Newly synthesized derivatives with a thiosemicarbazide group reduce the viability of cancer cell lines. Acute toxicity assessment in Zebrafish (Danio rerio) early life stages.

Due to the variability and ability of tumor to mutate, as well as the heterogeneity of tumor tissue, such drugs are sought that would act selectively and multidirectionally on the cancer cell. Therefore, two newly synthesized semicarbazide structured substances were evaluated for anticancer properties in our study: 1a and 1b. In order to evaluate the cytotoxicity and selectivity of the tested compounds, MTT and Neutral Red uptake assay on cell lines (HEK293, LN229, 769-P, HepG2 and NCI-H1563) and cell cycle analysis were performed. Acute toxicity and cardiotoxicity were also evaluated in the zebrafish model. The tested compounds (1a, 1b) showed cytotoxic activity, with the greatest selectivity noted against the glioblastoma multiforme cell line (LN229). However, compound 1b showed stronger selective activity than 1a. Both of compounds were shown to significantly affect the M phase of the cell cycle. Whereas, the conducted toxicological examination of newly synthesized thiosemicarbazide derivates showed, that direct exposition of Danio rerio embryos to compound 1a, but not 1b, causes a concentration-dependent increase in developmental malformations, indicating possible teratogenic effects.

Amaryllidaceae, Lycopodiaceae Alkaloids and Coumarins-A Comparative Assessment of Safety and Pharmacological Activity.

The study aimed to evaluate the safety and pharmacological activity Amaryllidaceae, Lycopodiaceae alkaloids and coumarins obtained from Narcissus triandrus L., Lycopodium clavatum L., Lycopodium annotinum L., Huperzia selago L. and Angelica dahurica (Hoffm.) Benth. & Hook.f. ex Franch. & Sav. In the in vivo studies. The influence of the tested compounds on the central nervous system of rats was assessed in behavioral tests (locomotor activity, Y-maze, passive avoidance). In order to investigate the mechanisms of action, biochemical determinations were performed (AChE activity, BChE activity, IL-1ß, IL-6 concentration). In order to assess safety, the concentrations of AST, ALT, GGT and urea and creatinine were determined. The results of the conducted studies indicate a high safety profile of the tested compounds. Behavioral tests showed that they significantly improved rodent memory in a passive avoidance test. The results of biochemical studies showed that by reducing the activity of AChE and BChE and lowering the concentration of IL-1ß and IL-6, the coumarin-rich Angelica dahurica extract shows the most promising potential for future therapeutic AD strategies.

The Role of Molecular and Inflammatory Indicators in the Assessment of Cognitive Dysfunction in a Mouse Model of Diabetes.

The brain is the most vulnerable organ to glucose fluctuations, as well as inflammation. Considering that cognitive impairment might occur at the early stage of diabetes, it is very important to identify key markers of early neuronal dysfunction. Our overall goal was to identify neuroinflammatory and molecular indicators of early cognitive impairment in diabetic mice. To confirm cognitive impairment in diabetic mice, series of behavioral tests were conducted. The markers related to cognitive decline were classified into the following two groups: Neuroinflammatory markers: IL-1ß, IL-6, tumor necrosis factor-α (TNF-α) and genetic markers (Bdnf, Arc, Egr1) which were estimated in brain regions. Our studies showed a strong association between hyperglycemia, hyperinsulinemia, neuroinflammation, and cognitive dysfunction in T2DM mice model. Cognitive impairment recorded in diabetes mice were associated not only with increased levels of cytokines but also decreased Arc and Egr1 mRNA expression level in brain regions associated with learning process and memory formation. The results of our research show that these indicators may be useful to test new forms of treatment of early cognitive dysfunction associated not only with diabetes but other diseases manifesting this type of disorders. The significant changes in Arc and Egr1 gene expression in early stage diabetes create opportunities it possible to use them to track the progression of CNS dysfunction and also to differential disease diagnosis running with cognitive impairment.