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Antiinflamm Antiallergy Agents Med Chem [JOURNAL]

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Diosgenin: Mechanistic Insights on its Anti-inflammatory Effects.

Karami-Mohajeri S, Mohammadinejad R, Ashrafizadeh M … +3 more , Mohamadi N, Mohajeri M, Sharififar F

Antiinflamm Antiallergy Agents Med Chem · 2022 · PMID 35346012 · Publisher ↗

Diosgenin (DG), a well-known steroid saponin, has shown anti-inflammatory effects. This review was aimed to discuss all published literature concerning the anti-inflammatory effects of diosgenin. Based on the modulatory... Diosgenin (DG), a well-known steroid saponin, has shown anti-inflammatory effects. This review was aimed to discuss all published literature concerning the anti-inflammatory effects of diosgenin. Based on the modulatory impact of DG on the NF-κB pathway, its supplementation is associated with downregulation of the NF-κB pathway and TGF-β, resulting in inhibition of inflammation. It appears that upstream modulators of NF-κB signaling pathways such as Tlrs and downstream mediators include iNOS and COX-2, leading to the inhibition of the inflammatory response and development of pathological conditions. Due to the low toxicity of the herbal compounds, the risk of the side effects of DG use for the management of inflammatory disorders such as asthma, rheumatism, rhinitis, and arthritis is lower than that of synthetic glucocorticoids. It has been shown that regulation of NF-κB and oxidative stress signaling pathways by DG is beneficial against cardiotoxicity induced by chemotherapeutic agents such as doxorubicin.

Post-COVID-19 Syndrome Clinical Manifestations: A Systematic Review.

Abdel-Gawad M, Zaghloul MS, Abd-Elsalam S … +8 more , Hashem M, Lashen SA, Mahros AM, Mohammed AQ, Hassan AM, Bekhit AN, Mohammed W, Alboraie M

Antiinflamm Antiallergy Agents Med Chem · 2022 · PMID 35346011 · Publisher ↗

BACKGROUND: Coronavirus disease-2019 (COVID-19) is a global pandemic health problem that causes a wide spectrum of clinical manifestations and considerable mortality rates. Unfortunately, recovered patients who survive C... BACKGROUND: Coronavirus disease-2019 (COVID-19) is a global pandemic health problem that causes a wide spectrum of clinical manifestations and considerable mortality rates. Unfortunately, recovered patients who survive COVID-19 may continue to report a wide variety of clinical manifestations of multisystem affection such as pulmonary embolism, deep vein thrombosis, acute myocardial infarction, depression, anxiety, myalgia, dyspnea, and fatigue. OBJECTIVE: We aimed to summarize the current literature regarding the prevalence of post-COVID- 19 manifestations. METHODS: We conducted a systematic review of post-COVID-19 manifestations by searching MEDLINE via PubMed, Scopus, Web of Science (WOS), EBSCO, Wily, and World health organization (WHO) databases. Screening, study selection, data extraction, data synthesis, and quality assessment were made by two independent reviewers. RESULTS: Of 1,371 references, 817 references remained after removing duplicates. Reviews, case reports, commentaries, and any article containing non-original information were excluded. According to the eligibility criteria for this systematic review, 12 studies were included for qualitative synthesis. The overall prevalence of post-COVID-19 manifestations ranged from 35% to 90.5%. Fatigue, dyspnea, neuropsychological disorders, and pain were the most frequent post-COVID-19 symptoms. CONCLUSION: This systematic review showed that 35% to 90.5% of recovered patients who survive COVID-19 continue to have a wide variety of clinical manifestations, including fatigue, dyspnea, neuropsychological disorders, and pain as the most frequent post-COVID-19 symptoms.

Xylopic Acid Suppresses Adjuvant-induced Arthritis in Sprague Dawley Rats via Reduction in Serum Levels of IL-6 and TNF-alpha.

