A Review of Plant Extracts and Plant-Derived Natural Compounds in the Prevention/Treatment of Neonatal Hypoxic-Ischemic Brain Injury.

Neonatal hypoxic-ischemic (HI) brain injury is one of the major drawbacks of mortality and causes significant short/long-term neurological dysfunction in newborn infants worldwide. To date, due to multifunctional complex mechanisms of brain injury, there is no well-established effective strategy to completely provide neuroprotection. Although therapeutic hypothermia is the proven treatment for hypoxic-ischemic encephalopathy (HIE), it does not completely chang outcomes in severe forms of HIE. Therefore, there is a critical need for reviewing the effective therapeutic strategies to explore the protective agents and methods. In recent years, it is widely believed that there are neuroprotective possibilities of natural compounds extracted from plants against HIE. These natural agents with the anti-inflammatory, anti-oxidative, anti-apoptotic, and neurofunctional regulatory properties exhibit preventive or therapeutic effects against experimental neonatal HI brain damage. In this study, it was aimed to review the literature in scientific databases that investigate the neuroprotective effects of plant extracts/plant-derived compounds in experimental animal models of neonatal HI brain damage and their possible underlying molecular mechanisms of action.

Medicinal plants for diabetes associated neurodegenerative diseases: A systematic review of preclinical studies.

Diabetes mellitus is a metabolic defect with many complications for the patients. Deaths due to diabetes and its complications are increasing, and one of the most serious consequences are the neurological disorders. Chemical treatments have irreversible side effect and therefore the aim of this study is to evaluate the medicinal plants used for treatment of cognitive impairments and neurodegenerative diseases associated with diabetes in 2004-2020 period. Electronic databases used were PubMed, Scopus and Cochrane library. The keywords used were "diabetes," "plant," "herb," "neurodegenerative," "neurodegeneration," "cognitive," "cognition," "Alzheimer," "dementia." The non-English articles, repetitive articles and review studies were excluded. From total of 3,590 results, 58 articles are included in the study. The results show that many chemical treatments considered for this disease simply control hyperglycemia, but cannot improve the complications of diabetes. Herbal medicine could be more effective due to the high antioxidant activity of some medicinal plants. Biologically active substances of medicinal plants can improve the neurological disorders caused by diabetes via several pathways. The most important pathway is related to antioxidant properties. Other pathways include antiinflammatory, anti-apoptotic, neurotoxicity inhibition, neuronal death, increasing the uptake of glucose by cells and improve neurotransmitters levels involved in learning and memory.

Attenuation of Nrf2/Keap1/ARE in Alzheimer's Disease by Plant Secondary Metabolites: A Mechanistic Review.

Alzheimer's disease (AD) is a progressive neuronal/cognitional dysfunction, leading to disability and death. Despite advances in revealing the pathophysiological mechanisms behind AD, no effective treatment has yet been provided. It urges the need for finding novel multi-target agents in combating the complex dysregulated mechanisms in AD. Amongst the dysregulated pathophysiological pathways in AD, oxidative stress seems to play a critical role in the pathogenesis progression of AD, with a dominant role of nuclear factor erythroid 2-related factor 2 (Nrf2)/Kelch-like ECH-associated protein-1 (Keap1)/antioxidant responsive elements (ARE) pathway. In the present study, a comprehensive review was conducted using the existing electronic databases, including PubMed, Medline, Web of Science, and Scopus, as well as related articles in the field. Nrf2/Keap1/ARE has shown to be the upstream orchestrate of oxidative pathways, which also ameliorates various inflammatory and apoptotic pathways. So, developing multi-target agents with higher efficacy and lower side effects could pave the road in the prevention/management of AD. The plant kingdom is now a great source of natural secondary metabolites in targeting Nrf2/Keap1/ARE. Among natural entities, phenolic compounds, alkaloids, terpene/terpenoids, carotenoids, sulfur-compounds, as well as some other miscellaneous plant-derived compounds have shown promising future accordingly. Prevailing evidence has shown that activating Nrf2/ARE and downstream antioxidant enzymes, as well as inhibiting Keap1 could play hopeful roles in overcoming AD. The current review highlights the neuroprotective effects of plant secondary metabolites through targeting Nrf2/Keap1/ARE and downstream interconnected mediators in combating AD.

Modulation of the oxidative plasmatic state in gastroesophageal reflux disease with the addition of rich water molecular hydrogen: A new biological vision.

Gastroesophageal reflux disease (GERD), a clinical condition characterized by reflux of gastroduodenal contents in the oesophagus, has proved to demonstrate a strong link between oxidative stress and the development of GERD. Proton pump inhibitors (PPIs) have been universally accepted as first-line therapy for management of GERD. The potential benefits of electrolysed reduced water (ERW), rich in molecular hydrogen, in improving symptoms and systemic oxidative stress associated with GERD was assessed. The study was performed on 84 GERD patients undergoing control treatment (PPI + tap water) or experimental treatment (PPI + ERW) for 3 months. These patients were subjected to the GERD-Health Related Quality of Life Questionnaire as well as derivatives reactive oxigen metabolites (d-ROMs) test, biological antioxidant potential (BAP) test, superoxide anion, nitric oxide and malondialdehyde assays, which were all performed as a proxy for the oxidative/nitrosative stress and the antioxidant potential status. Spearman's correlation coefficient was used to evaluate the correlation between scores and laboratory parameters. Overall results demonstrated that an optimal oxidative balance can be restored and GERD symptoms can be reduced rapidly via the integration of ERW in GERD patients. The relative variation of heartburn and regurgitation score was significantly correlated with laboratory parameters. Thus, in the selected patients, combination treatment with PPI and ERW improves the cellular redox state leading to the improvement of the quality of life as demonstrated by the correlation analysis between laboratory parameters and GERD symptoms.

