Neuroprotective effect of edible brown alga Eisenia bicyclis on amyloid beta peptide-induced toxicity in PC12 cells

Amyloid beta peptide (A??) oligomers increase intracellular reactive oxygen species (ROS) and calcium cation (Ca²⁺) concentrations, which causes neuronal cell death in Alzheimer??s disease (AD). Thus, the use of neuroprotective agents with antioxidative activity might be effective in the treatment of AD. In the present study, the neuroprotective effects of the methanol extract from edible brown alga Eisenia bicyclis (Laminariaceae) and its solvent soluble fractions together with the isolated phlorotannins on A??-induced toxicity were assessed by cell viability, intracellular ROS, and Ca²⁺ levels in PC12 cells. The addition of the methanol extract as well as its ethyl acetate and n-butanol fractions of E. bicyclis markedly reversed the A??-induced toxicity. Among six phlorotannins, including phloroglucinol (1), dioxinodehydroeckol (2), eckol (3), phlorofucofuroeckol A (4), dieckol (5), and 7-phloroeckol (6), isolated from the most active ethyl acetate fraction, 3?C6 significantly decreased A??-induced cell death. Furthermore, these compounds also inhibited intracellular ROS generation and Ca²⁺ generation, indicating the neuroprotective effects may be mediated through reduced intracellular ROS and Ca²⁺ generation. Thus, the results of the present study imply that E. bicyclis and its active components attenuated the oxidative stress and reduced neuronal cell death, suggesting that it may be used as a dietary neuroprotective agent in AD.     

Protective effects of triterpene compounds against the cytotoxicity of cadmium in HepG2 cells

The effects of triterpene compounds on cadmium toxicity were investigated in HepG2 cells. Ten triterpene compounds were examined, namely, betulin, soyasapogenol A, soyasapogenol B, ursolic acid, uvaol, oleanolic acid, friedelin, glycyrrhizin, 18alpha-glycyrrhetinic acid, and 18beta-glycyrrhetinic acid, and betulin, soyasapogenol A, and uvaol were found to reduce the toxicity of CdCl(2). In particular, betulin almost completely abolished the cytotoxicity of CdCl(2) at concentrations as low as 0. 1 microg/ml. The effects of betulin were particularly apparent when added to the culture medium before the addition of CdCl(2). Moreover, when HepG2 cells were incubated with betulin and then incubated in fresh betulin-free medium before the addition of CdCl(2), the toxic effects of cadmium were reduced. Betulin had no significant effect on the intracellular accumulation of cadmium, nor did it bind to cadmium, at least not in a test tube. When HepG2 cells were treated first with cycloheximide or actinomycin D, the subsequent protective effect of betulin against cadmium toxicity was significantly reduced, suggesting that betulin might protect cells against cadmium toxicity by inducing the synthesis of a certain protein or proteins. The synthesis of metallothionein, a protein that is known to reduce the toxicity of heavy metals, was not induced by betulin. However, using the differential display method, we confirmed that betulin promoted the expression of several genes. Our findings suggest that betulin might reduce cadmium toxicity by promoting the synthesis of certain proteins that protect cells against the toxic effects of cadmium.     

Protective effects of betulin and betulinic acid against ethanol-induced cytotoxicity in HepG2 cells

Plant triterpenes, such as oleanolic acid and betulin were described as hepatoprotectants active against cytotoxicity of acetaminophen or cadmium. The aim of this paper is to compare the cytoprotective activity of betulin, betulinic acid and oleanolic acid against ethanol-induced cytotoxicity in HepG2 cells. The influence of three triterpenes on ethanol-induced production of superoxide anion and hydrogen peroxide was also examined. Among the examined triterpenes, betulin was the most active protectant of HepG2 cells against ethanol-induced cytotoxicity. Betulin and betulinic acid significantly decreased ethanol-induced production of superoxide anion. Oleanolic acid inhibited only ethanol- and phorbol ester-induced production of hydrogen peroxide. The results indicate that cytoprotective or antioxidative activity of triterpenes depends on their chemical structure.     

Anti-inflammation mechanism of extract from Eisenia bicyclis (Kjellman) Setchell.

