Anti-Inflammatory and Anti-Allergy Agents in Medicinal Chemistry最新文献

Introduction: Polycystic Ovary Syndrome (PCOS) is the most common endocrine disorder in women of reproductive age. PCOS is a heterogeneous complex disorder of defined aetiology. Some studies report its association with various endocrine, metabolic and immunological abnormalities. The hunger hormones ghrelin and leptin affect the pathogenesis of PCOS and might lead to the development of Metabolic Syndrome (MS) in obese women.

Aim: The study aims at evaluating the role of ghrelin and leptin level in females with polycystic ovary syndrome as a biochemical marker for the diagnosis and monitoring progression.

Subjects and methods: The study included one hundred PCOS patients and fifty apparently healthy subjects with regular menstrual cycle, visiting gynecology outpatient clinic of Kalar General Hospital, from the beginning of February 2015 to the end of June 2015. Body Mass Index (BMI) along with serum ghrelin, leptin, Luteinizing Hormone (LH), Follicle Stimulating Hormone (FSH) and testosterone levels were measured for both groups. Serum leptin was determined using sandwich ELISA, while serum ghrelin was determined using competitive ELISA. Differences between patient and control groups were assessed by using a t-test. Also, one-way Anova was used to test the relationships among different groups.

Results: A significant decrease in ghrelin level and an increase in leptin levels in women with PCOS were observed compared to the control group. Also, a significant elevation in serum levels of LH, Testosterone, Prolactin, and a decrease in serum FSH in PCOS patients were observed, when compared to the control group. Additionally, serum ghrelin decreased and serum leptin level increased significantly in women with PCOS compared to controls in all age and BMI groups.

Conclusion: A significant decrease in ghrelin and an increase in leptin in PCOS patients were observed than in controls, indicating that they are at high risk for metabolic syndrome development.

Background: Pneumonia is an acute or chronic inflammatory disorder of the lungs, affecting the mucosal areas of the lung. It can be caused by bacteria, viruses or fungi. In some cases, it may be caused by physical or chemical irritants. Kolaviron, a natural bioflavonoid extract from Garcinia kola seeds, has been shown to possess anti-inflammatory properties in Flu-like conditions which are associated with cough. There has been a paucity of information on the likelihood of the effectiveness of kolaviron against pneumonia infections.

Objective: To evaluate the antibacterial and anti-inflammatory effects of kolaviron on albino Wistar rats induced with pneumonia using Klebsiella pneumonia.

Materials and methods: Powdered Garcinia kola seeds were extracted with n-hexane and 100% methanol as solvents by using Soxhlet extractor. A standard method was used to obtain kolaviron from the seed extracts. A total of 24 albino Wistar rats were randomly divided into six groups A to F, each comprising four rats. The rats were allowed to acclimatize for 1 hour in very cold environments using ice packs. A standardized 1.0 x10 ^-5 mg/ml culture suspension was intranasally inoculated to the rats for 10 days to induce pneumonia-like symptoms. Thereafter, the kolaviron was administered to the rats such that a 500mg/kg kolaviron extract was given once daily to groups A (male rats) and B (female rats). Groups C (male rats) and D (female rats) received 250mg/kg of kolaviron extract once daily, while group E rats were given 0.5 ml of dimethyl sulfoxide (DMSO) once daily, which served as the negative control. The rats in Group F received 2.86 mg/kg of ofloxacin once daily and served as the positive control. All the treatments were done for a period of 5 days. Then 10 days after the treatments, the animals were sacrificed and the lungs were harvested for hydrostatic lung test and histopathological examination. An overnight broth culture of Klebsiella pneumonia was streaked in sterile molten nutrient agar maintained at 37°C for 24hrs. Later, a stock of 500mg/ml of kolaviron was prepared in DMSO. Two-fold dilutions were performed to obtain the following concentrations of 100%, 50%, 25%, 12.5%, 6.25%, 3.125%, and 1.565% with the stock. The anti-Klebsiella pneumonia activity of the kolaviron extract was determined using agar well diffusion methods and incubation was done at 37 o C for 24 hrs. Student t-test and Oneway Analysis of variance (ANOVA) were used for comparison of mean differences between and among the groups.

