Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Anti-Inflammatory and Anti-Allergy Agents) - Volume 20, Issue 4, 2021

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.

Introduction:Pain is an immunological response to an infection or inflammation and long-term use of pain management therapy includes the use of Nonsteroidal anti-inflammatory drugs, which is associated with the occurrence of toxicity as well as gastrointestinal bleeding. Therefore, the investigation of new analgesic and anti-inflammatory agents remains a major challenge. Aims: The objective of this research study is to undergo the pharmacological evaluation of newly synthesized benzoxazole derivatives. These novel derivatives were evaluated for anti-nociceptive, anti-inflammatory and cytotoxic activity using various in-vivo and ex-vivo methods Methods: The study was carried out using swiss mice (adult male) weighing between 20gm to 30gm and were divided into groups containing (n=6) six animals in each group for treatment. The anti-nociceptive activity was performed by using 0.1ml of 0.6% v/v acetic acid as nociception inducer and evaluated by the diminished number of abdominal writhes. The anti-inflammatory activity was done using 0.1 ml of 2% w/v Carrageenan induced paw edema method was observed which was evaluated by calculating the percent maximum possible effect. Histopathological evaluation and cytotoxic activity of the compounds were carried out. Results: The results of this research study revealed that synthesized derivatives (a, b, c, d and e) showed promising anti-nociceptive and anti-inflammatory effects along significantly higher cytotoxic activity in MCF-7 cell lines. Conclusion: It can be concluded that synthesized derivatives (a, b, c, d and e) have potential anti- nociceptive and anti-inflammatory effects along with cytotoxic activity and certain modification in structure may result in the potent activity

Background: Today, the effects of growth factors and mesenchymal stem cells (MSCs) in promoting wound healing has been confirmed. Objective: This study aimed to investigate the effect of MSCs and platelet cryogel on wound healing. Methods: 40 male wistar rats were randomly divided into five groups (n=8). The control group was just dressed, the second group received platelet cryogel, the third group received platelet cryogel containing MSCs, the fourth group received plasma, and the fifth group received plasma plus MSCs. The biopsy was obtained from the wounds in the 2, 4, 6, and 8 days of the treatment. Then, pathological evaluation was conducted. Finally, qRT-PCR was performed to determine angiogenesis. Results: The intervention groups had faster wound healing and lower wound area than the control group (p<0.05). The highest wound healing rate and the smallest wound area was observed in the group receiving platelet cryogel plus MSCs. Angiogenesis, fibrosis, myoepithelial and epithelialization in the pathologic examination using H & E staining were not significantly different between the groups. The expression of Ang-1 in the intervention groups was higher than the control group and the highest expression was observed in the platelet cryogel plus MSCs, followed by the platelet cryogel group. The expression of VEGF in the plasma plus MSCs was higher than in the other groups. Conclusion: Further studies require to determine the effects of combined use of platelet cryogel plus MSCs on other types of wound and evaluate mechanisms involved in wound healing like collagenesis and inflammatory factors.

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: In the Iraqi community, abnormal pregnancy forms a major social and psychological health problem. The underlying etiology of this health phenomenon was varied and included sets of infections and autoimmune diseases. Globally human parvovirus 19 infection is common and the infection attributes to bad obstetric outcomes. The global maternal parvovirus B19 remote infection rate was within a range of 13.2% to 97.9%, while the range of acute infection was between 0.5% to 97.9%. In Arab countries, the IgG seroprevalence was from 53.3% to 74%, while IgM seroprevalence range was 2.2% to 84%. Objective: To evaluate the role of ParvovirusB19 as an etiology of bad obstetric outcome in women in Kirkuk, Iraq. Materials and Methods: Descriptive Case Control Study. Women included in the study were recruited from Kirkuk General Hospital and their age ranged from 14 to 48 years. A total of 663 women were included in the study, of them 237 were not pregnant, while 215 were pregnant. Additionally, the study included 211 women with inevitable abortion. Control group (306 women) women with a history of normal pregnancy included (Pregnant= 149; non-pregnant= 157). Clinical and laboratory investigations were conducted on all patients and control groups to exclude other causes. Medical and obstetric data and demographic characteristics were gathered through interviews according to a previously designed questionnaire. ELISA kits were used to determine Parvovirus B19 IgM and IgG antibodies. Results: The overall parvovirus seroprevalence was 93% and with no significant difference between women with normal (89.5%) and those with abnormal (93.1%) pregnancy outcomes. In addition, parvovirus IgM overall seroprevalence was at56.3%. Furthermore, current parvovirus infection was higher in women with BOH (52.6%) than that in women with normal pregnancy (49.7%) outcomes. Parvovirus IgM seroprevalence was 52.6% in women with BOH and 49.7% in women with normal pregnancy, however, the difference was not statistically significant. In contrast, the acute infection with parvovirus was significantly (X2=11.8, P=0.001) lower in women with normal pregnancy (49.7%) than in those with inevitable abortion (64.9%). While the IgG seroprevalence difference was not significant between the two groups, infection seroprevalence was more frequent in housewives, uneducated women, large families, non-smokers, in rural areas, non-animal exposure areas, women with repeated abortion, congenital anomalies and anaemia. Conclusion: Parvovirus B19 infection may be with bad obstetric outcomes if occurred during pregnancy and OR confirmed a significant association of the infection with parvovirus with smoking, occupation, crowding index, education, animal exposure and the number of repeated abortion.

