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At least 19 recordsLinked to original sources
PubMed2002

Isolation of scopoletin from leaves of Hevea brasiliensis and the effect of scopoletin on pathogens of H. brasiliensis.

Scopoletin (7-hydroxy-6-methoxy coumarin) which inhibited the conidial germination of Corynespora cassiicola was isolated from the uninfected mature leaves of Hevea brasiliensis. Scopoletin was not detected in uninfected immature rubber leaves. The immature leaves produced scopoletin after being infected with C. cassiicola. The concentration of scopoletin in infected leaves was higher than in uninfected mature leaves. Scopoletin also inhibited the conidial germination of other fungal pathogens of H. brasiliensis. However, no correlation was observed between scopoletin accumulation and clonal resistance.

Antifungal Agents↗
PubMed1995

Transient and steady-state kinetics of the oxidation of scopoletin by horseradish peroxidase compounds I, II and III in the presence of NADH.

Scopoletin, a naturally occurring fluorescent component of some plants and a proven plant growth inhibitor, is a known reactant with peroxidase. However, the kinetics of the elementary steps of the reaction have never been investigated, nor has the quantitative effect of interfering substances ever been explored in detail, despite the fact that scopoletin is widely used in a peroxidase assay for H2O2. In this work, we employed both transient-state and steady-state methods to determine the second-order rate constants for the oxidation of scopoletin by the horseradish peroxidase (HRP) intermediate compounds I and II: (3.7 +/- 0.1) x 10(6) M-1 s-1 and (8.5 +/- 0.5) x 10(5) M-1 s-1 at 20 degrees C, pH 6.0 and ionic strength of 0.1 M. We investigated the possible inhibitory effect of NADH on the reaction of scopoletin with HRP and also the effect of scopoletin on the NADH reaction. In the presence of NADH the rate constant for the reaction between HRP-I and scopoletin decreased slightly to (2.8 +/- 0.1) x 10(6) M-1 s-1. Thus, although NADH is also a peroxidase substrate, it cannot compete effectively for the oxidized forms of the enzyme. On the other hand, scopoletin stimulates the oxidation of NADH by the HRP/H2O2 system, apparently by forming a phenoxyl radical which then oxidizes NADH to NAD. radicals. We present spectral evidence showing that in the aerobic reaction between HRP and NADH at pH 7.0 (without exogenously added H2O2) HRP-II is the dominant enzyme intermediate with HRP-III also detectable. Addition of scopoletin to the HRP/NADH system leads to a biphasic reaction in which HRP-II and HRP-III disappear. The rate constants for both phases are linearly dependent on scopoletin concentration. We attribute the faster phase to the HRP-II reaction with scopoletin with a rate constant of (6.2 +/- 0.1) x 10(5) M-1 s-1 and the slower phase to the HRP-III reaction with scopoletin with rate constant (5.0 +/- 0.4) x 10(4) M-1 s-1. Our present work not only provides rate constants for the oxidation of scopoletin by HRP-I, II and III but also elucidates the interactions that possibly occur physiologically during NADH oxidation in the presence of scopoletin.

Horseradish Peroxidase↗
PubMed2000

Scopoletin uptake from culture medium and accumulation in the vacuoles after conversion to scopolin in 2,4-D-treated tobacco cells.

Tobacco (Nicotiana tabacum L. Bright Yellow) T-13 cell line has the ability to produce scopoletin endogenously and release some of it into the culture medium. We investigated the mechanism of scopoletin uptake following treatment of a tobacco culture with 2,4-dichlorophenoxyacetic acid (2,4-D). Addition of [14C]-labeled scopoletin showed that scopoletin was taken up by 2,4-D-treated cells and converted to scopolin, a 7-O-glucoside of scopoletin. This uptake of scopoletin began 6 h after 2,4-D addition to the cells. Experiments using several inhibitors showed that this uptake was energy-dependent. The phenomenon of 2,4-D-stimulated uptake was observed only for 7-hydroxycoumarins, such as scopoletin, umbelliferone and esculetin. To further investigate the site for scopoletin accumulation, we separated the vacuoles from T-13 cells and quantified the coumarin contents in this fraction. Most of the scopoletin in the vacuoles was present as glucoconjugate, scopolin. Moreover, glucosylation activity was absent from isolated vacuoles and, therefore, is likely to be located in the cytosol. Therefore, we can state that 2,4-D treatment of tobacco cells stimulated scopoletin uptake. The scopoletin was converted into scopolin in the cytoplasm, and then transferred into the vacuoles.

