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Silymarin and Cancer: A Dual Strategy in Both in Chemoprevention and Chemosensitivity.
Delmas, D, Xiao, J, Vejux, A, Aires, V
Molecules (Basel, Switzerland). 2020;(9)
Abstract
Silymarin extracted from milk thistle consisting of flavonolignan silybin has shown chemopreventive and chemosensitizing activity against various cancers. The present review summarizes the current knowledge on the potential targets of silymarin against various cancers. Silymarin may play on the system of xenobiotics, metabolizing enzymes (phase I and phase II) to protect normal cells against various toxic molecules or to protect against deleterious effects of chemotherapeutic agents on normal cells. Furthermore, silymarin and its main bioactive compounds inhibit organic anion transporters (OAT) and ATP-binding cassettes (ABC) transporters, thus contributing to counteracting potential chemoresistance. Silymarin and its derivatives play a double role, namely, limiting the progression of cancer cells through different phases of the cycle-thus forcing them to evolve towards a process of cell death-and accumulating cancer cells in a phase of the cell cycle-thus making it possible to target a greater number of tumor cells with a specific anticancer agent. Silymarin exerts a chemopreventive effect by inducing intrinsic and extrinsic pathways and reactivating cell death pathways by modulation of the ratio of proapoptotic/antiapoptotic proteins and synergizing with agonists of death domains receptors. In summary, we highlight how silymarin may act as a chemopreventive agent and a chemosensitizer through multiple pathways.
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The Role of Glycosaminoglycans in Protection from Neonatal Necrotizing Enterocolitis: A Narrative Review.
Burge, K, Bergner, E, Gunasekaran, A, Eckert, J, Chaaban, H
Nutrients. 2020;(2)
Abstract
Necrotizing enterocolitis, a potentially fatal intestinal inflammatory disorder affecting primarily premature infants, is a significant cause of morbidity and mortality in neonates. While the etiology of the disease is, as yet, unknown, a number of risk factors for the development of necrotizing enterocolitis have been identified. One such risk factor, formula feeding, has been shown to contribute to both increased incidence and severity of the disease. The protective influences afforded by breastfeeding are likely attributable to the unique composition of human milk, an extremely potent, biologically active fluid. This review brings together knowledge on the pathogenesis of necrotizing enterocolitis and current thinking on the instrumental role of one of the more prominent classes of bioactive components in human breast milk, glycosaminoglycans.
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3.
Cinnamomum zeylanicum (Darchini): A Boon to Medical Science and a Possible Therapy for Stress-Induced Ailments.
Hussain, Z, Khan, JA, Rashid, H
Critical reviews in eukaryotic gene expression. 2019;(3):263-276
Abstract
Plants have been an imperative source of medicine and drugs for therapy of different ailments in humans from the early history until today. Many phytochemicals present in plants act as antioxidants and are utilized as health-protecting agents. Cinnamon, a widely used spice and folk medicine obtained from Cinnamomum zeylanicum, is an effective therapy for various diseases because of its antioxidant and protective efficacy. In the present review, we investigate the beneficial effects of cinnamon on stress-induced ailments. The data regarding therapeutic effects of cinnamon on stress-induced conditions were systematically collected from PubMed, ScienceDirect, Google Scholar, and the Web of Science databases published in the English language from 2000 until July 2018 with the following terms: cinnamon, antioxidant properties, anti-inflammatory, and multifaceted plant. The articles reviewed demonstrated that free radicals play a significant role in the pathophysiology of oxidative stress-associated diseases; therefore cinnamon, with its free radical scavenging activity, represents a promising therapeutic option for ameliorating these debilitating conditions. In this context, the use of cinnamon and its derivatives might be a beneficial way to reduce oxidative stress-induced complications. However, more studies are needed at the molecular level to understand the pathophysiology of the clinical conditions observed as a result of oxidative stress.
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El Niño Altered Gut Microbiota of Children: A New Insight on Weather-Gut Interactions and Protective Effects of Probiotic.
