Antioxidant and Anti-Inflammatory Profiles of Spent Coffee Ground Extracts for the Treatment of Neurodegeneration

Spent coffee grounds (SCGs), waste products of coffee beverage production, are rich in organic compounds such as phenols. Different studies have demonstrated phenol beneficial effects in counteracting neurodegenerative diseases. These diseases are associated with oxidative stress and neuroinflammation, which initiates the degeneration of neurons by overactivating microglia. Unfortunately, to date, there are no pharmacological therapies to treat these pathologies. The aim of this study was to evaluate the phenolic content of 4 different SCG extracts and their ability to counteract oxidative stress and neuroinflammation. Caffeine and 5-O-caffeoylquinic acid were the most abundant compounds in all extracts, followed by 3-O-caffeoylquinic acid and 3,5-O-dicaffeoylquinic acid. The four extracts demonstrated a different ability to counteract oxidative stress and neuroinflammation in vitro. In particular, the methanol extract was the most effective in protecting neuron-like SH-SY5Y cells against H2O2-induced oxidative stress by upregulating endogenous antioxidant enzymes such as thioredoxin reductase, heme oxygenase 1, NADPH quinone oxidoreductase, and glutathione reductase. The water extract was the most effective in counteracting lipopolysaccharide-induced neuroinflammation in microglial BV-2 cells by strongly reducing the expression of proinflammatory mediators through the modulation of the TLR4/NF-κB pathway. On these bases, SCG extracts could represent valuable nutraceutical sources for the treatment of neurodegeneration.

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Heme Oxygenase-1 Deficiency and Oxidative Stress: A Review of 9 Independent Human Cases and Animal Models

International Journal of Molecular Sciences ◽

10.3390/ijms22041514 ◽

2021 ◽

Vol 22 (4) ◽

pp. 1514 ◽

Cited By ~ 1

Author(s):

Akihiro Yachie

Keyword(s):

Oxidative Stress ◽

Animal Models ◽

Heme Oxygenase ◽

Inflammatory Diseases ◽

Cell Types ◽

Pharmacological Intervention ◽

Heme Oxygenase 1 ◽

Inflammatory Reactions

Since Yachie et al. reported the first description of human heme oxygenase (HO)-1 deficiency more than 20 years ago, few additional human cases have been reported in the literature. A detailed analysis of the first human case of HO-1 deficiency revealed that HO-1 is involved in the protection of multiple tissues and organs from oxidative stress and excessive inflammatory reactions, through the release of multiple molecules with anti-oxidative stress and anti-inflammatory functions. HO-1 production is induced in vivo within selected cell types, including renal tubular epithelium, hepatic Kupffer cells, vascular endothelium, and monocytes/macrophages, suggesting that HO-1 plays critical roles in these cells. In vivo and in vitro studies have indicated that impaired HO-1 production results in progressive monocyte dysfunction, unregulated macrophage activation and endothelial cell dysfunction, leading to catastrophic systemic inflammatory response syndrome. Data from reported human cases of HO-1 deficiency and numerous studies using animal models suggest that HO-1 plays critical roles in various clinical settings involving excessive oxidative stress and inflammation. In this regard, therapy to induce HO-1 production by pharmacological intervention represents a promising novel strategy to control inflammatory diseases.

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Protective Effects of Taurine Chloramine on Experimentally Induced Colitis: NFκB, STAT3, and Nrf2 as Potential Targets

Antioxidants ◽

10.3390/antiox10030479 ◽

2021 ◽

Vol 10 (3) ◽

pp. 479

Author(s):

Seong Hoon Kim ◽

Hye-Won Yum ◽

Seung Hyeon Kim ◽

Wonki Kim ◽

Su-Jung Kim ◽

...