An extract from Eisenia bicyclis, previously shown to possess anti-inflammatory activity, was found to stabilize lysosomal membranes in vitro as determined by measurement of inhibition of the marker enzyme beta-glucuronidase. Some anti-inflammatory activity was also due to counterirritancy.     

Protective effects of panduratin A against oxidative damage of tert-butylhydroperoxide in human HepG2 cells

The protective effect of panduratin A, isolated from Kaempferia pandurata ROXB. (Zingiberaceae), against tert-butylhydroperoxide (t-BHP)-induced cytotoxicity was investigated in a human hepatoma cell line, HepG2. The tetrazolium dye colorimetric test (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay) was used to monitor cytotoxicity. Lipid peroxidation [malondialdehyde (MDA) formation] and intracellular glutathione level were estimated by fluorometric methods. Intracellular reactive oxygen species (ROS) formation was measured using a fluorescent probe 2',7'-dichlorofluorescein diacetate (DCFH-DA). Panduratin A significantly reduced the cell growth inhibition caused by t-BHP. Furthermore, panduratin A ameliorated lipid peroxidation as demonstrated by a reduction in MDA formation, and attenuated glutathione (GSH) depletion in a dose-dependent manner. It was also found that panduratin A reduced intracellular ROS formation caused by t-BHP. These results strongly suggest that panduratin A has significant protective ability against oxidative damage caused by reactive intermediates.     

Protective effect of proteins derived from Calotropis procera latex against acute inflammation in rat

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Protective effect of Lepidium sativum seed extract against hydrogen peroxide-induced cytotoxicity and oxidative stress in human liver cells (HepG2)

Context: Garden cress [Lepidium sativum (Brassicaceae)] has been widely used to treat a number of ailments in traditional medicine. The pharmacological and preventive potential of Lepidium sativum, such as anti-inflammatory, antipyretic, antihypertensive, anti-ashthamatic, anticancer, and anti-oxidant, are well known.

Objective: The present investigation was designed to study the protective effects of chloroform extract of Lepidium sativum seed (LSE) against oxidative stress and cytotoxicity induced by hydrogen peroxide (H₂O₂) in human liver cells (HepG2).

Materials and methods: Cytotoxicity of LSE and H₂O₂ was identified by (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), neutral red uptake (NRU) assays, and morphological changes in HepG2. The cells were pre-exposed to biologically safe concentrations (5–25?μg/ml) of LSE for 24 h, and then cytotoxic (0.25 mM) concentration of H₂O₂ was added. After 24 h of the exposures, cell viability by MTT, NRU assays, and morphological changes in HepG2 were evaluated. Further, protective effects of LSE on reactive oxygen species (ROS) generation, mitochondrial membrane potential (MMP), lipid peroxidation (LPO), and reduced glutathione (GSH) levels induced by H₂O₂ were studied.

Results: Pre-exposure of LSE significantly attenuated the loss of cell viability up to 48% at 25?µg/ml concentration against H₂O₂ (LD₅₀ value?=?2.5?mM). Results also showed that LSE at 25?µg/ml concentration significantly inhibited the induction of ROS generation (45%) and LPO (56%), and increases the MMP (55%) and GSH levels (46%).

Discussion and conclusion: The study suggests the cytoprotective effects of LSE against H₂O₂-induced toxicity in HepG2. The results also demonstrate the anti-oxidative nature of LSE.     

Protective effect of simple phenols from extravirgin olive oil against lipid peroxidation in intestinal Caco-2 cells

Complex polyphenols present in extravirgin olive oil are not directly absorbed, but undergo gastrointestinal biotransformation, increasing the relative amount of tyrosol (TYR) and hydroxytyrosol (HT) entering the small and large intestine. We investigated the capacity of TYR and HT to inhibit the insult of dietary lipid hydroperoxydes on the intestinal mucosa, using cultures of Caco-2, a cell line with enterocyte-like features, and studying the effect of tert-butyl hydroperoxide (TBH) treatment on specific cell membrane lipid targets. The effect of homovanillic alcohol (HVA), metabolite of HT in humans and detected as metabolite of HT in Caco-2 cells, was also evaluated. Exposure to TBH induced a significant increase of the level of MDA, the formation of fatty acid hydroperoxides and 7-ketocholesterol and the loss of α-tocopherol. Pretreatment with both HT and HVA protected Caco-2 cells from oxidative damage: there was no significant detection of oxidation products and the level of α-tocopherol was preserved. Noteworthy, TYR also exerted a protective action against fatty acids degradation. In vitro trials, where the simple phenols were tested during linoleic acid and cholesterol oxidation, gave evidence of a direct scavenging of peroxyl radicals and suggested a hydrogen atom-donating activity.     

