Traumatic brain injury (TBI) is a major health concern worldwide and is classified based on severity into mild, moderate, and severe. The mechanical injury in TBI leads to a metabolic and ionic imbalance, which eventually leads to excessive production of reactive oxygen species (ROS) and a state of oxidative stress. To date, no drug has been approved by the food and drug administration (FDA) for the treatment of TBI. Nevertheless, it is thought that targeting the pathology mechanisms would alleviate the consequences of TBI. For that purpose, antioxidants have been considered as treatment options in TBI and were shown to have a neuroprotective effect. In this review, we will discuss oxidative stress in TBI, the history of antioxidant utilization in the treatment of TBI, and we will focus on two novel antioxidants, mitoquinone (MitoQ) and edaravone. MitoQ can cross the blood brain barrier and cellular membranes to accumulate in the mitochondria and is thought to activate the Nrf2/ARE pathway leading to an increase in the expression of antioxidant enzymes. Edaravone is a free radical scavenger that leads to the mitigation of damage resulting from oxidative stress with a possible association to the activation of the Nrf2/ARE pathway as well.

Visfatin/NAMPT (nicotinamide phosphoribosyltransferase) is an adipocytokine with several intriguing properties. It was first identified as pre-B-cell colony-enhancing factor but turned out to possess enzymatic functions in nicotinamide adenine dinucleotide biosynthesis, with ubiquitous expression in skeletal muscles, liver, cardiomyocytes, and brain cells. Visfatin exists in an intracellular (iNAMPT) and extracellular (eNAMPT) form. Intracellularly, visfatin/iNAMPT plays a regulatory role in NAD⁺ biosynthesis and thereby affects many NAD-dependent proteins such as sirtuins, PARPs, MARTs and CD38/157. Extracellularly, visfatin is associated with many hormone-like signaling pathways and activates some intracellular signaling cascades. Importantly, eNAMPT has been associated with several metabolic disorders including obesity and type 1 and 2 diabetes. In this review, a brief overview about visfatin is presented with special emphasis on its relevance to metabolic diseases. Visfatin/NAMPT appears to be a unique molecule with clinical significance with a prospective promising diagnostic, prognostic, and therapeutic applications in many cardiovasculo-metabolic disorders.

Cardiac autonomic neuropathy (CAN) is one of the earliest complications of type 2 diabetes (T2D), presenting a silent cause of cardiovascular morbidity and mortality. Recent research relates the pathogenesis of cardiovascular disease in T2D to an ensuing chronic, low-grade proinflammatory and pro-oxidative environment, being the hallmark of the metabolic syndrome. Metabolic inflammation emerges as adipose tissue inflammatory changes extending systemically, on the advent of hyperglycemia, to reach central regions of the brain. In light of changes in glucose and insulin homeostasis, dysbiosis or alteration of the gut microbiome (GM) emerges, further contributing to inflammatory processes through increased gut and blood–brain barrier permeability. Interestingly, studies reveal that the determinants of oxidative stress and inflammation progression exist at the crossroad of CAN manifestations, dictating their evolution along the natural course of T2D development. Indeed, sympathetic and parasympathetic deterioration was shown to correlate with markers of adipose, vascular, and systemic inflammation. Additionally, evidence points out that dysbiosis could promote a sympatho-excitatory state through differentially affecting the secretion of hormones and neuromodulators, such as norepinephrine, serotonin, and γ-aminobutyric acid, and acting along the renin–angiotensin–aldosterone axis. Emerging neuronal inflammation and concomitant autophagic defects in brainstem nuclei were described as possible underlying mechanisms of CAN in experimental models of metabolic syndrome and T2D. Drugs with anti-inflammatory characteristics provide potential avenues for targeting pathways involved in CAN initiation and progression. The aim of this review is to delineate the etiology of CAN in the context of a metabolic disorder characterized by elevated oxidative and inflammatory load.

