Investigating anti-inflammatory and apoptotic actions of fucoidan concentrating on computational and therapeutic applications.

Fucoidan is linked to a variety of biological processes. Differences in algae species, extraction, seasons, and locations generate structural variability in fucoidan, affecting its bioactivities. Nothing is known about fucoidan from the brown alga Dictyota bartayresiana, its anti-inflammatory properties, or its inherent mechanism. This study aimed to investigate the anti-inflammatory properties of fucoidan isolated from D. bartayresiana against LPS-induced RAW 264.7 macrophages and to explore potential molecular pathways associated with this anti-inflammatory effects. Fucoidan was first isolated and purified from D. bartayresiana, and then, MTT assay was used to determine the effect of fucoidan on cell viability. Its effects on reactive oxygen species (ROS) formation and apoptosis were also studied using the ROS assay and acridine orange/ethidium bromide fluorescence labelling, respectively. Molecular docking and molecular dynamics simulation studies were performed on target proteins NF-κB and TNF-α to identify the route implicated in these inflammatory events. It was observed that fucoidan reduced LPS-induced inflammation in RAW 264.7 cells. Fucoidan also decreased the LPS-stimulated ROS surge and was found to induce apoptosis in the cells. Molecular docking and molecular dynamics simulation studies revealed that fucoidan's potent anti-inflammatory action was achieved by obstructing the NF-κB signalling pathway. These findings were particularly noteworthy and novel because fucoidan isolated from D. bartayresiana had not previously been shown to have anti-inflammatory properties in RAW 264.7 cells or to exert its activity by obstructing the NF-κB signalling pathway. Conclusively, these findings proposed fucoidan as a potential pharmaceutical drug for inflammation-related diseases.

NLRP3: a new therapeutic target in alcoholic liver disease.

The liver is in charge of a wide range of critical physiological processes and it plays an important role in activating the innate immune system which elicits the inflammatory events. Chronic ethanol exposure disrupts hepatic inflammatory mechanism and leads to the release of proinflammatory mediators such as chemokines, cytokines and activation of inflammasomes. The mechanism of liver fibrosis/cirrhosis involve activation of NLRP3 inflammasome, leading to the destruction of hepatocytes and subsequent metabolic dysregulation in humans. In addition, increasing evidence suggests that alcohol intake significantly modifies liver epigenetics, promoting the development of alcoholic liver disease (ALD). Epigenetic changes including histone modification, microRNA-induced genetic modulation, and DNA methylation are crucial in alcohol-evoked cell signaling that affects gene expression in the hepatic system. Though we are at the beginning stage without having the entire print of epigenetic signature, it is time to focus more on NLRP3 inflammasome and epigenetic modifications. Here we review the novel aspect of ALD pathology linking to inflammation and highlighting the role of epigenetic modification associated with NLRP3 inflammasome and how it could be a therapeutic target in ALD.

Fibrosis in Liver and Pancreas: a Review on Pathogenic Significance, Diagnostic Options, and Current Management Strategies.

Inflammation is one of the most natural ways of the body's biological response against invading foreign pathogens or injured cells which eventually can lead to a chronic or acute productive response. Fibrosis is an end-stage event associated with an inflammatory response addressed with tissue hardening, discoloration, and most importantly overgrowth of associated tissue. Various organs at different diseased conditions are affected by fibrosis including the liver, pancreas, brain, kidney, and lung. Etiological factors including internal like inflammatory cytokines, growth factors, and oxidative stress and external like alcohol and viruses contribute to the development of fibrosis in both the liver and pancreas. More frequently, these organs are associated with pathogenic progression towards fibrosis from acute and chronic conditions and eventually fail in their functions. The pathogenesis of the organ-fibrotic events mainly depends on the activation of residential stellate cells; these cells help to accumulate collagen in respective organs. Various diagnostic options have been developed recently, and various therapeutic options are in trial to tackle fibrosis. In this review, an overview on fibrosis, the pathogenesis of fibrosis in the liver and pancreas, various diagnostic options developed in recent years, and possible present therapeutic measures to overcome options of fibrosis in the liver and pancreas; thus, restoring the functional status of organs is discussed.