Recent Patents on Inflammation & Allergy Drug Discovery - Volume 13, Issue 2, 2019

Background: Various pieces of evidence have shown that people who consume foods rich in polyphenolic and flavonoids compounds have a lower incidence of inflammatory, autoimmune diseases and cancer. Objective: The study aimed to review the most potent compounds that affect the immune response and diseases associated with it. Methods: Publications in PubMed and EmBase, from 1974-2018, and patents form Free patents online, Scifinder, Espacenet and Mendeley in which flavonoids, their semi-synthetic and synthetic derivatives are involved in immunosuppressive or immunostimulatory responses in vitro and in vivo. Results: In vitro, flavonoids and their derivatives inhibit various transcriptional factors, which modulate differentiation, proliferation, activation of immune cells and enhance regulatory T cell generation. Some flavonoids exert anti-inflammatory effects through: Blockade of NF-ΚB, and NLRP3 inflammasome, inhibition of pro-inflammatory cytokine production, IL-1β, IL-2, IL-6, TNF-α, IL-17A, down regulation of chemokines, and reduction of reactive oxygen and nitrogen species. Nevertheless, several reports have shown that some flavonoids enhance immune response by enhancing: oxygen and nitrogen radicals, antibody production, cytotoxic activity against tumours by increasing activating receptors and down regulating inhibitory receptors. In consequence, flavonoids may be potentially useful for treatment of infectious diseases and cancer. Conclusion: The most potent flavonoids in inflammation that modify immune responses are apigenin, quercetin and Epigallocatechin-3-Gallate (EGCG) although, other compounds are still under study and cannot be excluded. The most relevant patents concerning the use of flavones and other polyphenols were revised. A promising future of these compounds in different therapies is discussed.

Background: Inflammation has become pathology in the majority of the prevalent diseases such as diabetes, atherosclerosis, epilepsy and neurodegenerative disorders. Anti-inflammatory drugs work wonder in all these conditions, where the patient has become refractory to standard treatment. However, available anti-inflammatory agents have side effects associated with chronic use, thus if we could develop safe and efficacious molecules, quality of health care provided will improve. Since plant sources have been extensively explored, the focus needs to be shifted on the alternative natural sources of anti-inflammatory agents. Water bodies especially the sea and ocean are under investigation to find agents which can tackle inflammation. Objective: This article reviews anti-inflammatory agents obtained from five types of marine organisms namely microalgae, sea cucumber, mussels, sponges and corals. Methods: A literature search was conducted using PubMed/Science Direct with keywords marine organisms, inflammation, marine sponges, sea cucumber, mussels, corals and microalgae. Patents were searched using the key terms inflammation, marine agents from www.google.com/patents, www.uspto.gov, http://espacenet.com, www.freepatentsonline.com, www.wipo.int/pctdb/en/searchsimp. jsp and www.freshpatents.com. Results: Literature and current patents have revealed applications of anti-inflammatory agents from marine organisms in pharmaceuticals and cosmeceuticals. These agents are used to treat inflammatory disorders ranging from minor allergy to chronic conditions like rheumatoid arthritis. Marine waste is also a valuable resource for nutraceuticals and anti-inflammatory agents. Conclusion: The findings reveal that marine organisms could be a promising source of novel antiinflammatory agents. However, further investigations are suggested for the isolation and identification of bioactive, exploring the mechanism of action and evaluating the efficacy in various inflammatory conditions.

Background: Among the various phenolics metabolites, ferulic acid is considered as the promising mitigating, restorative and antioxidant agent. Ferulic acid is one of the most commonly found natural products in vegetables, for example, tomatoes, sweet corn, and in rice grain. Phytochemicals are utilized in the treatment of human ailments and these are derived from the dietary compounds. Objective: The present review widely argued the calming restorative capability of ferulic acid alongside the scientific evidences and its proposed mechanism for activity. Furthermore, we provided the main practical points for the use of ferulic acid in oxidative damages during various diseases. Additionally, the relevant patents on ferulic acid with various therapeutic potential has been discussed. Methods: The approach consisted of searching several resources, including theses, technical reports, web-based scientific databases such as publications on PubMed, ScienceDirect, Springer, PROTA, Google Scholar, and other allied databases. Thus, recent patent regarding the role of ferulic acid therapeutic potenitial has been discussed. Results: One hundred and twenty references have been cited in the present review article. The cited references were found to be suitable and described the therapeutic application of ferulic acid thoroughly. Conclusion: Ferulic acids are known to contrarily down-manage an assortment of extracellular and intrcelullular molecular targets related to infection movement. Various patents on ferulic acid based moieties have been accounted for from 2018. The ferulic acids have a wide scope of impacts against different infections like malignant growth, diabetes, cardiovascular and neurodegenerative diseases. The current review deals with the antioxidant property of ferulic acid and the recent patent describes the role of ferulic acid against human diseases.

Background: Natural products represent a therapeutic option for the treatment of inflammation- associated diseases. Flavonoids which are one of the special categories of such natural products, have previously shown promising therapeutic potential. Objectives: The current review discusses the synthetic preview and anti-inflammatory potential of apigenin along with the underlying molecular mechanism in chronic human diseases especially cancer. In addition, the relevant patents on the therapeutic potential of apigenin have also been mentioned. Methods: A literature search was carried out using PubMed/Science, Google Scholar, etc. which was further expended by the different combination of keywords: apigenin, inflammation, mechanism, therapeutic potential, cancer, etc. Patent information was retrieved by searching the key terms: apigenin, inflammation, therapeutic potential from various databanks including Espacenet, Google Patents, Free Patents Online and Mendeley of WIPO, USPTO, SIPO, JPO, KIPO and EPO databases. Results: A total of 76 references have been found relevant with the theme of the manuscript. These citations have described recent ongoing advances in the area of inflammation and cancer with respect to apigenin. Conclusion: Studies related to the anti-inflammatory and anticancer potential of apigenin have been explored through this review article. Moreover, the patent analysis of apigenin has further strengthened its therapeutic role. Probing into the therapeutic properties of apigenin, further adds value to this molecule in terms of its downregulation of major inflammatory and cancer-associated signaling pathways. The article would simultaneously assist the scientific community to precisely understand the role of apigenin and design novel anti-cancer therapies.

