Recent Patents on Inflammation & Allergy Drug Discovery - Volume 10, Issue 2, 2016

Background: The modern way of life involves high stress levels, poor eating habits, lack of exercise, obesity and other detrimental health factors. Nutritional supplements (NS) are complexes of nutrients with variant activity that may infer reversal to nutrient depletion. They tend to be popular amongst social categories associated with the healthy life style, such as the elite and amateur athletes, military people and the general population. Objective: An overview of the state of play with regard to nutritional supplements - natural and synthetic-, is important both from toxicological and commercial point of view. Method: From a thorough literature review on nutritional supplements, several patents of application have been identified and herewith reviewed which recommend natural vegetable extracts as food supplements for prophylaxis, therapy, protection of immune system, diabetes, oxidative stress, cancer, chronic inflammations and other health conditions. Besides, nutritional supplements of pharmacological validity and high popularity are discussed relative to their contents and group of use. Results: Cases of adulteration or unintentional contamination of commercial products with abusing substances (doping substances, narcotics etc.) or toxic compounds (heavy metals, plant toxics) have shed light to the problem of causing recalls of some products by the FDA. Conclusion: From the safety/ quality point of view, NS lack of harmonisation and sovereign laws/ institutional controls on the market and their wide commercialization may possibly lead to risks to public health.

Background: In the recent past, a wider spectrum of nanotechnologybased drugs or drug-loaded devices and systems has been engineered and investigated with high interests. Objective: The key objective is to help for an enhanced/better quality of patient life in a secure way by avoiding/limiting drug abuse, or severe adverse effects of some in practice traditional therapies. Method: Various methodological approaches including in vitro, in vivo, and ex vivo techniques have been exploited, so far. Among them, nanoparticles-based therapeutic agents are of supreme interests for an enhanced and efficient delivery in the current biomedical sector of the modern world. Results: The development of new types of novel, effective and highly reliable therapeutic drug delivery system (DDS) for multipurpose applications is essential and a core demand to tackle many human health related diseases. In this context, nanotechnology-based several advanced DDS have been engineered with novel characteristics for biomedical, pharmaceutical and cosmeceutical applications that include but not limited to the enhanced/improved bioactivity, bioavailability, drug efficacy, targeted delivery, and therapeutically safer with an extra advantage of overcoming demerits of traditional drug formulations/designs. This review work is focused on recent trends/advances in nanotechnology-based drugs and formulations designed for targeted therapeutic delivery. Moreover, information is also reviewed and given from recent patents and summarized or illustrated diagrammatically to depict a better understanding. Recent patents covering various nanotechnology-based approaches for several applications have also been reviewed. Conclusion: The drug-loaded nanoparticles are among versatile candidates with multifunctional characteristics for potential applications in biomedical, and tissue engineering sector.

Background: Heat shock proteins (HSPs) are highly conserved proteins present in all kingdoms of organisms. These are expressed under stress conditions in order to protect the cells from injuries. The stress induced protein denaturation is rectified by refolding and remodelling. These are intracellular proteins but can be present in extracellular fluid like serum of the patients suffering from trauma, autoimmune and inflammatory disorders. Virtually in most inflammatory diseases, immune response towards HSPs is developed. Objective: The present review expedites the role of HSPs in inflammatory process and associated disorders, mainly in context to HSP70 and HSP90. Method: Commencing a thorough survey of the literature and patents available on HSPs and their role in the process of inflammation, from the authentic published resources available on Medline, Pubmed, Pubmed Central, Science Direct and other scientific databases; the information retrieved has been compiled and analyzed. Results: HSPs modulate the process of inflammation by producing anti-inflammatory cytokines in chronic inflammatory disease. HSPs mediated expression of IL10 contributes in anti-inflammatory role via TLR2 and TLR4-dependent mechanisms. Necroptosis, a caspase independent programmed apoptosis plays an important role in progression of several inflammatory disorders and its major components MLKL and RIPK-1 are the clients of HSP. Necroptosis is also involved in exposure of several damageassociated molecular patterns (DAMPs) including HSPs in extracellular environment leading to inflammation. Endocytosed or intracellular HSP70, is presented by MHC-II molecules and in absence of proper co stimulation, it lead to expansion of tolerogenic or regulatory T cells (Tregs) responses, which have inflammation suppressive activity by virtue of production of anti-inflammatory cytokines, suppression or killing of effector T cells or bringing the APC into tolerogenic state. HSP induced Tregs play an important role in combating autoimmunity and inflammation. Conclusion: Present review gives an insight towards the cause of inflammation and an account of different HSPs contributing various inflammatory disorders viz. inflammatory bowel disease (IBD), intestinal inflammation, atherosclerosis, rheumatoid arthritis (RA), multiple sclerosis etc. The importance of HSPs in handling inflammatory disorders has been depicted in recent patents also.

