Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Anti-Inflammatory and Anti-Allergy Agents) - Volume 10, Issue 6, 2011

The present study is aimed at improving the dissolution of poorly soluble drug, rofecoxib, using solid dispersion technique. The solid dispersions were prepared in different proportions using hydrophilic carriers like mannitol, and urea. The dissolution rate studies were performed in both simulated gastric fluid and simulated intestinal fluid. It is observed that the dissolution was affected by the acidity of the medium. Solid dispersions gave faster dissolution rate when compared to corresponding physical mixture and pure drug. In vivo absorption and anti-inflammatory activity studies of solid dispersions also confirmed the above results. The DSC thermogram and IR spectra revealed that there is no interaction of Rofecoxib with additives and the drug, rofecoxib is stable in solid dispersions.

Extra virgin olive oil (EVOO) is consumed as part of the health promoting Mediterranean diet and contains several phenolic compounds that are responsible for the unique and distinctive flavour of EVOO. The phenolic fraction of EVOO also imparts many beneficial effects on human health. Oleocanthal is an EVOO phenolic that shares a unique perceptual quality with the non-steroidal anti-inflammatory drug (NSAID) ibuprofen and also mimics the anti-inflammatory actions of this drug. Oleocanthal has therefore been deemed a naturally occurring NSAID because of its demonstrated attenuation of cyclooxygenase (COX) activity in a dose dependent manner. New and emerging research has reported that oleocanthal also acts on inflammatory markers associated with neurodegenerative disease, joint degenerative disease, and cancer. This review will give an up-to-date summary of the history of oleocanthal and the current evidence establishing oleocanthal as a potent natural anti-inflammatory agent.

In the last decade, substantial progress has been made in the study of eicosanoid autacoids, such as leukotrienes [LTs], which were already known to be heavily involved in inflammatory skin processes. The subject has extended from the detailed description of 5-lipoxygenase cascade products and regulation to the discovery of detailed interrelations among LT physiology and apparently loosely related fields such as peroxisome-proliferating activating receptors (PPARs), pro-resolving mediators, control of fibrosing processes, and nuclear signalling. Many of these advances clearly present aspects which could be relevant to experimental and clinical dermatology. Surprisingly enough, and unfortunately due at least in part to restrictive policies in off-label use of drugs all over the world, the use of available LT modulators in dermatology has remained the same as ten years ago, with the significant but marginal exception of Sjögren-Larsson syndrome. From a dermatological viewpoint, the state of the art is far from desirable. A survey of relevant advances, with special regards to medicinal chemistry topics related to anti-inflammatory intervention is provided, together with visionary proposals for future, substantial improvement in the management of patients suffering from inflammatory skin diseases, in which LT-related pathogenetic and resolving mechanism play so important a role.

Histamine is a biogenic amine with a broad spectrum of activities in various physiological and pathological conditions. Beside its well characterized effects in allergic responses and acute inflammation, histamine modulates the cytokine network, influencing T helper 1 and T helper 2 balance and antibody isotype. In multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), there are several steps in the autoimmune attack against myelin of the central nervous system where histamine has been shown to play important roles. In this review, we summarize the evidences supporting the hypothesis of a significant contribution for histamine in autoimmune demyelinating diseases of the central nervous system. A deeper appreciation of the mechanisms by which histamine regulates the development of EAE and MS might have relevance in the therapy of these diseases.

Severe asthma developed into a major health problem since many patients suffering from this disease exhibit a high degree of resistance towards corticosteroid treatment. Thus, to date there is no effective therapy available, which frequently leads to hospitalization and necessity for critical care measurements including mechanic ventilation. While mild-to-moderate allergic asthma arises from a typical T helper 2 (TH2) cell directed allergic immune response characterized by corticosteroid-sensitive eosinophils, airway inflammation in patients suffering from severe asthma is commonly dominated by corticosteroid-insensitive neutrophils and additionally display highly proinflammatory TH17 cells. Both cell types, neutrophils and TH17 cells, bear the potential to aggravate the inflammatory response underlying formation of this disease, since they produce a plethora of mediators enabling them to communicate with structural cells of the airway wall as well as with other inflammatory cells already present in asthmatic airways. However, to date the role played by these cells in the processes leading to severe asthma is for away from being understood. This article aims to summarize the latest findings on that issue in order to give an update on the immunopathogenesis of severe asthma.

Objectives: Bioactivity guided fractionation of leaves of Vitex negundo for their anti-allergic and antioxidant activity and structure elucidation of active fraction responsible for these activities. Methods: Ethyl acetate fraction of leaves of Vitex negundo was fractionated into aqueous sub fraction, acetone sub fraction and chloroform sub fraction according to possible separation of chemical spots present in ethyl acetate fraction using thin layer chromatography and developed solvent system. Anti-allergic activity of aqueous sub fraction, acetone sub fraction and chloroform sub fraction was carried out using homologous passive cutaneous anaphylaxis model in rat. Antioxidant activity of aqueous sub fraction, acetone sub fraction and chloroform sub fraction was carried out using egg albumin induced oxidative stress in guinea pigs. Various spectroscopy methods like Ultraviolet-visible (UV) spectroscopy, Fourier-transform infrared (FT-IR) spectroscopy, Electron impact (EI)-Mass spectroscopy and Proton nuclear magnetic resonance (H1 NMR) spectroscopy were used to determine structure of active sub fraction of leaves of Vitex negundo that possesses anti-allergic and antioxidant activity. Results: Aqueous sub fraction produced significant lesser amount of dye leakage at 200 mg/kg (1.6648±0.0372; p<0.001), when compared with the control group (4.0094±0.2474; p<0.001). Animals treated with aqueous sub fraction showed significantly higher superoxide dismutase (SOD) activity, catalase activity and reduced glutathione level and lower malondialdehyde (MDA) level as compared to untreated sensitized animals. Structure of aqueous sub fraction was determined as a 5-hydroxy- 3,6,7,3’,4’-pentamethoxy flavone. Conclusion: Aqueous sub fraction of leaves of Vitex negundo possesses anti-allergic and antioxidant activity. It is identified as a 5-hydroxy-3,6,7,3’,4’-pentamethoxy flavone. It may be useful in the treatment of various allergic and immunologic diseases and to prevent oxidative stress in many diseases like cancer, liver injury, cardiovascular disease, asthma etc.

In an attempt for better treatment of bacterial infections and burn wounds various topical formulations containing 1%w/w of Curcuma longa were prepared and evaluated for physical appearance, pH, rheological properties and stability studies. Antimicrobial activity of prepared formulations was found to be more effective against various strains of bacteria. Carbopol gel base is the most suitable dermatological base for Curcuma longa in comparison to various other dermatological bases. It also has aesthetic appeal, which other bases lack, an important aspect from patient compliance and consumer point of view. The therapeutic potential of such topical formulations may motivate researchers for its further exploitation so that it may be commercially viable. This innovative mode of formulation of Curcuma longa can be employed for enhancing the anti-microbial effect.