Is galactose a hormetic sugar? Evidence from rat hippocampal redox regulatory network

AbstractGalactose is a ubiquitous simple monosaccharide with yet incompletely understood biochemical and physiological role. Most of what we currently know about galactose is based on induction from the research on inherited disorders of galactose metabolism and animal models that exploit galactose-induced oxidative stress to model aging in rodents, however, recent evidence also demonstrates unique properties of galactose to conserve cellular function during the periods of starvation, and prevent and alleviate cognitive deficits in a rat model of sporadic Alzheimer’s disease. Here, we try to understand the molecular background of both detrimental and beneficial effects of galactose by exploring the acute systemic and hippocampal biochemical changes upon oral administration of galactose solution focusing primarily on the components of the redox regulatory network (RRN). Although orogastric gavage of galactose solution (200 mg/kg) was insufficient to induce systemic RRN disbalance in the first two hours upon administration, analysis of hippocampal RRN revealed a mild pro-oxidative shift accompanied by a paradoxical increase in tissue reductive capacity, suggesting overcompensation of endogenous antioxidant systems in the response to the pro-oxidative stimulus. The more thorough analysis revealed that galactose-induced increment of reductive capacity was accompanied by inflation of the hippocampal pool of nicotinamide adenine dinucleotide phosphates indicating ROS detoxification through disinhibition of the oxidative pentose phosphate pathway flux, reduced neuronal activity, and upregulation of Leloir pathway gatekeeper enzyme galactokinase-1. Based on the observed findings, and in the context of previous work on galactose, we propose a hormetic hypothesis of galactose action suggesting that the protective effects of galactose might be inseparable from its pro-oxidative effects at the biochemical level.

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Protective Effects of Morus nigra and Its Phytochemicals against Hepatotoxicity: A Review of Preclinical Studies

Pharmacology ◽

10.1159/000515032 ◽

2021 ◽

pp. 1-11

Author(s):

Ahmad Ghorbani ◽

Sara Hooshmand

Keyword(s):

Wide Spectrum ◽

Protective Effects ◽

High Fat ◽

Inherited Disorders ◽

Beneficial Effects ◽

The Core ◽

Morus Nigra ◽

Chemical Agents ◽

Vital Functions ◽

Different Parts

Background: Our liver has a variety of vital functions including removing poisons, storing energy, immunological roles, and secretory and excretory functions. It may face some kinds of diseases caused by viruses, hepatotoxic chemicals, drugs, alcohol, and inherited disorders. Oxidative stress and inflammation are in the core of mechanisms of liver damages induced by viruses or chemical agents. Summary: Morus nigra (M. nigra), generally known as black mulberry, exhibited wide-spectrum pharmacological effects including antidiabetic, antinociceptive, anticancer, and hepatoprotective activities. Different parts of this plant particularly the fruit and leaf have shown beneficial effects on hepatocytes in cell culture and animal models of liver damages induced by chemicals (e.g., CCl4), drugs (e.g., paracetamol), diet (e.g., high fat), diabetes, etc. The beneficial effects of M. nigra on the liver are attributed to the presence of considerable amounts of phenolic compounds such as anthocyanins, flavonols, and phenolic acids. The present review is aimed to focus on the hepatoprotective activities of M. nigra and its phytochemicals and the mechanisms responsible for these activities. Key Messages: The evidence reviewed in this study can help design clinical trials on M. nigra in patients with liver disorders and develop a hepatoprotective herbal medicine.

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Therapeutic Effects of Blue Honeysuckle on Lesions of Hyperthyroidism in Rats

The American Journal of Chinese Medicine ◽

10.1142/s0192415x16500804 ◽

2016 ◽

Vol 44 (07) ◽

pp. 1441-1456 ◽

Cited By ~ 11

Author(s):

Sang-In Park ◽

Young Joon Lee ◽

Seong Hun Choi ◽

Soo Jin Park ◽

Chang-Hyun Song ◽

...

