Diphlorethohydroxycarmalol isolated from Pae (Ishige okamurae) protects high glucose-induced damage in RINm5F pancreatic β cells via its antioxidant effects

Pancreatic β cells are very sensitive to oxidative stress and this may play an important role in β cell death in diabetes. The protective effect of diphlorethohydroxycarmalol (DPHC), one of phlorotannin polyphenol compound purified from pae (Ishige okamurae) against high glucoseinduced oxidative stress was investigated using RINm5F pancreatic β cells. High glucose (30 mM) treatment induced RINm5F pancreatic β cells cell death, but DPHC, at concentration 10 or 50 μg/mL, significantly inhibited the high glucose-induced glucotoxicity and apoptosis. Furthermore, treatment with DPHC dose-dependently decreased thiobarbituric acid reactive substances (TBARS), intracellular reactive oxygen species (ROS) generation and nitric oxide level increased by high glucose. In addition, DPHC treatment increased activities of antioxidant enzymes including catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-px) in high glucose pretreated RINm5F pancreatic β cells. DPHC treatment improved the secretory responsiveness following stimulation with glucose. These findings indicate that DPHC might be used as potential nutraceutical agent which will protect the glucotoxicity caused by hyperglycemia-induced oxidative stress associated with diabetes.     

Correlation of In Vivo and In Vitro Assay Results for Assessment of Free Radical Scavenging Activity of Green Tea Nutraceuticals

Green tea (GT)‐derived catechins; epigallocatechin gallate (EGCG) in particular are commonly used nutraceuticals for their free‐radical scavenging activity (FRSA). The influence of photodegradation on the protective power of GT nutracenticals against oxidative stress was thoroughly explored. Photodegradation of GT extracts was carried out and monitored using orthogonal stability‐indicating testing protocol; in vitro and in vivo assays. Total polyphenol content (TPC) and FRSA were determined spectrophotometrically while EGCG was selectively monitored using SPE‐HPLC. In vivo assessment of photodegraded samples was investigated via measuring a number of biomarkers for hepatic oxidative stress and apoptosis (caspase‐3, inducible nitric oxide synthase, nitric oxide, mitogen‐activated protein kinase, glutathione, thiobarbituric acid reactive substances, nuclear factor kappa beta, and nuclear factor erythroid 2‐related factor) as well as liver damage (alanine transaminase and aspartate transaminase) in serum of rats previously subjected to oxidative stress. Results showed complete degradation of EGCG in photodegraded green tea samples with no correlation with either TPC or FRSA. On the other hand, in vivo assay results revealed not only loss of activity but formation of harmful pro‐oxidants. Photostability was found crucial for the protective effect of GT extract against lead acetate insult. Results confirmed that careful design of quality control protocols requires correlation of chemical assays to bioassays to verify efficacy, stability, and most importantly safety of nutraceuticals.     

Aqueous and Ethanol Extracts of Daylily Flower (Hemerocallis fulva L.) Protect HUVE Cells Against High Glucose

The content of several phenolic acids and flavonoids in aqueous extract (AE) and ethanol extract (EE) of daylily flower (Hemerocallis fulva L.) was analyzed. The effects of AE or EE at 0.5%, 1%, or 2% in HUVE cells against high glucose‐induced cell death, oxidative, and inflammatory damage were examined. Results showed that seven phenolic acids and seven flavonoids could be detected in AE or EE, in the range of 29 to 205 and 41 to 273 mg/100 g, respectively. Compared with the control groups, high glucose raised the activity of caspase‐3 and caspase‐8; suppressed Bcl‐2 mRNA expression and increased Bax mRNA expression; and induced HUVE cells apoptosis. The pretreatments from AE or EE at 1% or 2% reduced caspase‐3 activity and Bax mRNA expression, and enhanced cell viability. High glucose decreased glutathione content; stimulated the production of reactive oxygen species, interleukin‐6, tumor necrosis factor‐alpha, and prostaglandin E₂; raised the activity of cyclooxygenase‐2 and nuclear factor kappa B p50/65 binding; and reduced the activity of glutathione peroxidase, glutathione reductase, and catalase in HUVE cells. AE pretreatments at 1% and 2% reversed these changes. These novel findings suggested that daylily flower was rich in phytochemicals, and could be viewed as a potent functional food against diabetes.     

