Acute administration of the olive constituent, oleuropein, combined with ischemic postconditioning increases myocardial protection by modulating oxidative defense

Oleuropein, one of the main polyphenolic constituents of olive, is cardioprotective against ischemia reperfusion injury (IRI). We aimed to assess the cardioprotection afforded by acute administration of oleuropein and to evaluate the underlying mechanism. Importantly, since antioxidant therapies have yielded inconclusive results in attenuating IRI-induced damage on top of conditioning strategies, we investigated whether oleuropein could enhance or imbed the cardioprotective manifestation of ischemic postconditioning (PostC). Oleuropein, given during ischemia as a single intravenous bolus dose reduced the infarct size compared to the control group both in rabbits and mice subjected to myocardial IRI. None of the inhibitors of the cardioprotective pathways, l-NAME, wortmannin and AG490, influence its infarct size limiting effects. Combined oleuropein and PostC cause further limitation of infarct size in comparison with PostC alone in both animal models. Oleuropein did not inhibit the calcium induced mitochondrial permeability transition pore opening in isolated mitochondria and did not increase cGMP production. To provide further insights to the different cardioprotective mechanism of oleuropein, we sought to characterize its anti-inflammatory potential in vivo. Oleuropein, PostC and their combination reduce inflammatory monocytes infiltration into the heart and the circulating monocyte cell population. Oleuropein's mechanism of action involves a direct protective effect on cardiomyocytes since it significantly increased their viability following simulated IRI as compared to non-treated cells. Οleuropein confers additive cardioprotection on top of PostC, via increasing the expression of the transcription factor Nrf-2 and its downstream targets in vivo. In conclusion, acute oleuropein administration during ischemia in combination with PostC provides robust and synergistic cardioprotection in experimental models of IRI by inducing antioxidant defense genes through Nrf-2 axis and independently of the classic cardioprotective signaling pathways (RISK, cGMP/PKG, SAFE)

Natural products in drug discovery: advances and opportunities

Natural products and their structural analogues have historically made a major contribution to pharmacotherapy, especially for cancer and infectious diseases. Nevertheless, natural products also present challenges for drug discovery, such as technical barriers to screening, isolation, characterization and optimization, which contributed to a decline in their pursuit by the pharmaceutical industry from the 1990s onwards. In recent years, several technological and scientific developments — including improved analytical tools, genome mining and engineering strategies, and microbial culturing advances — are addressing such challenges and opening up new opportunities. Consequently, interest in natural products as drug leads is being revitalized, particularly for tackling antimicrobial resistance. Here, we summarize recent technological developments that are enabling natural product-based drug discovery, highlight selected applications and discuss key opportunities

(WO2011057959) Indole and indazole derivatives as glycogen synthase activators: A patent evaluation

Scientific evaluation of a patent aiming for the development of indole and indazole derivatives from biaryloxymethylarene as glycogen synthase activators, a key enzyme involved in type 2 diabetes mellitus. © 2011 Informa UK, Ltd

Glycogen phosphorylase inhibitors: A patent review (2008-2012)

Introduction: Glycogen phosphorylase (GP) is the enzyme responsible for the synthesis of glucose-1-phosphate, the source of energy for muscles and the rest of the body. The binding of different ligands in catalytic or allosteric sites assures activation and deactivation of the enzyme. A description of the regulation mechanism and the implications in glycogen metabolism are given. Areas covered: Deregulation of GP has been observed in diseases such as diabetes mellitus or cancers. Therefore, it appears as an attractive therapeutic target for the treatment of such pathologies. Numbers of inhibitors have been published in academic literature or patented in the last two decades. This review presents the main patent claims published between 2008 and 2012. Expert opinion: Good inhibitors with interesting IC50 and in vivo results are presented. However, such therapeutic strategy raises questions and some answers are proposed to bring new insights in the field. © 2013 Informa UK, Ltd

Chios gum mastic: A review of its biological activities

The resin of Pistacia lentiscus (L.) var. chia (Duham), an evergreen shrub belonging to the family Anacardiaceae and uniquely cultivated in southern Chios, is known as mastic. It has been used for more than 2500 years in traditional Greek medicine for treating several diseases such as gastralgia and peptic ulcers, while the actions of the gum are mentioned in the works of Herodotus, Dioscorides and Galen. Several Roman, Byzantine, Arab and European authors make extensive references to mastic's healing properties. Modern scientific research has justified the beneficial action of mastic to gastric diseases, by revealing its in vivo and in vitro activity against Helicobacter pylori, which is considered as the main cause for gastric ulcers. Furthermore, studies of the antimicrobial, antifungal, antioxidant, hypolipidemic, anti-inflammatory, anti-Crohn and anticancer activities of mastic have characterized it as a wide-range therapeutic agent and a potential source of nature-originated treatments. © 2012 Bentham Science Publishers

Alkylresorcinol derivatives and sesquiterpene lactones from Cichorium spinosum

One new alkylresorcinol derivative, cichoriol B, and a mixture of three other ones, cichoriols A, C, and D, were isolated from the dichloromethane extract of Cichorium spinosum, a plant that is used traditionally in the Cretan diet. The methanol extract afforded one new sesquiterpene lactone, (4R)-3,4-dihydrolactucopicrin. The structures of the new compounds were determined by spectroscopic methods, mainly by the concerted application of 1D and 2D NMR techniques (HMQC, HMBC, NOESY)

Sarcomegistine, A New Dihydrofuroquinoline Alkaloid From SarcomeliCope Megistophylla 1

Sarcomegistine (1), a new dihydrofuroquinoline alkaloid,has been isolatedfrom the aerial parts of Sarcomelicope megistophylla. © 1995, Taylor & Francis Group, LLC. All rights reserved

Photo-activated DNA binding and antimicrobial activities of furoquinoline and pyranoquinolone alkaloids from Rutaceae

To find novel photo-active compounds of potential use in photochemotherapy from higher plants, photo-activated antimicrobial and DNA binding activities of the furoquinolines, skimmianine, kokusaginine, and haplopine, and a pyranoquinolone, flindersine, from two species of Rutaceae plants were investigated. TLC overlay assays against a methichillin-resistant strain of Staphylococcus aureus and Candida albicans were employed to test antimicrobial properties. All of the tested compounds showed photo-activated antimicrobial activity against S. aureus in the order of kokusaginine > haplopine, flindersine > skimmianine. Weaker activity was found for C. albicans. Photo-activated DNA binding activity of these compounds was investigated by a method using restriction enzymes and a specially designed 1.5 kb DNA fragment. Kokusaginine showed inhibition against all of the 16 restriction enzymes. Haplopine showed a similar inhibition pattern but the binding activity against Asc I and Sma I with restriction sequences consisting only of G and C was very weak. Skimmianine showed binding activity against Xba I, BciV I, Sal I, Pst I, Sph I and Hind III, but very weak or no activity was found for the other restriction enzymes. A pyranoquinolone, flindersine, showed no activity against any of the restriction enzymes. Photo-activated DNA binding activity of furoquinolines was therefore in the order of kokusaginine > haplopine > skimmianine, which was the same order as their photo-activated antimicrobial activity against S. aureus. Therefore, it was concluded that DNA is one of the cellular targets for the furoquinolines to exert their biological activities, similar to psoralens. However, because flindersine showed photo-activated antimicrobial activity against S. aureus but did not show photo-activated DNA binding activity, it is clear that there are other cellular target components for this compound to exert photo-toxic activity