Keyword(s):

Thyroid Gland ◽

Thyroid Hormones ◽

Body Weight Loss ◽

Therapeutic Effects ◽

Protective Effects ◽

Beneficial Effects ◽

Epididymal Fat ◽

Endogenous Antioxidant ◽

Fat Pads ◽

Blue Honeysuckle

Hyperthyroidism is a hypermetabolic syndrome characterized by an overproduction of thyroid hormones, which enhances the hormone-induced oxidative stress responsible for some complications in the liver, heart and muscle. Blue honeysuckle (BH) is an edible berry, rich in polyphenols, especially flavonoids or anthocyanins, known as strong antioxidants. The chemo-protective activities of the berry have been connected to the improvement of symptoms in cancer, diabetes mellitus, tumor or cardiovascular diseases. Therefore, the therapeutic effects of BH were examined in hyperthyroidism rat model. The hyperthyroidism was induced by injection with levothyroxine (LT4), and the model was treated with distilled water (LT4 control), propylthiouracil (PTU) or BH at 3 dosages of 500, 250 and 125[Formula: see text]mg/kg. The treatment was performed once a day for 15 days. Compared to LT4 control, the oral administration of BH dose-dependently ameliorated the hyperthyroidism, reducing thyroid hormones and increasing thyroid stimulating hormones. These effects were accompanied by improvement of body weight loss and atrophy in the thyroid gland, liver and epididymal fat pads. BH treatments also reduced the levels of hepatic enzymes (AST and ALT), which suggests BH exerts protective effects on hepatocytes. BH might also be involved in the augmentation of the anti-oxidant activities, supported by increased endogenous antioxidant (glutathione). In addition, the histopathological analyses revealed the beneficial effects of BH on the atrophic changes and cellular injuries in the thyroid gland, liver and epididymal fat pads. The therapeutic potentials of BH were either similar or more effective than PTU. These results provide valuable information that will guide more detailed studies to use the BH as a complementary and alternative medicine.

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Role of Heart Rate Reduction in the Management of Myocarditis

Current Pharmaceutical Design ◽

10.2174/1381612824666180111105923 ◽

2018 ◽

Vol 24 (3) ◽

pp. 365-378 ◽

Cited By ~ 2

Author(s):

Chen Guang-Yi ◽

Ge Li-Sha ◽

Li Yue-Chun

Keyword(s):

Heart Rate ◽

Nitrosative Stress ◽

Ventricular Remodeling ◽

Animal Experiments ◽

Viral Myocarditis ◽

Protective Effects ◽

Heart Rate Reduction ◽

Rate Reduction ◽

Beneficial Effects ◽

Biological Technique

The morbidity of myocarditis demonstrates an upward tendency by years, is commonly defined as the inflammation of myocytes and is caused by multiple factors. With the development of the molecular biological technique, great breakthroughs in the diagnosis and understanding of pathophysiological mechanisms of myocarditis have recently been achieved. Several questions remain unresolved, however, including standard treatment approaches to myocarditis, which remain controversial and ambiguous. Heart rate, as an independent risk factor, has been shown to be related to cardiac disease. Recent studies also show that the autonomic nervous system is involved in immunomodulatory myocarditis processes. Heart rate reduction treatment is recommended in myocarditis based on a number of animal experiments and clinical trials. It is possible that heart rate-lowering treatments can help to attenuate the inflammatory response and myocyte injury and reverse ventricular remodeling. However, how to execute the protective effects of heart rate reduction on myocarditis is still not clear. In this review, we discuss the pathogenesis and pathophysiological process of viral myocarditis and propose heart rate lowering as a therapeutic target for myocarditis, especially in light of the third-generation β-blockade carvedilol and funny channel blocker ivabradine. We also highlight some additional beneficial effects of such heart rate reduction agents, including anti-inflammatory, antioxidation, anti-nitrosative stress, anti-fibrosis and antiapoptosis properties.

