Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Anti-Inflammatory and Anti-Allergy Agents) - Volume 9, Issue 2, 2010

In the last years natural products have been re-discovered as valuable and effective pharmacological agents. In particular they were shown to exert positive effects in the therapy of acute and chronic diseases, like cancer and microbial syndromes, for which the use of chemotherapeutics or antibiotics failed due to increasing resistance. To this concern, many examples of natural products were reported in the recent and current literature. The aim of this special issue is to collect reviews from several research groups to get further insights in the up to date knowledge in the field of anti-inflammatory and anti-allergy agents obtained from the natural kingdom. Such an issue would be of great interest for several categories of scientists operating in natural product chemistry, phytochemistry, pharmacology, molecular biology, pharmacognosy, and others.

Recent research on the olive oil phenolic oleocanthal has led to speculation that it may confer some of the health benefits associated with a traditional Mediterranean diet. Oleocanthal produces a peppery, stinging sensation at the back of the throat similar to that of the non-steroidal anti-inflammatory drug (NSAID), ibuprofen. This led to the hypothesis that the perceptual similarity between oleocanthal and ibuprofen may indicate similar pharmacological properties. Subsequent studies have proved the hypothesis and oleocanthal was shown not only to inhibit inflammation in the same way as ibuprofen does, but on equi-molar basis it was found to be more potent than ibuprofen. It is important to note that inflammation has been demonstrated to play a significant role in the development of a number of chronic diseases, such as cardiovascular disease (CVD) and certain types of cancers. Therefore, as a result of dietary intake of olive oil, a reduction in inflammation produced by oleocanthal is speculated to be the mechanism that is partially responsible for the health benefits associated with the traditional Mediterranean diet. This review summarizes the current knowledge on oleocanthal, in terms of its physiological and sensory properties, as well as a discussion on the factors that have the ability to affect oleocanthal concentrations in extra virgin olive oils (EVOOs).

Today, chronic diseases, such as cancer, obesity and type II diabetes, cardiovascular diseases, neurodegenerative diseases, and aging are replacing worldwide morbidity and mortality from infectious diseases. In addition, various links have been established between diet and a range of chronic diseases. Thus, nutrition research has shifted from focusing exclusively on alleviating nutrient deficiencies to stressing chronic diseases prevention. The Mediterranean diet, representing the dietary pattern usually consumed among the populations bordering the Mediterranean Sea, has been widely reported to be a model of healthy eating for its contribution to a favorable health status and a better quality of life. Though the healthful properties of the Mediterranean diet as a whole gained recognition, basic researchers are nowadays concentrating their efforts on individual food items, e.g. cereals, fruits, vegetable, olive oil, and their components (e.g. fibers, vitamins, polyphenols). Today there is a growing interest in the composition of manufactured functional foods with health protective properties. Inflammation is a complex stereotypical reaction of the body expressing the response to damage of its cells and vascularized tissues. A number of various mediators are implicated in this phenomenon. Essentially, inflammation involves a cellular and oxidative component. The cellular component involves the movement of leukocytes from blood vessels into the inflamed tissue. Once leukocytes arrive at sites of infection and/or inflammation, they release mediators, which control the subsequent accumulation and activation of other cells. Many enzymes, like cellular phospholipases, especially phospholipase (PLA) A and C, are activated during inflammation and degrade phospholipids to arachidonic acid (AA) as well as the enzymes implicated in the enzymatic oxidation of AA like prostaglandin synthases, cyclooxygenases (COXs) and lipoxygenases (LOXs). In addition, reactive oxygen species (ROS), including hydroxyl radicals (.OH), superoxide anion (O2 -.), hydrogen peroxide and ferric radical, mediate cell damage in a variety of pathophysiological conditions and are responsible for oxidative injury of enzymes, lipid membranes, and DNA in living cells and tissues. Nitric oxide (NO) also plays a role as an effector in inflammation. Natural agents have been ethnomedically used for thousands of years for the treatment of several pathologies and have mostly proven to be safe. Recently, in vivo and in vitro studies showed potential anti-inflammatory role for some of the existing natural agents. Indeed, results from cross-sectional studies and feeding trials in Mediterranean populations suggest that the Med-Diet has beneficial anti-inflammatory effects. The recent observation that dietary compounds can epigenetically reprogram gene expression via DNA methylation changes has important implications for cancer prevention and chronic inflammatory disease. In a broader context, there is growing interest in dietary modulators of DNA methyltransferases, histone deacetylases (HDAC), and sirtuin (SIRT) deacetylases and their impact on epigenetic inflammatory mechanisms affecting health and disease. This review provides an overview of the literature related to the anti-inflammatory effects of some of the natural products included in Mediterranean diet which have potential value in the treatment of inflammatory diseases.