Results and discussion: The sensitivity of Klebsiella pneumonia to kolaviron was concentration- dependent. There was an increase in anti-Klebsiella pneumonia activity with a decrease in kolaviron concentration. Kolaviron (KV), at 500mg/kg concentration, was efficacious and showed significant anti-inflammatory effects (P<0.0001). This was also confirmed in the histop

Background: TThymus plants are well-known medicinal plants and it is believed that the pharmaceutical and therapeutical properties of these plants are related to their essential oils. The quality and quantity of the essential oils, as a secondary metabolite of an aromatic plant, are directly related to the physiological state of the plant. The role of jasmonates in the plant as signal molecules in mediation and up-regulation of plant defense and secondary metabolism processes is well recognized.

Objective: With the aim of increasing the performance and stimulating secondary metabolites, this study evaluates the influence of the foliar application of MJ on essential oil content and composition of three different Thymus species, whether as an elicitor or an activator Method: The experiment was arranged in a randomized block design with MJ treatments in four levels (0, 30, 60, 100 mM) and three replications Results: Compared to the control, the essential oil content of all three species increased in all treatment levels. However, the changes in essential oil composition were different. Under MJ treatments, the amount of sesquiterpenes (especially caryophyllene oxide) increased in T. daenensis and T. fedtschenkoi. In addition, the amount of thymol in T. daenensis, thymol, and γ-terpinene in T. vulgaris increased, whereas carvacrol methyl ether in T. daenensis and p-cymene in T. vulgaris decreased.

Conclusion: IIt seems the type of plant species has a specific role in determining the response. There were no interpretable changes between treatment levels.

Background: Body defenses and metabolic processes probably co-evolved in such a way that rapid, energy-intensive acute inflammatory repair is functionally integrated with energy allocation in a starvation/ infection / injury-prone primitive environment. Disruptive metabolic surplus, aggravated by sedentary lifestyle induces chronic under-activation of AMPK, the master regulator of intracellular energy homeostasis. Sudden increase in chronic, dysregulated 'sterile' inflammatory disorders probably results from a shift towards calorie rich, sanitized, cushioned, injury/ infection free environment, repositioning inflammatory repair pathways towards chronic, non-microbial, 'sterile', 'low grade', and 'parainflammation'. AMPK, (at the helm of energy provisioning) supervises the metabolic regulation of inflammasome activation, a common denominator in lifestyle disorders.

Discussion: In this review, we discuss various pathways linking AMPK under-activation and inflammasome activation. AMPK under-activation, the possible norm in energy-rich sedentary lifestyle, could be the central agency that stimulates inflammasome activation by multiple pathways such as 1: decreasing autophagy, and accumulation of intracellular DAMPs, (particulate crystalline molecules, advanced glycation end-products, oxidized lipids, etc.) 2: stimulating a glycolytic shift (pro-inflammatory) in metabolism, 3: promoting NF-kB activation and decreasing Nrf2 activation, 4: increasing reactive oxygen species (ROS) formation, Unfolded Protein Response (UPR) and Endoplasmic Reticulum (ER) stress.

Conclusion: The 'inverse energy crisis' associated with calorie-rich, sedentary lifestyle, advocates dietary and pharmacological interventions for treating chronic metabolic disorders by overcoming / reversing AMPK under-activation.