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Strawberry and Achenes Hydroalcoholic Extracts and Their Digested Fractions Efficiently Counteract the AAPH-Induced Oxidative Damage in HepG2 Cells

International Journal of Molecular Sciences ◽

10.3390/ijms19082180 ◽

2018 ◽

Vol 19 (8) ◽

pp. 2180 ◽

Cited By ~ 5

Author(s):

María Ariza ◽

Tamara Forbes-Hernández ◽

Patricia Reboredo-Rodríguez ◽

Sadia Afrin ◽

Massimiliano Gasparrini ◽

...

Keyword(s):

Biological Activity ◽

Oxidative Damage ◽

Hepg2 Cells ◽

In Vitro Digestion ◽

Protective Effects ◽

Beneficial Effects ◽

Positive Effects ◽

Digestion Process ◽

Phytochemical Compounds

Strawberry fruits are highly appreciated by consumers worldwide due to their bright red color, typical aroma, and juicy texture. While the biological activity of the complete fruit has been widely studied, the potential beneficial effects of the achenes (commonly named seeds) remain unknown. In addition, when raw fruit and achenes are consumed, the digestion process could alter the release and absorption of their phytochemical compounds, compromising their bioactivity. In the present work, we evaluated the protective effects against oxidative damage of nondigested and digested extracts from strawberry fruit and achenes in human hepatocellular carcinoma (HepG2) cells. For that purpose, cells were treated with different concentration of the extracts prior to incubation with the stressor agent, AAPH (2,2′-azobis(2-amidinopropane) dihydrochloride). Subsequently, intracellular accumulation of reactive oxygen species (ROS) and the percentage of live, dead, and apoptotic cells were determined. Our results demonstrated that all the evaluated fractions were able to counteract the AAPH-induced damage, suggesting that the achenes also present biological activity. The positive effects of both the raw fruit and achenes were maintained after the in vitro digestion process.

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Abstract 119: Protective Effects of Chloroquine on Ischemic and Nutrient Depleted Muscle are Mediated by HMGB1 and Caspase-1

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.37.suppl_1.119 ◽

2017 ◽

Vol 37 (suppl_1) ◽

Author(s):

Ulka Sachdev ◽

Xiangdong Cui ◽

Qian Sun ◽

Edith Tzeng ◽

Alex Chen ◽

...

Keyword(s):

Culture Media ◽

Statistical Significance ◽

High Mobility ◽

Maximal Activity ◽

Arterial Disease ◽

Protective Effects ◽

Artery Ligation ◽

Beneficial Effects ◽

Caspase 1 ◽

Ldh Activity

Introduction: Millions of Americans are at risk for amputation from severe peripheral arterial disease (PAD) when surgery is not possible. Pro-regenerative and angiogenic agents may improve outcome in that setting. Chloroquine (CQ) promotes wound healing in scleroderma but has not been tested in PAD. CQ promotes healing of ischemic muscle, increases muscle high mobility group box 1 (HMGB1), an inflammatory, pro-angiogenic protein, and activates caspase-1 in myoblasts. We hypothesize that HMGB1 mediates protective effects of CQ and is regulated by caspase-1 in muscle. Controlled rather than indiscriminate release of HMGB1 from damaged muscle may be protective during ischemia. Methods: C2C12 myoblasts in low serum were treated with CQ (0-50μM) ± Ac-YVAD-cmk (10 μg/ml), a caspase-1 inhibitor. HMGB1 release in supernatants was measured using ELISA. Cytotoxicity was assessed by comparing spontaneous lactate dehydrogenase (LDH) activity in culture media from control, treated and maximally lysed cells. CQ (50μg/ml) or placebo treated wild-type and inducible HMGB1 knockout (iHMGB1KO) mice underwent unilateral femoral artery ligation (FAL). Laser Doppler perfusion imaging (LDPI) before and 1,7,14 and 21d after FAL was reported as % improvement over time. ANOVA was used to assess statistical significance among groups. Results: CQ (5-10uM) attenuated spontaneous LDH leak after 12h from serum-depleted myoblasts (p <0.01, N=3), and modestly increased HMGB1 release (p <0.001, N=3). Ac-YVAD-cmk reversed the cytoprotective effects of CQ, significantly raising both LDH activity to 55% of maximal activity and HMGB1 in the supernatant. Compared to d1 post FAL, CQ improved perfusion recovery in WT mice by 300-800% over 21 days (p<0.03, N=7/group), but not in iHMGB1KO mice. Conclusion: We present the novel finding that in nutrient-depleted myoblasts, caspase-1 mediates the survival benefits of CQ and regulates HMGB1 release. In turn, HMGB1 is critical for CQ’s beneficial effects on perfusion after FAL, another stress condition. Regulated HMGB1 release may be immunomodulatory, regenerative and modifiable with drugs like CQ. Altering survival and inflammatory pathways through CQ may present a novel therapeutic strategy in PAD.

