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.

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.