Background: Antivenom is a gold-standard treatment for snakebite envenoming. However, adverse reactions to snake antivenom are common in many parts. Objective: The aim of this study was to evaluate the allergic reactions following intravenous administration of antivenom sera. Methods: This was retrospective study conducted on snakebites patients referred to the Rahimi Hospital in Khorramabad. The files of these patients were accessed for demographic data, snakebite-related data, treatment provided, clinical presentation and allergic reaction status as a result of antivenom treatment. Results: 141 cases were investigated, including 73.8% male and 26.2% female patients. The mean age of the patients was 38.1±17.1 years. Age group 30-39 years accounted for the highest number of snakebite cases (24.1%). A majority of victims (89.4%) were from rural areas. Most of the patients (51.8%) were bitten in the spring and highest number of snakebite were reported in May (39.1%). The most common site of snakebite was lower extremities (50.4%) and upper extremities (44.7%). Among clinical feature of snakebite, pain was the most prevalent in 135 cases (95.7%) followed by swelling (83.7%). The mean antivenom vials used were 6.5±3.7 vials. Allergic reactions occurred in 6 patients (4.26%); reactions were mild in 5 patients and severe in 1 patient. The commonest presentation was maculopapular rash (1.4%) and the least common were headache (0.71%), nausea (0.71%), fever (0.71) and hypotension (0.71%). Conclusion: Snakebite is one of the significant life-threatening environmental events. Immediate antivenom treatment can reduce mortality however, patients should be carefully monitored for adverse allergic reactions

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: The dietary model of metabolic syndrome has continued to aid our understanding of its pathogenesis and possible management interventions. However, despite progress in research, therapy continues to be challenging for humans; hence, the search for newer treatment and prevention options continues. Objective: The objective of this study was to evaluate the impact of dietary CQ10 supplementation on metabolic, oxidative, and inflammatory markers in a diet-induced mouse model of metabolic syndrome. Methods: Mouse groups were fed a Standard Diet (SD), High-Fat High-Sugar (HFHS) diet, and SD or HFHS diet (with incorporated CQ10) at 60 and 120 mg/kg of feed. At the completion of the study (8 weeks), blood glucose levels, Superoxide Dismutase (SOD) activity, plasma insulin, leptin, adiponectin, TNF-α, IL-10, serum lipid profile, and Lipid Peroxidation (LPO) levels were assessed. The liver was either homogenised for the assessment of antioxidant status or processed for general histology. Results: Dietary CQ10 mitigated HFHS diet-induced weight gain, decreased glucose, insulin, and leptin levels, and increased adiponectin levels in mice. Coenzyme-Q10 improved the antioxidant status of the liver and blood in HFHS diet-fed mice while also decreasing lipid peroxidation. Lipid profile improved, level of TNF-α decreased, and IL-10 increased following CQ10 diet. A mitigation of HFHS diet-induced alteration in liver morphology was also observed with CQ10. Conclusion: Dietary CQ10 supplementation mitigates HFHS diet-induced changes in mice, possibly through its anti-oxidant, anti-lipaemic, and anti-inflammatory potential.

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.