Journal Article↗
PubMed2001

Effect of scopoletin on PC3 cell proliferation and apoptosis.

AIM: To investigate the effect of scopoletin on cell proliferation and apoptosis of PC3 cells. METHODS: Cell growth curve, MTT assay, and acid phosphatase activity (ACP) were used to determine cell proliferation. Coomassie brilliant blue assay was used to measure the content of protein in cells. Light microscope, transmission electronmicroscope, and fluorescence microscope were used to observe scopoletin-induced morphological changes. Apoptosis rate and cell cycle distribution were determined by flow cytometry. RESULTS: The IC50 of scopoletin for inhibiting PC3, PAA, and Hela cell proliferation was (157 +/- 25), (154 +/- 51), and (294 +/- 100) mg/L, respectively. Scopoletin induced a marked time- and concentration-dependent inhibition of PC3 cell proliferation. Scopoletin reduced the protein content and decreased the ACP level in PC3 cells in a concentration-dependent manner. Cells treated by scopoletin showed typical morphologic changes of apoptosis by light microscope, fluorescence microscope, and transmission electronmicroscope. Apoptosis rate was 0.3 %, 2.1 %, 9.3 % and 35 % for scopoletin 0, 100, 200, and 400 mg/L, respectively, and cells in G2 phase decreased markedly after being treated with scopoletin. CONCLUSION: Scopoletin inhibited PC3 proliferation by inducing apoptosis of PC3 cells.

Apoptosis↗
PubMed2006

Use of scopoletin to inhibit the production of inflammatory cytokines through inhibition of the IkappaB/NF-kappaB signal cascade in the human mast cell line HMC-1.

Scopoletin (6-methoxy-7-hydroxycoumarin) is a coumarin compound and a pharmacologically active agent that has been isolated from several plant species. However, as yet there is no clear explanation of how scopoletin affects the production of inflammatory cytokine. We therefore used cells from the human mast cell line (HMC-1) to investigate this effect. Scopoletin significantly and dose-dependently inhibits the way in which phorbol 12-myristate 13-acetate (PMA) plus A23187 induces the production of inflammatory cytokines such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-8 (P<0.05). The maximal rates at which scopoletin (0.2 mM) inhibited the production of TNF-alpha, IL-6, and IL-8 were 41.6%+/-4.2%, 71.9%+/-2.5%, and 43.0%+/-5.7%, respectively. In activated HMC-1 cells, the expression level of nuclear factor (NF)-kappaB/Rel A protein was increased in the nucleus whereas the level of NF-kappaB/Rel A in nucleus was decreased by treatment with scopoletin. Scopoletin decreased PMA plus A23187-induced luciferase activity. Scopoletin also inhibits IkappaBalpha phosphorylation and degradation in cytoplasm. These results indicate that scopoletin has a potential regulatory effect on inflammatory reactions that are mediated by mast cells.

Anti-Inflammatory Agents↗
PubMed2004

Over-expression of a scopoletin glucosyltransferase in Nicotiana tabacum leads to precocious lesion formation during the hypersensitive response to tobacco mosaic virus but does not affect virus resistance.