Asthma is a chronic disease with abnormal inflammatory and immunological responses. The disease initiates by antigens in subjects with genetic susceptibility. However, environmental factors play a role in the initiation and exacerbation of asthma attack. Asthma is a T-helper 2 (Th2)-cell-mediated disease. Recent studies indicate that asthma is not a single disease entity, but it occurs with multiple phenotypes and endotypes. The pathophysiological changes in asthma include a series of continuous vicious circles of cellular activation contributing to the induction of chemokines and cytokines that potentiate inflammation. The heterogeneity of asthma influences the treatment response. The asthma pathogenesis is driven by varied sets of cells, such as eosinophils, basophils, neutrophils, macrophages, epithelial cells, and T cells. Macrophages induce a set of mediators that are involved in asthma pathogenesis and include MIF, Prostaglandin, CXCR3L, IL-12, IL-1ß, TSLP, IL-18, IL-33, LTC4, MMP-2, TNF-α, IL-17, IL-10, TGF-ß and IL-27. While, T-cells mediators effect in asthma is induced via TNF-α, IL-17, IL-10, TGF-ß, IL-27, Tim, GM-CSF, IL-2, IL-4, IL-13, INF- γ, and PPAR γ. However, the epithelial cells induced mediators potentiate proinflammatory effects, increase the number of Th2 cells, activate dendritic cells, increase the number of mast cells, and recruit eosinophils, basophils, neutrophils, T-cells, monocytes and dendritic cells. In this review, the role of T cells, macrophages, and epithelial cells is discussed.

Aim: To test the effectiveness of marketed polyherbal formulations on lipopolysaccharide-induced inflammatory conditions in macrophages.

Background: Usage of herbal compounds among patients suffering from arthritis and cancer is increasing every year. Many anti-inflammatory herbal products available in the market should be screened thoroughly for their possible mechanism of action.

Objective: Joint Pain Spl (JPS) is a polyherbal dietary food supplement composed of 13 herbal plants, and Rumalaya Forte (RF) is a polyherbal formulation comprising of 6 herbal plants. These were tested for their cytotoxicity, as well as antioxidant and anti-inflammatory activities in LPS treated IC-21 peritoneal macrophages.

Methods: Commercially available JPS and RF powder was used to prepare the extract. The aqueous and methanol extracts were quantified for the presence of phenolic and flavonoid compounds and confirmed with HPLC. In vitro DPPH free scavenging activity was performed. Cytotoxicity was tested by MTT assay. Anti-inflammatory activity was tested using lipopolysaccharide-stimulated IC-21 peritoneal macrophage cells.

Results: The phytochemical screening showed the presence of phenolic and flavonoid compounds in JPS and RF. The aqueous and methanol extracts of JPS and RF possesses significant DPPH free radical scavenging activity. MTT assay revealed that 90.64% (aqueous extract) and 92.21% (methanol extract) of exposed macrophages are viable even after 24h exposure of maximal tested concentrations of herbal formulations. Pre-treatment of JPS and RF on LPS induced IC-21 macrophages showed a reduction in nitric oxide production (maximal 79.95%) and a high level of superoxide anion scavenging activity (maximal 82.5%) over control.

Conclusion: The two tested polyherbal formulations, such as JPS and RF possess anti-inflammatory activity by modulating free radical generation in IC-21 macrophages. Thus the presence of the phenolic and flavonoid compounds may contribute to the antioxidant activity.

Background: Oleanolic acid (OA) is a naturally occurring pentacyclic triterpenoid with multifarious actions. The anti-inflammatory effect it exerts when taken orally is the most important; however, the underpinning mechanisms of such effects have not yet been fully explored.

Methods: In the present study, we evaluated the anti-inflammatory and anti-nociceptive effect of OA by injecting it directly into the knee joint using an animal model of osteoarthritis. Behavioral and electrophysiological studies were conducted to determine whether OA exerts a direct modulatory effect on primary sensory afferents that can lead to a decrease in pain-related behaviors and inflammatory responses. Rats were divided into two main groups: a pre- and a post-treatment group. Knee joint inflammation was induced by injecting a mixture of 3% kaolin and carrageenan (K/C). In the pre-treatment group, two different doses of OA [5 mg/ml (n=5) and 30 mg/ml (n=4); 0.1 ml per injection] were administered into the synovial cavity of the knee joint before induction of inflammation. In the post-treatment group, rats received only one dose [5 mg/ml (n=5)] of OA after induction of inflammation.

