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Isopimpinellin

About: Isopimpinellin is a(n) research topic. Over the lifetime, 227 publication(s) have been published within this topic receiving 4740 citation(s). The topic is also known as: 5,8-Dimethoxypsoralen & 5,8-Dimethoxypsoralene.


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Journal ArticleDOI
Abstract: A linear furocoumarin phytoalexin response was observed in stressed celery (Apium graveolens). Heretofore, linear furocoumarins found in diseased c

139 citations

Journal ArticleDOI
Abstract: Dark-grown cell suspension cultures of parsley, Petroselinum hortense, produce furanocoumarins after treatment with elicitor preparations of either Phytophthora megasperma f.sp. glycinea (Pmg elicitor) or Alternaria carthami Chowdhury (Ac elicitor). The linear furanocoumarins, psoralen and xanthotoxin, and the benzodipyrandione, graveolone, are the major products synthesized in response to Pmg elicitor, besides small amounts of the furanocomarin bergapten. Treatment with Ac elicitor induces predominantly the formation of bergapten and the furanocoumarin isopimpinellin, as well as small amounts of graveolone. While Pmg elicitor leads to cell death within a few days, cell mass increased for at least 6 days after treatment with Ac elicitor. Brefeldin A, a phytotoxin produced by A. carthami, inhibits growth of parsley cell suspension cultures considerably at a concentration of 0.01 mM and growth of the cells ceased at a concentration of 0.1 mM toxin. Concomitantly, furanocoumarin biosynthesis was suppressed in our system by a concentration of brefeldin A within 0.01–0.1 mM.

135 citations

Journal ArticleDOI
TL;DR: The augmentation of lymphocyte proliferation was closely correlated to an increase in the number of lymphocytes including CD8+ T cells and activated PBMC, whereas elevation of IFN-γ secretion was due to the activated CD8- T cells.
Abstract: Carrots, celery, coriander, fennel and parsley of the Umbelliferae family have been used as common vegetables and spices in many different cultures of the world. In this study, we evaluated the immunomodulatory activities of coumarins and flavonoids obtained from the above foods on human peripheral blood mononuclear cells (PBMC). Studies were conducted on lymphocyte transformation, ELISA assay and flow cytometry. Results provided the evidence of a health-modulating effect of these vegetables and spices which possessed a direct role in immunomodulatory function. Some of non-nutritional constituents of these foods such as coumarins and flavonoids also exhibited a similar immunomodulatory activity. At non-cytotoxic concentrations, the above phytoconstituents exhibited three types of immunomodulation including type 1 of PHA, ConA and quercetin (increased lymphocyte activation and IFN-γ secretion); type 2 of isopimpinellin (enhanced lymphocyte activation) and type 3 of rutin, bergapten and xanthotoxin (elevated IFN-γ secretion). The augmentation of lymphocyte proliferation was closely correlated to an increase in the number of lymphocyte cells including CD8⁺ T cells and activated PBMC, whereas elevation of IFN-γ secretion was due to the activated CD8⁺ T cells.

92 citations

Journal ArticleDOI
TL;DR: The results suggest that the coumarin-type compounds in particular interact with the active sites of Cyp2a-5 and CYP2A6, and the active Sites are structurally different, since a number of compounds inhibited mouse, but not human COH activity.
Abstract: Coumarin is 7-hydroxylated by the P450 isoform Cyp2a-5 in mice and CYP2A6 in humans. Various drugs, endogenous substances, plant substances and carcinogens, altogether about 90 chemicals, were evaluated as possible inhibitors of coumarin 7-hydroxylase (COH) activity in mouse microsomes. The effects of selected compounds on COH activity in human liver microsomes were also tested. The furanocoumarin derivatives methoxsalen (8-methoxypsoralen) and psoralen proved to be the most potent inhibitors of mouse COH activity (IC50 values 1.0 and 3.1 microM, respectively). The furanocoumarins bergapten (5-methoxypsoralen), isopimpinellin (5,8-dimethoxypsoralen), imperatorin and sphondin also effectively inhibited mouse COH activity (IC50 values 19-40 microM). Methoxsalen, isopimpinellin and metyrapone were also inhibitors in mice in vivo. Methoxsalen was a potent inhibitor of COH activity also in human liver microsomes, (IC50 value 5.4 microM), whereas bergapten, isopimpinellin and imperatorin had no effect. The imidazole antimycotic miconazole was a potent but non-specific inhibitor of COH activity. Several known substrates and inhibitors of members in the CYP1A, CYP2B, CYP2C, CYP2D and CYP3A subfamilies were poor inhibitors of COH activity. These results suggest that (i) the coumarin-type compounds in particular interact with the active sites of Cyp2a-5 and CYP2A6, and (ii) the active sites of Cyp2a-5 and CYP2A6 are structurally different, since a number of compounds inhibited mouse, but not human COH activity.