Osafo N, Antwi AO, Otu-Boakye S

Antiinflamm Antiallergy Agents Med Chem · 2022 · PMID 35272600 · Publisher ↗

BACKGROUND: Xylopic acid (XA) is the principal constituent obtained from the biofractionation of the dried fruits of Xylopia aethiopica. Our initial reports have established the acute anti-inflammatory activity of this k... BACKGROUND: Xylopic acid (XA) is the principal constituent obtained from the biofractionation of the dried fruits of Xylopia aethiopica. Our initial reports have established the acute anti-inflammatory activity of this kaurene diterpene. OBJECTIVE: Currently, we investigate the chronic anti-inflammatory activity of xylopic acid. METHODS: The adjuvant-induced arthritis model in rats was employed in carrying out the study. RESULTS: It was observed from the study that XA significantly (P < 0.05) suppressed the oedema associated with adjuvant arthritis while preventing associated joint deformation as identified from the radiographs. Histopathological analysis of joints of treated animals revealed signs of bone reformation and re-calcification following XA administration. From the haematological analysis, xylopic acid significantly decreased eosinophil sedimentation rate (ESR) while also decreasing white blood cells (WBC), which were increased after arthritis induction. Serum analysis showed the inhibitory effect of XA on serum expression of IL-6 and TNF-alpha in arthritic rats. CONCLUSION: Our study demonstrates the anti-arthritic activity of orally administered XA while pointing to a possible mechanism of its anti-inflammatory action.

Evaluation of Pleotropic Protective Activity of Capparis spinose Extract on Arthritis Rat Model.

Yosri M, Elaasser MM, Abdel-Aziz MM … +2 more , Ahmed HY, Amin BH

Antiinflamm Antiallergy Agents Med Chem · 2022 · PMID 35152871 · Publisher ↗

BACKGROUND: Capparis spinosa grows in Asian and Mediterranean desert areas. Different parts of Capparis spinosa, including flowers, have been used in various folk medicine applications. OBJECTIVE: This study aims to eval... BACKGROUND: Capparis spinosa grows in Asian and Mediterranean desert areas. Different parts of Capparis spinosa, including flowers, have been used in various folk medicine applications. OBJECTIVE: This study aims to evaluate the anti-arthritic potential of ethanolic extract of Egyptian Capparis spinosa flowers in a rat model of rheumatoid arthritis. Moreover, analysis of Capparis spinosa extract was performed using LC-qTOF-MS/MS. METHODS: Animals were split into six groups: negative control group, induced arthritic animals, arthritic rats receiving 7, 14 and 28 mg/kg of Capparis spinosa extract, respectively, in three groups to detect the optimum dose, and the induced group receiving a standard drug. The arthritic score was checked daily for 15 days after induction. After animals were sacrificed, their joints and muscles were subjected to microscopic and ultra-structure examinations. Ex vivo culturing of osteoclasts was performed. Cytokine levels were measured in all examined groups. RESULTS: The results revealed 7 mg/kg of Capparis spinosa extract as the optimal dose, which decreased inflammation signs through controlling chondrocytes, osteoclasts, and levels of inflammatory mediators. CONCLUSION: LC-Mass analysis revealed Capparis spinosa extract to contain a mixture of flavonol glycosides, flavan-3-ols and hydroxycinnamic acid derivatives, which may provide beneficial multifunction in regulating arthritic symptoms.

Synthesis and Biological Activity of the Pyridine-hexacyclic-steroid Derivative on a Heart Failure Model.

Lauro FV, Maria LR, Francisco DC … +5 more , Marcela RN, Virginia MM, Magdalena AR, Tomas LG, Idalia AC

