Current Medicinal Chemistry - Volume 23, Issue 4, 2016

A comprehensive outline for understanding and recommending the therapeutic use of ozone in combination with established therapy in diseases characterized by a chronic oxidative stress is currently available. The view of the absolute ozone toxicity is incorrect, because it has been based either on lung or on studies performed in artificial environments that do not correspond to the real antioxidant capacity of body compartments. In fact, ozone exerts either a potent toxic activity or it can stimulate biological responses of vital importance, analogously to gases with prospective therapeutic value such as NO, CO, H2S, H2, as well as O2 itself. Such a crucial difference has increasingly become evident during the last decade. The purpose of this review is to explain the aspects still poorly understood, highlighting the divergent activity of ozone on the various biological districts. It will be clarified that such a dual effect does not depend only upon the final gas concentration, but also on the particular biological system where ozone acts. The real significance of ozone as adjuvant therapeutic treatment concerns severe chronic pathologies among which are cardiovascular diseases, chronic obstructive pulmonary diseases, multiple sclerosis, and the dry form of age-related macular degeneration. It is time for a full insertion of ozone therapy within pharmaceutical sciences, responding to all the requirements of quality, efficacy and safety, rather than as either an alternative or an esoteric approach.

Background. Moyamoya disease (MMD) is a slowly progressing steno-occlusive cerebrovascular disease. The typical moyamoya vessels, which originate from an initial stenosis of the internal carotid, highlight that increased and/or abnormal angiogenic, vasculogenic and arteriogenic processes are involved in the disease pathophysiology. Objective. Herein, we summarize the current knowledge on the most important signaling pathways involved in MMD vessel formation, particularly focusing on the expression of growth factors and function of endothelial progenitor cells (EPCs). Methods and Results. Higher plasma concentrations of vascular endothelial growth factor, matrix metalloproteinase, hepatocyte growth factor, and interleukin-1β were reported in MMD. A specific higher level of basic fibroblast growth factor was also found in the cerebrospinal fluid of these patients. Finally, the number and the functionality of EPCs were found to be increased. In spite of the available data, the approaches and findings reported so far do not give an evident correlation between the expression levels of the aforementioned growth factors and MMD severity. Furthermore, the controversial results provided by studies on EPCs, do not permit to understand the true involvement of these cells in MMD pathophysiology. Conclusion. Further studies should thus be implemented to extend our knowledge on processes regulating both the arterial stenosis and the excessive formation of collateral vessels. Moreover, we suggest advances of integrated approaches and functional assays to correlate biological and clinical data, arguing for the development of new therapeutic applications for MMD.

The pharmacological treatment of Parkinson´s disease (PD) is limited to dopamine agonists and anti-cholinergic drugs that do not stop the progress of disease. LDopa was introduced to the treatment in 1967; this drug is still the best and most commonly used drug since it generates a real improvement in patient quality of life, but the disadvantage of L-dopa is that this positive effect is followed by severe side effects such as dyskinesia. The search for a new drug in the treatment of PD is limited to compounds which decrease the side effects of the drugs used in the treatment of the disease, such as L-dopa-induced dyskinesia. One possible explanation for pharmaceutical companies not developing new drugs to stop disease development is because the mechanism which induces the loss of dopaminergic neurons containing neuromelanin of the nigrostriatal system is still unknown. The discovery of genes (alpha-synuclein, parkin, pink-1, DJ- 1, LRRK2, GBA1, etc.) associated with familial forms of PD resulted in an enormous input into basic research in order to understand the role of these proteins in the disease. It is generally accepted that the loss of dopaminergic neurons containing neuromelanin involves mitochondrial dysfunction, protein degradation dysfunction, the aggregation of alpha-synuclein to neurotoxic oligomers, oxidative neuroinflammation and endoplasmic reticulum stress, but the question of what induces these mechanisms remains unanswered. Aminochrome, the product of dopamine oxidation and the precursor of neuromelanin, is directly involved in five of the six mechanisms and may be a better PD preclinical model.

This review covers the compounds isolated from marine sponges with neuroprotective activities during the period between 1999 and 2014 based on their chemical structures, collections sites, sponge taxonomy and neuroprotective effects. These compounds were isolated from marine sponges collected from 18 countries, most of them in Indonesia, followed by Japan. A total of 90 compounds were reported to exhibit a range of neuroprotective efficacy. These compounds were shown to inhibit β-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1), modulate the synthesis or activity of some neurotransmitters such as acetylcholinesterase and glutamate, enhancement of serotonin, reducing oxidative stress, inhibition of kinases and proteases, and enhancement of neurite growth. None of them have yet progressed into any marine pharmaceutical development pipeline, therefore sustained researches will be required to enhance the potential of utilizing these compounds in the future for prevention and therapeutic treatment of neurodegenerative diseases.

Natural products, especially bioactive molecules as drug lead compounds, have attracted extensive attention in health promotion and in drug discovery and development. It is essential to understand the structures and functional mechanisms of these lead molecules prior to drug development. This review provides comprehensive information for more than 130 newly reported peroxides appeared in the literature in the recent years. The compounds are natural peroxides with bioactivities. While some of them appeared in previous reviews, a great number of newly-found natural peroxides with up-dated information are extensively reviewed in this article, which focuses on the biological activities based on various structural classes including monoterpenoids, sesquiterpenoids, diterpenoids, sesterterpenoids, triterpenoids and steroidal peroxy compounds isolated from terrestrial and marine sources. These natural peroxides are valuable sources in drug discovery with antitumor and antimalarial activities.