Keyword(s):

Oxidative Stress ◽

Protective Effect ◽

Parent Compound ◽

Oxidative Stress Marker ◽

Heme Oxygenase 1 ◽

Trinitrobenzene Sulfonic Acid ◽

Protective Effects ◽

Taurine Chloramine ◽

Proinflammatory Mediators ◽

Experimentally Induced

Taurine chloramine (TauCl) is an endogenous anti-inflammatory substance which is derived from taurine, a semi-essential sulfur-containing β-amino acid found in some foods including meat, fish, eggs and milk. In general, TauCl as well as its parent compound taurine downregulates production of tissue-damaging proinflammatory mediators, such as chemokines and cytokines in many different types of cells. In the present study, we investigated the protective effects of TauCl on experimentally induced colon inflammation. Oral administration of TauCl protected against mouse colitis caused by 2,4,6-trinitrobenzene sulfonic acid (TNBS). TauCl administration attenuated apoptosis in the colonic mucosa of TNBS-treated mice. This was accompanied by reduced expression of an oxidative stress marker, 4-hydroxy-2-nonenal and proinflammatory molecules including tumor necrosis factor-α, interleukin-6 and cyclooxygenase-2 in mouse colon. TauCl also inhibited activation of NFκB and STAT3, two key transcription factors mediating proinflammatory signaling. Notably, the protective effect of TauCl on oxidative stress and inflammation in the colon of TNBS-treated mice was associated with elevated activation of Nrf2 and upregulation of its target genes encoding heme oxygenase-1, NAD(P)H:quinone oxidoreductase, glutamate cysteine ligase catalytic subunit, and glutathione S-transferase. Taken together, these results suggest that TauCl exerts the protective effect against colitis through upregulation of Nrf2-dependent cytoprotective gene expression while blocking the proinflammatory signaling mediated by NFκB and STAT3.

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Allopurinol ameliorates liver injury in type 1 diabetic rats through activating Nrf2

International Journal of Immunopathology and Pharmacology ◽

10.1177/20587384211031417 ◽

2021 ◽

Vol 35 ◽

pp. 205873842110314

Author(s):

Fei Zeng ◽

Jierong Luo ◽

Hong Han ◽

Wenjie Xie ◽

Lingzhi Wang ◽

...

Keyword(s):

Oxidative Stress ◽

Liver Injury ◽

Caspase 3 ◽

Serum Levels ◽

Diabetic Rats ◽

Heme Oxygenase 1 ◽

Liver Protein ◽

Lipid Peroxidation Product ◽

Protein Expressions

Hyperglycemia-induced oxidative stress plays important roles in the development of non-alcoholic fatty liver disease (NAFLD), which is a common complication in diabetic patients. The Nrf2-Keap1 pathway is important for cell antioxidant protection, while its role in exogenous antioxidant mediated protection against NAFLD is unclear. We thus, postulated that antioxidant treatment with allopurinol (ALP) may attenuate diabetic liver injury and explored the underlying mechanisms. Control (C) and streptozotocin (STZ)-induced diabetes rats (D) were untreated or treated with ALP for 4 weeks starting at 1 week after diabetes induction. Serum levels of alanine aminotransferase (ALT) and aspartate transaminase (AST), production of lipid peroxidation product malondialdehyde (MDA), and serum superoxide dismutase (SOD) were detected. Liver protein expressions of cleaved-caspase 3, IL-1β, nuclear factor-erythroid-2-related factor-2 (Nrf2), heme oxygenase-1 (HO-1), P62, Kelch-like ECH-associated protein 1 (Keap1), and LC3 were analyzed. In vitro, cultured rat normal hepatocytes BRL-3A were grouped to normal glucose (5.5 mM, NG) or high glucose (25 mM, HG) and treated with or without allopurinol (100 µM) for 48 h. Rats in the D group demonstrated liver injury evidenced as increased serum levels of ALT and AST. Diabetes increased apoptotic cell death, enhanced liver protein expressions of cleaved-caspase 3 and IL-1β with concomitantly increased production of MDA while serum SOD content was significantly reduced (all P < 0.05 vs C). In the meantime, protein levels of Nrf2, HO-1, and P62 were reduced while Keap1 and LC3 were increased in the untreated D group as compared to control ( P < 0.05 vs C). And all the above alterations were significantly attenuated by ALP. Similar to our findings obtained from in vivo study, we got the same results in in vitro experiments. It is concluded that ALP activates the Nrf2/p62 pathway to ameliorate oxidative stress and liver injury in diabetic rats.