A Novel Biological Role of α-Mangostin in Modulating Inflammatory Response Through the Activation of SIRT-1 Signaling Pathway.

Several studies have shown that xanthones obtained from Garcinia Mangostana (GM) have remarkable biological activities. α-mangostin (α-MG) is the main constituent of the fruit hull of the GM. Several findings have suggested that SIRT-1, a nuclear histone deacetylase, could influence cellular function by the inhibition of NF-kB signaling. ROS can inhibit SIRT-1 activity by initiating oxidative modifications on its cysteine residues, and suppression of SIRT-1 enhances the NF-κB signaling resulting in inflammatory responses. The goals of the present study were to evaluate the quantity of α-MG in the methanolic extract of GM (Vithagroup Spa) and to investigate the activity of this xanthone in U937 cell line and in human monocytes from responsive to inflammatory insult analyzing the possible changes on the activation of SIRT-1 protein via NF-Kb. Cells were treated with the methanolic extract of GM and/or LPS. The chromatographic separation of α-MG was performed by an HPLC analysis. EX 527, a specific SIRT-1 inhibitor, was used to determine if SIRT-1/NfkB signaling pathway might be involved in α-MG action on cells. Our results show that α-MG inhibits p65 acetylation and down-regulates the pro-inflammatory gene products as COX-2, iNOS via SIRT-1 activation. Cells treated with EX 527 showed an up-regulation of NFkB acetylation and an over expression of inducible enzymes and their product of catalysis (NO and PGE2). These results suggest that α-MG may be useful for the development of alternative pharmacological strategies aimed at reducing the inflammatory process. J. Cell. Physiol. 231: 2439-2451, 2016. © 2016 Wiley Periodicals, Inc.

Carotenoids and vitamins C and E in the prevention of cardiovascular disease.

Atherosclerotic cardiovascular diseases (CVD) are a major source of mortality and morbidity in the general population. Oxidative modification of low-density lipoprotein cholesterol (LDL-C) represents the most important determinant factor in the development and progression of atherosclerotic lesions. Oxidative damage and the production of free radicals (FRs) in the endothelium are some of the main factors involved in the pathogenesis of the atherosclerotic process that causes CVD. Appropriate nutritional practices are of central importance in managing risk and treatment of CVD; in fact, many current guidelines for a healthy general population contain nutritional recommendations to reduce the risk of these diseases. Observational studies of vitamins C and E, the most prevalent natural antioxidant vitamins, suggest that supplemental use of these vitamins may lower the risk for coronary events. Despite these data, several large, randomized controlled trials have failed to confirm the benefits of vitamin C and E in cardiovascular prevention. The aim of this review is to examine the published studies regarding the effect of vitamins (C and E) and beta-carotene supplementation in the prevention of CVD due to atherosclerosis.

Novel phytonutrient contributors to antioxidant protection against cardiovascular disease.

The associations linking endothelial inflammation, endothelial oxidative stress, and atherogenesis and the potential for dietary phytonutrients to decrease the impact of these associations were assessed. A detailed literature review was conducted and summarized. A large body of scientific evidence describes the interactions among endothelial inflammation, endothelial oxidative stress, and atherogenesis. A growing body of research indicates that several dietary phytonutrients (astaxanthin, lycopene, lutein, and glabridin) can decrease the risk for atherosclerosis by decreasing endothelial inflammation and oxidative stress. The consumption of foods or dietary supplements that provide astaxanthin, lycopene, lutein, and glabridin can ameliorate endothelial inflammation and oxidative stress, retard atherogenesis, and decrease the risk for atherogenic cardiovascular disease.

Antiinflammatory effects in THP-1 cells treated with verbascoside.

Verbascum thapsus commonly known as 'mullein' is part of a large family of Scrophulariaceae consisting of more than 360 species. From antiquity Verbascum thapsus has been used as a medicinal herb, it contains diverse polysaccharides, iroid glycosides, flavonoids, saponins, volatile oils and phenylentanoids. Inducible nitric oxide synthase (iNOS) represents one of the three isoforms that produce nitric oxide using L-arginine as a substrate in response to an increase in superoxide anion activated by NF-kB. It is implicated in different pathophysiological events and its expression increases greatly during an inflammatory process, due to oxidative stress and the activation of the enzymes of the antioxidant network such as SOD, CAT and GPx.In this study an inflammatory state was reproduced by treating THP-1 cells (human myelomonocytic leukaemia) with pro-inflammatory stimuli, such as LPS and IFN-gamma, obtaining an up-regulation both in the expression and in the activity of iNOS. The aim of the work was to investigate the antiinflammatory action of verbascoside using a concentration of 100 mum. The results show a significant decrease of the expression and activity of iNOS, extracellular O(2) (-) production, SOD, CAT and GPx activity when the cells were treated with verbascoside. Based on these results it is hypothesized that verbascoside has antiinflammatory properties since it reduces the production of superoxide radicals and consequently reduces the activity of iNOS.