HLDF-6 peptides exhibit neuroprotective effects in the experimental model of preclinical Parkinson's disease.

The mechanisms of the neuroprotective action of the hexapeptides HLDF-6 encoded by the amino acid sequence 41-46 of Human Leukemia Differentiation Factor and its homoserine derivative HLDF-6H were studied in an experimental 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced model of Parkinson's disease (PD). C57Bl/6 mice received two intraperitoneal injections of 18 mg/kg MPTP-HCl, with an interval of 2 hours. MPTP-induced motor dysfunction was assessed using horizontal grid test. Our data show that chronic intranasal administration of peptides (3 weeks, 300 µg/kg/day) restored normal levels of dopamine and improved its turnover rates in the striatum. Furthermore, peptide administration increased serum estradiol levels and led to a significant improvement in motor functions in MPTP-treated mice. Additionally, peptide treatment increased the levels of mRNA encoding neurotrophin BDNF, but normalized the levels of mRNA encoding the inflammatory mediators TGFß1, IL1ß and IFNγ in the brain. Collectively, our behavioral and biochemical studies demonstrate that HLDF-6 peptides have a therapeutic potential for treating PD. We propose that HLDF-6 peptides may exert their neuroprotective mechanism, at least in part, by normalizing estradiol levels and modulating the expression of key factors involved in neurotrophic support and neuroinflammation.

Rhizosphere Bacterium Rhodococcus sp. P1Y Metabolizes Abscisic Acid to Form Dehydrovomifoliol.

The phytohormone abscisic acid (ABA) plays an important role in plant growth and in response to abiotic stress factors. At the same time, its accumulation in soil can negatively affect seed germination, inhibit root growth and increase plant sensitivity to pathogens. ABA is an inert compound resistant to spontaneous hydrolysis and its biological transformation is scarcely understood. Recently, the strain Rhodococcus sp. P1Y was described as a rhizosphere bacterium assimilating ABA as a sole carbon source in batch culture and affecting ABA concentrations in plant roots. In this work, the intermediate product of ABA decomposition by this bacterium was isolated and purified by preparative HPLC techniques. Proof that this compound belongs to ABA derivatives was carried out by measuring the molar radioactivity of the conversion products of this phytohormone labeled with tritium. The chemical structure of this compound was determined by instrumental techniques including high-resolution mass spectrometry, NMR spectrometry, FTIR and UV spectroscopies. As a result, the metabolite was identified as (4RS)-4-hydroxy-3,5,5-trimethyl-4-[(E)-3-oxobut-1-enyl]cyclohex-2-en-1-one (dehydrovomifoliol). Based on the data obtained, it was concluded that the pathway of bacterial degradation and assimilation of ABA begins with a gradual shortening of the acyl part of the molecule.

A new derivative of acetylsalicylic acid and carnosine: synthesis, physical and chemical properties, biological activity.

PURPOSE: The aim of this study was to create and assess biological activity of a new compound based on carnosine and acetylsalicylic acid (ASA) that will comprise antioxidant effect with antiplatelet activity, while simultaneously preventing side effects on the gastrointestinal tract. METHODS: Salicyl-carnosine (SC) was synthesized by condensation of ASA and carnosine. Antioxidant activity was determined by spectrophotometric and chemiluminescence methods. Antiplatelet activity was carried out by the light transmission-aggregometry method using the inductor ADP. Chronic gastric ulcer in rats was modeled using glacial acetic acid. RESULTS: Using SOD-like activity, iron-induced chemiluminescence, BaSO4-activated respiratory burst, and evaluation of red blood cell structure stabilization during oxidative damage induced by sodium hypochlorite, it was shown that SC possesses antioxidant activity analogous, or better, than that of carnosine. Antiplatelet activity of SC was evaluated in the blood of healthy individuals, and was also shown to be comparable to, or exceeding that of ASA. Also SC demonstrates high resistance to hydrolysis by tissue and serum carnosinases. Most importantly, it was shown that SC has protected the gastric mucosa against the formation of stomach ulcerative lesions and promoted their epithelization, therefore overcoming the undesirable inherent side effects of ASA. CONCLUSIONS: SC preserves pharmacologically significant properties of ASA and carnosine while retaining an anti-ulcer activity and resistance to the carnosinase hydrolysis at the same time. These properties are particularly promising for the potential development of new anti-inflammatory and antithrombotic drugs. Graphical abstract .

Synthesis of (5Z,8Z,11Z,14Z)-18- and 19-azidoeicosa-5,8,11,14-tetraenoic acids and their [5,6,8,9,11,12,14,15-3H8]-analogues through a common synthetic route.

Total synthesis of (5Z,8Z,11Z,14Z)-18- and 19-azidoeicosa-5,8,11,14-tetraenoic acids and their [5,6,8,9,11,12,14,15-3H8]-analogues via the corresponding p-toluenesulphonates is reported. This synthetic approach allows the preparation of radioactively labelled arachidonic acid derivatives following a common synthetic route. Activity assays indicated that 15-lipoxygenases may tolerate the azido group in the substrate binding pocket and thus, radioactively labelled azido compounds may be used as photo-affinity probes to investigate mechanistic features of eicosanoid biosynthesis.