Nicotiana tabacum Togt encodes a scopoletin glucosyltransferase (UDPglucose:scopoletin O -beta-D-glucosyltrans- ferase, EC 2.4.1.128) known to act in vitro on many different substrates including the 6-methoxy-7-hydroxy- coumarin scopoletin. This phenolic compound accumulates in vast amounts, essentially in its glucosylated form scopolin, in tobacco during the hypersensitive response (HR) to tobacco mosaic virus (TMV). To identify the physiological role of this pathogen-inducible UDP-Glc glucosyltransferase (UGT), we generated TOGT over-expressing transgenic plants. Although no endogenous scopoletin or scopolin could be detected before infection, the accumulation of both the aglycone and the glucoside was found to be 2-fold higher in transgenic plants after inoculation with TMV than in wild-type plants. Scopoletin UGT activity in plants over-expressing Togt was significantly higher during the HR than in control plants. This up-regulated activity was associated with a strong increase of the bright blue fluorescence surrounding the HR-necrotic lesions under UV light, which is known to correlate with scopoletin and scopolin abundance. Necrosis appeared sooner in transgenic plants and lesions developed faster, suggesting an accelerated HR. Unexpectedly, the viral content in each lesion was not significantly different in transgenic and in wild-type plants. These results are discussed in relation to the role of TOGT as the major UDP-Glc: scopoletin glucosyltransferase and to the importance of scopoletin accumulation during the HR.

Coumarins↗
PubMed2002

Downregulation of a pathogen-responsive tobacco UDP-Glc:phenylpropanoid glucosyltransferase reduces scopoletin glucoside accumulation, enhances oxidative stress, and weakens virus resistance.

Plant UDP-Glc:phenylpropanoid glucosyltransferases (UGTs) catalyze the transfer of Glc from UDP-Glc to numerous substrates and regulate the activity of compounds that play important roles in plant defense against pathogens. We previously characterized two tobacco salicylic acid- and pathogen-inducible UGTs (TOGTs) that act very efficiently on the hydroxycoumarin scopoletin and on hydroxycinnamic acids. To identify the physiological roles of these UGTs in plant defense, we generated TOGT-depleted tobacco plants by antisense expression. After inoculation with Tobacco mosaic virus (TMV), TOGT-inhibited plants exhibited a significant decrease in the glucoside form of scopoletin (scopolin) and a decrease in scopoletin UGT activity. Unexpectedly, free scopoletin levels also were reduced in TOGT antisense lines. Scopolin and scopoletin reduction in TOGT-depleted lines resulted in a strong decrease of the blue fluorescence in cells surrounding TMV lesions and was associated with weakened resistance to infection with TMV. Consistent with the proposed role of scopoletin as a reactive oxygen intermediate (ROI) scavenger, TMV also triggered a more sustained ROI accumulation in TOGT-downregulated lines. Our results demonstrate the involvement of TOGT in scopoletin glucosylation in planta and provide evidence of the crucial role of a UGT in plant defense responses. We propose that TOGT-mediated glucosylation is required for scopoletin accumulation in cells surrounding TMV lesions, where this compound could both exert a direct antiviral effect and participate in ROI buffering.

Chlorogenic Acid↗
PubMed2005

Scopoletin induces apoptosis in human promyeloleukemic cells, accompanied by activations of nuclear factor kappaB and caspase-3.

Scopoletin (6-methoxy-7-hydroxycoumarin) is a phenolic coumarin and a member of the phytoalexins. In this study we investigated whether scopoletin caused apoptosis in HL-60 promyelocytic cells and, if so, by what mechanisms. We found that scopoletin induced apoptosis as confirmed by a characteristic ladder pattern of discontinuous DNA fragments in a dose-dependent manner. The signal cascade activated by scopoletin included the heterodimeric redox-sensitive transcription factor NF-kappaB, which exhibited an upregulation of nuclear factor-kappa B (NF-kappaB) translocation to the nucleus by increase of IkappaBalpha degradation. In addition, scopoletin activated caspase-3 as was evidenced by both the proteolytic cleavage of the proenzyme and increased protease activity. Activation of caspase-3 resulted in the cleavage of 116 kDa poly(ADP-ribose) polymerase (PARP) to 85 kDa cleavage product in time-and dose-dependent fashions. Prior treatment of the cells with pyrrolidine dithiocarbamate, a potent inhibitor of NF-kappaB activation, or Ac-DEVD-CHO, a specific caspase-3 inhibitor, prevented scopoletin-induced caspase-3 activation, PARP cleavage, and finally DNA fragmentation. Taken together, these results suggest that scopoletin induces NF-kappaB activation, which, in turn, causes activation of caspase-3, degradation of PARP, and eventually leads to apoptotic cell death in HL-60 cells.