Protective effect of Cordyceps militaris against high glucose-induced oxidative stress in human umbilical vein endothelial cells

The protective effect of Cordyceps militaris against high glucose-induced oxidative stress in human umbilical vein endothelial cells (HUVECs), as compared with Cordyceps sinensis, was examined. The cytotoxicity of HUVECs induced by 40 mM glucose was ameliorated by water extracts of C. militaris (CME) and water extracts of C. sinensis (CSE). CME and CSE inhibited the increase in ROS and NO in HUVECs induced by 40 mM high glucose. Moreover, CME increased the Bcl-2/Bax ratio, modulated the mitochondrial membrane potential and reduced the caspase-3 activity in high glucose-induced HUVECs. In addition, cordycepin, a component of CME and CSE, displayed protective effects against oxidative stress, which was partly responsible for the cytoprotective effects of CME and CSE against high glucose-induced oxidative stress in HUVECs. Overall, the obtained results show C. militaris helps preventing diabetic endothelial dysfunction and related complications.     

Grape seed proanthocyanidin extracts alleviate oxidative stress and ER stress in skeletal muscle of low‐dose streptozotocin‐ and high‐carbohydrate/high‐fat diet‐induced diabetic rats

Although ER stress in pancreas, liver, and adipose tissue was reported to be a novel event linked to the pathogenesis of type 2 diabetes mellitus, there is much less information on this event in skeletal muscle. Some studies indicated that treatment with antioxidants had beneficial effects on ER stress and diabetes. This study focuses on the effects of a strong antioxidant, grape seed proanthocyanidin extracts (GSPE), on skeletal muscle in diabetic rats induced with low dose streptozotocin‐ and a high‐carbohydrate/high‐fat diet. After 16 wk of GSPE treatment, diabetic rats showed decreased plasma glucose levels and insulin resistance. The efficacious effect of GSPE was manifested by the amelioration of muscular damage and dysfunction, as observed by histological examination and periodic acid Schiff staining. Concurrently, calcium overload and the abnormal activities of antioxidant enzymes and ATPases in diabetic muscles were partially reversed by GSPE treatment. GSPE also increased the activity of protein kinase B (a mediator of insulin's metabolic action) and partially alleviated severe ER stress. These findings suggest that GSPE may have auxiliary therapeutic potential for type 2 diabetes mellitus by decreasing oxidative stress and ER stress in skeletal muscle.     

Oral Administration of Puerh Tea Polysaccharides Lowers Blood Glucose Levels and Enhances Antioxidant Status in Alloxan‐Induced Diabetic Mice

Abstract: The polysaccharides, named puerh tea polysaccharides (PTPS), were isolated from puerh tea. Physicochemical characteristics, hypoglycemic and antioxidant effects of PTPS in alloxan‐induced diabetic mice were investigated. PTPS was found to be a kind of acid heteropolysaccharides conjugate, but the physicochemical characteristics of which were different from the polysaccharides from other kinds of teas in literature. Meanwhile, daily administration of PTPS (40 mg/kg BW) could significantly lower the blood glucose levels, which was not different (P > 0.05) from the effects of metformin (15 mg/kg BW) throughout the entire experiment. Furthermore, after 4‐wk administration of PTPS (40 mg/kg BW), the superoxide dismutase activity and malondialdehyde contents both in serum and liver were improved to the levels of those in normal mice. In regards to the serum GSH‐Px activity, it was even significantly higher (P < 0.05) than that in normal mice, indicating the oxidative stress induced by alloxan could be reversed by administration of PTPS. Practical Application: Control of blood sugar levels and inhibition of oxidative stress are suggested to be important in the treatment of diabetes. In the present work, the effects of the polysaccharides from puerh tea (PTPS) on blood glucose levels and antioxidant status in alloxan‐induced diabetic mice were investigated. The information obtained will be valuable for potential application of PTPS in the treatment of diabetes.     