Antiinflamm Antiallergy Agents Med Chem · 2022 · PMID 34951373 · Publisher ↗

BACKGROUND: Several drugs with inotropic activity have been synthesized; however, there is very little information on biological activity exerted by steroid derivatives in the cardiovascular system. OBJECTIVE: The aim of... BACKGROUND: Several drugs with inotropic activity have been synthesized; however, there is very little information on biological activity exerted by steroid derivatives in the cardiovascular system. OBJECTIVE: The aim of this research was to prepare a steroid-pyridine derivative to evaluate the effect it exerts on left ventricular pressure and characterize its molecular interaction. METHODS: The first stage was carried out through the synthesis of a steroid-pyridine derivative using some chemical strategies. The second stage involved the evaluation of the biological activity of the steroid-pyridine derivative on left ventricular pressure using a model of heart failure in the absence or presence of the drugs, such as flutamide, tamoxifen, prazosin, metoprolol, indomethacin, and nifedipine. RESULTS: The results showed that steroid-pyridine derivative increased left ventricular pressure in a dose-dependent manner (0.001-100 nM); however, this phenomenon was significantly inhibited only by nifedipine at a dose of 1 nM. These results indicate that positive inotropic activity produced by the steroid-pyridine derivative was via calcium channel activation. Furthermore, the biological activity exerted by the steroid-pyridine derivative on the left ventricle produces changes in cAMP concentration. CONCLUSION: It is noteworthy that positive inotropic activity produced by this steroid-pyridine derivative involves a different molecular mechanism compared to other positive inotropic drugs. Therefore, this steroid could be a good candidate for the treatment of heart failure.

In vitro Anti-hemolytic Effect, in vivo Anti-inflammatory and in vitro Anti-oxidant Activity of Anchusa azurea Mill.

Boussoualim N, Trabsa H, Krache I … +3 more , Ouhida S, Arrar L, Baghiani A

Antiinflamm Antiallergy Agents Med Chem · 2022 · PMID 34852750 · Publisher ↗

BACKGROUND: Anchusa azurea Mill. (AA) is a medicinal plant largely used traditionally in folk medicine in Algeria; it is locally named hamham. It is effective in the treatment of various diseases. OBJECTIVES: The aim of... BACKGROUND: Anchusa azurea Mill. (AA) is a medicinal plant largely used traditionally in folk medicine in Algeria; it is locally named hamham. It is effective in the treatment of various diseases. OBJECTIVES: The aim of the present study is to determine the antioxidant, anti-inflammatory, and anti- hemolytic effects of phenolic fractions from Anchusa azurea Mill. METHODS: In this study, various extracts from Anchusa azurea Mill. (AA) using solvents with increasing polarity were prepared. The quantification of polyphenols and flavonoids was determined. The anti-radical activity of the different extracts was evaluated using DPPH and by measuring the inhibition of the oxidative degradation of β-carotene. The In-vitro antihemolytic effect of the plant extracts is determined (CrE, ChE, AcE, and AqE). For each extract, four concentrations were tested: 10.59, 21.18, 42.37, 84.74 μg/ml. Vitamin C is used as a standard. The free-radical attack was measured by measuring the HT (Half-Hemolysis Time). The anti-inflammatory effect using PMA on mice of the methanolic extract (CrE) was evaluated. RESULTS: The quantification of polyphenols and flavonoids showed that ethyl acetate extract (AcE) contains a higher amount of polyphenols. However, chloroform extract (ChE) presents a higher amount of flavonoids. AcE showed an important scavenging activity using the DPPH radical (IC= 68.35 μg/ml). The results showed that AcE also exhibited a significant inhibition effect on the oxidation of β-carotene/linoleic acid (84.33 %). All extracts increased the HT50 values (Half-Hemolysis Time) in a dose-dependent manner. The three highest concentrations (21.18, 42.37, and 84.74 μg / ml) of ChE caused a very significant delay (p ≤ 0.001) of hemolysis compared to the negative control and the positive control "VIT C". The anti-inflammatory effect of using PMA on mice showed that the methanolic extract (CrE) of AA reduced the weight of the ear edema. CONCLUSION: This plant has a strong pharmacological power, which supports its traditional medicinal use.

Inflammation in Asthma Pathogenesis: Role of T Cells, Macrophages, Epithelial Cells and Type 2 Inflammation.

Alobaidi AH, Alsamarai AM, Alsamarai MA

Antiinflamm Antiallergy Agents Med Chem · 2021 · PMID 34544350 · Publisher ↗

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... 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.