Analysis of Variance↗
PubMed2006

Comparative immunomodulatory effect of scopoletin on tumoral and normal lymphocytes.

Some coumarins possess enhancing effects on lymphocyte mitogen responsiveness. In this investigation, the activity of scopoletin, a coumarin that has been isolated from different plants and in this case specifically from T. cordata Mill., was evaluated. For this purpose, normal T lymphocytes and a hyperproliferative T lymphoma cell line were used. Scopoletin was found to exert a dual action on tumoral lymphocytes exhibiting both a cytostatic and a cytotoxic effect. These effects varied with the concentrations analysed and the time of cell incubation (EC(50): 251+/-15 microg/ml) and were associated to the induction of apoptosis. Scopoletin induced cell proliferation on normal T lymphocytes (Proliferation stimulation index: 1 microg/ml scopoletin: 1.26+/-0.1; 10 microg/ml scopoletin: 3+/-0.25; 100 microg/ml scopoletin: 1.86+/-0.08); this stimulatory action was found to be due to the interaction with kinase C (PKC) protein. These results indicate that scopoletin could be a potential antitumoral compound to be used for cancer treatment.

Animals↗
PubMedDate not supplied

Combination of extractive solvent addition and immobilization culture for continuous production of scopoletin by tobacco cells.

Extractive solvent addition was combined with immobilization cultures of Nicotiana tabacum cells to produce scopoletin. Using various solvents, the partition coefficients of scopoletin between the solvent and water phases and the solvent toxicity to the cell viability were investigated. The effect of the solvent addition on cell growth and scopoletin production was elucidated in the suspension cultures. Coconut oil, one of the natural vegetable oils, was selected as the most suitable extractive solvent. The cells were immobilized in the calcium alginate gel bead coated with a cell-free gel film and then the batch cultures with the addition of various volumes of the coconut oil were performed. The total scopoletin production increased with the solvent volume according to the amount of scopoletin transferred from the medium to the solvent. The maximum productivity obtained in the batch immobilization cultures was about 16 times larger than that in the suspension culture without solvent. A continuous production system, in which the fresh solvent was supplied to the culture system and the solvent containing scopoletin was recovered from it, was constructed. The integrated scopoletin production in the effluent oil attained 2.21 mg/gDCW for 30 days at 100 cm(3)/day without cell leakage.

Scopoletin↗
PubMed1999

Comparative effects of scopoletin and cyanide on rat brain, 1: histopathology.

Four week old male Wistar rats were used to study the effects of scopoletin and cyanide on the histopathology of rat brain. The rats were divided into a control and three experimental groups (2-4) and fed rations containing 0.07 microg scopoletin/100 g, 0.07 microg scopoletin + 1.8 mg cyanide/100 g and 1.8 mg cyanide/100 g, respectively. These levels of scopoletin and cyanide corresponded to levels found in a processed cassava diet. The first group was fed the same ration as the others but without scopoletin and cyanide. The rats were fed these rations for twelve months. Rats from each group were sacrificed at the third, sixth, ninth and twelfth months; the relative brain weight of the rats (% of body weight) and histology of their brains were studied. The lipid peroxide levels of the rat brains were also studied at the twelfth month. The results showed that the relative brain weights of the rats fed scopoletin + cyanide were significantly (p<0.05) less than that of the control from the third month. There were no significant changes in the lipid peroxide levels of the rat brains in the various groups. Histological examination of the brains of the rats suggested that scopoletin is involved in the pathogenesis of the neuropathy seen in cassava consuming populations.

Animals↗
PubMedDate not supplied

Comparative effects of scopoletin and aflatoxin B1 on bovine hepatic mitochondrial respiration in vitro.

