Protective effects of HBOC on pulmonary vascular leakage after haemorrhagic shock and the underlying mechanisms

: Chronic Noncommunicable Diseases (NCDs), mostly represented by cardiovascular diseases, diabetes, chronic pulmonary diseases, cancers, and several chronic pathologies, are one of the main causes of morbidity and mortality, and are mainly related to the occurrence of metabolic risk factors. Anthocyanins (ACNs) possess a wide spectrum of biological activities, such as anti-inflammatory, antioxidant, cardioprotective and chemopreventive properties, which are able to promote human health. Although ACNs present an apparent low bioavailability, their metabolites may play an important role in the in vivo protective effects observed. : This article directly addresses the scientific evidences supporting that ACNs could be useful to protect human population against several NCDs not only acting as antioxidant but through their capability to modulate cell redox-dependent signaling. In particular, ACNs interact with the NF-κB and AP-1 signal transduction pathways, which respond to oxidative signals and mediate a proinflammatory effect, and the Nrf2/ARE pathway and its regulated cytoprotective proteins (GST, NQO, HO-1, etc.), involved in both cellular antioxidant defenses and elimination/inactivation of toxic compounds, so countering the alterations caused by conditions of chemical/oxidative stress. In addition, supposed crosstalks could contribute to explain the protective effects of ACNs in different pathological conditions characterized by an altered balance among these pathways. Thus, this review underlines the importance of specific nutritional molecules for human health and focuses on the molecular targets and the underlying mechanisms of ACNs against various diseases.

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Melatonin Successfully Rescues the Hippocampal Molecular Machinery and Enhances Anti-oxidative Activity Following Early-Life Sleep Deprivation Injury

Antioxidants ◽

10.3390/antiox10050774 ◽

2021 ◽

Vol 10 (5) ◽

pp. 774

Author(s):

Hung-Ming Chang ◽

Hsing-Chun Lin ◽

Hsin-Lin Cheng ◽

Chih-Kai Liao ◽

To-Jung Tseng ◽

...

Keyword(s):

Sleep Deprivation ◽

Early Life ◽

Cognitive Activity ◽

Oxidative Activity ◽

Protective Effects ◽

Long Term Effects ◽

Ionic Distribution ◽

Melatonin Administration ◽

Molecular Machinery ◽

Underlying Mechanisms

Early-life sleep deprivation (ESD) is a serious condition with severe cognitive sequelae. Considering hippocampus plays an essential role in cognitive regulation, the present study aims to determine whether melatonin, a neuroendocrine beard with significant anti-oxidative activity, would greatly depress the hippocampal oxidative stress, improves the molecular machinery, and consequently exerts the neuro-protective effects following ESD. Male weanling Wistar rats (postnatal day 21) were subjected to ESD for three weeks. During this period, the animals were administered normal saline or melatonin (10 mg/kg) via intraperitoneal injection between 09:00 and 09:30 daily. After three cycles of ESD, the animals were kept under normal sleep/wake cycle until they reached adulthood and were sacrificed. The results indicated that ESD causes long-term effects, such as impairment of ionic distribution, interruption of the expressions of neurotransmitters and receptors, decreases in the levels of several antioxidant enzymes, and impairment of several signaling pathways, which contribute to neuronal death in hippocampal regions. Melatonin administration during ESD prevented these effects. Quantitative evaluation of cells also revealed a higher number of neurons in the melatonin-treated animals when compared with the saline-treated animals. As the hippocampus is critical to cognitive activity, preserving or even improving the hippocampal molecular machinery by melatonin during ESD not only helps us to better understand the underlying mechanisms of ESD-induced neuronal dysfunction, but also the therapeutic use of melatonin to counteract ESD-induced neuronal deficiency.