The etiology of oxidative stress in the various species of animals,a review

Oxidative stress is the consequence of an imbalance of pro‐oxidants and antioxidants leading to cell damage and tissue injury. The exhaustion of antioxidant systems is one of the reasons for the occurrence of oxidative stress, which results in avalanche production of reactive oxygen species (ROS) or free radicals. High oxidative stress is common in organs and tissues with high metabolic and energy demands, including skeletal and heart muscle, liver and blood cells. Stress arises in animals in response to unavoidable or adverse environmental conditions. In the external environment, which affects the body of the cow, there are four main groups of stressors: physical, chemical, biological and psychological. Physical stressors include fluctuations in ambient temperature as well as mechanical injuries. High ambient temperature is one of the factors affecting the productivity of cows. Biological stressors are conditioned by errors and irregularities in habits. Both of these phenomena have an adverse impact on both the resistance of animals and fertility and are the etiological agent of oxidative stress. Various mechanisms may be responsible for metal‐induced oxidative stress: direct or indirect generation of ROS, depletion of glutathione and inhibition of antioxidant enzymes are well known for all redox‐active and redox‐inactive metals. © 2014 Society of Chemical Industry     

Cocoa‐rich diet attenuates beta cell mass loss and function in young Zucker diabetic fatty rats by preventing oxidative stress and beta cell apoptosis

We have recently shown that cocoa flavanols may have anti‐diabetic potential by promoting survival and function of pancreatic beta‐cells in vitro. In this work, we investigated if a cocoa‐rich diet is able to preserve beta‐cell mass and function in an animal model of type 2 diabetes and the mechanisms involved. Our results showed that cocoa feeding during the prediabetic state attenuates hyperglycaemia, reduces insulin resistant, and increases beta cell mass and function in obese Zucker diabetic rats. At the molecular level, cocoa‐rich diet prevented beta‐cell apoptosis by increasing the levels of Bcl‐xL and decreasing Bax levels and caspase‐3 activity. Cocoa diet enhanced the activity of endogenous antioxidant defenses, mainly glutathione peroxidase, preventing thus oxidative injury induced by the pre‐diabetic condition and leading to apoptosis prevention. These findings provide the first in vivo evidence that a cocoa‐rich diet may delay the loss of functional beta‐cell mass and delay the progression of diabetes by preventing oxidative stress and beta‐cell apoptosis.     

榆干离褶伞溶栓酶对氧化应激损伤人脐静脉内皮细胞的保护作用

目的：探讨榆干离褶伞（Lyophyllum ulmarium,L.u）溶栓酶对H2O2诱导人脐静脉内皮细胞（humanumbilical vein endothelial cell,HUVEC）损伤的保护作用。方法：用H2O2诱导HUVEC氧化损伤,采用四甲基偶氮唑蓝（methyl thiazolyl tetrazolium,MTT）法观察细胞存活率;用流式细胞仪检测细胞线粒体跨膜电位（ΔΨm）和总活性氧（reactive oxygen species,ROS）水平;Western blotting法检测Caspase-8、Caspase-9、Caspase-3等蛋白的表达水平。结果：L.u溶栓酶可显著提高HUVEC的存活率,明显抑制H2O2诱导的细胞内ROS生成和线粒体跨膜电位的下降,并能降低Caspase-8、Caspase-9和Caspase-3的表达水平。结论：L.u溶栓酶对氧化应激损伤的HUVEC有保护作用,其机制可能与抑制细胞凋亡有关。     

Arginine-rich coconut kernel diet influences nitric oxide synthase activity in alloxandiabetic rats

