RESUMEN
Significance: Extracellular traps (ETs) represent structured frameworks that comprised DNA embellished with histones and granular proteins extruded by immune cells in response to various stimuli. Immune cells contribute to adverse effects of chronic inflammation via ET generation, promoting the release of nuclear chromatin, reactive oxygen species (ROS), and bioactive proteins into the extracellular matrix. Recent Advances: The occurrence of ET formation has been documented across diverse immune cell types. The excessive production of ROS during the activation of these cells has the potential to initiate substantial DNA damage, culminating in chromosome decondensation. The inflammatory microenvironment fosters ROS and ET generation, impacting tissue microenvironment remodeling. Recent studies reveal ET involvement in sustaining persistent inflammation, promoting angiogenesis, and initiating thrombotic processes. Critical Issues: This review elucidates ET participation in chronic inflammatory disease etiology, detailing ROS-dependent and ROS-independent ET formation mechanisms and their contextual manifestations. It discusses diverse immune cell-derived ETs in the inflammatory milieu and their responses to therapies. Furthermore, the review emphasizes the significance of ETs as potential biomarkers and envisions prophylactic strategies against ET-associated chronic inflammation. Future Directions: Subsequent investigations are warranted to uncover the intricate mechanisms governing the resolution of inflammation through ETs in normal physiological processes. Moreover, a comprehensive understanding of the aberrant pathways driving ET formation in persistent inflammation is imperative. Prospective research endeavors should focus on executing expansive clinical studies to discern the involvement of ETs in both the diagnostic and prognostic facets of inflammatory diseases, thereby shedding light on their prospective utility as biomarkers.
RESUMEN
There have been magnificent advancements in the understanding of molecular mechanisms of chronic diseases over the past several years, but these diseases continue to be a considerable cause of death worldwide. Most of the approved medications available for the prevention and treatment of these diseases target only a single gene/protein/pathway and are known to cause severe side effects and are less effective than they are anticipated. Consequently, the development of finer therapeutics that outshine the existing ones is far-reaching. Natural compounds have enormous applications in curbing several disastrous and fatal diseases. Oroxylin A (OA) is a flavonoid obtained from the plants Oroxylum indicum, Scutellaria baicalensis, and S. lateriflora, which have distinctive pharmacological properties. OA modulates the important signaling pathways, including NF-κB, MAPK, ERK1/2, Wnt/ß-catenin, PTEN/PI3K/Akt, and signaling molecules, such as TNF-α, TGF-ß, MMPs, VEGF, interleukins, Bcl-2, caspases, HIF-1α, EMT proteins, Nrf-2, etc., which play a pivotal role in the molecular mechanism of chronic diseases. Overwhelming pieces of evidence expound on the anti-inflammatory, anti-bacterial, anti-viral, and anti-cancer potentials of this flavonoid, which makes it an engrossing compound for research. Numerous preclinical and clinical studies also displayed the promising potential of OA against cancer, cardiovascular diseases, inflammation, neurological disorders, rheumatoid arthritis, osteoarthritis, etc. Therefore, the current review focuses on delineating the role of OA in combating different chronic diseases and highlighting the intrinsic molecular mechanisms of its action.