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Vitamin E beyond Its Antioxidant Label

Antioxidants ◽

10.3390/antiox10050634 ◽

2021 ◽

Vol 10 (5) ◽

pp. 634

Author(s):

Anca Ungurianu ◽

Anca Zanfirescu ◽

Georgiana Nițulescu ◽

Denisa Margină

Keyword(s):

Vitamin E ◽

Signaling Pathways ◽

Molecular Mechanisms ◽

Protective Effects ◽

Cellular Effects ◽

Inflammatory Status ◽

Anti Cancer ◽

Key Factor ◽

Exciting Potential ◽

Underlying Mechanisms

Vitamin E, comprising tocopherols and tocotrienols, is mainly known as an antioxidant. The aim of this review is to summarize the molecular mechanisms and signaling pathways linked to inflammation and malignancy modulated by its vitamers. Preclinical reports highlighted a myriad of cellular effects like modulating the synthesis of pro-inflammatory molecules and oxidative stress response, inhibiting the NF-κB pathway, regulating cell cycle, and apoptosis. Furthermore, animal-based models have shown that these molecules affect the activity of various enzymes and signaling pathways, such as MAPK, PI3K/Akt/mTOR, JAK/STAT, and NF-κB, acting as the underlying mechanisms of their reported anti-inflammatory, neuroprotective, and anti-cancer effects. In clinical settings, not all of these were proven, with reports varying considerably. Nonetheless, vitamin E was shown to improve redox and inflammatory status in healthy, diabetic, and metabolic syndrome subjects. The anti-cancer effects were inconsistent, with both pro- and anti-malignant being reported. Regarding its neuroprotective properties, several studies have shown protective effects suggesting vitamin E as a potential prevention and therapeutic (as adjuvant) tool. However, source and dosage greatly influence the observed effects, with bioavailability seemingly a key factor in obtaining the preferred outcome. We conclude that this group of molecules presents exciting potential for the prevention and treatment of diseases with an inflammatory, redox, or malignant component.

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Green Tea and Epigallocatechin Gallate (EGCG) for the Management of Nonalcoholic Fatty Liver Diseases (NAFLD): Insights into the Role of Oxidative Stress and Antioxidant Mechanism

Antioxidants ◽

10.3390/antiox10071076 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1076

Author(s):

Guoyi Tang ◽

Yu Xu ◽

Cheng Zhang ◽

Ning Wang ◽

Huabin Li ◽

...

Keyword(s):

Oxidative Stress ◽

Fatty Liver ◽

Green Tea ◽

Liver Diseases ◽

Randomized Clinical Trials ◽

Epigallocatechin Gallate ◽

Protective Effects ◽

Nonalcoholic Fatty Liver ◽

Nonalcoholic Fatty Liver Diseases ◽

Underlying Mechanisms

Nonalcoholic fatty liver diseases (NAFLD) represent a set of liver disorders progressing from steatosis to steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma, which induce huge burden to human health. Many pathophysiological factors are considered to influence NAFLD in a parallel pattern, involving insulin resistance, oxidative stress, lipotoxicity, mitochondrial dysfunction, endoplasmic reticulum stress, inflammatory cascades, fibrogenic reaction, etc. However, the underlying mechanisms, including those that induce NAFLD development, have not been fully understood. Specifically, oxidative stress, mainly mediated by excessive accumulation of reactive oxygen species, has participated in the multiple NAFLD-related signaling by serving as an accelerator. Ameliorating oxidative stress and maintaining redox homeostasis may be a promising approach for the management of NAFLD. Green tea is one of the most important dietary resources of natural antioxidants, above which epigallocatechin gallate (EGCG) notably contributes to its antioxidative action. Accumulative evidence from randomized clinical trials, systematic reviews, and meta-analysis has revealed the beneficial functions of green tea and EGCG in preventing and managing NAFLD, with acceptable safety in the patients. Abundant animal and cellular studies have demonstrated that green tea and EGCG may protect against NAFLD initiation and development by alleviating oxidative stress and the related metabolism dysfunction, inflammation, fibrosis, and tumorigenesis. The targeted signaling pathways may include, but are not limited to, NRF2, AMPK, SIRT1, NF-κB, TLR4/MYD88, TGF-β/SMAD, and PI3K/Akt/FoxO1, etc. In this review, we thoroughly discuss the oxidative stress-related mechanisms involved in NAFLD development, as well as summarize the protective effects and underlying mechanisms of green tea and EGCG against NAFLD.

