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1.
Inhibition of mRNA processing, including splicing in the nucleus, is a potential anti-cancer candidate. To obtain mRNA processing inhibitors, we have screened for active constituents from spices. Ginger, clove, and cinnamon showed an inhibitory effect on mRNA processing in the nucleus. Two components in ginger, 6-gingerol and 6-shogaol, exhibited the inhibition of mRNA processing.  相似文献   

2.
Compounds from rhizomes of Zingiber officinale, commonly called ginger, have been purported to have anti-inflammatory actions. We have used an in vitro test system to test the anti-inflammatory activity of compounds isolated from ginger rhizome. U937 cells were differentiated and exposed to lipopolysaccharide (LPS) from Escherichia coli (1 microg/ml) in the presence or absence of organic extracts or standard compounds found in ginger (6-, 8-, 10-gingerol or 6-shogaol) for 24 h. Supernatants were collected and analyzed for the production of prostaglandin E(2) (PGE(2)) and tumor necrosis factor alpha (TNF-alpha) by standard ELISA assays. Predominant compounds in the organic extracts were identified as 6-, 8- 10-gingerols and 6-, 8-, 10-shogaols. Organic extracts or standards containing gingerols were not cytotoxic, while extracts or standards containing predominantly shogaols were cytotoxic at concentrations above 20 microg/ml. Crude organic extracts of ginger were capable of inhibiting LPS induced PGE(2) (IC(50)<0.1 microg/ml) production. However, extracts were not nearly as effective at inhibiting TNF-alpha (IC(50)>30 microg/ml). Thirty three fractions and subfractions, prepared by column chromatography, were analyzed for bioactivity. Extracts containing either predominantly gingerols or shogaols (identified by HPLC) were both highly active at inhibiting LPS-induced PGE(2) production (IC(50)<0.1 microg/ml), while extracts that contained unknown compounds were less effective (IC(50)<3.2 microg/ml). Extracts or standards containing predominantly gingerols were capable of inhibiting LPS-induced COX-2 expression while shogaol containing extracts had no effect on COX-2 expression. These data demonstrate that compounds found in ginger are capable of inhibiting PGE(2) production and that the compounds may act at several sites.  相似文献   

3.
Ishiguro K  Ando T  Watanabe O  Goto H 《FEBS letters》2008,582(23-24):3531-3536
6-Shogaol and 6-gingerol are ginger components with similar chemical structures. However, while 6-shogaol damages microtubules, 6-gingerol does not. We have investigated the molecular mechanism of 6-shogaol-induced microtubule damage and found that the action of 6-shogaol results from the structure of alpha,beta-unsaturated carbonyl compounds. alpha,beta-Unsaturated carbonyl compounds such as 6-shogaol react with sulfhydryl groups of cysteine residues in tubulin, and impair tubulin polymerization. The reaction with sulfhydryl groups depends on the chain length of alpha,beta-unsaturated carbonyl compounds. In addition, alpha,beta-unsaturated carbonyl compounds are more reactive with sulfhydryl groups in tubulin than in 2-mercaptoethanol, dithiothreitol, glutathione and papain, a cysteine protease.  相似文献   

4.
6-Gingerol, a major component of ginger, has antioxidant, anti-apoptotic, and anti-inflammatory activities. However, some dietary phytochemicals possess pro-oxidant effects as well, and the risk of adverse effects is increased by raising the use of doses. The aim of this study was to assess the genotoxic effects of 6-gingerol and to clarify the mechanisms, using human hepatoma G2 (HepG2) cells. Exposure of the cells to 6-gingerol caused significant increase of DNA migration in comet assay, increase of micronuclei frequencies at high concentrations at 20–80 and 20–40 μM, respectively. These results indicate that 6-gingerol caused DNA strand breaks and chromosome damage. To further elucidate the underlying mechanisms, we tested lysosomal membrane stability, mitochondrial membrane potential, the intracellular generation of reactive oxygen species (ROS) and reduced glutathione (GSH). In addition, the level of oxidative DNA damage was evaluated by immunocytochemical analysis on 8-hydroxydeoxyguanosine (8-OHdG). Results showed that lysosomal membrane stability was reduced after treatment by 6-gingerol (20–80 μM) for 40 min, mitochondrial membrane potential decreased after treatment for 50 min, GSH and ROS levels were significantly increased after treatment for 60 min. These suggest 6-gingerol induces genotoxicity probably by oxidative stress; lysosomal and mitochondrial damage were observed in 6-gingerol-induced toxicity.  相似文献   