Concomitant use of Tyrosine-Kinase Inhibitor and Mepolizumab in Asthma Secondary to Chronic Myeloid Leukemia with Hypereosinophilia.

Gidaro A, Salvi E, Carraro MC … +2 more , Rossi RS, Castelli R

Antiinflamm Antiallergy Agents Med Chem · 2021 · PMID 34420510 · Publisher ↗

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:... 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.

Parvovirus B19 Seroprevalence in Women with Bad Obstetric History in Kirkuk.

Alsamarai AM, Hassan HM, Alsamarai MA … +1 more , Aljumaili ZK

Antiinflamm Antiallergy Agents Med Chem · 2021 · PMID 34315400 · Publisher ↗

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 di... 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.

Effects of Xenogen Mesenchymal Stem Cells and Cryo-Platelet Gel on Intractable Wound Healing in Animal Model (Rat).

Alavi-Farzaneh B, Shojaeian A, Banitalebi-Dehkordi M … +5 more , Mirahmadi F, Mehri-Ghahfarrokhi A, Ghorbanpour A, Rahmati-Dehkordi S, Yazdani F

Antiinflamm Antiallergy Agents Med Chem · 2021 · PMID 33992068 · Publisher ↗

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 woun... 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.

Anti-Inflammatory, Anti-Oxidant, and Anti-Lipaemic Effects of Daily Dietary Coenzyme-Q10 Supplement in a Mouse Model of Metabolic Syndrome.

Onaolapo OJ, Omotoso SA, Olofinnade AT … +1 more , Onaolapo AY

Antiinflamm Antiallergy Agents Med Chem · 2021 · PMID 33906592 · Publisher ↗

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 challen... 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.

Evaluation of the Role of Ghrelin and Leptin as Biochemical Markers in Female with Polycystic Ovarian Syndrome.

Ibrahim MK, Alobaidi AHA

Antiinflamm Antiallergy Agents Med Chem · 2021 · PMID 33888052 · Publisher ↗

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 v... 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.

Identification of Phytoconstituents of Tragia Involucrata leaf Extracts and Evaluate their Correlation with Anti-inflammatory & Antioxidant Properties.

Velu V, Banerjee S, Radhakrishnan V … +7 more , Gupta G, Chellappan DK, Fuloria NK, Fuloria S, Mehta M, Dua K, Malipeddi H

Antiinflamm Antiallergy Agents Med Chem · 2021 · PMID 33573582 · Publisher ↗

AIMS: The present investigation was aimed at exploring the phytoconstituents using Gas Chromatography Mass Spectroscopy and to evaluate antioxidant and anti-inflammatory properties of the leaf extracts. MATERIALS AND MET... AIMS: The present investigation was aimed at exploring the phytoconstituents using Gas Chromatography Mass Spectroscopy and to evaluate antioxidant and anti-inflammatory properties of the leaf extracts. MATERIALS AND METHODS: The extracts were obtained sequentially with petroleum ether, ethyl acetate and water using Soxhlet apparatus. The anti-inflammatory property of the identified compounds using GC- MS spectroscopy was evaluated in silico. The antioxidant activity was performed by DPPH and HO method whereas anti-inflammatory study was carried out by HRBC membrane stabilization method. Terpenoids were found to be a major constituents in petroleum ether extract while, phenols and flavonoids were predominantly found in ethyl acetate extract. RESULTS AND DISCUSSION: The GC-MS analysis of the extract revealed six major molecules including Squalene, 19β, 28-epoxyleanan-3-ol and 2-tu-Butyl-5-chloromethyl-3-methyl-4-oxoimidazolidine- 1-carboxylic acid. The ethyl acetate extract showed a significant antioxidant activity (P<0.01) in both DPPH method (70.87%) and HO method (73.58%) at 200 μg mL. Increased membrane stabilization of petroleum ether extract was observed in the in vitro anti-inflammatory activity study. A strong relationship between the terpenoid content and anti-inflammatory activity was obtained from the correlation (0.971) and docking study. CONCLUSION: These results justify T. involucrata to be a rich source of terpenoids with potent anti- inflammatory property.

