The regulating effect of curcumin on NF-κB pathway in neurodegenerative diseases: a review of the underlying mechanisms.

Neurodegenerative diseases are part of the central nervous system (CNS) disorders that indicate their presence with neuronal loss, neuroinflammation, and increased oxidative stress. Several pathophysiological factors and biomarkers are involved in this inflammatory process causing these neurological disorders. The nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is an inflammation element, which induced transcription and appears to be one of the important players in physiological procedures, especially nervous disorders. NF-κB can impact upon series of intracellular actions and induce or inhibit many inflammation-related pathways. Multiple reports have focused on the modification of NF-κB activity, controlling its expression, translocation, and signaling pathway in neurodegenerative disorders and injuries like Alzheimer's disease (AD), spinal cord injuries (SCI), and Parkinson's disease (PD). Curcumin has been noted to be a popular anti-oxidant and anti-inflammatory substance and is the foremost natural compound produced by turmeric. According to various studies, when playing an anti-inflammatory role, it interacts with several modulating proteins of long-standing disease signaling pathways and has an unprovocative consequence on pro-inflammatory cytokines. This review article determined to figure out curcumin's role in limiting the promotion of neurodegenerative disease via influencing the NF-κB signaling route. Preclinical studies were gathered from plenty of scientific platforms including PubMed, Scopus, Cochrane, and Google Scholar to evaluate this hypothesis. Extracted findings from the literature review explained the repressing impact of Curcumin on the NF-κB signaling pathway and, occasionally down-regulating the cytokine expression. Yet, there is an essential need for further analysis and specific clinical experiments to fully understand this subject.

Protective Effects of Plant-Derived Compounds Against Traumatic Brain Injury.

Inflammation in the nervous system is one of the key features of many neurodegenerative diseases. It is increasingly being identified as a critical pathophysiological primitive mechanism associated with chronic neurodegenerative diseases following traumatic brain injury (TBI). Phytochemicals have a wide range of clinical properties due to their antioxidant and anti-inflammatory effects. Currently, there are few drugs available for the treatment of neurodegenerative diseases other than symptomatic relief. Numerous studies have shown that plant-derived compounds, in particular polyphenols, protect against various neurodegenerative diseases and are safe for consumption. Polyphenols exert protective effects on TBI via restoration of nuclear factor kappa B (NF-κB), toll-like receptor-4 (TLR4), and Nod-like receptor family proteins (NLRPs) pathways. In addition, these phytochemicals and their derivatives upregulate the phosphatidylinositol-3-Kinase/Protein Kinase B (PI3K/AKT) and nuclear factor erythroid 2-related factor 2 (Nrf2) pathways, which have critical functions in modulating TBI symptoms. There is supporting evidence that medicinal plants and phytochemicals are protective in different TBI models, though future clinical trials are needed to clarify the precise mechanisms and functions of different polyphenolic compounds in TBI.

Therapeutic effects of anti-diabetic drugs on traumatic brain injury.

AIMS: In this narrative review, we have analyzed and synthesized current studies relating to the effects of anti-diabetic drugs on traumatic brain injury (TBI) complications. METHODS: Eligible studies were collected from Scopus, Google Scholar, PubMed, and Cochrane Library for clinical, in-vivo, and in-vitro studies published on the impact of anti-diabetic drugs on TBI. RESULTS: Traumatic brain injury (TBI) is a serious brain disease that is caused by any type of trauma. The pathophysiology of TBI is not yet fully understood, though physical injury and inflammatory events have been implicated in TBI progression. Several signaling pathways are known to play pivotal roles in TBI injuries, including Nuclear factor erythroid 2-related factor 2 (Nrf2), High mobility group box 1 protein/Nuclear factor kappa B (HMGB1/NF-κB), Adiponectin, Mammalian Target of Rapamycin (mTOR), Toll-Like Receptor (TLR), Wnt/ß-catenin, Janus Kinase/Signal Transducers and Activators of Transcription (JAK/STAT), Nod-like receptor protein3 (NLRP3) inflammasome, Phosphoglycerate kinase 1/Kelch-like ECH-associated protein 1 (PGK1/KEAP1)/Nrf2, and Mitogen-activated protein kinase (MAPK) . Recent studies suggest that oral anti-diabetic drugs such as biguanides, thiazolidinediones (TZDs), sulfonylureas (SUs), sodium-glucose cotransporter-2 inhibitors (SGLT2is), dipeptidyl peptidase-4 inhibitors (DPPIs), meglitinides, and alpha-glucosidase inhibitors (AGIs) could have beneficial effects in the management of TBI complications. These drugs may downregulate the inflammatory pathways and induce antioxidant signaling pathways, thus alleviating complications of TBI. CONCLUSION: Based on this comprehensive literature review, antidiabetic medications might be considered in the TBI treatment protocol. However, evidence from clinical trials in patients with TBI is still warranted.