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Total flavonoids from Astragalus alleviate endothelial dysfunction by activating the Akt/eNOS pathway

Journal of International Medical Research ◽

10.1177/0300060517717358 ◽

2017 ◽

Vol 46 (6) ◽

pp. 2096-2103 ◽

Cited By ~ 4

Author(s):

Qian Liu ◽

Ling Zhang ◽

Qiyuan Shan ◽

Yuxia Ding ◽

Zhaocai Zhang ◽

...

Keyword(s):

Cell Proliferation ◽

Vascular Endothelial Cells ◽

Ex Vivo ◽

Umbilical Vein ◽

Cell Counting ◽

Total Flavonoids ◽

Vascular Endothelial ◽

Protective Effects ◽

Hypoxic Conditions ◽

Underlying Mechanisms

Objective To investigate the vasodilative and endothelial-protective effects and the underlying mechanisms of total flavonoids from Astragalus (TFA). Methods The vasodilative activities of TFA were measured with a myograph ex vivo using rat superior mesenteric arterial rings. The primary human umbilical vein endothelial cell (HUVEC) viabilities were assayed using the cell counting kit-8 after hypoxia or normoxia treatment with or without TFA. Akt, P-Akt, eNOS, P-eNOS, Erk, P-Erk, Bcl-2 and Bax expression were analyzed using western blotting. Results TFA showed concentration-dependent vasodilative effects on rat superior mesenteric arterial rings, but had no effects on normal or potassium chloride precontracted arterial rings. TFA did not affect HUVEC viabilities in normoxia, but dramatically promoted cell proliferation in the concentration range of 1 to 30 µg/mL under hypoxia. Moreover, TFA significantly increased the ratios of P-Akt/Akt and P-eNOS/eNOS in vascular endothelial cells under hypoxic conditions, but did not change the P-Erk/Erk or Bcl-2/Bax ratios. Conclusions TFA might exhibit vasorelaxant and endothelial-protective effects via the Akt/eNOS signaling pathway.

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Guarana (Paullinia cupana) Extract Protects Caenorhabditis elegans Models for Alzheimer Disease and Huntington Disease through Activation of Antioxidant and Protein Degradation Pathways

Oxidative Medicine and Cellular Longevity ◽

10.1155/2018/9241308 ◽

2018 ◽

Vol 2018 ◽

pp. 1-16 ◽

Cited By ~ 15

Author(s):

Patrícia Ferreira Boasquívis ◽

Giovanna Melo Martins Silva ◽

Franciny Aparecida Paiva ◽

Rodrigo Marinho Cavalcanti ◽

Cecília Verônica Nunez ◽

...

Keyword(s):

Caenorhabditis Elegans ◽

Protein Misfolding ◽

Therapeutic Potential ◽

High Energy ◽

Protective Effects ◽

Independent Manner ◽

Paullinia Cupana ◽

Age Related ◽

Polyq Protein ◽

Underlying Mechanisms

Guarana (Paullinia cupana) is largely consumed in Brazil in high energy drinks and dietary supplements because of its stimulant activity on the central nervous system. Although previous studies have indicated that guarana has some protective effects in Parkinson’s (PD), Alzheimer’s (AD), and Huntington’s (HD) disease models, the underlying mechanisms are unknown. Here, we investigated the protective effects of guarana hydroalcoholic extract (GHE) in Caenorhabditis elegans models of HD and AD. GHE reduced polyglutamine (polyQ) protein aggregation in the muscle and also reduced polyQ-mediated neuronal death in ASH sensory neurons and delayed β-amyloid-induced paralysis in a caffeine-independent manner. Moreover, GHE’s protective effects were not mediated by caloric restriction, antimicrobial effects, or development and reproduction impairment. Inactivation of the transcription factors SKN-1 and DAF-16 by RNAi partially blocked the protective effects of GHE treatment in the AD model. We show that the protective effect of GHE is associated with antioxidant activity and modulation of proteostasis, since it increased the lifespan and proteasome activity, reduced intracellular ROS and the accumulation of autophagosomes, and increased the expression of SOD-3 and HSP-16.2. Our findings suggest that GHE has therapeutic potential in combating age-related diseases associated with protein misfolding and accumulation.