Cancer is the second most life-threatening disease and has become a global health and economic problem worldwide. Due to the multifactorial nature of cancer, its pathophysiology is not completely understood so far, which makes it hard to treat. The current therapeutic strategies for cancer lack the efficacy due to the emergence of drug resistance and the toxic side effects associated with the treatment. Therefore, the search for more efficient and less toxic cancer treatment strategies is still at the forefront of current research. Propolis is a mixture of resinous compounds containing beeswax and partially digested exudates from plants leaves and buds. Its chemical composition varies widely depending on the bee species, geographic location, plant species, and weather conditions. Since ancient times, propolis has been used in many conditions and aliments for its healing properties. Propolis has well-known therapeutic actions including antioxidative, antimicrobial, anti-inflammatory, and anticancer properties. In recent years, extensive in vitro and in vivo studies have suggested that propolis possesses properties against several types of cancers. The present review highlights the recent progress made on the molecular targets and signaling pathways involved in the anticancer activities of propolis. Propolis exerts anticancer effects primarily by inhibiting cancer cell proliferation, inducing apoptosis through regulating various signaling pathways and arresting the tumor cell cycle, inducing autophagy, epigenetic modulations, and further inhibiting the invasion and metastasis of tumors. Propolis targets numerous signaling pathways associated with cancer therapy, including pathways mediated by p53, β-catenin, ERK1/2, MAPK, and NF-κB. Possible synergistic actions of a combination therapy of propolis with existing chemotherapies are also discussed in this review. Overall, propolis, by acting on diverse mechanisms simultaneously, can be considered to be a promising, multi-targeting, multi-pathways anticancer agent for the treatment of various types of cancers.

Colorectal cancer (CRC) is the third most common type of cancer in terms of incidence and mortality worldwide. Here we have investigated the anti-colon cancer potential of Origanum majorana essential oil (OMEO) and its underlying mechanisms of action. We showed that OMEO significantly inhibited the cellular viability and colony growth of human HT-29 colorectal cancer cells. OMEO induced protective autophagy, associated with downregulation of the mTOR/p70S6K pathway, and activated caspase-8 and caspase-9-dependent apoptosis. Blockade of autophagy with 3-methyladenine (3-MA) and chloroquine (CQ), two autophagy inhibitors, potentiated the OMEO-induced apoptotic cell death. Inversely, inhibition of apoptosis with the pan-caspase inhibitor, Z-VAD-FMK, significantly reduced cell death, suggesting that apoptosis represents the main mechanism of OMEO-induced cell death. Mechanistically, we found that OMEO induces protective autophagy and apoptotic cells death via the activation of the p38 MAPK signaling pathway. Pharmacological inhibition of p38 MAPK by the p38 inhibitors SB 202190 and SB 203580 not only significantly decreased apoptotic cell death, but also reduced the autophagy level in OMEO treated HT-29 cells. Strikingly, we found that OMEO also induces p38 MAPK-mediated caspase-dependent cleavage of p70S6K, a protein reported to be overexpressed in colon cancer and associated with drug resistance. Our findings suggest that OMEO inhibits colon cancer through p38 MAPK-mediated protective autophagy and apoptosis associated with caspase-dependent cleavage of p70S6K. To the best of our knowledge, this study is the first to report on the implications of the p38 MAPK signaling pathway in targeting p70S6K to caspase cleavage.

Nowadays, marine microalgae are recognized to be a considerably novel and rich origin of bioactive moieties utilized in the sectors of nutraceuticals and pharmaceuticals. In the present study, Nannochloropsis oculata extract (AME) was associated with a wide variety of pharmacological studies such as in vitro antioxidant, antibacterial, and antifungal and anticancer activity (MDA-MB-231) in cancer cells through in vitro models. In the study, the chemical composition and structure of the bioactive compounds found in the AME extract were studied using the LC-MS technique. The results of the anticancer activity showed a decrease in the percentage of cell viability of the MDA-MB-231 cells in a concentration- and time-dependent manner (400 μg/mL at 24 h, 300 μg/mL at 48 h, and 200 μg/mL at 72 h). We have also observed morphological changes in the cells that could be associated with treatment with AME extract. Our observation of the AME extract-treated MDA-MB231 cells under light microscopy showed that when the concentration increased, the number of cells began to decrease. As far as LC-MS analysis is concerned, it showed the presence of the bioactive molecules was terpenoids along with carotenoids, polyphenolic and fatty acids. The result revealed that the AME extract exhibited noteworthy in vitro free radical scavenging potential, with an IC₅₀ value of 52.10 ± 0.85 µg/L in DPPH assay, 122.84 ± 2.32 µg/mL in H₂O₂ assay and, 96.95 ± 1.68 µg/mL in ABTS assay. The activity was found to be highly significant against bacteria (Gram-positive and negative) and moderately significant against fungal strain with minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC)/minimum fungicidal concentration (MFC) values between 15.63 and 500 µg/mL.