91 citations

Journal ArticleDOI
TL;DR: The role of P450 1a1 and 1b1 in the metabolic activation of DMBA in mouse epidermis is demonstrated and provides a mechanistic explanation for the differential effects of naturally occurring furanocoumarins (and 7,8-BF) on polycyclic aromatic hydrocarbon skin carcinogenesis.
Abstract: The current study was designed to determine the mechanistic basis for differences in the effects of naturally occurring furanocoumarins on skin tumor initiation by 7,12-dimethylbenz[a]anthracene (DMBA). Female SENCAR mice were pretreated topically with bergamottin, imperatorin, or isopimpinellin (100-3200 nmol), 7,8-benzoflavone (7,8-BF, 5-40 nmol, a known inhibitor of DMBA skin carcinogenesis in mice), or acetone (vehicle control) 5 min prior to topical treatment with DMBA (10 nmol). Imperatorin, isopimpinellin, and 7,8-BF, but not bergamottin, significantly blocked total DMBA-DNA adduct formation. HPLC analysis of DNA adducts revealed that bergamottin preferentially inhibited formation of anti-DMBA diol-epoxide (DMBADE) derived DNA adducts, imperatorin, and isopimpinellin inhibited both anti- and syn- derived adducts, whereas 7,8-BF showed some selectivity for reduction of syn-DMBADE-DNA adducts. Mouse embryo fibroblast C3H/10T1/2 (10T1/2) cells, and mouse hepatoma-derived 1c1c7 (Hepa-1) cells, which preferentially express P450 1b1 and P450 1a1, respectively, were co-incubated with 2 microM bergamottin, imperatorin, isopimpinellin, and 7,8-BF, and with DMBA (2 microM). Hepa-1 cells (P450 1a1) formed mainly anti-DMBADE-DNA adducts. In contrast, 10T1/2 cells (P450 1b1) formed mainly syn-DMBADE-DNA adducts. Bergamottin inhibited DMBA metabolism to DMBA-3,4-diol and blocked DNA adduct formation in Hepa-1 cells, but had little effect in 10T1/2 cells. In contrast, 7,8-BF completely blocked DMBA metabolism and DNA adduct formation in 10T1/2 cells, but had little effect in Hepa-1 cells. Imperatorin and isopimpinellin inhibited DMBA bioactivation in both cell lines. These results indicate that bergamottin is a more selective inhibitor of P450 1a1 and overall a less effective inhibitor of the metabolic activation of DMBA in mouse epidermis. In contrast, imperatorin, isopimpinellin, and especially 7,8-BF, which block metabolic activation of DMBA in mouse epidermis, appear more selective for P450 1b1. On the basis of our studies using 10T1/2 cells and Hepa-1 cells, it appears that P450 1a1 is primarily responsible for converting DMBA-3,4-diol to anti-DMBADE, whereas P450 1b1 is primarily responsible for converting DMBA-3,4-diol to syn-DMBADE. These data demonstrate the role of P450 1a1 and 1b1 in the metabolic activation of DMBA in mouse epidermis and provide a mechanistic explanation for the differential effects of naturally occurring furanocoumarins (and 7,8-BF) on polycyclic aromatic hydrocarbon skin carcinogenesis.

86 citations

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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
20217
20206
20196
20184
20177
20166