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Antioxidant and Neuroprotective Activity of Extra Virgin Olive Oil Extracts Obtained from Quercetano Cultivar Trees Grown in Different Areas of the Tuscany Region (Italy)

Antioxidants ◽

10.3390/antiox10030421 ◽

2021 ◽

Vol 10 (3) ◽

pp. 421

Author(s):

Maria Cristina Barbalace ◽

Lorenzo Zallocco ◽

Daniela Beghelli ◽

Maurizio Ronci ◽

Serena Scortichini ◽

...

Keyword(s):

Neurodegenerative Diseases ◽

Olive Oil ◽

Virgin Olive Oil ◽

Thioredoxin Reductase ◽

Extra Virgin Olive Oil ◽

Bioactive Molecules ◽

Neuroprotective Activity ◽

Heme Oxygenase 1 ◽

Quinone Oxidoreductase ◽

Phenol Composition

Neurodegenerative diseases are driven by several mechanisms such as inflammation, abnormal protein aggregation, excitotoxicity, mitochondrial dysfunction and oxidative stress. So far, no therapeutic strategies are available for neurodegenerative diseases and in recent years the research is focusing on bioactive molecules present in food. In particular, extra-virgin olive oil (EVOO) phenols have been associated to neuroprotection. In this study, we investigated the potential antioxidant and neuroprotective activity of two different EVOO extracts obtained from Quercetano cultivar trees grown in two different areas (plain and hill) of the Tuscany region (Italy). The different geographical origin of the orchards influenced phenol composition. Plain extract presented a higher content of phenyl ethyl alcohols, cinnammic acids, oleacein, oleocanthal and flavones; meanwhile, hill extract was richer in lignans. Hill extract was more effective in protecting differentiated SH-SY5Y cells from peroxide stress thanks to a marked upregulation of the antioxidant enzymes heme oxygenase 1, NADPH quinone oxidoreductase 1, thioredoxin Reductase 1 and glutathione reductase. Proteomic analysis revealed that hill extract plays a role in the regulation of proteins involved in neuronal plasticity and activation of neurotrophic factors such as BDNF. In conclusion, these data demonstrate that EVOOs can have important neuroprotective activities, but these effects are strictly related to their specific phenol composition.

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Centella Asiatica Improves Memory and Promotes Antioxidative Signaling in 5XFAD Mice

Antioxidants ◽

10.3390/antiox8120630 ◽

2019 ◽

Vol 8 (12) ◽

pp. 630 ◽

Cited By ~ 6

Author(s):

Donald G Matthews ◽

Maya Caruso ◽

Charles F Murchison ◽

Jennifer Y Zhu ◽

Kirsten M Wright ◽

...

Keyword(s):