Background: Probiotics constitute the viable and beneficial microbes, which offer a dietary means to sustain the balance of gastro-intestinal (GI) microflora. Owing to their multiple health benefits, these have recently gained wide attention among researchers for exploring their potential in safeguarding the health of humans and animals. Probiotics could also modulate host-immune responses, thereby help in counteracting the immunological dysfunctions. Probiotics can inhibit the systemic invasion of pathogens entering through the GI mucosa/ oral cavity and have been found to possess effective prophylactic and therapeutic utilities against various infectious pathogens as well as non-infectious diseases and disorders. Objective: The present review expedites the role of probiotics in curing the ailments related to allergic and inflammatory disease conditions. Method: A thorough reviewing of the literature and patents available on probiotics and their role in countering inflammation and allergy was conducted using authentic published resources available on Medline, PubMed, PubMed Central, Science Direct and other scientific databases. The information retrieved has been compiled and analysed pertaining to the theme of the study. Results: Various micro-organisms have been evaluated for their probiotic efficacy, among these, the lactic acid bacteria viz. Lactobacillus sp. and Bifidobacterium sp. have extensively been studied and widely exploited. In the current post-globalized era of self and complementary medicines, the concept of probiotics and their therapeutic as well as prophylactic usage is gaining wide acceptance. As more and more bacterial strains are being proven for their pronounced influence on down regulation of immune regulation, atopic, inflammatory conditions, the use of probiotics is getting increased especially in the developed countries where such indications are high in prevalence. Apart from usage in immune related disorders, probiotics have been found to be effective in treating pouchitis, infantile diarrhoea due to infections, bacterial vaginosis, urinary tract infections, dental carries, diabetes, cancers as well augmenting the gut mucosal tolerance to various antibiotics and lactose intolerance. Conclusion: The resent review gives an insight towards potent utility of this branch of beneficial microbial therapy in allergy and inflammations, which is still in the emerging phase and more scientific evidences need to be explored regarding exploration of the mechanisms of action, further experimental trials and validation of controlled clinical studies in humans along with designing novel strategies for monitoring the possible microbial changes in their composition and metabolism associated with their interaction upon host immune system.

Background: Nuclear factor-kappaB (NF-kappaB) has been reported to regulate various genes involved in cancer and inflammation. Accordingly, drugs inhibiting NF-kappaB may possess both anti-inflammatory and anticancer properties. So there is a need to discover novel compounds which should not only be a potential lead but also less toxic and cost effective. Objectives: The aim of the study was to develop new synthetic anti-inflammatory and cytotoxic agents targeting NF-kappaB. Methods: Test compounds were synthesized and characterized by UV, IR, 1H-NMR, 13C-NMR and mass spectrometry. The synthesized compounds were evaluated for in vitro cytotoxicity by MTT assay against various cancer cell lines and in vivo anti-inflammatory in carrageenan-induced paw edema model. Selected compounds were subjected to cell cycle analysis using propidium iodide. Docking study was done into an active site of NF-kappaB using Auto Dock 4.2. Result: Three series of compounds were synthesized and characterized by various spectroscopic techniques. The test compounds (10b), (1c) and (2c) were found to be the most potent anti-inflammatory agents, whereas compounds such as (10b), (6b), (4b), (2b), (6a), (4a), (5c) and (3c) have shown promising cytotoxicity in different cancer cell lines, followed by cell cycle analysis of selected compounds ((10b) and (4b)). The free energy of binding of ligands was in the range between -6.47 to -12.50.Kcal/ mole. Conclusion: compound (10b) was found to be the most potent as both anti-inflammatory and cytotoxic agents. In silico approach was in good tune with the wet lab experiments. The promising compounds have shown to induce cell cycle arrest at G2/M Phase.

Background: No trial has examined the effect of lovastatin on the brain metabolites in patients with bipolar mood disorder. Objectives: Current medications for treating bipolar disorders cause metabolic syndrome. It is supposed that lovastatin not only decreases the rate of metabolic syndrome but also impacts some brain metabolites and their ratio like common treatments that are measured by Magnetic Resonance Spectroscopy. Methods: 27 Manic phase patients were randomly allocated into two groups, lovastatin and placebo as their adjuant medication. Clinical symptoms were assessed at baseline, weeks 2, 4. The brain metabolites were measured at baseline and week 4. Result: Regarding the change of clinical symptoms, no significant difference was found between two groups. However, lovastatin significantly increased the level of NAA in cingulate gyrus in comparison to the placebo group. Moreover, lovastatin more than placebo increased creatine in the left basal ganglia. Furthermore, choline/ creatine showed a significant decrease in the left basal ganglia in lovastatin group. Conclusion: Using MRS after treating with lovastatin showed lovastatin increases NAA in cingulate gyrus, indicating the possible effect of NAA for increasing the reduced viable neuron. Moreover, the increment of Cr by lovastatin in the left basal ganglia suggests the role of lovastatin for maintaining energy homeostasis, anti-apoptotic activity and ATP production in bipolar disorder. Some patents using lovastatin as an adjuant therapy for treating bipolar patients and depression in MDD patients are also outlined. This trial was registered in the Iranian Clinical Trials Registry (http://www.irct.ir/) (IRCT201302203930N18).