Lau, ASY, Mitsuyama, E, Odamaki, T, Xiao, JZ, Liong, MT
Journal of medicinal food. 2019;(3):230-240
Abstract
Changes in weather often trigger a myriad of negative impacts on the environment, which eventually affect human health. During the early months of 2016, Malaysia experienced El Niño, with an extremely dry season of almost zero rainfall. At the same time, an increase of more than twofold in fecal secretary immunoglobulin-A (SIgA) levels of healthy preschool children aged 2-6 years was observed, accompanied by an increase in phylum Bacteroidetes, predominantly attributed to genus Bacteroides and Odoribacter, which also positively correlated with fecal SIgA levels. Here, we present evidence to illustrate the detrimental effects of weather change on a microscopic "environment," the human gut ecosystem. We also discuss the protective effects of probiotic against dysbiosis as induced by weather change. The increase in Bacteroidetes was at an expense of decreased genus Faecalibacterium and Veillonella (phylum Firmicutes), whereas children consuming probiotic had a decrease in genus Collinsella, Atopobium, and Eggerthella (phylum Actinobacteria) instead.
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Oxidative stress - Related spontaneous preterm delivery challenges in causality determination, prevention and novel strategies in reduction of the sequelae.
Stefanovic, V, Andersson, S, Vento, M
Free radical biology & medicine. 2019;:52-60
Abstract
Spontaneous preterm birth (PTB) is one of the major complications of pregnancy and the main cause of neonatal mortality and morbidity. Despite the efforts devoted to the understanding of this obstetrical syndrome and improved medical care, there has been a tendency for the PTB rate to increase in the last decades globally. The costs of the screening for spontaneous PTB, its management, and treatment of the sequelae represent a major burden to the health service economy of high-income countries. In this scenario, it has been widely acknowledged that oxidative stress (OS) plays an important role in the pathogenicity of human disease in wide range of areas of medicine. There is an emerging evidence that an imbalance between pro-and-antioxidants may be associated with spontaneous PTB. However, there are still many controversies on the mechanisms by which OS are involved in the pathogenesis of prematurity. Moreover, the crucial question whether the OS is the cause or consequence of the disease is yet to be answered. The purpose of this article is to briefly summarize the current knowledge and controversies on oxidative stress-related spontaneous PTB and to give a critical approach on future perspectives on this topic as a classical example of translational medicine. Placenta-mediated pregnancy adverse outcome associated with OS leading to iatrogenic PTB (e.g. pre-eclampsia, intrauterine growth restriction, gestational diabetes) will not be discussed.
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Antidotal or protective effects of honey and one of its major polyphenols, chrysin, against natural and chemical toxicities.
Samarghandian, S, Azimi-Nezhad, M, Pourbagher Shahri, AM, Farkhondeh, T
Acta bio-medica : Atenei Parmensis. 2019;(4):533-550
Abstract
OBJECTIVE Honey and its polyphenolic compounds are of main natural antioxidants that have been used in traditional medicine. The aim of this review was to identify the protective effects of honey and chrysin (a polyphenol available in honey) against the chemical and natural toxic agents. METHOD The scientific databases such as MEDLINE, PubMed, Scopus, Web of Science and Google Scholar were searched to identify studies on the antidotal effects of honey and chrysin against toxic agents. RESULTS This study found that honey had protective activity against toxic agents-induced organ damages by modulating oxidative stress, inflammation, and apoptosis pathways. However, clinical trial studies are needed to confirm the efficacy of honey and chrysin as antidote agents in human intoxication. CONCLUSION Honey and chrysin may be effective against toxic agents. (www.actabiomedica.it).
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Can vitamin D protect against age-related macular degeneration or slow its progression?
Kaarniranta, K, Pawlowska, E, Szczepanska, J, Jablkowska, A, Błasiak, J
Acta biochimica Polonica. 2019;(2):147-158
Abstract
Dietary vitamin D plays an important role in maintaining proper vision. Age-related macular degeneration (AMD) is a complex eye disease with unknown pathogenesis. Studies on dietary supplementation and AMD occurrence and progression have produced conflicting results. In its advanced stage, AMD may be associated with apoptosis, pyroptosis or necroptosis of retinal cells. Vitamin D has been reported to play a role in modulating each of these programmed death pathways. Vitamin D is a modulator of the immune system and it acts synergistically with two members of the regulators of complement activation family H and I, whose specific variants are the most important genetic factors for AMD pathogenesis. Angiogenesis is an essential component of the neovascular form of AMD, the most devastating type of the disease and vitamin D is reputed to possess antiangiogenic properties. Cellular DNA damage response is weakened in AMD patients and so it is another process that can be modulated by vitamin D. Finally, impaired autophagy is claimed to play a role in AMD and emerging evidence suggests that vitamin D can influence autophagy. Therefore, several pathways of vitamin D metabolism and AMD pathogenesis overlap, suggesting that vitamin D could modulate the course of AMD.