Evaluation of Allergic Reactions Following Intravenous Infusion of Polyvalent Antivenom in Snakebite Patients.

Mahmoudi GA, Ahadi M, Fouladvand A … +3 more , Rezaei B, Bodagh Z, Astaraki P

Antiinflamm Antiallergy Agents Med Chem · 2021 · PMID 33563188 · Publisher ↗

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... 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.

Anti-nociceptive and Anti-inflammatory Activity of Synthesized Novel Benzoxazole Derivatives.

Patil ML, Gaikwad SS, Gaikwad NJ

Antiinflamm Antiallergy Agents Med Chem · 2021 · PMID 33535962 · Publisher ↗

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 occurren... 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.

Changes in Essential Oil Profile of Thymus daenensis Celak., Thymus fedtschenkoi Ronniger., and Thymus vulgaris L. Under Methyl Jasmonate Treatment.

Shayganfar A, Akhzari D

Antiinflamm Antiallergy Agents Med Chem · 2021 · PMID 33459247 · Publisher ↗

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 esse... 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.

The Correlation Between the Autotaxin Enzyme and Pruritus in Egyptian Patients Suffering from Chronic Liver Disease.

Asal F, Ziada D, Wageh A … +4 more , El-Kohy M, Hawash N, Abd-Elsalam S, Badawi R

Antiinflamm Antiallergy Agents Med Chem · 2021 · PMID 33459246 · Publisher ↗

BACKGROUND & AIMS: Pruritus associated with liver diseases confines daily activities and causes sleep deprivation in patients with chronic liver diseases. Autotoxin enzyme (ATX) was found to be higher in sera of patients... BACKGROUND & AIMS: Pruritus associated with liver diseases confines daily activities and causes sleep deprivation in patients with chronic liver diseases. Autotoxin enzyme (ATX) was found to be higher in sera of patients with intrahepatic cholestasis and it was found to be associated with the intensity of itching. The aim of this study was to assess the correlation between the autotaxin enzyme and pruritus in Egyptian patients suffering from chronic liver disease (CLD). METHODS: This cross-sectional study was carried on a total number of 80 patients with chronic liver disease divided into four groups: Group A and B included cirrhotic patients suffering from pruritis with and without cholestasis, while group C and D included patients without pruritis with or without cholestasis and group E included 17 healthy controls. They were subjected to measurement of serum autotoxin concentration by ELISA in addition to routine investigations including liver function tests: Total and direct bilirubin, ALT, AST, Alkaline phosphatase, Gama- glutamyl transferase, and serum albumin. RESULTS: There was a significant increase in autotaxin in the four groups included chronic liver disease patients (P-value <0.001*) compared to control group (group E). Autotoxin level was the only marker that had a significant increase in pruritus groups (groups A & B) compared to non-pruritus groups (groups C & D) with cut off value ≥ 32. CONCLUSION: Serum autotaxin level was elevated in patients with chronic liver diseases with pruritus. Autotaxin enzyme may play a key role in the induction of hepatogenic pruritus. So, autotaxin enzyme inhibitors and lysophosphatidic acid (LPA) receptor blockers could be a future line of treatment of hepatogenic pruritus.

Cytotoxicity and Anti-Inflammatory Effects of Polyherbal Formulations, Joint Pain Spl and Rumalaya Forte on Lipopolysaccharide Induced Inflammation in IC-21 Macrophages.

Koodalingam A, Rajalakshmi A, Parthiban E

Antiinflamm Antiallergy Agents Med Chem · 2021 · PMID 33397275 · Publisher ↗

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 c... 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.

Relationship Between Oxidative Stress, Tau Level and Antioxidant Mechanisms of the KEAP-1/NRF-2/HO-1 in Children with Hydrocephalus.