Protective effect of polypeptides from larva of housefly (Musca domestica) on hydrogen peroxide-induced oxidative damage in HepG2 cells

Housefly (Musca domestica) is an important medical insect and its larva is an ideal high protein food source. We isolated from housefly larvae the polypeptides hydrolyzed by neutral protease (PHNP), and investigated the protective effect of PHNP on hydrogen peroxide (H₂O₂)-induced oxidative damage in HepG2 cells. Cells exposed to H₂O₂ showed a marked decrease in proliferation and intracellular superoxide dismutase (SOD) activity, and a significant increase in reactive oxygen species (ROS) level and malondialdehyde (MDA) content. H₂O₂ also caused apoptosis and mitochondrial dysfunction including mitochondrial fragmentation and the loss of mitochondrial membrane potential. Pretreatment with PHNP at concentrations of 2.5, 5, 10 μg/mL blocked these H₂O₂-induced cellular events in a dose-dependent manner. The effect of PHNP at 10 μg/mL is equal to that of ascorbic acid at 10 μM. In summary, PHNP has a protective effect against H₂O₂-induced oxidative injury in cells due to its ability to decrease intracellular ROS and elevate antioxidant enzyme activities.     

Antioxidative and antigenotoxic effect of vitamin E against patulin cytotoxicity and genotoxicity in HepG2 cells

Patulin (PAT) is a mycotoxin produced in fruits, mainly in apples, by certain species of Penicillium, Aspergillus, and Byssochlamys. It has been shown that PAT is cytotoxic, genotoxic, and mutagenic in different cell types. Several studies incriminate the oxidative stress as a mechanism of PAT‐mediated toxicity. In this context, our aim was to investigate the protective role of Vitamin E (Vit E), an antioxidant agent, against PAT induced cytotoxicity and genotoxicity in cultured HepG2 cells. The obtained results showed that addition of Vit E in cells treated with PAT significantly reduce cell mortality induced by this toxin. In the same conditions, Vit E decreased the intracellular level of ROS, reduced PAT induced p53 expression, and reversed PAT induced DNA damage. In addition, Vit E prevented significantly the percentage of chromosome aberrations induced by PAT in HepG2 cells in a concentration dependant manner. These results suggest that Vit E, an exogenous antioxidant agent, plays an important role in defense against PAT‐induced cytotoxicity and genotoxicity, which confirms the involvement of oxidative stress in the induction of DNA damage by PAT in HepG2 cells. © 2011 Wiley Periodicals, Inc. Environ Toxicol, 2013.     

Protective role of intestinal bacterial metabolism against baicalin-induced toxicity in HepG2 cell cultures

Baicalin, a glycoside present in Scutellaria baicalensis Georgi, is metabolized to its aglycone, baicalein, in intestine. In the present study, possible role of metabolism of baicalin by intestinal bacteria to baicalein in baicalin-induced toxicity was investigated in HepG2 cell cultures. As an intestinal bacterial metabolic system for baicalin, human fecal preparation containing intestinal microflora (fecalase) was employed. Initially, when cytotoxic effects of baicalin and baicalein were compared, baicalin was more cytotoxic than baicalein in HepG2 cells. When baicalin was incubated with fecalase, it was metabolized to baicalein. In addition, baicalin-incubated with fecalase reduced cytotoxicity of HepG2 cells in a concentration-dependent manner. Moreover, baicalin-incubated with fecalase significantly caused an increase in Bcl-2 expression together with a decrease in Bax expression and cleaved Caspase-3. Furthermore, anti-apoptotic effect by the incubation of baicalin with fecalase was also confirmed by the terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick-end labeling assay. Taken all together, the findings suggested that metabolism of baicalin by human fecalase to baicalein might have protective effects against baicalin-induced toxicity in HepG2 cells.     

