Phytochemicals as Modulators of Paraoxonase?1 in Health and Diseases

Chronic diseases such as cardiovascular disease (CVD), atherosclerosis, chronic liver disease, and neurodegenerative diseases are major causes of mortality. These diseases have gained much attention due to their complications, and therefore novel approaches with fewer side effects are an important research topic. Free radicals and oxidative stress are involved in the molecular mechanisms of several diseases. Antioxidants can scavenge free radicals and mitigate their adverse effects. One of the most important antioxidant enzymes are paraoxonases (PONs). These enzymes perform a wide range of physiological activities ranging from drug metabolism to detoxification of neuroleptics. Paraoxonase?1 (PON1) is produced in the liver and then transferred to the bloodstream. It has been demonstrated that PON1 could have beneficial effects in numerous diseases such as atherosclerosis, CVD, diabetes mellitus, and neurodegenerative diseases by modulating relevant signalling pathways involved in inflammation and oxidative stress. These pathways include peroxisome proliferator?activated receptor gamma (PPAR??) and protein kinase B/nuclear factor kappa?light?chain?enhancer of activated B cells (AKT/NF??B)?dependent signalling pathways. Increasing PON1 could potentially have protective effects and reduce the incidence of various diseases by modulating these signalling pathways. Several studies have reported that dietary factors are able to modulate PON1 expression and activity. This review aimed at summarizing the state of the art on the effects of dietary phytochemicals on PON1 enzyme activity and the relevant signalling pathways in different diseases

Ginger and its constituents : role in treatment of inflammatory bowel disease

Inflammatory bowel diseases (IBD), with obscure etiology, are rising and are of worldwide concern. Of the various components of IBD pathogenesis and progression, irritation appears to play a major part. Investigations on the molecular and cellular pathways that activate the IBD provide the focus for the development of useful therapies. Ginger (the rhizome of Zingiber officinale) has a broad spectrum of clinical applications due to its anti-inflammatory and anti-oxidative functions. Inflammation and oxidative stress are the key pathogenic factors in many diseases, including IBD. The most established components of ginger are phenolic compounds called gingerols. A wide range of pharmacological activities of the potential therapeutic benefit of Z. officinale have been detailed. In this regard, the anti-inflammatory activity of ginger has been documented by many researchers. It was shown that ginger is a potent inhibitor of the nuclear factor kappa B (NF-κB), signal transducer of activators of transcription (STATs), Nod-like receptor family proteins (NLRPs), toll-like receptors (TLRs), mitogen-activated protein kinase (MAPKs), and mTOR (mTOR) pathways, as well as inhibiting various pro-inflammatory cytokines. In the present report, the potential application of ginger in the management of IBD is reviewed in detail, with an emphasis on the relevant properties of ginger and its bioactive components. The significance of the functions, side effects, and delivery of ginger to the digestive system for particular application in IBD are also considered

Regulatory Effects of Statins on SIRT1 and Other Sirtuins in Cardiovascular Diseases

Adverse cardiovascular disease (CVD) outcomes, such as sudden cardiac death, acute myocardial infarction, and stroke, are often catastrophic. Statins are frequently used to attenuate the risk of CVD-associated morbidity and mortality through their impact on lipids and they may also have anti-inflammatory and other plaque-stabilization effects via different signaling pathways. Different statins, including atorvastatin, rosuvastatin, pravastatin, pitavastatin, and simvastatin, are administered to manage circulatory lipid levels. In addition, statins are potent inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase via modulating sirtuins (SIRTs). During the last two decades, SIRTs have been investigated in mammals and categorized as a family of nicotinamide adenine dinucleotide (NAD)-dependent histone deacetylases (HDACs) with significant oxidative stress regulatory function in cells-a key factor in extending cell lifespan. Recent work has demonstrated that statins upregulate SIRT1 and SIRT2 and downregulate SIRT6 in both in vitro and in vivo experiments and clinical trials. As statins show modulatory properties, especially in CVDs, future investigations are needed to delineate the role of SIRT family members in disease and to expand knowledge about the effects of statins on SIRTs. Here, we review what is currently known about the impact of statins on SIRTs and how these changes correlate with disease, particularly CVDs

Protective effects of curcumin against traumatic brain injury

Neuroinflammation is a key pathophysiological mechanism implicated in the neurodegenerative condition. One  such condition implicating neuroinflammation is traumatic brain injury (TBI). Over the past decades, various  alternative natural compounds, such as curcumin, have been investigated as novel therapeutic options to miti?gate the pathophysiological pathways and clinical sequelae involved in TBI. As the main component of turmeric  (Curcuma longa), curcumin has a broad range of clinical properties due to its considerable antioxidative and anti?inflammatory actions. This review discusses the pleiotropic mechanisms, the side effects, curcumin’s delivery to  the central nervous system (CNS), and its immunomodulatory and protective effects on TBI. Clinical trials, in  vivo, and in vitro studies were extracted from different scientific databases, including PubMed, Scopus, and  Google Scholar, to assess the effects of curcumin or its derivatives in TBI. Findings reveal that curcumin exhibited  some protective effects on TBI via modulation of cell signaling pathways including toll-like receptor-4 (TLR-4),  nuclear factor kappa B (NF-κB), and Nod-like receptor family proteins (NLRPs). Moreover, curcumin upregulates  the brain-derived Neurotrophic Factor/Tropomyosin receptor kinase B (BDNF/TrkB) signaling pathway,  phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT), nuclear factor erythroid 2-related factor 2 (Nrf2),  which have crucial functions in modulation of TBI pathophysiological-mediated pathways. Curcumin displays  beneficial immunomodulatory functions and protective capacities in different TBI models, although more clinical  experiments are required to clarify curcumin’s precise mechanisms and function in TBI.  </p