BACKGROUND The aim of this study was to evaluate the cardiovascular effects of N-phenyl-itaconimide (Imide-1), N-4-methyl-phenyl-itaconimide (Imide-2), N-4-methoxy-phenyl-itaconimide (Imide-3) and N-4-chloro-phenyl-itaconimide (Imide-4), and investigate the mechanisms of action involved in the observed responses. METHODS The relaxant effect was investigated in rat superior mesenteric arteries by using isometric tension measurements. Additionally, in isolated atria were evaluated the heart rate and force of cardiac contraction and in vivo experiments was evaluated blood pressure and heart rate. RESULTS Cumulative administration of itaconimides (3 × 10-8 to 3 × 10-4 M) in pre-contracted mesenteric artery rings with phenylephrine, 1 μM, induced endothelium-independent vasorelaxation. The itaconimides showed similar maximum efficacies. Additionally, Imide-3 induced vasorelaxation in rings exposed to a depolarizing-tyrode solution containing 60 mM KCl or 20 mM KCl similar to the control, suggesting the non-particidia.About 40% of the papers within the scientific oeuvre of Manfred Göthert (1939-2019) were dedicated to serotonin (5-hydroxytryptamine, 5-HT). He was not only the witness of the gradual definition of the fourteen 5-HT receptor subtypes but also was involved directly by identifying 5-HT1B, 5-HT1D and 5-HT3 receptors. Moreover, he identified presynaptic 5-HT receptors on central and/or peripheral serotoninergic, noradrenergic and/or cholinergic neurones. Two inhibitory (5-HT1B, 5-HT1D) and two facilitatory (5-HT3, 5-HT4) receptors were found, the 5-HT1B receptor representing a possible target for antidepressant drugs. Ten years earlier than electrophysiologists, he identified ligand-gated receptors like the 5-HT3 and the nicotinic acetylcholine (nACh) receptor as targets of halothane. Simultaneously with, but independent of, other authors he found that ethanol allosterically inhibits N-methyl-D-aspartate (NMDA) receptors, which are affected at an even lower concentration than 5-HT3 and nACh receptors.  https://www.selleckchem.com/products/rin1.html  The latter two receptors were shown to be subject to allosteric inhibition also by cannabinoids via a mechanism unrelated to cannabinoid CB1 or CB2 receptors; cannabinoid inhibition of 5-HT3 receptors may represent a new target for the treatment of neuropathic pain.BACKGROUND Parkinson's disease (PD) is the second most common neurodegenerative disease of the elderly. Current therapies are only symptomatic, and have no disease-modifying effect. Therefore, disease progresses continuously over time, presenting with both motor and non-motor features. The precise molecular basis for PD is still elusive, but the aggregation of the protein alpha-synuclein (α-syn) is a key pathological hallmark of the disease and is, therefore, a major focus of current research. Considering the intrinsic properties of cell-penetrating peptides (CPPs) for mediating drug delivery of neurotherapeutics across the blood brain barrier (BBB), these might open novel opportunities for the development of new solutions for the treatment of brain-related aspects of PD and other neurodegenerative disorders. METHODS Here, we synthesized solid-phase CPPs using an amphipathic model peptide (MAP) conjugated with the drug Rasagiline (RAS), which we named RAS-MAP, and evaluated its effect on α-syn inclusion formation in a human cell-based model of synucleinopathy. RESULTS We found that treatment with RAS-MAP at low concentrations (1-3 µM) reduced α-syn aggregation in cells. CONCLUSIONS For the first time, we report that conjugation of a current drug used in the therapy of PD with CPP reduces α-syn aggregation, which might prove beneficial in PD and other synucleinopathies.BACKGROUND Acute liver injury (ALI) is a serious health condition associated with rising morbidity and sudden progression. This study was designed to investigate the possible hepatocurative potential of two dose levels (30 and 60 mg/kg) of Mycophenolate mofetil (MMF), an immune-suppressant agent, against Concanavalin A (Con A)-induced ALI in mice. METHOD A single dose of Con A (20 mg/kg, IV) was used to induce ALI in mice. MMF (30 mg/kg and 60 mg/kg) was administered orally for 4 days post Con A injection. RESULTS MMF (30 mg/kg) failed to cause significant amelioration in Con A-induced ALI while MMF (60 mg/kg) significantly alleviated Con A-induced ALI. Administration of MMF (60 mg/kg) significantly decreased Con A-induced increase in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. Additionally, MMF significantly restored the disrupted oxidant/antioxidants status induced by Con A. MMF caused marked increase in hepatic nuclear factor erythroid 2-related factor 2 (Nrf2) and hemA, GSH reduced glutathione, HO-1 Heme oxygenase-1, IL-1β Interleukin-1β, IFN-γ Interferon-γ, MDA Malondialdehyde, NF-κB Nuclear Factor Kappa B, Nrf2 Nuclear factor erythroid 2-related factor 2, NO Nitric Oxide, SOD Superoxide Dismutase, TLR4 Toll-like receptor 4, TNF-α tumor necrosis factor-α.BACKGROUND Oxidative stress plays an important role in the pathogenesis of myocardial ischemia-reperfusion (IR) injury. Morin, a bioflavonoid, has demonstrated antioxidant, anti-inflammatory and other diverse pharmacological activities in various experimental models such as isoproterenol-induced myocardial injury, doxorubicin-induced cardiotoxicity and neurotoxicity, as well as cisplatin-induced nephrotoxicity. Thus, this study aimed to evaluate the effect of morin in myocardial IR injury model and its underlying mechanisms. METHOD To accomplish this, male albino Wistar rats were pre-treated with morin (40 and 80 mg/kg; po) for 28 days and on 29th day, rats experienced 45-min myocardial ischemia followed by 60-min reperfusion. RESULTS In comparison to IR-control group, morin pre-treatment significantly normalized hemodynamic parameters, restored antioxidant status, improved pathological changes, reduced the release of cardiac injury markers, inhibited inflammation (TNF-α/IL-6/NFκB/IKKβ) and apoptosis (increased Bcl-2, decreased Bax/Caspase-3 and TUNEL positivity) in the myocardium. This improvement in antioxidant, inflammation and anti-apoptosis markers could be due to downregulation of SAPK (p38/JNK) pathway and upregulation of survival kinase, i.e. RISK pathway (ERK/eNOS) in the myocardium. CONCLUSION Thus, morin attenuated myocardial IR injury in rats by regulation of RISK/SAPK pathways.