Oxidative Stress ◽

Amyloid Β ◽

Water Extract ◽

Centella Asiatica ◽

Antioxidant Response ◽

Plaque Burden ◽

Heme Oxygenase 1 ◽

Synaptic Density ◽

Cognitive Benefits ◽

5Xfad Mice

Centella asiatica (CA) herb is a traditional medicine, long reputed to provide cognitive benefits. We have reported that CA water extract (CAW) treatment improves cognitive function of aged Alzheimer’s disease (AD) model Tg2576 and wild-type (WT) mice, and induces an NRF2-regulated antioxidant response in aged WT mice. Here, CAW was administered to AD model 5XFAD female and male mice and WT littermates (age: 7.6 +/ − 0.6 months), and object recall and contextual fear memory were tested after three weeks treatment. CAW’s impact on amyloid-β plaque burden, and markers of neuronal oxidative stress and synaptic density, was assessed after five weeks treatment. CAW antioxidant activity was evaluated via nuclear transcription factor (erythroid-derived 2)-like 2 (NRF2) and NRF2-regulated antioxidant response element gene expression. Memory improvement in both genders and genotypes was associated with dose-dependent CAW treatment without affecting plaque burden, and marginally increased synaptic density markers in the hippocampus and prefrontal cortex. CAW treatment increased Nrf2 in hippocampus and other NRF2 targets (heme oxygenase-1, NAD(P)H quinone dehydrogenase 1, glutamate-cysteine ligase catalytic subunit). Reduced plaque-associated SOD1, an indicator of oxidative stress, was observed in the hippocampi and cortices of CAW-treated 5XFAD mice. We postulate that CAW treatment leads to reduced oxidative stress, contributing to improved neuronal health and cognition.

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Heme oxygenase-1 induction by hemin prevents oxidative stress-induced acute cholestasis in the rat

Clinical Science ◽

10.1042/cs20180675 ◽

2019 ◽

Vol 133 (1) ◽

pp. 117-134 ◽

Cited By ~ 7

Author(s):

Pamela L. Martín ◽

Paula Ceccatto ◽

María V. Razori ◽

Daniel E.A. Francés ◽

Sandra M.M. Arriaga ◽

...

Keyword(s):

Oxidative Stress ◽

Heme Oxygenase ◽

Bile Flow ◽

Driving Forces ◽

Membrane Lipids ◽

Ex Vivo ◽

Heme Oxygenase 1 ◽

Canalicular Transporters

Abstract We previously demonstrated in in vitro and ex vivo models that physiological concentrations of unconjugated bilirubin (BR) prevent oxidative stress (OS)-induced hepatocanalicular dysfunction and cholestasis. Here, we aimed to ascertain, in the whole rat, whether a similar cholestatic OS injury can be counteracted by heme oxygenase-1 (HO-1) induction that consequently elevates endogenous BR levels. This was achieved through the administration of hemin, an inducer of HO-1, the rate-limiting step in BR generation. We found that BR peaked between 6 and 8 h after hemin administration. During this time period, HO-1 induction fully prevented the pro-oxidant tert-butylhydroperoxide (tBuOOH)-induced drop in bile flow, and in the biliary excretion of bile salts and glutathione, the two main driving forces of bile flow; this was associated with preservation of the membrane localization of their respective canalicular transporters, bile salt export pump (Bsep) and multidrug resistance-associated protein 2 (Mrp2), which are otherwise endocytosed by OS. HO-1 induction counteracted the oxidation of intracellular proteins and membrane lipids induced by tBuOOH, and fully prevented the increase in the oxidized-to-total glutathione (GSHt) ratio, a sensitive parameter of hepatocellular OS. Compensatory elevations of the activity of the antioxidant enzymes catalase (CAT) and superoxide dismutase (SOD) were also prevented. We conclude that in vivo HO-1 induction protects the liver from acute oxidative injury, thus preventing consequent cholestasis. This reveals an important role for the induction of HO-1 and the consequently elevated levels of BR in preserving biliary secretory function under OS conditions, thus representing a novel therapeutic tool to limit the cholestatic injury that bears an oxidative background.

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Raphanus sativus ameliorates atherogeneic lipid profiles in hypercholesterolemic rats and hypercholesterolemia-associated peroxidative liver damage

JOURNAL OF ADVANCES IN CHEMISTRY ◽

10.24297/jac.v7i3.2374 ◽

2011 ◽

Vol 7 (3) ◽

pp. 1385-1394 ◽

Cited By ~ 1

Author(s):

Mozammel Haque ◽

Jahirul Islam ◽

Asiqur Rahaman ◽

Fowzia Akter Selina ◽

Mohammad Azizur Rahman ◽

...