BACKGROUND: Coconut kernel protein (CKP) has been reported to contain significant amounts of L ‐arginine. Its potential effect on glucose homeostasis, possibly through the nitric oxide synthase (NO) pathway, was therefore investigated in alloxan‐induced diabetic rats. Diabetes was induced by a single intraperitoneal dose of alloxan (150 mg kg^?1 body weight). Experimental rats were grouped as follows: Group I, normal control; Group II, diabetic control; Group III, diabetic + CKP; Group IV, diabetic + L ‐arginine; Group V, diabetic + L ‐arginine + L ‐N^G‐Nitroarginine methyl ester (L ‐NAME). Purified CKP isolated from dried coconut kernel and L ‐arginine was administered to rats along with a semi‐synthetic diet for 45 days. L ‐NAME (0.5 mg kg^?1 body weight) was given to Group V animals. After the experimental period, serum glucose, insulin, activities of liver nitric oxide synthase and arginase, liver glycogen levels and histopathology of the pancreas were evaluated. RESULTS: Serum glucose, insulin and antioxidant enzyme activities and liver glycogen levels were found to be restored to basal levels in CKP‐fed rats. Decreased arginase and increased nitric oxide synthase (NOS) activities were found in CKP‐ and arginine‐fed rats. L ‐NAME treatment showed a partial effect on these parameters. Histopathology revealed that CKP and L ‐arginine feeding reduced the diabetes‐related pancreatic damage in treated rats compared to the diabetic control. CONCLUSION: The results observed in this study indicate that the potential antidiabetic activity of CKP may be through an arginine‐NO pathway leading to pancreatic beta cell regeneration. Copyright © 2012 Society of Chemical Industry     

苦荞清蛋白酶解物对高糖诱导的HepG2细胞胰岛素抵抗的保护作用

目的:建立胰岛素抵抗HepG2细胞模型,观察苦荞清蛋白酶解物(tartary buckwheat albumin hydrolysate,TBAH)对HepG2细胞胰岛素抵抗的影响.方法:采用碱性蛋白酶水解苦荞清蛋白制备TBAH,超滤法截留分子质量小于3 kDa的TBAH;利用高糖高胰岛素诱导HepG2细胞36 h建立...     

Changes in Antioxidant Activity of Cyphomandra betacea (Cav.) Sendtn. Fruits During Maturation and Senescence

Antioxidants are extremely important substances that possess the ability to protect the body from damage caused by free radical induced oxidative stress. Antioxidants are derived from dietary sources, such as fruits, vegetables, and beverages. In this study, the antioxidant activity of different maturity stages of two varieties of Cyphomandra betacea fruits of Darjeeling was evaluated in vitro. The radical scavenging properties on 2,2-diphenyl-1-picrylhydrazyl, superoxide anion, hydroxyl radical, lipid peroxidation, nitric oxide, and reducing power as well as the flavonoids, phenolics, lycopene, and total carotene contents of methanolic extracts of the fruits were determined. All fruit extracts, mainly the mature red fruit of purple-red variety exhibited strong scavenging activity towards all radicals tested due to the presence of relatively high total phenol, flavonoids, and lycopene as well as total carotene contents. The findings suggest that purple red variety of C. betacea fruit is endowed with antioxidant phytochemicals, which could provide protection against oxidative stress induced diseases.     

The anti‐diabetic effect of anthocyanins in streptozotocin‐induced diabetic rats through glucose transporter 4 regulation and prevention of insulin resistance and pancreatic apoptosis

Hyperglycemia, abnormal lipid and antioxidant profiles are the most usual complications in diabetes mellitus. Thus, in this study, we investigated the anti‐diabetic and anti‐oxidative effects of anthocyanins (ANT) from black soybean seed coats in streptozotocin (STZ)‐induced diabetic rats. The administration of ANT markedly decreased glucose levels and improved heart hemodynamic function (left ventricular end diastolic pressure, ±dp/dt parameters). ANT not only enhanced STZ‐mediated insulin level decreases, but also decreased the triglyceride levels induced by STZ injection in serum. Diabetic rats exhibited a lower expression of glucose transporter 4 proteins in the membrane fractions of heart and skeletal muscle tissues, which was enhanced by ANT. In addition, ANT activated insulin receptor phosphorylation, suggesting an increased utilization of glucose by tissues. Moreover, ANT protected pancreatic tissue from STZ‐induced apoptosis through regulation of caspase‐3, Bax, and Bcl‐2 proteins. Furthermore, ANT significantly suppressed malondialdehyde levels and restored superoxide dismutase and catalase activities in diabetic rats. Interestingly, the observed effects of ANT were superior to those of glibenclamide. Taken together, ANT from black soybean seed coat have anti‐diabetic effects that are due, in part, to the regulation of glucose transporter 4 and prevention of insulin resistance and pancreatic apoptosis, suggesting a possible use as a drug to regulate diabetes.     