洋参抗衰合剂对H2O2诱导HepG2细胞氧化损伤的保护作用

目的 考察洋参抗衰合剂对H₂O₂致HepG2细胞氧化应激损伤的保护作用,并初步分析洋参抗衰合剂对H₂O₂诱导HepG2细胞氧化损伤的保护机制。方法 以H₂O₂诱导培养的HepG2细胞为模型,检测洋参抗衰合剂对HepG2细胞中谷胱甘肽(glutathione,GSH)含量、过氧化氢酶(catalase, CAT)活力和丙二醛(malondialdehyde, MDA)含量的变化,分析洋参抗衰合剂的抗氧化作用。结果 随着洋参抗衰合剂质量浓度的增加,H₂O₂诱导HepG2细胞的谷胱甘肽(GSH) 和过氧化氢酶(CAT)含量上升,丙二醛(MDA)的含量有所下降。结论 洋参抗衰合剂对H₂O₂诱导HepG2细胞损伤有抗氧化作用,其机理可能是通过促进还原物质的合成,增加抗氧化酶的活性进而减少脂质过氧化物。     

Antimicrobial effect of phlorotannins from marine brown algae

Marine organisms exhibit a rich chemical content that possess unique structural features as compared to terrestrial metabolites. Among marine resources, marine algae are a rich source of chemically diverse compounds with the possibility of their potential use as a novel class of artificial food ingredients and antimicrobial agents. The objective of this brief review is to identify new candidate drugs for antimicrobial activity against food-borne pathogenic bacteria. Bioactive compounds derived from brown algae are discussed, namely phlorotannins, that have anti-microbial effects and therefore may be useful to explore as potential antimicrobial agents for the food and pharmaceutical industries.     

2016-2018年天津儿童医院含β2受体激动剂药品使用情况分析

目的了解天津市儿童医院含β2受体激动剂药品的使用情况,为临床药品管理和合理用药提供参考。方法收集天津市儿童医院2016-2018年门诊药房使用含β2受体激动剂药品的相关数据信息,统计药品相关指标,并分析其变化趋势。结果 2016-2018年含β2受体激动剂药品的用药金额及使用率呈现逐年递增趋势,尤其在2018年,口服用含β2受体激动剂药品的用药金额大幅增长,使用率明显增高。应用含β2受体激动剂药品的用药频度(DDDs)排序前3位的药品依次是盐酸丙卡特罗片、盐酸丙卡特罗口服液、布地奈德福莫特罗粉吸入剂(80μg∶4.5μg);日均费用(DDC)最高的是硫酸特布他林雾化溶液,口服药品中DDC最高的是氨溴特罗口服液。结论天津市儿童医院含β2受体激动剂药品的用药金额和使用率与儿童呼吸系统疾病季节性发病特点密切相关,临床应用基本合理,同时应及时了解临床用药现状,规范管理,合理用药。     

Protective effect of a phenolic-rich fraction from Schisandra chinensis against H2O2-induced apoptosis in SH-SY5Y cells

We have investigated the neuroprotective effects of a phenolic-rich fraction (PRF) on the hydrogen peroxide (H(2)O(2))-induced apoptosis of cultured SH-SY5Y cells. The PRF was obtained from the 80% ethanol extract of the fruits of Schisandra chinensis by Sepabeads SP-850 column chromatography. Cell viability assays revealed that pretreating SH-SY5Y cells with PRF (10-200 mugmL(-1)) resulted in significant dose-dependent protection against H(2)O(2)-induced cell death. The protective effect of PRF against H(2)O(2)-induced apoptosis was assessed by flow cytometric analysis of DNA contents using propidium iodide (PI) staining. Pre-incubation of cells with PRF at different concentrations for 24 h partially protected apoptosis by H(2)O(2) (150 muM). Moreover, cells treated with PRF reduced H(2)O(2)-induced caspase-3 activation and poly (ADP-ribose) polymerase cleavage and exerted an apparent suppressive effect on oxidative stress induced by reactive oxygen species (ROS). We concluded that PRF may be useful in the treatment and prevention of neurodegenerative diseases associated with elevated ROS levels.     