5.
Using techniques previously employed to identify ginger constituents in fresh organically grown Hawaiian white and yellow ginger varieties, partially purified fractions derived from the silica gel column chromatography and HPLC of a methylene chloride extract of commercially processed dry ginger, Zingiber officinale Roscoe, Zingiberaceae, which demonstrated remarkable anti-inflammatory activity, were investigated by gas chromatography-mass spectrometry. In all, 115 compounds were identified, 88 with retention times (R(t)) >21 min and 27 with <21 min. Of those 88 compounds, 45 were previously reported by us from fresh ginger, 12 are cited elsewhere in the literature and the rest (31) are new: methyl [8]-paradol, methyl [6]-isogingerol, methyl [4]-shogaol, [6]-isoshogaol, two 6-hydroxy-[n]-shogaols (n=8 and 10), 6-dehydro-[6]-gingerol, three 5-methoxy-[n]-gingerols (n=4, 8 and 10), 3-acetoxy-[4]-gingerdiol, 5-acetoxy-[6]-gingerdiol (stereoisomer), diacetoxy-[8]-gingerdiol, methyl diacetoxy-[8]-gingerdiol, 6-(4'-hydroxy-3'-methoxyphenyl)-2-nonyl-2-hydroxytetrahydropyran, 3-acetoxydihydro-[6]-paradol methyl ether, 1-(4'-hydroxy-3'-methoxyphenyl)-2-nonadecen-1-one and its methyl ether derivative, 1,7-bis-(4'-hydroxy-3'-methoxyphenyl)-5-methoxyheptan-3-one, 1,7-bis-(4'-hydroxy-3'-methoxyphenyl)-3-hydroxy-5-acetoxyheptane, acetoxy-3-dihydrodemethoxy-[6]-shogaol, 5-acetoxy-3-deoxy-[6]-gingerol, 1-hydroxy-[6]-paradol, (2E)-geranial acetals of [4]- and [6]-gingerdiols, (2Z)-neral acetal of [6]-gingerdiol, acetaldehyde acetal of [6]-gingerdiol, 1-(4-hydroxy-3-methoxyphenyl)-2,4-dehydro-6-decanone and the cyclic methyl orthoesters of [6]- and [10]-gingerdiols. Of the 27 R(t)<21 min compounds, we had found 5 from fresh ginger, 20 others were found elsewhere in the literature, and two are new: 5-(4'-hydroxy-3'-methoxyphenyl)-pent-2-en-1-al and 5-(4'-hydroxy-3'-methoxyphenyl)-3-hydroxy-1-pentanal. Most of the short R(t) compounds are probably formed by thermal degradation during GC (which mimics cooking) and/or commercial drying. The concentrations of gingerols, the major constituents of fresh ginger, were reduced slightly in dry ginger, while the concentrations of shogaols, the major gingerol dehydration products, increased.  相似文献   

6.
《Life sciences》1994,54(19):PL321-PL326
A reductive metabolism of S-(+)-[6]-gingerol [1-(4'-hydroxy-3'-methoxyphenyl)-5-hydroxydecan-3-one], the major pungent principle of ginger, was investigated in vitro with phenobarbital-induced rat liver 10,000 x g supernatant containing the NADPH-generating system. The ethyl acetate-extractable products were isolated and two metabolites were identified as diastereomers of [6]-gingerdiol by gas chromatrography/mass spectrometry. The ratio of two isomers formed in the above reaction was about 1:5, suggesting the stereospecific reduction of S-(+)-[6]-gingerol by carbonyl reductase activity present in the postmitochondrial supernatant fraction of rat liver. The enzymic reduction of S-(+)-[6]-gingerol thus introduces the second asymmetric carbon center in the molecule with concomitant production of S,S- and R,S-isomers of [6]-gingerdiol in different proportions. This stereospecific reduction of [6]-gingerol may be relevant to the clinical use of the compound.  相似文献   