Keyword(s):

Oxidative Stress ◽

Raphanus Sativus ◽

Disease Risk ◽

Cardiovascular Disease Risk ◽

Water Extract ◽

Density Lipoprotein ◽

Lipid Peroxide ◽

Hot Water

Objective: Raphanus sativus is a hugely used edible root vegetable. We investigated whether the feeding of the Raphanus sativus hot water extract (RSE) ameliorates atherogenic lipid profile and oxidative stress in hypercholesterolemia. Methods: After feeding of the RSE to hypercholesterolemic rats for 6 weeks, the levels of plasma and hepatic total cholesterol (TC), triglyceride (TG), and plasma high density lipoprotein-cholesterol (HDL-C) and fecal TC levels were studied. The effects of RSE on the hepatic enzymes, namely alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP), the levels of lipid peroxide (LPO) and liver histology were also evaluated. Results: Hypercholesterolemia increased the levels of TC and TG in the plasma and livers. The levels of ALT, AST and ALP in plasma and LPO in the liver also increased. The dietary RSE, however, significantly ameliorated the above atherogenic lipids and liver enzymes. The RSE significantly reduced the levels of LPO in the liver, suggesting an in vivo protection against of oxidative stress. The RSE also inhibited the in vitro Fenton’s reagent-induced oxidative stress, thus corroborating the in vivo anti-LPO actions of RSE. The levels of hepatic LPO were positively correlated with plasma AST (r=0.76; P <0.05) and ALT (r=0.43; P<0.05) levels. Histologically, the livers of the RSE-fed hypercholesterolemic rats exhibited lesser fatty droplets and reduced inflammatory cells. Conclusion: Finally, R. sativus extract lowers the cardiovascular disease risk factors under hypercholesterolemic situation by increasing the plasma/hepatic clearance of cholesterol and improving the hypercholesterolemia-induced oxidative damage of hepatic tissues.

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Discovery of a dual inhibitor of NQO1 and GSTP1 for treating glioblastoma

Journal of Hematology & Oncology ◽

10.1186/s13045-020-00979-y ◽

2020 ◽

Vol 13 (1) ◽

Author(s):

Kecheng Lei ◽

Xiaoxia Gu ◽

Alvaro G. Alvarado ◽

Yuhong Du ◽

Shilin Luo ◽

...

Keyword(s):

Oxidative Stress ◽

Crystal Structures ◽

Active Sites ◽

Redox Homeostasis ◽

Growth Factor Receptor ◽

Quinone Oxidoreductase ◽

Cancer Proliferation ◽

Dual Inhibitor

Abstract Background Glioblastoma (GBM) is a universally lethal tumor with frequently overexpressed or mutated epidermal growth factor receptor (EGFR). NADPH quinone oxidoreductase 1 (NQO1) and glutathione-S-transferase Pi 1 (GSTP1) are commonly upregulated in GBM. NQO1 and GSTP1 decrease the formation of reactive oxygen species (ROS), which mediates the oxidative stress and promotes GBM cell proliferation. Methods High-throughput screen was used for agents selectively active against GBM cells with EGFRvIII mutations. Co-crystal structures were revealed molecular details of target recognition. Pharmacological and gene knockdown/overexpression approaches were used to investigate the oxidative stress in vitro and in vivo. Results We identified a small molecular inhibitor, “MNPC,” that binds to both NQO1 and GSTP1 with high affinity and selectivity. MNPC inhibits NQO1 and GSTP1 enzymes and induces apoptosis in GBM, specifically inhibiting the growth of cell lines and primary GBM bearing the EGFRvIII mutation. Co-crystal structures between MNPC and NQO1, and molecular docking of MNPC with GSTP1 reveal that it binds the active sites and acts as a potent dual inhibitor. Inactivation of both NQO1 and GSTP1 with siRNA or MNPC results in imbalanced redox homeostasis, leading to apoptosis and mitigated cancer proliferation in vitro and in vivo. Conclusions Thus, MNPC, a dual inhibitor for both NQO1 and GSTP1, provides a novel lead compound for treating GBM via the exploitation of specific vulnerabilities created by mutant EGFR.