Guzelcicek A, Koyuncu I, Gönel A … +2 more , Cigdem G, Karadag M

Antiinflamm Antiallergy Agents Med Chem · 2021 · PMID 33371862 · Publisher ↗

BACKGROUND: Hydrocephalus is a complex neurologic disorder that has a widespread impact on the central nervous system and a multifactor disease which affects the CSF dynamics and causes severe neurological impairments in... BACKGROUND: Hydrocephalus is a complex neurologic disorder that has a widespread impact on the central nervous system and a multifactor disease which affects the CSF dynamics and causes severe neurological impairments in children. The pathophysiology of hydrocephalus is not fully understood. However, increasing evidence suggests that oxidative stress may be an important factor in the pathogenesis of hydrocephalus. OBJECTIVE: The purpose of this study is to investigate the relationship of the KEAP-1/NRF-2/HO-1 pathway, one of the main regulators of the antioxidant system in the hydrocephalus pathology, on oxidative stress and tau protein level. METHODS: The study included 32 patients with hydrocephalus and 32 healthy controls. KEAP-1, NRF-2, HO-1, TAU, and MPO levels are measured using ELISA method TAS, TOS, and Total THIOL colorimetric method. RESULTS: KEAP-1, TAS, and Total THIOL levels were found significantly lowerer in the hydrocephalus group than in the control group. Nevertheless, it was identified that in the hydrocephalus group that the NRF-2, HO-1, TAU, MPO, TOS, and OSI levels were significantly elevated. CONCLUSION: In conclusion, although the KEAP-1/NRF-2/HO-1 pathway is activated in patients with hydrocephalus, it is identified that the antioxidant defense system is insufficient and ultimately leads to elevated oxidative stress. The elevation in the tau level may be an indicator of oxidative stress induced neurodegenerative damage.

Triazol-phenyl Antipyretic Derivatives Inhibit mPGES-1 mRNA Levels in LPS-Induced RAW 264.7 Macrophage Cells.

Dos Santos LD, Froes TQ, Contin de Melo MC … +3 more , Petto de Souza GE, Soares DM, Castilho MS

Antiinflamm Antiallergy Agents Med Chem · 2021 · PMID 33292158 · Publisher ↗

BACKGROUND: Microsomal prostaglandin E synthase-1 (mPGES-1) catalyzes the terminal step of prostaglandin E2 (PGE2) production, which plays an important role in the regulation of febrile response. In our previous work, li... BACKGROUND: Microsomal prostaglandin E synthase-1 (mPGES-1) catalyzes the terminal step of prostaglandin E2 (PGE2) production, which plays an important role in the regulation of febrile response. In our previous work, ligand-based pharmacophore models, built with mPGES-1 inhibitors, were employed to identify a novel series of compounds that reduce the febrile response in rats. OBJECTIVES: The study aimed to evaluate the mechanism of action of the most active compound (1). METHODS: For in vivo assays, rats were pretreated with the antipyretic compounds 1-8, 30 min before LPS injection. For in vitro assays, RAW 264.7 macrophage cells were incubated with the antipyretic compounds 1-8 for 1 hour before LPS stimulus. After 16 h, quantitative real-time PCR was carried out. Additionally, the PGE concentration in the hypothalamus was quantified by ELISA and the inhibitory effect of N-cyclopentyl-N'-[3-(3-cyclopropyl-1H-1,2,4-triazol- 5-yl)phenyl]ethanediamide (1) over human COX-2 enzymatic activity was determined with a COX Colorimetric Inhibitor Screening Assay Kit. RESULTS: Compound 1 and CAY10526 showed comparable efficacy to reduce the febrile response when injected i.v. (compound 1: 63.10%, CAY10526: 70.20%). Moreover, compound 1 significantly reduced the mPGES-1 mRNA levels, in RAW264.7 cells, under inflammatory conditions. A chemically-similar compound (8-) also significantly reduced the mRNA levels of the gene target. On the other hand, compounds 6 and 7, which are also somewhat similar to compound 1, did not significantly impact mPGES-1 mRNA levels. CONCLUSIONS: PGE2 concentration reduction in the hypothalamus, due to compound 1 central injection, is related to decreased mPGES-1 mRNA levels but not to COX-2 inhibition (IC50> 50 μM). Therefore, compound 1 is a promising lead for innovative antipyretic drug development.
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