Background: Giardiasis is an important cause of waterborne and foodborne diarrhea, daycare center outbreaks, and traveler's diarrhea. Objective: The study aimed to provide an update on the evaluation, diagnosis, and treatment of giardiasis. Methods: A PubMed search was completed in Clinical Queries using the key terms “giardiasis”, "Giardia lamblia", "Giardia duodenalis" and "Giardia intestinalis". The search strategy included metaanalyses, randomized controlled trials, clinical trials, observational studies, and reviews. The search was restricted to the English literature. Patents were searched using the key term “giardiasis” from www.freepatentsonline.com. Results: Giardiasis is caused by the protozoan parasite Giardia lamblia. The parasite is transmitted by the fecal-oral route, frequently through ingestion of contaminated water and food or person-to person transmission. Risk factors for infection include children in day-care settings, child-care workers, institutionalized individuals, travelers in endemic areas, ingestion of contaminated or recreational water, immunodeficiency, cystic fibrosis, and oral-anal sex. Approximately 50 to 75% of infected children are asymptomatic. Other children present acute or chronic diarrhea. Direct fluorescent antibody tests that detect intact organisms, enzyme immunoassays that detect soluble antigens, and multiplex real-time polymerase chain reaction assays that detect specific genes of the parasite in stool samples have improved sensitivity and specificity compared with microscopic examination of stool specimens for the detection of Giardia trophozoites or cysts. Drugs used in the treatment of symptomatic giardiasis are reviewed in this study. Moreover, recent patents related to the management of giardiasis are also discussed. Conclusion: Metronidazole, tinidazole, and nitazoxanide are drugs of choice. Resistance to common antigiardial drugs has increased in recent years, therefore, the search for new molecular targets for antigiardial drugs is urgently needed. In general, treatment of asymptomatic carriers is not recommended. Purification of water supply is an important preventive measure.

Background: Antifungal azoles are the first-line agents used to treat topical and, above all, systemic mycosis. The latter could be life-threating infections in immunocompromised patients. Chemotherapeutic antibiotics, including antifungal azoles, may induce hypersensitivity reactions; however, such immunologic adverse reactions have not been defined and carefully investigated. Objective: The study aims to provide an update on the evaluation and diagnosis of skin allergy to azole antifungal agents. Methods: This is a systematic review performed on PubMed and Google Schoolbarusing using the key terms “allergy, hypersensitivity, anaphylaxis, immediate-type reaction, delayed-type reaction, ketoconazole, fluconazole, posaconazole, voriconazole, itraconazole, triazoles, imidazoles, antifungals, antimycotics”. The search strategy included meta-analyses, randomized controlled trials, clinical trials, observational studies, reviews and case reports. Results: One hundred twenty-four articles matched our search terms. The most common adverse events reported were T-cell mediated delayed-type hypersensitivity reactions, fixed drug eruptions, exanthematous dermatitis, Steven-Johnson syndrome, toxic epidermal necrolysis and acute generalized exhanthematous pustulosis. Rarely a drug rash with eosinophilia systemic symptoms, has been described. Also, immediate-type reactions such as urticaria-angioedema or anaphylaxis have been reported following the administration of antifungal imidazoles, although not so frequently. Conclusion: Despite their widespread use, triazoles seem to induce rare cutaneous hypersensitivity reactions, but the pathomechanisms, risk factors, diagnostic and management strategies, including skin tests and challenge tests, are little known and poorly investigated.

Background: Endothelial injury occurring during cardiopulmonary bypass is a major contributing factor in the development of organ dysfunction, which leads to many of the postoperative complications occurring during cardiac surgery. Objective: This narrative review aims to summarize the main mechanisms of cardiopulmonary bypass - related disease, evaluating the unfavorable events leading to tissue injury, with a description of current pharmacologic and non-pharmacologic mechanisms to reduce CPB-related injury. Methods: A Medline/Pubmed/Scopus search was conducted using clinical queries with the key terms "cardiac surgery", “cardiopulmonary bypass”, "inflammation" and “endothelial injury”, and related MeSH terms, until July 2019. The search strategy included meta-analyses, randomized controlled trials, clinical trials, reviews and pertinent references. Patents were searched using the same key terms from https://patents.google.com/, www.uspto.gov, and www.freepatentsonline.com. Results: In this review, we discuss the current knowledge of the mechanisms of vascular endothelial cell injury, the acute inflammatory response, and the regulatory factors that control the extent of vascular injury during extracorporeal circulation, summarizing the main target of anti-inflammatory pharmacologic and non-pharmacologic strategies. Conclusion: Inflammatory response and endothelial dysfunction following cardiopulmonary bypass are the prices to pay for the benefits offered during cardiac surgery procedures. Counteracting the detrimental effect of extracorporeal circulation appears to be crucial to improve clinical outcomes in pediatric and adult cardiac surgery. The intrinsic complexity and the tight interplay of the factors involved might require a holistic approach against inflammation and endothelial response.