Superoxide dismutase: a key target for the neuroprotective effects of curcumin.

Over the past few years, the prevalence of neurodegenerative diseases (NDD) has increased dramatically. The community health system is burdened by the high healthcare costs associated with NDD. Superoxide dismutase (SOD) is a type of metalloenzyme that possesses a distinct characteristic of protecting the body from oxidative stress through antioxidants. In this way, SOD supplementation may activate the endogenous antioxidant mechanism in various pathological conditions and could be used to neutralize free radical excess. Several factors are responsible for damaging DNA and RNA in the body, including the overproduction of reactive species, particularly reactive oxygen species (ROS) and reactive nitrogen species (RNS). Excessive ROS/RNS have deleterious effects on mitochondria and their metabolic processes, mainly through increased mitochondrial proteins, lipids and DNA oxidation. Studies have shown that oxidative stress is implicated in the etiology of many diseases, including NDD. It is thought that anti-inflammatory compounds, particularly phytochemicals, can interfere with these pathways and regulate inflammation. Extensive experimental and clinical research has proven that curcumin (Cur) has anti-inflammatory and anti-neurologic properties. In this review, we have compiled the available data on Cur's anti-inflammatory properties, paying special attention to its therapeutic impact on NDD through SOD.

Pharmacological activities of turmerones.

Turmerones are major bioactive compounds of Curcuma species with several beneficial pharmacological activities. In addition, various in vivo and in vitro studies noted that turmerones could affect different cytokines, metabolic pathways, and targets. Turmerones will have the potential to be a candidate agent to lessen many pathological and immunological conditions as a result of these pharmacological activities. In this review, we provided information about the pharmacological actions of turmerones using search engines such as PubMed, Google Scholar, Scopus, and Web of Science.

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 mitigate 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.

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-γ) and protein kinase B/nuclear factor kappa-light-chain-enhancer of activated B cells (AKT/NF-κB)-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.

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.

Licofelone, a potent COX/5-LOX inhibitor and a novel option for treatment of neurological disorders.

Neurological disorders result in disability and morbidity. Neuroinflammation is a key factor involved in progression or resolution of a series of neurological disorders like Huntington disease (HD), Parkinson's disease (PD), Alzheimer's disease (AD), Spinal Cord Injury (SCI), and Seizure. Thereby, anti-inflammatory drugs have been developed to improve the neurodegenerative impairments. Licofelone is an approved osteoarthritis drug that inhibits both the COX (cyclooxygenase) and 5-LOX (lipoxygenase) pathways. Licofelone has pain-relieving and anti-inflammatory effects and it was shown to have neuroprotective properties in the central nervous system, which is implicated in its regulatory effect on the COX/5-LOX pathway, inflammatory cytokines, and immune responses. In this study, we briefly review the various features of neurological disorders and the function of COX/LOX in their flare up and current pharmacological products for their management. Moreover, this review attempts to summarize potential therapeutics that target the immune responses within the central nervous system. A better understanding of the interactions between Licofelone and the nervous systems will be crucial to demonstrate the possible efficacy of Licofelone in neurological disorders.