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Calpain activation mediates microgravity-induced myocardial abnormalities in mice via p38 and ERK1/2 MAPK pathways

Journal of Biological Chemistry ◽

10.1074/jbc.ra119.011890 ◽

2020 ◽

Vol 295 (49) ◽

pp. 16840-16851

Author(s):

Liwen Liang ◽

Huili Li ◽

Ting Cao ◽

Lina Qu ◽

Lulu Zhang ◽

...

Keyword(s):

Nadph Oxidase ◽

Simulated Microgravity ◽

Heart Weight ◽

Calpain Inhibitor ◽

Protective Effects ◽

Tail Suspension ◽

Calpain Activation ◽

Microgravity Conditions ◽

Underlying Mechanisms ◽

Nadph Oxidase Activation

The human cardiovascular system has adapted to function optimally in Earth's 1G gravity, and microgravity conditions cause myocardial abnormalities, including atrophy and dysfunction. However, the underlying mechanisms linking microgravity and cardiac anomalies are incompletely understood. In this study, we investigated whether and how calpain activation promotes myocardial abnormalities under simulated microgravity conditions. Simulated microgravity was induced by tail suspension in mice with cardiomyocyte-specific deletion of Capns1, which disrupts activity and stability of calpain-1 and calpain-2, and their WT littermates. Tail suspension time-dependently reduced cardiomyocyte size, heart weight, and myocardial function in WT mice, and these changes were accompanied by calpain activation, NADPH oxidase activation, and oxidative stress in heart tissues. The effects of tail suspension were attenuated by deletion of Capns1. Notably, the protective effects of Capns1 deletion were associated with the prevention of phosphorylation of Ser-345 on p47phox and attenuation of ERK1/2 and p38 activation in hearts of tail-suspended mice. Using a rotary cell culture system, we simulated microgravity in cultured neonatal mouse cardiomyocytes and observed decreased total protein/DNA ratio and induced calpain activation, phosphorylation of Ser-345 on p47phox, and activation of ERK1/2 and p38, all of which were prevented by calpain inhibitor-III. Furthermore, inhibition of ERK1/2 or p38 attenuated phosphorylation of Ser-345 on p47phox in cardiomyocytes under simulated microgravity. This study demonstrates for the first time that calpain promotes NADPH oxidase activation and myocardial abnormalities under microgravity by facilitating p47phox phosphorylation via ERK1/2 and p38 pathways. Thus, calpain inhibition may be an effective therapeutic approach to reduce microgravity-induced myocardial abnormalities.

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The Protective Role of Feruloylserotonin in LPS-Induced HaCaT Cells

Molecules ◽

10.3390/molecules24173064 ◽

2019 ◽

Vol 24 (17) ◽

pp. 3064 ◽

Cited By ~ 3

Author(s):

Yuzhu He ◽

Byung-gook Kim ◽

Hye-Eun Kim ◽

Qiaochu Sun ◽

Shuhan Shi ◽

...

Keyword(s):

Antioxidant Activities ◽

Protective Role ◽

Related Factor ◽

Nuclear Factor ◽

Hacat Cells ◽

Protective Effects ◽

Hydroxycinnamic Acid Amides ◽

Anti Inflammatory ◽

Underlying Mechanisms

Epidermal inflammation is caused by various bacterial infectious diseases that impair the skin health. Feruloylserotonin (FS) belongs to the hydroxycinnamic acid amides of serotonin, which mainly exists in safflower seeds and has been proven to have anti-inflammatory and antioxidant activities. Human epidermis mainly comprises keratinocytes whose inflammation causes skin problems. This study investigated the protective effects of FS on the keratinocyte with lipopolysaccharides (LPS)-induced human HaCaT cells and elucidated its underlying mechanisms of action. The mechanism was investigated by analyzing cell viability, PGE2 levels, cell apoptosis, nuclear factor erythroid 2-related factor 2 (Nrf2) translocation, and TLR4/NF-κB pathway. The anti-inflammatory effects of FS were assessed by inhibiting the inflammation via down-regulating the TLR4/NF-κB pathway. Additionally, FS promoted Nrf2 translocation to the nucleus, indicating that FS showed anti-oxidative activities. Furthermore, the antioxidative and anti-inflammatory effects of FS were found to benefit each other, but were independent. Thus, FS can be used as a component to manage epidermal inflammation due to its anti-inflammatory and anti-oxidative properties.