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Resveratrol and cardiac fibrosis prevention and treatment

Current Pharmaceutical Biotechnology ◽

10.2174/1389201022666210212125003 ◽

2021 ◽

Vol 22 ◽

Author(s):

Parinaz Zivarpour ◽

Željko Reiner ◽

Jamal Hallajzadeh ◽

Liaosadat Mirsafaei

Keyword(s):

Cardiovascular Diseases ◽

Cardiac Fibrosis ◽

Therapeutic Potential ◽

Developed Countries ◽

Clinical Results ◽

Matrix Proteins ◽

Protective Effects ◽

Beneficial Effects ◽

Laboratory Models

: Cardiovascular diseases are some of the major causes of morbidity and mortality in developed or developing countries but in developed countries as well. Cardiac fibrosis is one of the most often pathological changes of heart tissues. It occurs as a result of extracellular matrix proteins accumulation at myocardia. Cardiac fibrosis results in impaired cardiac systolic and diastolic functions and is associated with other effects. Therapies with medicines have not been sufficiently successful in treating chronic diseases such as CVD. Therefore, the interest for therapeutic potential of natural compounds and medicinal plants has increased. Plants such as grapes, berries and peanuts contain a polyphenolic compound called "resveratrol" which has been reported to have various therapeutic properties for a variety of diseases. Studies on laboratory models that show that resveratrol has beneficial effects on cardiovascular diseases including myocardial infarction, high blood pressure cardiomyopathy, thrombosis, cardiac fibrosis, and atherosclerosis. In vitro animal models using resveratrol indicated protective effects on the heart by neutralizing reactive oxygen species, preventing inflammation, increasing neoangiogenesis, dilating blood vessels, suppressing apoptosis and delaying atherosclerosis. In this review, we are presenting experimental and clinical results of studies concerning resveratrol effects on cardiac fibrosis as a CVD outcome in humans.

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Potential Risks and Benefits of Phytoestrogen-Rich Diets

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831.73.2.120 ◽

2003 ◽

Vol 73 (2) ◽

pp. 120-126 ◽

Cited By ~ 105

Author(s):

Cassidy

Keyword(s):