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Defense and protection mechanisms in lung exposed to asbestiform fiber: the role of macrophage migration inhibitory factor and heme oxygenase-1

European Journal of Histochemistry ◽

10.4081/ejh.2020.3073 ◽

2020 ◽

Vol 64 (2) ◽

Author(s):

Carla Loreto ◽

Rosario Caltabiano ◽

Adriana Carol Eleonora Graziano ◽

Sergio Castorina ◽

Claudia Lombardo ◽

...

Keyword(s):

Oxidative Stress ◽

Heme Oxygenase ◽

Migration Inhibitory Factor ◽

Macrophage Migration Inhibitory Factor ◽

Inhibitory Factor ◽

Lung Fibroblasts ◽

Heme Oxygenase 1 ◽

Macrophage Migration

Fluoro-edenite (FE), an asbestiform fiber, is responsible for many respiratory pathologies: chronic obstructive diseases, pleural plaques, fibrosis, and malignant mesothelioma. Macrophage migration inhibitory factor (MIF) is one of the first cytokines produced in response to lung tissue damage. Heme oxygenase-1 (HO-1) is a protein with protective effects against oxidative stress. It is up regulated by several stimuli including pro-inflammatory cytokines and factors that promote oxidative stress. In this research, the in vivo model of sheep lungs naturally exposed to FE was studied in order to shed light on the pathophysiological events sustaining exposure to fibers, by determining immunohistochemical lung expression of MIF and HO-1. Protein levels expression of HO-1 and MIF were also evaluated in human primary lung fibroblasts after exposure to FE fibers in vitro. In exposed sheep lungs, MIF and HO-1 immunoexpression were spread involving the intraparenchymal stroma around bronchioles, interstitium between alveoli, alveolar epithelium and macrophages. High MIF immunoexpression prevails in macrophages. Similar results were obtained in vitro, but significantly higher values were only detected for HO-1 at concentrations of 50 and 100 μg/mL of FE fibers. MIF and HO-1 expressions seem to play a role in lung self-protection against uncontrolled chronic inflammation, thus counteracting the strong link with cancer development, induced by exposure to FE. Further studies will be conducted in order to add more information about the role of MIF and HO-1 in the toxicity FE-induced.

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Cpt1a promoted ROS-induced oxidative stress and inflammation in liver injury via the Nrf2/HO-1 and NLRP3 inflammasome signaling pathway

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2020-0165 ◽

2020 ◽

Author(s):

Xigang Luo ◽

Dapeng Sun ◽

Yinxiang Wang ◽

Fengxiang Zhang ◽

Yi Wang

Keyword(s):

Oxidative Stress ◽

Liver Injury ◽

Signaling Pathway ◽

Nlrp3 Inflammasome ◽

Receptor Protein ◽

Heme Oxygenase 1 ◽

Related Factor ◽

Over Expression ◽

Vitro Model

Various liver diseases caused by liver damage seriously affect people’s health. The purpose of this study was to clarify that the effects and mechanism of Carnitine palmitoyltransferase 1 (Cpt1a) on oxidative stress and inflammation in liver injury. It was found that the expression of Cpt1a mRNA was up-regulated in model mice of liver injury. So, over-expression of Cpt1a increased reactive oxygen species (ROS) production and malondialdehyde (MDA) levels, and reduced superoxide dismutase (SOD), glutathione (GSH) and glutathione peroxidase (GSH-px) levels in vitro model of liver injury. It was also shown that over-expression of Cpt1a suppressed the Nuclear factor-erythroid-2-related factor 2 (Nrf2)/ heme oxygenase-1 (HO-1) signaling pathway. In summary, these data indicate that Cpt1a promotes ROS-induced oxidative stress in liver injury via the Nrf2/HO-1 and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome signaling pathway.

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