A comparative study of the in vitro effects of the coumarin compounds, scopoletin and aflatoxin B1 (AFB1), on bovine (Bos indicus) hepatic mitochondrial respiration was carried out polarographically, using isocitrate -NAD+ (3 - site), succinate (2 - site), and reduced cytochrome c (1 - site), as respiratory substrates. Both scopoletin and AFB1 elicited a substrate--dependent stimulation or inhibition of the mitochondrial states 4 and 3 respiration. The results suggest that AFB1 has a higher tendency to inhibit the mitochondrial respiration than scopoletin, while scopoletin showed higher uncoupling effects than AFB1. The effects of scopoletin and AFB1 on mitochondria were more pronounced on the electron transport than on phosphorylation reaction. The extent (3-35%) of AFB1 induced inhibition of bovine mitochondrial respiration observed in this study, was appreciably lower than the values indicated in other animal species (rats and guinea fowls) reported in previous studies using equivalent concentrations of the toxin. These results were discussed in terms of the susceptibility of the animal species to the toxic effects of scopoletin and AFB1.

Aflatoxin B1↗
PubMed2001

Plant hormone regulation on scopoletin metabolism from culture medium into tobacco cells.

Tobacco (Nicotiana tabacum L. Bright Yellow) T-13 cell line has an ability for production of scopoletin. In this cell culture, scopoletin is taken up from culture medium and accumulated in vacuoles after conversion to scopolin when cells are treated with 2,4-dichlorophenoxyacetic acid (2,4-D) (Taguchi et al. (2000)). To clarify the effect of 2,4-D on tobacco cells, its interaction with several other plant hormones was investigated. Other auxins also stimulated the uptake in the same manner as 2,4-D did, although higher concentrations were required than that of 2,4-D. When p-chlorophenoxyisobutyric acid (PCIB), an antiauxin, was added to the cell culture before 2,4-D, it inhibited 2,4-D-stimulated scopoletin uptake. This result suggests that the stimulation of scopoletin uptake was one of the auxin effects on tobacco cells. Among other classes of plant hormones that were tested, only salicylic acid stimulated the uptake. When these hormones were added to the cell cultures before 2,4-D, methyl jasmonate and kinetin reduced scopoletin uptake. These results suggest that this scopoletin uptake by tobacco cells is regulated by the interaction between different plant hormones.

Journal Article↗
PubMed2002

Scopoletin expression in elicitor-treated and tobacco mosaic virus-infected tobacco plants.

Localized acquired resistance (LAR) characterizes a narrow zone of living cells expressing strong defense responses and surrounding cells undergoing a hypersensitive response (HR). In Samsun NN tobacco plants, tissues undergoing tobacco mosaic virus-induced or elicitor-induced LAR exhibit a strong blue fluorescence under UV light. We have shown that scopoletin and its glucoside, scopolin, accounted for the fluorescence: (1) both compounds were identified after extraction and purification by thin layer and high performance liquid chromatography; (2) there was a strict correlation between the occurrence of fluorescence and accumulation of high amounts of scopoletin; and (3) infiltration of commercial scopoletin caused a similar fluorescence to that occurring in LAR tissues. There was a 20-fold increase in scopoletin levels in LAR tissues compared to tissues treated with a non-HR dose of elicitor, while PR1 protein accumulated in similar amounts in both types of tissues. Scopoletin was able to suppress the elicitor-induced HR only when co-infiltrated with very low HR-dose of elicitor. These two observations suggested that, although scopoletin alone would not be able to control the development of the HR through its known antioxidant activity, it may nevertheless participate to such function of LAR tissues in combination with other antioxidant molecules.

Journal Article↗
PubMed1986

The metabolism of sunflower phytoalexins ayapin and scopoletin: plant-fungus interactions.