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Hepatoprotection by L-Ornithine L-Aspartate in Non-Alcoholic Fatty Liver Disease.
Butterworth, RF, Canbay, A
Digestive diseases (Basel, Switzerland). 2019;(1):63-68
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is the leading chronic hepatic condition worldwide and new approaches to management and treatment are limited. SUMMARY L-ornithine L-aspartate (LOLA) has hepatoprotective properties in patients with fatty liver of diverse etiology and results of a multicenter randomized clinical trial reveal that 12 weeks treatment with oral LOLA (6-9 g/d) results in a dose-related reduction in activities of liver enzymes and triglycerides together with significant improvements of liver/spleen CT ratios. A preliminary report described improvements of hepatic microcirculation in patients with non-alcoholic steatohepatitis (NASH) following treatment with LOLA. Mechanisms responsible for the beneficial effects of LOLA in NAFLD/NASH involve, in addition to its established ammonia-lowering effect, metabolic transformations of the LOLA-constituent amino acids L-ornithine and L-aspartate into L-glutamine, L-arginine, and glutathione. These metabolites have well-established actions implicated in the prevention of lipid peroxidation, improvement of hepatic microcirculation in addition to anti-inflammatory, and anti-oxidant properties. Key Messages: (1) LOLA is effective for the treatment of key indices in NAFLD/NASH. (2) Mechanisms other than LOLA's ammonia-lowering action have been postulated. (3) Further assessments in the clinical setting are now required.
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9.
Protective Mechanisms of Butyrate on Inflammatory Bowel Disease.
Silva, JPB, Navegantes-Lima, KC, Oliveira, ALB, Rodrigues, DVS, Gaspar, SLF, Monteiro, VVS, Moura, DP, Monteiro, MC
Current pharmaceutical design. 2018;(35):4154-4166
Abstract
Inflammatory bowel disease (IBD) is a multifactorial chronic disease, commonly associated with alteration in the composition and function of gut microbiota. This process can lead to a decreased production of short chain fatty acids (SCFAs) by the gut microbiota, mainly butyrate, which is an important immunomodulatory molecule in the intestine. Butyrogenic bacteria normally produces butyrate through carbohydrate fermentation or amino acids degradation pathways. This molecule plays an important protective role in intestinal homeostasis acting in both adaptive immunity and innate immunity. This review summarizes the current knowledge about the role of butyrate on the development of IBD and the protective mechanisms of this metabolite on the intestinal mucosa and the whole body, as reported by in vitro and in vivo studies. Thus, butyrate can regulate the activation of regulatory T cells, increasing the acetylation of histones and decreasing the activation of NF-κB. In addition, it can also stimulate the mucus production from epithelial cells and the rearrangement of tight junction proteins.
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10.
Prevention of progression in Parkinson's disease.
Aaseth, J, Dusek, P, Roos, PM
Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine. 2018;(5):737-747
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Abstract
Environmental influences affecting genetically susceptible individuals seem to contribute significantly to the development of Parkinson's disease (PD). Xenobiotic exposure including transitional metal deposition into vulnerable CNS regions appears to interact with PD genes. Such exposure together with mitochondrial dysfunction evokes a destructive cascade of biochemical events, including oxidative stress and degeneration of the sensitive dopamine (DA) production system in the basal ganglia. Recent research indicates that the substantia nigra degeneration can be decelerated by treatment with iron binding compounds such as deferiprone. Interestingly compounds known to decrease PD risk including caffeine, niacin, nicotine and salbutamol also possess iron binding properties. Adequate function of antioxidative mechanisms in the vulnerable brain cells can be restored by acetylcysteine supplementation to normalize intracellular glutathione activity. Other preventive measures to reduce deterioration of dopaminergic neurons may involve life-style changes such as intake of natural antioxidants and physical exercise. Further research is recommended to identify therapeutic targets of the proposed interventions, in particular protection of the DA biosynthesis by oxygen radical scavengers and iron binding agents.