7.
Metabolism of [6]-gingerol in rats   总被引:3,自引:0,他引:3  
Nakazawa T  Ohsawa K 《Life sciences》2002,70(18):2165-2175
The metabolic fate of [6]-gingerol, one of the active constituents of Zingiber officinale Roscoe, was investigated using rats. The bile of rats orally administered [6]-gingerol was shown to contain a major metabolite (1) by HPLC analysis. Although the metabolites derived from [6]-gingerol were not detected in the urine, the ethyl acetate extract of the urine after enzymatic hydrolysis was shown to contain six minor metabolites (2-7). Their structures were determined to be (S)-[6]-gingerol-4'-O-beta-glucuronide (1), vanillic acid (2), ferulic acid (3), (S)-(+)-4-hydroxy-6-oxo-8-(4-hydroxy-3-methoxyphenyl) octanoic acid (4), 4-(4-hydroxy-3-methoxyphenyl)butanoic acid (5), 9-hydroxy [6]-gingerol (6) and (S)-(+)-[6]-gingerol (7) based on spectroscopic and chemical data. The total cumulative amount of 1 excreted in the bile and 2-7 in the urine during 60 h after the oral administration of [6]-gingerol were approximately 48% and 16% of the dose, respectively. The excretion of 2-7 in the urine decreased after gut sterilization. On the other hand, the incubations of [6]-gingerol with rat liver showed the presence of 9-hydroxy [6]-gingerol, gingerdiol (8), and (S)-[6]-gingerol-4'-O-beta-glucuronide (1). These findings suggest that the gut flora and enzymes in the liver play an important part in the metabolism of [6]-gingerol.  相似文献   

8.
[6]-Gingerol is an active component of ginger that shows antipyretic and anti-inflammation activities. To find a novel skin-whitening agent, the melanogeneis inhibitory effects and action mechanisms of [6]-gingerol were investigated. In the present study, the effects of [6]-gingerol on mushroom tyrosinase, tyrosinase activity, and melanin content were determined spectrophotometrically, and the expression of tyrosinase and related proteins in B16F10 murine melanoma cells was evaluated by Western blotting. Furthermore, a possible signaling pathway involved in [6]-gingerolmediated depigmentation was investigated by means of specific inhibitors. The results revealed that [6]-gingerol (25-100 μM) effectively suppresses murine tyrosinase activity and decreases the amount of melanin in a dose-dependent manner. Additionally, it also effectively decreased the intracellular reactive oxygen species (ROS) level in a dose-dependent pattern in the same dose range. Our results indicate that [6]-gingerol inhibits melanogenesis of B16F10 melanoma and can function as a good skinwhitening agent.  相似文献   

9.
A rapid high-performance liquid chromatography–mass spectrometry (HPLC–MS) method was developed and validated for simultaneous quantification of 6-gingerol, 8-gingerol, 10-gingerol and 6-shogaol in rat plasma after oral administration of ginger oleoresin. Plasma samples extracted with a liquid–liquid extraction procedure were separated on an Agilent Zorbax StableBond-C18 column (4.6 mm × 50 mm, 1.8 μm) and detected by MS with electrospray ionization interface in positive selective ion monitoring (SIM) mode. Calibration curves (1/x2 weighted) offered satisfactory linearity (r2 > 0.995) in a wide linear range (0.0104–13.0 μg/mL for 6-gingerol, 0.00357–4.46 μg/mL for 8-gingerol, 0.00920–11.5 μg/mL for 10-gingerol and 0.00738–9.22 μg/mL for 6-shogaol). The lower limit of quantification (LLOQ) was in a range of 3.57–10.4 ng/mL. The analytes and internal standard can be baseline separated within 6 min. Inter- and intra-day assay variation was less than 15%. This developed method was successfully applied to pharmacokinetic studies of ginger oleoresin after oral administration to rats. Glucuronide of 6-gingerol was determined after β-glucuronidase hydrolysis for more information, and the intestinal glucuronidation was further confirmed by comparison of plasma samples of hepatic portal vein and femoral vein.  相似文献   

