Research into how carvacrol and metformin affect several human proteins in a hyperglycemic condition: A comparative study in silico and in vitro.

Carvacrol (CV) is an organic compound found in the essential oils of many aromatic herbs. It is nearly unfeasible to analyze all the current human proteins for a query ligand using in vitro and in vivo methods. This study aimed to clarify whether CV possesses an anti-diabetic feature via Docking-based inverse docking and molecular dynamic (MD) simulation and in vitro characterization against a set of novel human protein targets. Herein, the best poses of CV docking simulations according to binding energy ranged from -7.9 to -3.5 (kcal/mol). After pathway analysis of the protein list through GeneMANIA and WebGestalt, eight interacting proteins (DPP4, FBP1, GCK, HSD11ß1, INSR, PYGL, PPARA, and PPARG) with CV were determined, and these proteins exhibited stable structures during the MD process with CV. In vitro application, statistically significant results were achieved only in combined doses with CV or metformin. Considering all these findings, PPARG and INSR, among these target proteins of CV, are FDA-approved targets for treating diabetes. Therefore, CV may be on its way to becoming a promising therapeutic compound for treating Diabetes Mellitus (DM). Our outcomes expose formerly unexplored potential target human proteins, whose association with diabetic disorders might guide new potential treatments for DM.

Uncovering the antidiabetic potential of heart-friendly and diuretic bioactive compounds through computer-based drug design.

Avicenna, a pioneer of modern medicine, recommended diuretic therapy to treat diabetes. Like Avicenna's approach, current medicine frequently prescribes oral antidiabetic pills with diuretic and hypoglycemic effects by blocking the absorption of sodium and glucose. To this end, the paper sought natural compounds with potential antidiabetic, cardioprotective, and diuretic properties through computer-based drug design (CADD) techniques, targeting the inhibition of SGLT2 proteins. We identified several bioactive compounds from various sources exhibiting potential multifunctionality through high-throughput virtual screening (HTVS) of vast compound libraries. Subsequent molecular docking and dynamics simulations were employed to assess these compounds' binding efficacy and stability with their respective targets, alongside ADMET prediction, to evaluate their pharmacokinetic and safety profiles. The top hits, phenylalanyltryptophan, tyrosyl-tryptophan, tyrosyl-tyrosine, celecoxib, and DIBOA trihexose, had superior docking scores ranging from -11,4 to -9,8 kcal/mol. The molecular dynamics simulations displayed steady interactions between target proteins and biocompounds throughout 100 ns without significant conformational shifts. These findings lay the groundwork for lead optimization and preclinical testing. This meticulous process ensures the safety and efficacy of potential treatments, marking a meaningful step toward developing innovative treatments for managing diabetes and its associated health complications.

Dual action of exosomes derived from in vitro Aß toxicity model: The role of age for pathological response.

Exosomes released from different cell types of the central nervous system play an essential role in the pathogenesis of Alzheimer's disease (AD). In this study, we aimed to create an animal model by injecting exosomes that carry AD markers into the brain to shed light on the mechanism behind Alzheimer's pathology. Exosomes obtained from mouse Neuro2A, to which Aß toxicity model applied, were used as a mediator to build an AD phenotype. For this purpose, exosomes were administered into hippocampal CA3 region of mice with different ages. Firstly, the possible role of exosomes on brain volume was analyzed. Then, neurons and astrocytes were evaluated for survival. In addition, the progenitor cells' differentiation capacity was investigated via BrdU staining. AKT signaling pathway components were examined to detect the molecular mechanisms behind the exosomal function. We found different responses in different age groups. Expression of APP upregulated only in young animals upon delivery of Aß-exosomes. Interestingly, young animals represented increased numbers of neurons in the hippocampus, and neurogenesis was found to be restricted after Aß-Ex injections. However, in relation to exosome administration, the glial intensity increased in aged animals. Lastly, phosphorylation of survival kinase AKT was downregulated due to the presence of Aß in both young and old animals. The findings reveal that the exosomes from an in vitro Aß toxicity model may induce different responses in an age-dependent manner. This study is the first to report the relationship between exosomal function and aging by evaluating the key molecules.