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Effects of Gastrodin against Lead-Induced Brain Injury in Mice Associated with the Wnt/Nrf2 Pathway

Nutrients ◽

10.3390/nu12061805 ◽

2020 ◽

Vol 12 (6) ◽

pp. 1805

Author(s):

Chan-Min Liu ◽

Zhi-Kai Tian ◽

Yu-Jia Zhang ◽

Qing-Lei Ming ◽

Jie-Qiong Ma ◽

...

Keyword(s):

Phenolic Glycoside ◽

Related Factor ◽

Protective Effects ◽

Neuroprotective Effects ◽

Nrf2 Pathway ◽

Wnt Inhibitor ◽

Research Findings ◽

Anti Oxidant ◽

Underlying Mechanisms ◽

Induced Apoptosis

Gastrodin (GAS), the main phenolic glycoside extracted from Gastrodia elata Blume, exhibited potential neuroprotective properties. Here we examined the protective effects of GAS against lead(Pb)-induced nerve injury in mice, and explores its underlying mechanisms. Our research findings revealed that GAS improved behavioral deficits in Pb-exposed mice. GAS reduced the accumulation of p-tau and amyloid-beta (Aβ). GAS inhibited Pb-induced inflammation in the brain, as indicated by the decreased levels of pro-inflammatory cytokines, including tumor necrosis factor-a (TNF-α), cyclooxygenase-2 (COX-2). GAS increased the expression levels of NR2A and neurotrophin brain-derived neurotrophic factor (BDNF). GAS inhibited Pb-induced apoptosis of neurons in hippocampus tissue, as indicated by the decreased levels of pro-apoptotic proteins Bax and cleaved caspase-3. Furthermore, the neuroprotective effects of GAS were associated with inhibiting oxidative stress by modulating nuclear factor-erythroid 2-related factor 2 (Nrf2)-mediated antioxidant signaling. GAS supplement activated the Wnt/β-catenin signaling pathway and reduced the expression of Wnt inhibitor Dickkopf-1 (Dkk-1). Collectively, this study clarified that GAS exhibited neuroprotective property by anti-oxidant, anti-inflammatory and anti-apoptosis effects and its ability to regulate the Wnt/Nrf2 pathway.

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Sodium Butyrate Protects N2a Cells against Aβ Toxicity In Vitro

Mediators of Inflammation ◽

10.1155/2020/7605160 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9

Author(s):

Jingxuan Sun ◽

Boyu Yuan ◽

Yancheng Wu ◽

Yuhong Gong ◽

Wenjin Guo ◽

...

Keyword(s):

Sodium Butyrate ◽

Cell Injury ◽

Cell Damage ◽

Protective Effects ◽

Neuroprotective Effects ◽

Fatty Acid Salt ◽

Cognitive Improvement ◽

N2a Cells ◽

Underlying Mechanisms

Alzheimer’s disease (AD) is a common neurodegenerative disease. Aβ plays an important role in the pathogenesis of AD. Sodium butyrate (NaB) is a short-chain fatty acid salt that exerts neuroprotective effects such as anti-inflammatory, antioxidant, antiapoptotic, and cognitive improvement in central nervous system diseases. The aim of this study is to research the protective effects of NaB on neurons against Aβ toxicity and to uncover the underlying mechanisms. The results showed that 2 mM NaB had a significant improvement effect on Aβ-induced N2a cell injury, by increasing cell viability and reducing ROS to reduce injury. In addition, by acting on the GPR109A receptor, NaB regulates the expression of AD-related genes such as APP, NEP, and BDNF. Therefore, NaB protects N2a cells from Aβ-induced cell damage through activating GPR109A, which provides an innovative idea for the treatment of AD.

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