Biological Effects ◽

Physiological Role ◽

Intestinal Bacteria ◽

Optimal Dose ◽

Biologically Active ◽

Pharmacokinetic Data ◽

Potential Health ◽

Beneficial Effects ◽

Age Related

Interest in the physiological role of bioactive compounds present in plants has increased dramatically over the last decade. Of particular interest in relation to human health are the class of compounds known as the phytoestrogens, which embody several groups of non-steroidal oestrogens including isoflavones & lignans that are widely distributed within the plant kingdom. Data from animal and in vitro studies provide plausible mechanisms to explain how phytoestrogens may influence hormone dependent states, but although the clinical application of diets rich in these oestrogen mimics is in its infancy, data from preliminary studies suggest potential beneficial effects of importance to health. Phytoestrogens are strikingly similar in chemical structure to the mammalian oestrogen, oestradiol, and bind to oestrogen receptors (ER) with a preference for the more recently described ERb. This suggests that these compounds may exert tissue specific effects. Numerous other biological effects independent of the ER (e.g. antioxidant capacity, antiproliferative and antiangiogenic effects) have been ascribed to these compounds. Whether phytoestrogens have any biological activity in humans, either hormonal or non hormonal is a contentious issue and there is currently a paucity of data on human exposure. Much of the available data on the absorption and metabolism of dietary phytoestrogens is of a qualitative nature; it is known that dietary phytoestrogens are metabolised by intestinal bacteria, absorbed, conjugated in the liver, circulated in plasma and excreted in urine. Recent studies have addressed quantitatively what happens to isoflavones following ingestion – with pure compound and stable isotope data to compliment recent pharmacokinetic data for soy foods. The limited studies conducted so far in humans clearly confirm that soya isoflavones can exert hormonal effects. These effects may be of benefit in the prevention of many of the common diseases observed in Western populations (such as breast cancer, prostate cancer, menopausal symptoms, osteoporosis) where the diet is typically devoid of these biologically active naturally occurring compounds. However since biological effects are dependent on many factors including dose, duration of use, protein binding affinity, individual metabolism and intrinsic oestrogenic state, further clinical studies are necessary to determine the potential health effects of these compounds in specific population groups. However we currently know little about age related differences in exposure to these compounds and there are few guidelines on optimal dose for specific health outcomes.

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Salvia Officinalis Protects Pancreatic Beta-cells Against Streptozotocin-Induced Damage; A Stereological Study

Jundishapur Journal of Natural Pharmaceutical Products ◽

10.5812/jjnpp.109906 ◽

2021 ◽

Vol 17 (1) ◽

Author(s):

Soheil Ashkani-Esfahani ◽

Ali Noorafshan ◽

Alireza Ebrahimi ◽

Maryam Bahmani-Jahromi ◽

Mohammad-Hossein Imanieh ◽

...

Keyword(s):

Beta Cells ◽

Pancreatic Beta Cells ◽

Pancreatic Injury ◽

Food Supplement ◽

Salvia Officinalis ◽

Diabetic Group ◽

Protective Effects ◽

Sprague Dawley ◽

Beneficial Effects ◽

Patients With Diabetes

Background: Diabetes mellitus (DM) is a chronic disease, progressing due to inadequate secretion of insulin by pancreas. Salvia officinalis (SVO) has anti-inflammatory and anti-oxidative potentials, which may be beneficial in regulating underlying causes of DM. Objectives: In this study, we aimed to estimate the protective effects of SVO against Streptozotocin (STZ)-induced pancreatic injury in rat models of DM. Methods: Forty-eight male Sprague-Dawley rats were randomly divided into four groups (n = 12); C1: normal group with no treatment, C2: diabetic group with no treatment, E1: diabetic group treated with 200 mg/kg of the SVO extract, and E2: diabetic group treated with 400 mg/kg of the SVO extract. All groups received a single dose of STZ on day 7 except C1. Pancreas volume, shrinkage, volume densities of the islets, numerical densities, and volume of the beta cells were measured using stereological methods. Results: Blood sugar (BS) levels were significantly lower in SVO-treated groups comparing to C2 group. Also, volume densities and total number of islets and beta cells in E1 and E2 groups were higher than C2 (P < 0.05), but lower than C1 (P < 0.05). Volume densities of the islets and beta cells, and total number of beta cells in E1, and volume densities of the islets and beta cells in E2 groups were considerably higher than C2 group (P < 0.05). Conclusions: Our result showed the beneficial effects of SVO extract regarding pancreatic damage. We concluded that SVO might be prescribed as a therapeutic food supplement for patients with diabetes.

