Mur ligase F as a new target for the flavonoids quercitrin, myricetin, and (-)-epicatechin.

MurC, D, E, and F are ATP-dependent ligases involved in the stepwise assembly of the tetrapeptide stem of forming peptidoglycan. As highly conserved targets found exclusively in bacterial cells, they are of significant interest for antibacterial drug discovery. In this study, we employed a computer-aided molecular design approach to identify potential inhibitors of MurF. A biochemical inhibition assay was conducted, screening twenty-four flavonoids and related compounds against MurC-F, resulting in the identification of quercitrin, myricetin, and (-)-epicatechin as MurF inhibitors with IC50 values of 143 µM, 139 µM, and 92 µM, respectively. Notably, (-)-epicatechin demonstrated mixed type inhibition with ATP and uncompetitive inhibition with D-Ala-D-Ala dipeptide and UM3DAP substrates. Furthermore, in silico analysis using Sitemap and subsequent docking analysis using Glide revealed two plausible binding sites for (-)-epicatechin. The study also investigated the crucial structural features required for activity, with a particular focus on the substitution pattern and hydroxyl group positions, which were found to be important for the activity. The study highlights the significance of computational approaches in targeting essential enzymes involved in bacterial peptidoglycan synthesis.

Herbal Products Used in Menopause and for Gynecological Disorders.

Herbal products are often used as an alternative to pharmacological therapy. Menopausal symptoms and gynecological disorders (such as premenstrual syndrome and dysmenorrhea) are the indications where pharmacological therapy may have serious adverse events, hence many women prefer to use herbal products to help with these symptoms. Here, we reviewed plants and derived products, which are commonly used for the abovementioned indications, focusing on clinical data, safely profile and whether or not their use is justified. We noted that limited data are available on the use of some plants for alleviating the symptoms of menopause and gynecological disorders. While black cohosh (Cimicifuga racemose) and red clover (Trifolium pretense) were consistently shown to help reduce menopausal symptoms in clinical studies, currently available data do not fully support the use of fenugreek (Trigonella foenum-graecum), hops (Humulus lupulus), valerian (Valeriana officinalis), and soybean (Glycine max and Glycine soja) for this indication. For premenstrual syndrome and premenstrual dysphoric disorder, chaste tree (Vitex agnus-castus) shows effectiveness, but more clinical studies are needed to confirm such effect upon the use of evening primrose (Oenothera biennis).

Accumulation of heavy metals from soil in medicinal plants.

Medicinal plants accumulate heavy metals from contaminated soil, and their consumption can cause poisoning. Our objective was to determine the levels of Pb, Cd, Zn, Cu, Fe, and Mn in four medicinal plant species (Achillea millefolium, Hypericum perforatum, Plantago lanceolata, and Urtica dioica) and their native soil, all sampled at a former smelter. The highest soil Cd, Pb, and Zn levels surpassed the maximum allowed limit 75-fold, 48-fold, and 14-fold, respectively. Their soil levels correlated with those in the plants, but this was not the case with Cu, Fe, and Mn. Heavy metal accumulation seems to depend on the plant species, yet even so, medicinal herbs should be cultivated and gathered only from controlled (uncontaminated) areas. Polluted areas should be monitored on a regular basis, while further research should investigate the connection between the heavy metal levels in the soil, their levels available for plants, and the levels extractable from plants.