10.
The rhizome of ginger (Zingiber officinale) is employed in Asian traditional medicine to treat mild forms of rheumatoid arthritis and fever. We have profiled ginger constituents for robust effects on proinflammatory signaling and cytokine expression in a validated assay using human whole blood. Independent of the stimulus used (LPS, PMA, anti-CD28 Ab, anti-CD3 Ab, and thapsigargin), ginger constituents potently and specifically inhibited IL-1β expression in monocytes/macrophages. Both the calcium-independent phospholipase A(2) (iPLA(2))-triggered maturation and the cytosolic phospholipase A(2) (cPLA(2))-dependent secretion of IL-1β from isolated human monocytes were inhibited. In a fluorescence-coupled PLA(2) assay, most major ginger phenylpropanoids directly inhibited i/cPLA(2) from U937 macrophages, but not hog pancreas secretory phospholipase A(2). The effects of the ginger constituents were additive and the potency comparable to the mechanism-based inhibitor bromoenol lactone for iPLA(2) and methyl arachidonyl fluorophosphonate for cPLA(2), with 10-gingerol/-shogaol being most effective. Furthermore, a ginger extract (2 μg/ml) and 10-shogaol (2 μM) potently inhibited the release of PGE(2) and thromboxane B2 (>50%) and partially also leukotriene B(4) in LPS-stimulated macrophages. Intriguingly, the total cellular arachidonic acid was increased 2- to 3-fold in U937 cells under all experimental conditions. Our data show that the concurrent inhibition of iPLA(2) and prostanoid production causes an accumulation of free intracellular arachidonic acid by disrupting the phospholipid deacylation-reacylation cycle. The inhibition of i/cPLA(2), the resulting attenuation of IL-1β secretion, and the simultaneous inhibition of prostanoid production by common ginger phenylpropanoids uncover a new anti-inflammatory molecular mechanism of dietary ginger that may be exploited therapeutically.  相似文献   

11.
12.
In this study, we demonstrated that the two ginger-derived components have a potent and unique pharmacological function in 3T3-L1 adipocytes via different mechanisms. Both pretreatment of 6-shogaol (6S) and 6-gingerol (6G) significantly inhibited the tumor necrosis factor-α (TNF-α) mediated downregulation of the adiponectin expression in 3T3-L1 adipocytes. Our study demonstrate that (1) 6S functions as a PPARγ agonist with its inhibitory mechanism due to the PPARγ transactivation, and (2) 6G is not a PPARγ agonist, but it is an effective inhibitor of TNF-α induced c-Jun-NH2-terminal kinase signaling activation and thus, its inhibitory mechanism is due to this inhibitory effect.  相似文献   

13.
6]-Gingerol inhibits metastasis of MDA-MB-231 human breast cancer cells   总被引:1,自引:0,他引:1  
Gingerol (Zingiber officinale Roscoe, Zingiberaceae) is one of the most frequently and heavily consumed dietary condiments throughout the world. The oleoresin from rhizomes of ginger contains [6]-gingerol (1-[4′-hydroxy-3′-methoxyphenyl]-5-hydroxy-3-decanone) and its homologs which are pungent ingredients that have been found to possess many interesting pharmacological and physiological activities, such as anti-inflammatory, antihepatotoxic and cardiotonic effects. However, the effects of [6]-gingerol on metastatic processes in breast cancer cells are not currently well known. Therefore, in this study, we examined the effects of [6]-gingerol on adhesion, invasion, motility, activity and the amount of MMP-2 or -9 in the MDA-MB-231 human breast cancer cell line. We cultured MDA-MB-231 cells in the presence of various concentrations of [6]-gingerol (0, 2.5, 5 and 10 μM). [6]-Gingerol had no effect on cell adhesion up to 5 μM, but resulted in a 16% reduction at 10 μM. Treatment of MDA-MB-231 cells with increasing concentrations of [6]-gingerol led to a concentration-dependent decrease in cell migration and motility. The activities of MMP-2 or MMP-9 in MDA-MB-231 cells were decreased by treatment with [6]-gingerol and occurred in a dose-dependent manner. The amount of MMP-2 protein was decreased in a dose-dependent manner, although there was no change in the MMP-9 protein levels following treatment with [6]-gingerol. MMP-2 and MMP-9 mRNA expression were decreased by [6]-gingerol treatment. In conclusion, we have shown that [6]-gingerol inhibits cell adhesion, invasion, motility and activities of MMP-2 and MMP-9 in MDA-MB-231 human breast cancer cell lines.  相似文献   

