Reviews on Clinical Pharmacology and Drug Therapy

There is a growing trend to replace synthetic products or additives with natural alternatives. Historical experience and developments in human health science demonstrate the adverse effects of xenobiotics on human health and metabolism. The shift toward natural products is essential for enhancing vitality, social activity, and overall quality of life, while preventing adverse events and diseases. Industries such as pharmaceutical, cosmetic, and food are increasingly turning to natural and biologically active chemicals isolated from plants or microorganisms. However, the primary challenge lies in developing effective and eco-friendly methods for their isolation. Deep eutectic solvents are a mixture of two or more components with unique properties like low volatility, low melting points, ease of preparation, cost-effective starting materials, and minimal toxicity to humans. They have gained popularity as environmentally friendly agents for extracting biologically active substances from medicinal plants and as safe alternatives for various industries, including food and pharmaceuticals. Traditional organic solvent extraction methods have several drawbacks, including long extraction times, safety concerns, environmental damage, high cost, and the need for large solvent volumes. This review summarizes research progress on the benefits of using deep eutectic solvents for extracting bioactive compounds, including phenolic acid, flavonoids, isoflavones, catechins, polysaccharides, curcuminoids, proanthocyanidin, phycocyanin, gingerols, ginsenosides, anthocyanins, rutin, and chlorogenic acids. Additionally, it examines the biological activity of these extracts, including antioxidant, antibacterial, and antitumor properties.

Breast cancer stands as the leading cause of cancer-related deaths among women worldwide. Endocannabinoids and their exogenous analogs, e.g., tetrahydrocannabinol, exhibit antitumor effects in various animal models of cancer. However, several studies have shown that under certain conditions, treatment with cannabinoids can stimulate the proliferation of cancer cells in vitro and disrupt the immune system’s involvement in suppressing tumors. Additionally, conflicting reports exist regarding the antitumor role of endocannabinoid system in cancer. This review aims to consider the main mechanisms of action of key ligands and receptors of the endocannabinoid system within the context of breast cancer.

BACKGROUND: Gonadotropin preparations, particularly human chorionic gonadotropin (hCG), are commonly used to induce ovulation and treat reproductive disorders in women, albeit with associated side effects. Low-molecular-weight allosteric agonists of the luteinizing hormone receptor (LHR), such as thieno[2,3-d]pyrimidine derivatives, offer a potential alternative.

AIM: This study aims to compare the effects of thieno[2,3-d]pyrimidine TP03 and hCG on ovarian weight, corpus luteum formation, and plasma levels of estradiol, progesterone, and luteinizing hormone in immature female rats pre-treated with Follimag®. It also examines their impact on ovarian gene expression related to LHR and steroidogenesis.

MATERIALS AND METHODS: TP03 and hCG were administered 48 h after the Follimag® injection at a dose of 20 mg/kg (i.p.) and 15 IU/rat (s.c.), respectively. Parameters were assessed at 1, 2, 4, 8, 16, and 24 h after TP03 and hCG administration. Plasma hormone levels were measured via ELISA, and ovarian gene expression was analyzed using real-time PCR.

RESULTS: TP03 increased ovarian weight, progesterone levels in the blood, and expression of steroidogenic genes encoding the cholesterol-transporting protein StAR and the cytochromes CYP11A1 and CYP17A1. TP03 also stimulated corpus luteum formation (16–24 h after treatment). The temporal dynamics of its stimulating effects were similar to those of hCG, although their magnitude was slightly inferior to those of gonadotropin. TP03-induced decrease in blood estradiol levels and aromatase gene expression in the ovaries was also more moderate. Unlike hCG, which suppressed LHR gene expression 8 h after treatment, TP03 maintained a high LHR gene expression, preserving ovarian sensitivity to endogenous luteinizing hormone.

CONCLUSIONS: TP03 exhibits potential as an ovulation inducer with milder stimulating effects on ovarian steroidogenesis than hCG, which reduces the risks of developing ovarian hyperstimulation syndrome and resistance to gonadotropins.

BACKGROUND: Osteoporosis remains one of the most important medical problems worldwide with significant economic consequences. The development of new drugs based on unique biologically active compounds can contribute significantly to osteoporosis management.

AIM: To evaluate the osteogenesis processes by evaluating bone-remodeling markers in the blood serum during the treatment of experimental osteoporosis complicated by type 2 diabetes mellitus.

MATERIALS AND METHODS: The study was performed on an experimental model of osteoporosis, followed by the induction of type 2 diabetes mellitus, using biochemical methods to analyze markers of osteoporosis in the blood serum.

RESULTS: The results of the analysis of bone remodeling markers revealed that the antiosteoporotic activity of a composite preparation based on succinic acid salts is dependent on glucose metabolism disorders such as diabetes mellitus. The high efficacy of the new drug in monotherapy and combination with vitamin D₃ in the activation of osteogenesis in experimental osteoporosis was balanced by impaired metabolic processes in type 2 diabetes mellitus.

CONCLUSIONS: The results indicate the dependence of the pharmacological effectiveness of the antiosteoporosis agent on metabolic disorders, such as type 2 diabetes mellitus, in female rats with experimental osteoporosis.

The article is devoted to the possibility and prospects of using nitazoxanide in a wide range of diseases. Based on literature data, the authors evaluate the pharmacological effectiveness and substantiate the potential of using nitazoxanide in bacterial, helminthic, protean, viral and oncological diseases. This information is of interest and can be used to decide on the need to conduct clinical trials of nitazoxanide in Russia. A systematic search for current information was conducted in four databases until December 1, 2023: PubMed, EMBASE, Web of Science and Cochrane Library. The work included preclinical studies in vitro and in vivo, as well as randomized clinical trials comparing the pharmacological effectiveness of nitazoxanide and placebo. The broad-spectrum thiazolide drug nitazoxanide has antibacterial, antiprotozoal, anthelmintic, antiviral and antitumor activity. This is achieved through its pharmacological properties, namely: regulation of the cell cycle, apoptosis, cell proliferation and migration; activation of innate immunity; influence on the synthesis and activation of cell proteins, some of which are links in cellular signaling pathways; binding to proteins of viruses, bacteria, protozoa and helminths with disruption of their vital functions; immunomodulating effect by regulating the activity of pro- and anti-inflammatory cytokines. The article systematizes and summarizes current information on the pharmacodynamics of nitazoxanide, as well as the results of preclinical and clinical studies of the drug, and discusses further prospects.