Unraveling the Mechanisms of Cannabidiol's Pharmacological Actions: A Comprehensive Research Overview.

Cannabis sativa has long been used for neurological and psychological healing. Recently, cannabidiol (CBD) extracted from cannabis sativa has gained prominence in the medical field due to its non-psychotropic therapeutic effects on the central and peripheral nervous systems. CBD, also acting as a potent antioxidant, displays diverse clinical properties such as anticancer, antiinflammatory, antidepressant, antioxidant, antiemetic, anxiolytic, antiepileptic, and antipsychotic effects. In this review, we summarized the structural activity relationship of CBD with different receptors by both experimental and computational techniques and investigated the mechanism of interaction between related receptors and CBD. The discovery of structural activity relationship between CBD and target receptors would provide a direction to optimize the scaffold of CBD and its derivatives, which would give potential medical applications on CBD-based therapies in various illnesses.

From NAD+ to Nickel Pincer Complex: A Significant Cofactor Evolution Presented by Lactate Racemase.

Lactate racemase (LarA), a new nickel enzyme discovered recently, catalyzes the racemization between d- and l-lactates with a novel nickel pincer cofactor (Ni-PTTMN) derived from nicotinic acid. In this study, by using DFT and a 200-atom active-site model, LarA is revealed to employ a modified proton-coupled hydride-transfer mechanism in which a hydride is transferred to a cofactor pyridine carbon from the substrate α-carbon along with proton transfer from the substrate hydroxy group to a histidine, and then moved back from the opposite side. Tyr294 and Lys298 provide significant acceleration effects by orientating substrates and stabilizing the negative charge developing at the substrate hydroxy oxygen. The barrier was determined to be 12.0 kcal mol-1 , which reveals enhanced racemase activity relative to the LarA reaction using NAD+ -like cofactors. Compared with NAD+ , Ni-PTTMN has a stronger hydride-addition reactivity in moderate and high environmental polarity and may fit perfectly the moderately polar active site of LarA.

The Legionella pneumophila Dps homolog is regulated by iron and involved in multiple stress tolerance.

Iron homeostasis is essential to almost all organisms. In this study, we identified the putative homolog of the iron-storage protein-encoding gene, dpsL, in the intracellular pathogen Legionella pneumophila and demonstrated its expression under iron-limited conditions and its responses to multiple stresses. Quantitative real-time PCR analysis indicated that the expression of dpsL was enhanced under iron limitation regardless of the growth phase. Compared with the wild-type cells, the cells devoid of dpsL were heat and H(2)O(2)-sensitive. In contrast to the dps mutants of other bacteria, the growth of the dpsL mutant in an iron-deprived medium was delayed but finally reached the same cell density as wild-type cells during the stationary phase of growth. The finding that the dpsL mutant is salt resistant suggested the involvement of DpsL in virulence.