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Hydroxyl-radical scavenging activity of hydrogen does not significantly contribute to its biological function

10.1101/2021.03.13.435216 ◽

2021 ◽

Author(s):

Qinjian Li ◽

Fei Xie ◽

Yang Yi ◽

Pengxiang Zhao ◽

Xin Zhang ◽

...

Keyword(s):

Hydroxyl Radicals ◽

Radical Scavenging Activity ◽

Radical Scavenging ◽

Published Data ◽

Oh Radicals ◽

Dependent Manner ◽

Protective Effects ◽

Beneficial Effects ◽

Wide Range ◽

Depth Study

AbstractSince Ohsawa et al. reported a biological antioxidant function of hydrogen in 2007, researchers have now shown it to exert protective effects in a wide range of human and animal disease models. Clinical observations and scientific arguments suggest that a selective scavenging property of H2 cannot adequately explain the beneficial effects of hydrogen. However, there is no experiment challenging the original published data, which suggested that molecular hydrogen dissolved in solution reacts with hydroxyl radicals in cell-free systems. Here we report that a hydrogen-saturated solution (0.6 mM) did not significantly reduce hydroxyl radicals in the Fenton system using 1 mM H2O2. We replicated the same condition as Ohsawa’s study (i.e. 5 μM H2O2), and observed a decrease in •OH radicals in both the H2-rich and N2-rich solutions, which may be caused by a decreased dissolved oxygen concentration. Finally, we determined the effect of hydrogen on a high-valence iron enzyme, horseradish peroxidase (HRP), and found that hydrogen could directly increase HRP activity in a dose-dependent manner. Overall, these results indicate that although H2 and •OH can react, the reaction rate is too low to have physiological function. The target of hydrogen is more complex, and its interaction with enzymes or other macro-molecules deserve more attention and in-depth study.

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Key Mechanisms and Potential Implications of Hericium erinaceus in NLRP3 Inflammasome Activation by Reactive Oxygen Species during Alzheimer’s Disease

Antioxidants ◽

10.3390/antiox10111664 ◽

2021 ◽

Vol 10 (11) ◽

pp. 1664

Author(s):

Marika Cordaro ◽

Angela Trovato Salinaro ◽

Rosalba Siracusa ◽

Ramona D’Amico ◽

Daniela Impellizzeri ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Nlrp3 Inflammasome ◽

Neuronal Degeneration ◽

Behavioral Changes ◽

Antioxidant Systems ◽

Inflammasome Activation ◽

Protective Effects ◽

Behavioral Alteration ◽

Hericium Erinaceus

Alzheimer’s disease (AD) is the principal cause of dementia, and its incidence increases with age. Altered antioxidant systems and inflammation have an important role in the etiology of neurodegenerative disorders. In this study, we evaluated the effects of Hericium erinaceus, a nutritional mushroom with important antioxidant effects, in a rat model of AD. Animals were injected with 70 mg/Kg of AlCl3 daily for 6 weeks, and Hericium erinaceus was administered daily by gavage. Before the experiment’s end date, behavioral test training was performed. At the end of the study, behavioral changes were assessed, and the animals were euthanized. Brain tissues were harvested for further analysis. AlCl3 mainly accumulates in the hippocampus, the principal region of the brain involved in memory functions and learning. Hericium erinaceus administration reduced behavioral changes and hippocampal neuronal degeneration. Additionally, it reduced phosphorylated Tau levels, aberrant APP overexpression, and β-amyloid accumulation. Moreover, Hericium erinaceus decreased the pro-oxidative and pro-inflammatory hippocampal alterations induced by AD. In particular, it reduced the activation of the NLRP3 inflammasome components, usually activated by increased oxidative stress during AD. Collectively, our results showed that Hericium erinaceus has protective effects on behavioral alteration and histological modification associated with AD due to the modulation of the oxidative and inflammatory pathways, as well as regulating cellular brain stress.

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