The coumarin phytoalexins ayapin and scopoletin accumulate in longitudinal stem sections of sunflower (Helianthus annuus L., Compositae) following inoculation with fungi both pathogenic (Alternaria helianthi) and nonpathogenic (Helminthosporium carbonum) to this plant. Both compounds were induced more rapidly, and they attained higher levels in tissue inoculated with the heterologous pathogen H. carbonum as compared with the sunflower pathogen A. helianthi. Similarly, scopoletin and ayapin accumulated to comparatively low concentrations following inoculation with a second sunflower pathogen, Phoma macdonaldii. Scopoletin was biosynthesized de novo following inoculation, although levels of its glucoside scopolin exceeded those of the aglucone in both infected and control tissues. Both scopoletin and scopolin were routinely detected in trace amounts in uninoculated tissue. In contrast, ayapin was not detected as a component of uninfected plants. When [(14)C]scopoletin was supplied to induced sunflower stem sections about 36% of the recovered radioactivity was in the form of ayapin. In vitro studies demonstrated that A. helianthi possessed the ability to rapidly degrade both scopoletin and ayapin, whereas H. carbonum was much less efficient in these traits. The differential degradation of these compounds by phytopathogenic fungi which do not attack sunflower is also discussed.

Journal Article↗
PubMed2006

Evaluation of the antithyroid, antioxidative and antihyperglycemic activity of scopoletin from Aegle marmelos leaves in hyperthyroid rats.

Scopoletin (7-hydroxy-6-methoxy coumarin) was isolated from the leaves of Aegle marmelos and evaluated for its potential to regulate hyperthyroidism, lipid peroxidation and hyperglycemia in levo-thyroxine-induced hyperthyroid rats. Scopoletin (1.00 mg/kg, p.o.) administered daily for 7 days to levo-thyroxine-treated animals decreased the levels of serum thyroid hormones and glucose as well as hepatic glucose-6-phosphatase activity, demonstrating its potential to regulate hyperthyroidism and hyperglycemia. Scopoletin also inhibited hepatic lipid peroxidation and increased the activity of antioxidants, superoxide dismutase and catalase. Compared with the standard antithyroid drug, propylthiouracil, scopoletin exhibited a superior therapeutic activity, since unlike propylthiouracil, it also inhibited hepatic lipid peroxidation. These findings indicate that scopoletin has the potential to inhibit thyroid function and hyperglycemia without hepatotoxicity.

Aegle↗
PubMed2001

Intracellular calcium mobilization as a target for the spasmolytic action of scopoletin.

The coumarin scopoletin was isolated in a pure form from the roots of Brunfelsia hopeana Benth. (Solanaceae). In isolated rat aortic rings, scopoletin (26-520 microM) inhibited to approximately the same extent the contractions induced by a variety of substances, including phenylephrine, potassium chloride, serotonin and PGF(2) (alpha). The effect of the coumarin on phenylephrine-induced contractions was not affected by endothelium removal or NO-synthase blockade by L-NAME (100 microM). Scopoletin (78 - 590 microM) antagonized in a concentration-dependent manner (IC(50) = 300 +/- 20 microM, n = 5), transient contractions in Ca(2+)-free media induced by noradrenaline, but not those induced by caffeine. Also, scopoletin did not interfere with the refilling of noradrenaline-sensitive intracellular calcium stores. It is suggested that the non-specific spasmolytic action of scopoletin can be attributed, at least in part, to its ability to inhibit the intracellular calcium mobilization from the noradrenaline-sensitive stores.

Animals↗
PubMed2005

Hypouricemic action of scopoletin arising from xanthine oxidase inhibition and uricosuric activity.

Scopoletin exhibited an immediate and dose-dependent hypouricemic effect after intraperitoneal administration (50, 100, 200 mg/kg) in hyperuricemic mice induced by potassium oxonate; however, it did not affect the serum uric acid level in normal mice at the tested doses. For exploring the involved mechanisms of action of scopoletin, potential inhibitory effects on xanthine oxidase and possible uricosuric effects were investigated. Scopoletin (50, 100, 200 mg/kg) significantly inhibited the activity of xanthine oxidase in liver homogenates of hyperuricemic mice although it only showed a relatively weak, albeit competitive-type, inhibition of xanthine oxidase in a commercial assay. Furthermore, a potent uricosuric effect of scopoletin (100, 200 mg/kg) was ascertained. These results demonstrated for the first time that scopoletin exhibits, hypouricemic activities through decreasing uric acid production and as well as a uricosuric mechanism.

Animals↗