounds identified in the essential oil comprised 95.5% of the total essential oil. The main compound was trans-carveol (15.9%), followed by isopulegol (7.7%,), 1,3,8, -p-menthatriene (7.3%) and isoborneol (6.9%). The compounds of lavender essential oil were categories in seven groups including monoterpenes, sesquiterpenes, benzenoids, ketones, benzenes, alcohols, and aldehydes. The highest numbers of compounds was related to monoterpenes (n=22, 67%) followed by benzenoids (n=6, 12.9%) and sesquiterpenes (n=9, 11.6%). Twenty molecular structures of the lavender essential oil compounds were evaluated in SwissADME website. All compounds had a molecular weight of less than 500 Da. They showed H-bond acceptor <2 and H-bond donor <1. The obtained molar refractivity was in a rangeof 45 to 71. The topological polar surface area was in a range of 0 to 27 Å. The relative solubility as the partition coefficient (P) of the substance is traditionally given between octanol-1 and water. Log P in our study was in a range of 2 to 4. Beta-caryophyllene and germacrene-D compounds were not permeable in the blood brain barrier (BBB), while 1,3,8,-p-menthatriene, gamma-3-carene, gamma-terpinene, p-cymene, alpha-pinene, alpha-phellandrene, Limonene, beta-caryophyllene and germacrene-D were absorbed gastrointestinally in a small amount. Others had suitable permeability in the BBB and gastrointestinal absorption. Beta-caryophyllene and caryophyllene epoxide were CYP2C19 inhibitors; gamma-3-carene, alpha-pinene, limonene, beta-caryophyllene and caryophyllene epoxide inhibited CYP2C9; thymol was CYP1A2 inhibitor, and CYP2D6 was inhibited by p-cymene.

Discussion :

The essential oil of lavender plant cultivated in Alborz province, northern Iran has 41 compounds comprising 95.5 % of the total essential oil. The major identified component was trans-carveol followed by isopulegol, 1,3,8,-p-menthatriene, isoborneol and carvacrol acetate, while the amounts of linalool, citral, beta-ionone, eugenol, 1, octen-3-ol and 5-hepten-1-ol were very low. Camphor, Thymol, beta-Thujone and trans-Carveol compounds of lavender essential oil can lead to inhibiting NMDAR and improving learning and memory in neurodegenerative diseases.