The protective effects of melanoidins in adriamycin‐induced oxidative stress in isolated rat hepatocytes

The importance of the antioxidants contained in foods is well recognized both for preserving the foods themselves and for supplying essential antioxidants in vivo. Among these, the melanoidins formed during food processing and storage represent a significant part of our diet, with an average intake of several grams per day. Melanoidins exhibit antioxidant properties in vitro through their protective effect against reactive oxygen species. Here we investigated the protective effect of the model glucose–glycine melanoidins on oxidative stress induced by adriamycin in hepatocytes isolated from rats. The study was performed by examining cell toxicity (lactate dehydrogenase) release in the medium, lipoperoxidation, protein oxidation, GSH and ATP levels. The addition of 50 µg glucose–glycine melanoidins to the hepatocytes treated with 25 and 75 µM of adriamycin decreased the cell oxidative damage. The cell toxicity, lipoperoxidation and the protein oxidation decreased significantly in the presence of melanoidins. The effect of melanoidins on the intracellular antioxidant GSH when co‐incubated the adriamycin–hepatocytes with melanoidins resulted in a recovery of GSH levels. Furthermore, from the study of ATP levels we found that the damage to the mitochondria induced by adriamycin is decreased in the presence of melanoidins. According to these results, we suggest that melanoidins are capable of preventing cell oxidation. Based on these mechanisms, the ingestion of melanoidins present in food could be play a role important in the prevention of oxidative damage and prevention the diseases related to free radicals. Copyright © 2004 Society of Chemical Industry     

Hepatoprotective effect of Cassia obtusifolia seed extract and constituents against oxidative damage induced by tert‐butyl hydroperoxide in human hepatic HepG2 cells

The aim of the present study was to investigate the hepatoprotective effects of different soluble fractions of methanolic derived Cassia obtusifolia seeds extract (COE) and its active components in tert‐butyl hydroperoxide (t‐BHP)‐induced oxidative stress in HepG2 cells. Among the tested fractions, the ethyl acetate (EtOAc) fraction was the most active hepatoprotective fraction. From the active EtOAc fraction, six anthraquinones (alaternin, emodin, aloe emodin, 2‐hydroxyemodin 1‐methyl ether, chryso‐obtusin‐2‐O‐β‐d ‐glucoside, and questin) and one naphthopyrone glycoside (cassiaside) were isolated. The cytotoxic effect in 200 µM t‐BHP‐induced HepG2 cells was inhibited by COE and their bioactive compounds. The protective effect of COE in 200 µM t‐BHP‐induced HepG2 cells may be associated with positive regulation of glutathione (GSH) and decreased in reactive oxygen species (ROS) formation of their bioactive compounds. The increased ROS and decreased GSH levels observed in t‐BHP‐treated HepG2 cells were ameliorated by pretreatment with cassiaside, alaternin, and aloe emodin, indicating that the hepatoprotective effects of these major constituents are mediated by induction of cellular defense against oxidative stress. Overall, COE displayed a significant cytoprotective effect against oxidative stress, which may most likely be because of active compounds like cassiaside, alaternin, and aloe emodin in COE, which leads to maintenance of the normal redox status of cells.

Practical applications

The dried and roasted seeds of Cassia obtusifolia are commonly consumed as brew tea and medicinal foods in Korea. The seeds have multiple therapeutic actions related to the treatment of liver disease, dementia, diabetes, eye inflammation, photophobia and lacrimation, dysentery, headache, as well as dizziness. The present study demonstrates the hepatoprotective effect through prevention of oxidative stress, suggesting that C. obtusifolia and its constituents may have beneficial effects in preventing hepatic diseases.     