14.
Recently, increased attention has been directed towards medicinal extracts as potential new drug candidates for dementia. Ginger has long been used as an important ingredient in cooking and traditional herbal medicine. In particular, ginger has been known to have disease-modifying effects in Alzheimer's disease (AD). However, there is no evidence of which constituents of ginger exhibit therapeutic effects against AD. A growing number of experimental studies suggest that 6-shogaol, a bioactive component of ginger, may play an important role as a memory-enhancing and anti-oxidant agent against neurological diseases. 6-Shogaol has also recently been shown to have anti-neuroinflammatory effects in lipopolysaccharide (LPS)-treated astrocytes and animal models of Parkinson’s disease, LPS-induced inflammation and transient global ischemia. However, it is still unknown whether 6-shogaol has anti-inflammatory effects against oligomeric forms of the Aβ (AβO) in animal brains. Furthermore, the effects of 6-shogaol against memory impairment in dementia models are also yet to be investigated. In this study, we found that administration of 6-shogaol significantly reduced microgliosis and astrogliosis in intrahippocampal AβO-injected mice, ameliorated AβO and scopolamine-induced memory impairment, and elevated NGF levels and pre- and post-synaptic marker in the hippocampus. All these results suggest that 6-shogaol may play a role in inhibiting glial cell activation and reducing memory impairment in animal models of dementia.  相似文献   

15.
The extract of ginger (Zingiber officinale Roscoe) and its major pungent components, [6]-shogaol and [6]-gingerol, have been shown to have an anti-proliferative effect on several tumor cell lines. However, the anticancer activity of the ginger extract in pancreatic cancer is poorly understood. Here, we demonstrate that the ethanol-extracted materials of ginger suppressed cell cycle progression and consequently induced the death of human pancreatic cancer cell lines, including Panc-1 cells. The underlying mechanism entailed autosis, a recently characterized form of cell death, but not apoptosis or necroptosis. The extract markedly increased the LC3-II/LC3-I ratio, decreased SQSTM1/p62 protein, and enhanced vacuolization of the cytoplasm in Panc-1 cells. It activated AMPK, a positive regulator of autophagy, and inhibited mTOR, a negative autophagic regulator. The autophagy inhibitors 3-methyladenine and chloroquine partially prevented cell death. Morphologically, however, focal membrane rupture, nuclear shrinkage, focal swelling of the perinuclear space and electron dense mitochondria, which are unique morphological features of autosis, were observed. The extract enhanced reactive oxygen species (ROS) generation, and the antioxidant N-acetylcystein attenuated cell death. Our study revealed that daily intraperitoneal administration of the extract significantly prolonged survival (P = 0.0069) in a peritoneal dissemination model and suppressed tumor growth in an orthotopic model of pancreatic cancer (P < 0.01) without serious adverse effects. Although [6]-shogaol but not [6]-gingerol showed similar effects, chromatographic analyses suggested the presence of other constituent(s) as active substances. Together, these results show that ginger extract has potent anticancer activity against pancreatic cancer cells by inducing ROS-mediated autosis and warrants further investigation in order to develop an efficacious candidate drug.  相似文献   

16.
Natural and complementary therapies in conjunction with mainstream cancer care are steadily gaining popularity. Ginger extract (GE) confers significant health-promoting benefits owing to complex additive and/or synergistic interactions between its bioactive constituents. Recently, we showed that preservation of natural “milieu” confers superior anticancer activity on GE over its constituent phytochemicals, 6-gingerol (6G), 8-gingerol (8G), 10-gingerol (10G) and 6-shogaol (6S), through enterohepatic recirculation. Here we further evaluate and compare the effects of GE and its major bioactive constituents on cytochrome P450 (CYP) enzyme activity in human liver microsomes by monitoring metabolites of CYP-specific substrates using LC/MS/MS detection methods. Our data demonstrate that individual gingerols are potent inhibitors of CYP isozymes, whereas GE exhibits a much higher half-maximal inhibition value, indicating no possible herb-drug interactions. However, GE''s inhibition of CYP1A2 and CYP2C8 reflects additive interactions among the constituents. In addition, studies performed to evaluate transporter-mediated intestinal efflux using Caco-2 cells revealed that GE and its phenolics are not substrates of P-glycoprotein (Pgp). Intriguingly, however, 10G and 6S were not detected in the receiver compartment, indicating possible biotransformation across the Caco-2 monolayer. These data strengthen the notion that an interplay of complex interactions among ginger phytochemicals when fed as whole extract dictates its bioactivity highlighting the importance of consuming whole foods over single agents. Our study substantiates the need for an in-depth analysis of hepatic biotransformation events and distribution profiles of GE and its active phenolics for the design of safe regimens.  相似文献   