Tribuli fructus constituents protect against tacrine-induced cytotoxicity in HepG2 cells

A new phenolic amide, tribulusimide D (4-hydroxy-N-[3-(4-hydroxy-3-methoxyphenyl)-1-oxo-2-propen-1-yl]-3-methoxybenzamide) (1), together with a known phenolic amide, terrestriamide ((E)-3-(4-hydroxy-3-methoxyphenyl)-N-[2-(4-hydroxyphenyl)-2-oxoethyl]-prop-2-enamide) (2) and a flavonol glycoside, quercetin-3-O-β-d-glucopyranosyl-(1→6)-β-d-glucopyranoside (3) were isolated from the H₂O extract of Tribuli Fructus. Compounds 1 and 3 showed significant hepatoprotective activities, with EC₅₀ values of 13.46 ± 0.2 and 7.06 ± 0.7 μM, respectively, against tacrine-induced cytotoxicity in HepG2 cells.     

N-acetylcysteine does not protect HepG2 cells against acetaminophen-induced apoptosis

Acetaminophen in large doses is well-known as hepatotoxic, and early therapy with N-acetylcysteine is frequently life-saving. However, in later stages of acetaminophen poisoning, treatment with N-acetylcysteine is not always effective. Although some of the pathways of acetaminophen toxicity and the effect of N-acetylcysteine have been elucidated, in depth information on this process is still lacking. Hepatoma-derived HepG2 cultured cells were exposed to acetaminophen (5 and 10 mM), with or without N-acetylcysteine (5 mM), for 24 and 48 hr. For the assessment of oxidative damage, apoptosis and necrosis, we followed redox status, glutathione content, nuclear fragmentation, phosphatidylserine externalization and ultrastructural changes. Variations in Ca2+ level and number of mitochondrial dense granules were also studied. Acetaminophen treatment of HepG2 cells caused oxidative damage and apoptosis. Significant decrease of cellular redox potential and glutathione content were time- and concentration-dependent. The protective effect of N-acetylcysteine was expressed by an increase of intracellular glutathione and of the level of metabolic reduction of the redox indicator Alamar Blue. The apoptogenic effect of acetaminophen was assessed by flow cytometry of annexin V binding, nuclear hypodiploidity, intracellular Ca2+, as well as by ultrastructural examination. Beyond 24 hr of acetaminophen exposure, necrosis was also noticed. We conclude that acetaminophen-induced oxidative damage in HepG2 cultured cells can be prevented by exposure to N-acetylcysteine. However, apoptosis, either early or late, here demonstrated, is not avoided by exposure to N-acetylcysteine. N-Acetylcysteine did not prevent acetaminophen-induced plasma membrane asymmetry, nuclear damage, alterations of Ca2+ homeostasis and ultrastructural changes.     

Protective effect of a polysaccharide from Hizikia fusiformis against ethanol-induced cytotoxicity in IEC-6 cells

In the present study, we examined the signaling pathways related to the ethanol-protective effect of Hf-PS-1 in IEC-6 cells. Ethanol induced the death of IEC-6 cells in a dose-dependent manner, and pretreatment with Hf-PS-1 abrogated the ethanol toxicity. When we examined whether the effect of Hf-PS-1 on ethanol cytotoxicity was associated with insulin growth factor-I receptor signaling pathways, involving mitogen-activated protein kinase (MAPK), we found that ethanol treatment decreased the phosphorylation of Shc and the binding of Grb2 to Shc, and Hf-PS-1 pretreatment increased them. Ethanol treatment also induced the phosphorylation of JNK and ERK, whereas Hf-PS-1 pretreatment decreased JNK activation but not ERK activation. Using a JNK inhibitor (SP600125), we examined GSH levels to determine whether Hf-PS-1 pretreatment mi20 ght protect against ethanol-induced gastric intestinal damage by down-regulating JNK. Co-treatment with SP600125 and ethanol decreased GSH levels, indicating that JNK phosphorylation is a critical factor during ethanol-induced injury and that the effect of Hf-PS-1 occurs via JNK down-regulation. We have thus demonstrated the protective effect of Hf-PS-1 against ethanol-induced cellular damage. Therefore, Hf-PS-1 may be useful as a bio-functional food source to protect against ethanol-induced gastrointestinal injury.