Administration of a β-glucan-enriched extract activates beneficial hepatic antioxidant and anti-inflammatory mechanisms in streptozotocin-induced diabetic rats

The beneficial effect of a commercially available β-glucan-enriched extract (BGEE) from cereal grain, against a diabetes-induced hepatic redox imbalance and inflammatory response in streptozotocin-induced diabetic rats was evaluated. Diabetic rats that were treated with BGEE exhibited lower hyperglycaemia and improved biochemical parameters of liver damage. BGEE attenuated hepatic oxidative stress, revealed by a decreased concentration of thiobarbituric acid reactive substances and a restored GSH/GSSG ratio. BGEE also exerted an anti-inflammatory effect on the liver, evidenced by the normalization of the serum concentrations of the “positive” and “negative” acute-phase proteins, α₂-macroglobulin and albumin, respectively, as well as by upregulation of anti-inflammatory cytokine IL-10 and IL-4 mRNA expression, and inhibition of RAGE/NF-κB signaling. These findings suggest that BGEE application exerts a beneficial effect in the liver of streptozotocin-induced diabetic rats via its antioxidant and anti-inflammatory activities, and that it therefore possesses an important potential in diabetes management.     

Genome‐wide map of Apn1 binding sites under oxidative stress in Saccharomyces cerevisiae

The DNA is cells is continuously exposed to reactive oxygen species resulting in toxic and mutagenic DNA damage. Although the repair of oxidative DNA damage occurs primarily through the base excision repair (BER) pathway, the nucleotide excision repair (NER) pathway processes some of the same lesions. In addition, damage tolerance mechanisms, such as recombination and translesion synthesis, enable cells to tolerate oxidative DNA damage, especially when BER and NER capacities are exceeded. Thus, disruption of BER alone or disruption of BER and NER in Saccharomyces cerevisiae leads to increased mutations as well as large‐scale genomic rearrangements. Previous studies demonstrated that a particular region of chromosome II is susceptible to chronic oxidative stress‐induced chromosomal rearrangements, suggesting the existence of DNA damage and/or DNA repair hotspots. Here we investigated the relationship between oxidative damage and genomic instability utilizing chromatin immunoprecipitation combined with DNA microarray technology to profile DNA repair sites along yeast chromosomes under different oxidative stress conditions. We targeted the major yeast AP endonuclease Apn1 as a representative BER protein. Our results indicate that Apn1 target sequences are enriched for cytosine and guanine nucleotides. We predict that BER protects these sites in the genome because guanines and cytosines are thought to be especially susceptible to oxidative attack, thereby preventing large‐scale genome destabilization from chronic accumulation of DNA damage. Information from our studies should provide insight into how regional deployment of oxidative DNA damage management systems along chromosomes protects against large‐scale rearrangements. Copyright © 2017 John Wiley & Sons, Ltd.     

Phytochemical characteristics and hypoglycaemic activity of fraction from mushroom Inonotus obliquus

BACKGROUND: Inonotus obliquus is a medicinal mushroom that has been used as an effective agent to treat various diseases such as diabetes, tuberculosis and cancer. In order to elucidate the active fraction and its constituents, the effects of ethyl acetate fraction from I. obliquus (EAFI) on hyperglycaemia were investigated and the main constituents of EAFI were isolated and identified. RESULTS: EAFI treatment led to a significant decrease in blood glucose level (P < 0.05) in alloxan‐induced diabetic mice. It significantly decreased the total cholesterol level in serum, increased glutathione peroxidase activity and improved the growth physiological characteristics. In addition, EAFI treatment decreased the levels of triglyceride and malondialdehyde and increased the high‐density lipoprotein cholesterol level in serum and the hepatic glycogen level in liver of diabetic mice. Five compounds were isolated from EAFI and identified as lanosterol (1), 3β‐hydroxy‐lanosta‐8,24‐diene‐21‐al (2), inotodiol (3), ergosterol peroxide (4) and trametenolic acid (5) by spectral methods. Inotodiol and trametenolic acid were found to have an inhibitory effect on α‐amylase activity and a scavenging effect on 1,1‐diphenyl‐2‐picrylhydrazyl radicals. CONCLUSION: EAFI showed significant antihyperglycaemic and antilipidperoxidative effects in alloxan‐induced diabetic mice. Terpenoid and sterol compounds appeared to be the major active constituents of I. obliquus. Copyright © 2009 Society of Chemical Industry