17.
The present study investigated the effects of the herbal medicine Dai-kenchu-to (DKCT) and its 4 individual ingredients on intestinal blood flow (IBF) in rats by laser Doppler flowmetry. Intraduodenal administration of DKCT (30, 100 and 300 mg/kg) increased IBF in a dose-dependent manner, whereas the mean arterial blood pressure was not affected. One of the ingredients in DKCT is dried ginger rhizome (150 mg/kg), whose main component is [6]-shogaol (2 mg/kg), both of which showed similar effects to those shown by DKCT, while the other ingredients in DKCT only slightly increased IBF or had no effect. The calcitonin gene-related peptide (CGRP) receptor antagonist, CGRP (8-37), completely abolished the hyperemia induced by DKCT, dried ginger rhizome and [6]-shogaol. However, the vasoactive intestinal polypeptide (VIP) receptor antagonist, [4-Cl-DPhe6, Leul7]-VIP, and atropine were less inhibitory than CGRP (8-37), and the substance P (SP) receptor antagonist, spantide, had no effect. The present study demonstrated that DKCT and one of its active components, [6]-shogaol, produced an increase in IBF which was mainly mediated by CGRP and suggests that DKCT may be useful in the treatment of intestinal ischemia-related diseases.  相似文献   

18.
[6]-Gingerol, a naturally occurring plant phenol, is one of the major components of fresh ginger (Zingiber officinale Roscoe, Zingiberaceae) and has diverse pharmacologic effects. Here, we describe its novel anti-oxidant, anti-apoptotic, and anti-inflammatory activities in vitro and in vivo. In vitro, pre-treatment with [6]-gingerol reduced UVB-induced intracellular reactive oxygen species levels, activation of caspase-3, -8, -9, and Fas expression. It also reduced UVB-induced expression and transactivation of COX-2. Translocation of NF-kappaB from cytosol to nucleus in HaCaT cells was inhibited by [6]-gingerol via suppression of IkappaBalpha phosphorylation (ser-32). Examination by EMSAs and immunohistochemistry showed that topical application of [6]-gingerol (30 microM) prior to UVB irradiation (5 kJ/m(2)) of hairless mice, also inhibited the induction of COX-2 mRNA and protein, as well as NF-kappaB translocation. These results suggest that [6]-gingerol could be an effective therapeutic agent providing protection against UVB-induced skin disorders.  相似文献   

19.

Introduction

The aim of the study was to estimate potential availability of essential oil in some brands of herbal products.

Methods

A comparison was performed on the basis of the essential oil yield in the unprocessed raw materials such as leaves of peppermint and lemon balm and inflorescence of chamomile as well as herbal tea bags and in dietary supplements. The yield of essential oil was determined by distillation. Essential oil was analyzed by GC-FID and GC-MS.

Results

It was found that the average potential availability of essential oils in the products such as dietary supplements for the doses recommended by the producers is lower than in the corresponding tea infusions: for peppermint formulations approximately 6-fold lower, for the formulations with lemon balm about 4-fold lower, and for the chamomile preparations about 3-fold lower. It was found that essential oils extracted from herbal teas have a similar chemical profile with characteristic deviations in the amount of individual components, which arise from the origin of the raw material.

Discussion

In contrast to homogenous pharmaceutical herbal mixtures consistent with, the Pharmacopoeia requirements, herbal teas (available in grocery stores) and dietary supplements are often out of control in terms of the yield and composition of the essential oil, which is primarily responsible for the health benefits and aromatic qualities of these products. Analysis of the composition of the dietary supplements showed that they contain on average significantly lower amounts of plant material compared to the herbal teas.  相似文献   

20.
We isolated the highly potent attachment-inhibitors (three times more active than standard CuSO4 in the blue mussel assay), trans-6-, 8-, and 10-shogaols, from a hexane extract of the roots of ginger, Zingiber officinale Roscoe. Trans-8-shogaol showed the highest antifouling activity comparable with that of tributyltin fluoride (TBTF), which is recognized as one of the most effective antifouling agents, in the conventional submerged assay.  相似文献   

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