Triterpene derivatives as inhibitors of protein involved in the inflammatory process: molecules interfering with phospholipase A2, cycloxygenase, and lipoxygenase

Over the past years, there was an explosion in the knowledge of the protein target and molecular mechanism associated with various disease types and in the new research of drugs of natural origin. The key idea is to evaluate bioactive natural products interacting with protein domains of different genetic origin but structurally preserved to develop libraries of compounds biologically validated and selected from an evolutionistic point of view. Compared with synthetic compounds, natural products have a major number of unused scaffolds and not comparable to the libraries of synthetic compounds, and could represent a promising starting points for the discovery of new bioactive compounds. Many natural products are reported to interact with proteins involved in serious diseases, such as inflammation and cancer. Recently various chemical classes of plant secondary metabolites have emerged as potential therapeutic compounds in several inflammatory diseases. Owing to the findings that triterpenoids, a common class of plant secondary metabolites, have anti-inflammatory and anti-cancer effects on humans, the interest in their potential application in human health and disease is increasing. The present review describes anti-inflammatory triterpenes derivatives from plant and fungi reported during the last two decades in order to provide an account of this field of investigation, sorting compounds according to their targets, phospholipase A(2) (PLA(2)), cycloxygenase (COX), and lipoxygenase (LOX). The attempt is also being made to enumerate the possible leads for further synthetic and drug discovery program development.     

Psychological risks associated with appearance-altering procedures: issues "facing" cosmetic surgery

There is a dynamic and fluid relationship between cosmetic surgery and psychology that requires careful and constant attention from the surgeon. Surgeons all desire a "short and sweet" checklist evaluation that tells them if it is safe for the patient to undergo an elective surgical procedure. Obviously, this is wishful thinking. It is asking too much for surgeons to be able to quantify the overall psychological risk. Rather, they should objectively screen, review, and evaluate as many of the variables as possible. These include but are not limited to the surgical issue, the personality of the patient, the patient's family and/or relationships, and the overall context of the situation. Surgeons should also reflect on both their technical expertise and limitations and the patient's personal resiliency.     

Delayed apoptosis of human monocytes exposed to immune complexes is reversed by oxaprozin: role of the Akt/I��B kinase/nuclear factor ��B pathway

Background and purpose

Monocytes-macrophages play a key role in the initiation and persistence of inflammatory reactions. Consequently, these cells represent an attractive therapeutic target for switching off overwhelming inflammatory responses. Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most common drugs for the symptomatic treatment of rheumatic diseases. Their effects have been explained on the basis of cyclooxygenase (COX) inhibition. However, some of the actions of these drugs are not related to inhibition of prostaglandin synthesis.

Experimental approach

We examined the effect of oxaprozin on apoptosis of immune complex-activated monocytes in comparison with drugs of the same class, and the signalling pathway that leads activated monocytes exposed to oxaprozin to apoptosis. In particular, we studied the activity of caspase-3, the involvement of IκB kinase (IKK)-nuclear factor κB (NF-κB) system and the activity of X-linked mammalian inhibitor of apoptosis protein (XIAP), Akt and mitogen-activated protein kinase (MAPK) in activated monocytes in the presence of oxaprozin.

Key results

Immune complexes caused the inhibition of monocyte apoptosis. Oxaprozin reversed in a dose-dependent manner immune complex-induced survival of monocytes, without affecting the apoptosis of resting cells. Other NSAIDs are ineffective. The activity of oxaprozin was related to inhibition of Akt activation that, in turn, prevented p38 MAPK, IKK and NF-κB activation. Consistently, the inhibition of NF-κB activation reduced the production of the anti-apoptotic molecule XIAP, leading to uncontrolled activity of caspase 3.

Conclusions and implications

These results suggest that oxaprozin exerts its anti-inflammatory activity also through COX-independent pathways. It is likely that oxaprozin-mediated inhibition of the Akt/IKK/NF-κB pathway contributes to its anti-inflammatory properties.     

Post-methionine load test: A more sensitive tool to reveal hyperhomocysteinemia in Alzheimer patients?

ObjectiveTo identify the real number of hyperhomocysteinemic Alzheimer's patients who may benefit from homocysteine-lowering therapy.MethodsBasal and post-methionine load homocysteine levels were assessed by rp-HPLC system.ResultsPML test revealed twice as many hyperhomocysteinemic AD subjects with respect to the fasting analysis.ConclusionPML test resulted useful in detecting higher number of hyperhomocysteinemic AD patients who may have the chance of an early folate treatment.