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

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 HT₅₀ (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 (IC₅₀= 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.

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.

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.

Background: Saccharumoside-B and its analogs were found to have anticancer potential in vitro. The present study reports acute toxicity, molecular docking, ADMET profile analysis, and in vitro and in vivo anti-inflammatory activity of saccharumoside-B for the first time.

Methods: The in vitro enzyme inhibitory activity of saccharumoside-B on PLA2, COX-1, COX-2, and 5-LOX enzymes was evaluated by the cell-free method, and its effect on TNF-α, IL1β, and IL- 6 secretion levels in LPS stimulated THP-1 human monocytes was determined by ELISA-based methods. The anti-inflammatory activity was evaluated in vivo by carrageenan-induced rat paw edema model. To test its binding affinity at the active site pockets of PLA2 enzymes and assess drug-like properties, docking experiments and ADMET studies were performed.

Results: Saccharumoside-B showed selective inhibition of the sPLA2 enzyme (IC50 = 7.53 ± 0.232 μM), and thioetheramide-PC was used as a positive control. It showed significant inhibition (P ≤ 0.05) of TNF-α, IL-1β, and IL-6 cytokines compared to the positive control dexamethasone. Saccharumoside-B showed a dose-dependent inhibition of carrageenan-induced rat paw edema, with a maximum inhibition (76.09 ± 0.75) observed at 3 hours after the phlogistic agent injection. Saccharumoside-B potentially binds to the active site pocket of sPLA2 crystal protein (binding energy -7.6 Kcal/Mol). It complies with Lipinski's Rule of Five, showing a promising safety profile. The bioactivity scores suggested it to be a better enzyme inhibitor.

Conclusion: Saccharumoside-B showed significant PLA2 inhibition. It can become a potential lead molecule in synthesizing a new class of selective PLA2 inhibitors with a high safety profile in the future.

Alzheimer's disease (AD), the most prevalent form of age-related dementia, is typified by progressive memory loss and spatial awareness with personality changes. The increasing socioeconomic burden associated with AD has made it a focus of extensive research. Ample scientific evidence supports the role of neuroinflammation and oxidative stress in AD pathophysiology, and there is increasing research into the possible role of anti-inflammatory and antioxidative agents as disease modifying therapies. While, the result of numerous preclinical studies has demonstrated the benefits of anti-inflammatory agents, these benefits however have not been replicated in clinical trials, necessitating a further search for more promising anti-inflammatory agents. Current understanding highlights the role of diet in the development of neuroinflammation and oxidative stress, as well as the importance of dietary interventions and lifestyle modifications in mitigating them. The current narrative review examines scientific literature for evidence of the roles (if any) of dietary components, nutraceuticals and functional foods in the prevention or management of AD. It also examines how diet/ dietary components could modulate oxidative stress/inflammatory mediators and pathways that are crucial to the pathogenesis and/or progression of AD.

Inflammation is an acute adaptive response to injury. However, if the initial inflammatory response to an injury is not completely healed, it becomes chronic low-level inflammation that is strongly associated with many chronic disease states, including metabolic (obesity and diabetes), cardiovascular, auto-immune, and neurogenerative disorders as well as cancer. The healing process is far more complex than the initiation of inflammation. Within that complexity of healing is a sequence of events that are under profound dietary control and can be defined by specific blood markers. Those molecular events of the healing process that are under significant dietary control are termed as the Resolution Response. The purpose of this review is to describe the molecular components of the Resolution Response and how different dietary factors can either optimize or inhibit their actions. In particular, those dietary components that optimize the Resolution Response include a calorie-restricted, protein-adequate, moderate-carbohydrate, low-fat diet referred to as the Zone diet, omega-3 fatty acids, and polyphenols. The appropriate combination of these dietary interventions constitutes the foundation of Pro-Resolution Nutrition. The effect of these dietary components the actions of NF-κB, AMPK, eicosanoids, and resolvins are described in this review, as well as ranges of appropriate blood markers that indicate success in optimizing the Resolution Response by dietary interventions.

Background: A large amount of evidence has described that asthma may be associated with a high epilepsy risk, and epilepsy may be linked with high asthma risk, especially among children and individuals in their 30s. Curiously, asthma has also been associated with an increased risk for schizophrenia. Most interestingly, a bidirectional link between schizophrenia and epilepsy has also been established and has been of interest for many years.