Inflammation is nowadays well known to be involved in the development of several chronic diseases such as arteriosclerosis, obesity, diabetes, neurodegenerative diseases, and cancer. Treatment for chronic inflammatory disorders has not been solved yet, and there is an urgent need to find new and safe anti-inflammatory preventive and therapeutic compounds. Medicinal mushrooms have been traditionally used in Asian countries to manage and treat different diseases. On the other hand, edible mushrooms have recently attracted much interest as a functional food because of their antimutagenic, anti-tumoral, anti-viral, anti-thrombotic, hypocholesterolemic, hypolipidemic, and anti-oxidant properties. Among all of these healthy properties, special attention was paid to the immunomodulatory activity of some fungal compounds such as polysaccharides, mainly β-glucans. Recently, some studies have demonstrated that both whole mushrooms and extracts may show anti-inflammatory activity due to the presence of bioactive compounds. This review summarizes the most recent studies investigating immunomodulatory and especially, anti-inflammatory properties of both medicinal and edible mushrooms, the compounds putatively implicated and the mechanisms that were already established.

Skin aging is intrinsic and among the main causes there is the exposure to solar ultraviolet (UV) radiation, which can also lead to skin cancer. The photo-aging or cancer mechanisms include inflammation, oxidative stress from reactive oxygen species (ROS), altered expression of genes, and direct or indirect damage to cellular molecules. The primary inflammatory mediators are interleukin-1 (IL-1), interleukin -6 (IL-6), tumor necrosis factor-alpha (TNF-α) and cycloxygenases (COX)/prostaglandins (PGs). Skin aging and cancer manifests as damage to the extracellular matrix (ECM) composed predominantly of collagen, elastin, and fibrillin. The cells responsible for ECM alterations include epidermal keratinocytes, dermal fibroblasts, and neutrophils. The remodeling of the ECM, primarily as the consequence of inflammation, in skin aging or cancer is from reduced synthesis and increased expression of matrixmetalloproteinases (MMPs). The MMPs degrade the extracellular matrix (ECM) and facilitate metastasis. The predominant classes of MMPs include collagenases (MMP-1, 3) and gelatinases (MMP-2, 9) that degrade the interstitial collagen and basement membrane. In addition, the cellular inhibitors of MMPs, tissue inhibitors of MMPs (TIMPs), and a primary regulator of extracellular matrix (ECM) deposition, transforming growth factor-β (TGF-β), are lowered in skin aging and/or cancer. Polyphenols and flavonoids may be the solution to inflammation associated with skin aging and cancer. P. leucotomos (a tropical fern plant) extract is rich in polyphenols with properties to counteract skin aging mechanisms from its antioxidant and anti-inflammatory properties: it inhibits oxidative stress, lipid peroxidation, dermal mast cell infiltration, inflammatory cytokines, DNA damage, and UV induced tumors. The anti-inflammatory effects of xanthohumol, a flavanoid, include inhibition of COX/PGs and NF-kB transcription factor that is associated with pro-oxidation and inflammation. Further, xanthohumol inhibits nitric oxide production. In addition to the inhibition of inflammatory mediators, polyphenols and flavonoids may stimulate anti-inflammatory mediators such as TGF-β for skin health.

Accumulating epidemiological, clinical, and experimental evidence demonstrates that chronic inflammation plays a critical role in multistep oncogenesis. While long-term users of selective cycloxygenase (COX)-2 inhibitors (- coxibs) and non-steroidal anti-inflammatory drugs (NSAIDs) exert a reduced risk of development of certain types of cancer, including colorectal cancer (CRC), the adverse gastrointestinal and cardiovascular side effects associated with these drugs have limited their daily use for cancer chemoprevention. The role of various proinflammatory mediators during carcinogenesis and their promise as potential targets for chemoprevention of inflammation-associated carcinogenesis has been recently highlighted. A variety of chemopreventive phytochemicals and phytonutrients are able to alter or correct undesired cellular functions caused by abnormal pro-inflammatory signal transmissions that are mediated by NF-kappaB, etc. Modulation of cellular signaling involved in chronic inflammatory responses, induced by anti-inflammatory agents, hence provides a rational and practical strategy in molecular target-based cancer chemoprevention. This short review will focus on the role of chronic inflammation in colorectal oncogenesis and introduce dietary cancer chemopreventive agents with anti-inflammatory activity.

Oxyprenylated natural products (isopentenyloxy-, geranyloxy- and the less spread farnesyloxy- compounds and their biosynthetic derivatives) represent a family of secondary metabolites that have been considered for years just as biosynthetic intermediates of the most naturally widespread C-prenylated derivatives. Only in the last decade have these natural products been recognized as interesting and valuable biologically active phytochemicals. Up to now about 300 molecules were isolated from plants mainly belonging to the families of Rutaceae, Apiaceae, and Compositae, comprising common edible vegetables and fruits. A wide variety of compounds containing a prenyloxy side chain has been isolated and among these coumarins, cinnamic acids and aromatic ketones displayed the most efficient and promising biological activities as anti-inflammatory agents. The aim of this review is to examine in detail the anti-inflammatory properties of these novel class of natural products.