Results: Results indicate that intra-articular injection of OA improves motor coordination and attenuates nociceptive behavior and inflammatory reactions. More importantly, we observed a direct depolarizing action of OA on articular sensory fibers, a crucial mechanism that activates descending inhibitory pathways and controls incoming nociceptive signals to the spinal cord.

Conclusion: Overall, our findings suggest that OA can be used as a preventive and therapeutic approach for the management of osteoarthritis.

Introduction: Asthma and hypereosinophilia have been treated with different therapeutics in the past. Some of them appear to be more effective in symptoms resolution and decreasing eosinophilic count.

Case presentation: We report here an unusual case of asthma with hypereosinophilia secondary to Chronic Myeloid Leukemia (CML) with high prevalence of eosinophilic infiltrate, treated simultaneously with an anti-IL-5 antibody (Mepolizumab) and Tyrosine-kinase Inhibitors (TKI: Imatinib and Bosutinib) for three years. The patient showed a promising reduction of pulmonary exacerbations and good control of CML without developing side effects.

Conclusion: We hope that this finding could inspire further studies on the efficacy and safety of the concomitant use of anti-IL-5 and TKI.

Objective: The objective of the study was to develop new Cyclooxygenase-2 inhibitors as anti-inflammatory agents from the synthetic route.

Materials and methods: The 2-phenyl-4H-chromen-4-one and 2-phenyl-2,3-dihydro-4H-chromenone hybrids were synthesised and characterised by using UV, IR, ¹H-NMR, and mass spectrometry. An attempt was made for consolidated lead flavones and flavanones scaffolds by determining ADME/ T properties. Molecular docking simulations were performed by using Autodock.4 to understand the binding interaction over the targeted enzyme Cyclooxygenase-2. The titled compounds were evaluated for various in-vitro models for antioxidant and anti-inflammatory activities and based upon the IC₅₀ values, the selected compounds were screened for in vivo anti-inflammatory activity by both acute and chronic models.

Results and discussion: Twenty titled compounds were synthesised and elucidated their structure for confirmation of their functional groups by various spectroscopic techniques. Among the synthesized compounds, flavone derivatives such as HFc (7-hydroxy-3-(4-methoxy phenyl)-4H-chromen-4- one), HF_d (2-(2,4-di methoxy-phenyl)-7-hydroxy-4H-chromen-4-one) and HFe (7-hydroxy-2- (thiophen-2-yl)-4H-chromen-4-one) produced higher potency. Flavanone derivatives HFAc (7- hydroxy-2-(4-hydroxy-3-methoxy phenyl)-2,3-dihydro-4H-chromen-4-one), HFAb (7-hydroxy-2-(4- methoxy phenyl)-2,3-dihydro-4H-chromen-4-one) and HFA_d (7-hydroxy-2-(thiophen-2-yl)-2,3- dihydro-4H-chromen-4-one) showed significant anti-inflammatory activity compared to the standard COX-2 inhibitors.

Conclusion: The flavone and flavanone scaffolds possess their excellent inhibitory action over the Cyclooxygenase-2 and act as a potential anti-inflammatory agent. The results of computational studies were also significantly correlated and concluded that those naturally mimicking flavonoid analogues were tremendous candidates to fight against the inflammatory diseases in drug discovery.

Background: For the first time, the investigation of six anti-inflammatory drugs and six antihistaminic drugs for inhibitory activities against alpha-amylase has been evaluated using a new inhibition detection method in order to find new treatments for some diseases caused by α-amylase.

Objective: The first part of this work was devoted to the evaluation of the inhibition activity of these drugs on salivary α-amylase in vitro. Then to study the nature of interactions and structure-activity relationship, using the Autodockvina program for molecular docking.

Materials and methods: The evaluation of the inhibitory activity of our drugs is achieved using a new method that has proved its sensitivity, quickness, and effectiveness.

Results: The results of this study show that betamethasone and loratadine are potent α-amylase inhibitors with IC50 values 0.7mg/ml and 1.03 mg/ml, respectively compared to acarbose with IC50=5.6 μg/ml.

Conclusion: The results showed that the loratadine and the betamethasone have a strong potential to inhibit the alpha-amylase.