Objective: Bearing in mind the experience of our group in the field of Ca²⁺/cAMP signalling pathways, this article discussed, beyond inflammation, the role of these signalling pathways in this link among epilepsy, asthma, and schizophrenia.

Methods: Publications involving these signalling pathways, asthma, epilepsy, and schizophrenia (alone or combined) were collected by searching PubMed and EMBASE.

Results and conclusion: There is a clear relationship between Ca²⁺ signalling, e.g. increased Ca²⁺ signals and inflammatory responses. In addition to Ca²⁺, cAMP regulates pro- and anti-inflammatory responses. Then, beyond inflammation, the comprehension of the link among epilepsy, asthma, and schizophrenia could improve the drug therapy.

Background: In Algerian traditional medicine, Centaurea species are well known in traditherapy. Centaurea africana has been used in folk medicine for the treatment of several inflammatory disorders.

Objective: This study aims to examine the antioxidant, anti-inflammatory and anti-proliferative potential of both n-Butanol (BECA) and ethyl acetate (EAECA) extracts of Centaurea africana.

Methods: The phytochemical analysis of both BECA and EAECA were explored and the antioxidant activities were investigated by measuring the DPPH° scavenging effect, the reducing power and the inhibition of lipid peroxidation (LPO) induced by by Fe²⁺/ ascorbic acid system. The antiinflammatory properties were determined by measuring the NO° scavenging effect and by using carrageenan-induced rat paw oedema. The antiproliferative activity was studied on HT29 (human colorectal adenocarcinoma), OV2008 (human ovarian cancer) and C6 (Rattus norvegicus brain glioma) cell lines using the Sulforhodamine B assay.

Results: The total polyphenol contents (TPC) of EAECA and BECA are recorded at 125.24±10.14 and 53.03±2.50 mgGAE/g extract, respectively. Both extracts revealed the antioxidant activity in a concentration-dependent manner; this effect is more pronounced with EAECA. The BECA exhibited a higher anti-inflammatory activity. This anti-inflammatory activity was reflected in a reduction of swelling of carrageenan-evoked edemas (48.45 %), inhibition of nitric oxide (84.7 %), effective decrease in myeloperoxidase activity (58.82 %) and malondialdehyde level (65.58 %). The cytotoxic effect of BECA was found to be more pronounced against C6 cell lines (IC₅₀ value: 131.93 μg/mL) while the cytotoxic activity of EAECA was more effective against HT29 and OV2008 cell lines.

Conclusion: The obtained results indicated that EAECA exhibited a high antioxidant activity, while BECA has significant anti-inflammatory activity. Both extracts showed cytotoxic effects against cancer cell lines at certain concentrations in a cell-specific manner.

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 H₂O₂ 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 H₂O₂ method (73.58%) at 200 μg mL^-1. 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.

Introduction: Benign Prostatic Hyperplasia (BPH) is a benign tumor in males, which is histopathologically known with an increase of epithelial cells and prostatic stroma. Androgens, estrogens, stroma-epithelial interactions, growth factors, and chronic inflammation play a key role in the occurrence of BPH. Chronic inflammation in BPH is characterized by excessive expression of COX-2, which will trigger the expression of Bcl-2 anti-apoptotic protein. Dayak onion (Eleutherine Americana Merr) is a typical Kalimantan plant that is known as the treatment for prostate disease. This plant contains flavonoids which can inhibit the COX-2 enzyme thus causing a reduction in the production of prostaglandin E2.

Methods: This research was experimental research computationally and in vitro laboratory experimental research to determine COX-2 inhibitory activity by ethanol extracts of Dayak onion.

Results and discussion: In in silico flavonoid, it was strongly related to COX-2 receptor on the active side of TYR371. Thus, it had the potential to inhibit COX-2. COX-2 inhibitor would cause BCL-2 to be inactive so that apoptosis occurr in BPH. In the in vitro research using human whole blood assay, the Dayak Onion bulb ethanol extract had IC50 COX-2 of 40.57 ng/ml and IC50 COX-1 of 364.89 ng/ml. Therefore, the ratio of IC50 COX-2 to IC50 COX-1 was 0.11.

Conclusion: Ethanol extract of Dayak onion bulb has an inhibitory activity against COX-2. Thus, it has a potential of being an innovation for BPH treatment. Patient Summary: A healthy male, age 25-35 years old (history taking, physical and laboratory examination), and not using NSAIDs for the past 2 weeks.