Pipemidic Acid Hydrate

Myocardial ischemia reperfusion injury (MIRI) remains a major clinical challenge. Polyphenols derived from Potentilla anserina L (PPA) were found to possess anti-hypoxic-ischemic in vitro. The aim of this study was to examine (1) whether this plant exerts a protective effect and (2) whether the underlying mechanisms involving inflammatory responses and the Wnt/β-catenin signaling pathway were involved in rats. Rats were randomly divided as follows (1): Sham operation (2); ischemia-reperfusion (MIRI) (3); polyphenols (PPA) (4); Wnt inhibitor group (XAV939). In cardiomyocytes (1), HE staining was used to examine morphology (2), enzyme-linked immunosorbent assay to determine interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) levels and (3) Western blot to measure protein expression of Wnt and β-catenin. HE staining showed in MIRI edema of cardiomyocytes, localized inflammatory cell infiltration, unclear outline of cells and cell fragmentation, and some cardiomyocytes were seen to have disordered arrangement of tissues. PPA markedly lowered the morphological alterations in MIRI. The levels of levels of IL-1β and TNF-α in MIRI were significantly elevated; however, PPA reduced these cytokine concentrations compared to MIRI. Western blot analysis demonstrated that MIRI increased the relative protein expression levels of Wnt and β-catenin. Treatment of MIRI with PPA resulted in a significant decrease in protein expression levels of Wnt and β-catenin. The involvement of the Wnt/β-catenin pathway in MIRI was further affirmed with the use Wnt inhibitor group (XAV939) that also diminished protein expression levels of Wnt and β-catenin.

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition characterized by a range of symptoms including impaired social interaction and cognitive deficits. Although the exact pathogenesis of ASD is not well established, recent clinical findings suggest a decline in levels of biogenic amine agmatine in autistic patients. The present study was designed to investigate the impact of postnatal propionic acid (PPA) exposure on hippocampal agmatine homeostasis in male rat pups and to explore a new therapeutic intervention for ASD using agmatine as a biological target. PPA is commonly used in experimental models of ASD due to its ability to induce social deficits, cognitive impairments, and stereotyped behaviors, which closely resemble key characteristics of ASD. Male rat pups were administered with PPA via the intrahippocampal route bilaterally (25 μg/0.25 μl per side) on PND-21 to simulate the ASD phenotype, and its subsequent effect on the endogenous agmatinergic system. The influence of agmatine treatment and its endogenous modulation on ASD-like phenotypes was also investigated. Behavioral assessments revealed that PPA exposure reduced sociability and social preference, caused learning and memory impairment in the Morris water maze, increased anxiety-like behavior in the elevated plus maze, and reduced exploratory behavior in the hole board test. Neurochemical analyses showed a decrease in agmatine concentration and an increase in its degrading enzyme agmatinase in the hippocampus. PPA treatment altered the content of GABA, glutamate, TNF-α, IL-6, BDNF, and also resulted in increased astrogliosis and neurotoxicity within the hippocampus. Chronic agmatine treatment and its endogenous modulation ameliorated the behavioral and biochemical disruptions induced by PPA exposure. This study highlights the critical role of hippocampal agmatinergic pathway in the etiopathogenesis of ASD, positioning agmatine as a promising therapeutic target for its treatment.