Search

Objective: Modern treatment of peptic ulcers includes antibacterial and gastroprotective medications. However, current anti-ulcer drugs possess severe side effects. Therefore, all attempts to find new effective medications free from side effects are justified. Though Berberis vulgaris is a medicinal plant commonly used for the treatment of numerous disorders, gastroprotective effect of its leaf extract was not investigated before.Materials and Methods: Gastric ulcer was modelled in Sprague-Dawley rats after treatment with B. vulgaris leaf extract containing 0.07% of alkaloids, 0.48% of flavonoids and 8.05% of tanning substances, 10 or 50 mg of dry extract/kg, changes in the stomach mucosa were assessed semi-quantitatively, and the gastric wall was evaluated for prostaglandin E2 level using ELISA and assessed histologically by calculation of the lesion index.Results: B. vulgaris leaf extract at the dose of 50 mg/kg reduced the macroscopic ulcer score and the microscopic lesion index, increased prostaglandin E2 concentration in the gastric wall significantly higher than atropine and B. vulgaris leaf extract 10 mg/kg.Conclusion: The gastroprotective effect of the high dose of B. vulgaris leaf extract may be due to stimulation of prostaglandin E2 secretion in the stomach, and anti-oxidative and anti-inflammatory properties of polyphenolic complex of flavonoids and tannins present in the leaves of this plant.

The most common primary malignant brain tumors in adults are gliomas. Glioblastoma is the most prevalent and aggressive tumor subtype of glioma. Current standards for the treatment of glioblastoma include a combination of surgical, radiation, and drug therapy methods. The drug therapy currently includes temozolomide (TMZ), an alkylating agent, and bevacizumab, a recombinant monoclonal IgG1 antibody that selectively binds to and inhibits the biological activity of vascular endothelial growth factor. Supplementation of glioblastoma radiation therapy with TMZ increased patient survival from 12.1 to 14.6 months. The specificity of TMZ effect on brain tumors is largely determined by special aspects of its pharmacokinetics. TMZ is an orally bioavailable prodrug, which is well absorbed from the gastrointestinal tract and is converted to its active alkylating metabolite 5-(3-methyl triazen-1-yl)imidazole-4-carbozamide (MTIC) spontaneously in physiological condition that does not require hepatic involvement. MTIC produced in the plasma is not able to cross the BBB and is formed locally in the brain. A promising way to increase the effectiveness of TMZ chemotherapy for glioblastoma is to prevent its hydrolysis in peripheral tissues and thereby increase the drug concentration in the brain that nanoscale delivery systems can provide. The review discusses possible ways to increase the efficacy of TMZ using nanocarriers.

PCSK9 has now become an important target to create new classes of lipid-lowering drugs. The prevention of its interaction with LDL receptors allows an increase in the number of these receptors on the surface of the cell membrane of hepatocytes, which leads to an increase in the uptake of cholesterol-rich atherogenic LDL from the bloodstream. The PCSK9 antagonists described in this review belong to different classes of compounds, may have a low molecular weight or belong to macromolecular structures, and also demonstrate different mechanisms of action. The mechanisms of action include preventing the effective binding of PCSK9 to LDLR, stimulating the degradation of PCSK9, and even blocking its transcription or transport to the plasma membrane/cell surface. Although several types of antihyperlipidemic drugs have been introduced on the market and are actively used in clinical practice, they are not without disadvantages, such as well-known side effects (statins) or high costs (monoclonal antibodies). Thus, there is still a need for effective cholesterol-lowering drugs with minimal side effects, preferably orally bioavailable. Low-molecular-weight PCSK9 inhibitors could be a worthy alternative for this purpose.

Traumatic brain injury (TBI) is a leading cause of death and disability in individuals worldwide. Producing a clinically relevant TBI model in small-sized animals remains fairly challenging. For good screening of potential therapeutics, which are effective in the treatment of TBI, animal models of TBI should be established and standardized. In this study, we established mouse models of closed head injury using the Shohami weight-drop method with some modifications concerning cognitive deficiency assessment and provided a detailed description of the severe TBI animal model. We found that 250 g falling weight from 2 cm height produced severe closed head injury in C57BL/6 male mice. Cognitive disorders in mice with severe closed head injury could be detected using passive avoidance test on day 7 after injury. Findings from this study indicate that weight-drop injury animal models are suitable for further screening of brain neuroprotectants and potentially are similar to those seen in human TBI.