Coumarins

Estévez‐Braun, Ana; González, Antonio G.

doi:10.1039/np9971400465

Cited by 160 publications

(65 citation statements)

References 84 publications

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“…Herniarin, scopoletin, isoscopoletin, scoparone and limettin have been isolated from the aerial parts of B. fruticescens [45,54] and virgatenol, capensin, fraxetin, prenyletin and aesculetin from B. fruticosum. [55,56] Furthermore, complex pyranocoumarin derivatives, such as anomalin and praeruptorin A, have been isolated from B. falcatum and B. marginatum roots. [35,57] …”

Section: Coumarinsmentioning

confidence: 99%

Genus Bupleurum: a review of its phytochemistry, pharmacology and modes of action

Ashour

Wink

2010

Journal of Pharmacy and Pharmacology

218

161

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Objectives Radix Bupleuri represents one of the most successful and widely used herbal drugs in Asia for treatment of many diseases over the past 2000 years. Thorough studies have been carried out on many species of this genus and have generated immense data about the chemical composition and corresponding biological activity of extracts and isolated secondary metabolites. In this work, we review the chemistry and pharmacology of the genus Bupleurum and explore the relationships between the pharmacological effects and the chemical composition of these drugs. Key findings Early studies on the genus Bupleurum had focused only on the traditional uses of the plants in the treatment of inflammatory disorders and infectious diseases. After chemical profiling, several groups of secondary metabolites were characterized with relevant biological activity: triterpene saponins (saikosaponins), lignans, essential oils and polysaccharides. As a result, present interest is now focused on the bioactivity of the isolated triterpene saponins acting as immunomodulatory, anti-inflammatory and antiviral agents, as well as on the observed ant-iulcer activity of the polysaccharides and anti-proliferative activity of different lignans. Many saikosaponins exhibited very potent anti-inflammatory, hepatoprotective and immunomodulatory activities both in vivo and in vitro. Conclusions Further investigations and screenings are required to explore other Bupleurum species, to evaluate the clinical safety and possible interactions with other drugs or herbs. Standardization of Bupleuri extracts is crucial for them being integrated into conventional medicine due to large chemical and biological variations between different species and varieties.

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Section: Coumarinsmentioning

confidence: 99%

Genus Bupleurum: a review of its phytochemistry, pharmacology and modes of action

Ashour

Wink

2010

Journal of Pharmacy and Pharmacology

218

161

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“…All subsequent steps converting demethylsuberosin to psoralen or osthenol to angelicin are supposedly catalyzed by highly analogous enzymes (34), but only the linear series has been studied in detail. Enzyme studies conducted mostly with elicited A. majus or P. crispum cells (35)(36)(37)(38) identified marmesin and psoralen synthases as well as psoralen 5-monooxygenase as separate cytochrome P450 (CYP) 3 entities for the consecutive conversion of demethylsuberosin to bergaptol, which then is methylated to bergapten (39). These studies became possible, because furanocoumarins are completely lacking from the cell suspensions propagated in the dark but accumulate rapidly in the cells and culture fluid upon treatment with fungal elicitor.…”

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confidence: 99%

Molecular Cloning and Functional Characterization of Psoralen Synthase, the First Committed Monooxygenase of Furanocoumarin Biosynthesis

Larbat

Kellner

Specker

et al. 2007

Journal of Biological Chemistry

135

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Ammi majus L. accumulates linear furanocoumarins by cytochrome P450 (CYP)-dependent conversion of 6-prenylumbelliferone via (؉)-marmesin to psoralen. Relevant activities, i.e. psoralen synthase, are induced rapidly from negligible background levels upon elicitation of A. majus cultures with transient maxima at 9 -10 h and were recovered in labile microsomes. Expressed sequence tags were cloned from elicited Ammi cells by a nested DD-RT-PCR strategy with CYP-specific primers, and full-size cDNAs were generated from those fragments correlated in abundance with the induction profile of furanocoumarin-specific activities. One of these cDNAs representing a transcript of maximal abundance at 4 h of elicitation was assigned CYP71AJ1. Functional expression in Escherichia coli or yeast cells initially failed but was accomplished eventually in yeast cells after swapping the N-terminal membrane anchor domain with that of CYP73A1. The recombinant enzyme was identified as psoralen synthase with narrow substrate specificity for (؉)-marmesin. Psoralen synthase catalyzes a unique carbon-chain cleavage reaction concomitantly releasing acetone by syn-elimination. Related plants, i.e. Heracleum mantegazzianum, are known to produce both linear and angular furanocoumarins by analogous conversion of 8-prenylumbelliferone via (؉)-columbianetin to angelicin, and it was suggested that angelicin synthase has evolved from psoralen synthase. However, (؉)-columbianetin failed as substrate but competitively inhibited psoralen synthase activity. Analogy modeling and docked solutions defined the conditions for high affinity substrate binding and predicted the minimal requirements to accommodate (؉)-columbianetin in the active site cavity. The studies suggested that several point mutations are necessary to pave the road toward angelicin synthase evolution.Furanocoumarins are produced by many plants, mostly of the Apiaceae, Rutaceae, Moraceae, or the Coronilla and Psoralea genera of the Fabaceae (1-3). Multiple pharmacological effects have been ascribed to several of these metabolites (4 -6), which were included in clinical screenings but received attention also for their inhibitory effect on monooxygenases involved in drug metabolism (7-9) and potential toxicity (10). The (dihydro)furan-substituted 2H-1-benzopyran-2-one forms the characteristic core structure, and the annulation type distinguishes the linear furanocoumarins or psoralens from the angular furanocoumarins (Fig.

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“…3) Coumarin has been found to exhibit a wide range of bioactivities, such as hemoprevention against pathogens, 4) herbivores, 5) and abiotic stresses, 6) suggesting that physiological roles of coumarins for plants for the adaption to environmental stresses. Some coumarin derivatives are also known to act beneficially on human health due to their therapeutic effects such as inhibitory activities against various tumor cells, 7,8) mycobacteria, 9) antioxidant, 10,11) antihyperglycemic, 12) antifungal, 13) and antiasthmatic 14) which have been extensively studied in the medical and pharmaceutical fields for the treatment of diseases of human.…”

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confidence: 99%

Antinociceptive Profiles and Mechanisms of Orally Administered Coumarin in Mice

Park

Sim

Kang

et al. 2013

Biological & Pharmaceutical Bulletin

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In the present study, the antinociceptive profiles of coumarin were examined in ICR mice. Coumarin administered orally (from 1 to 10 mg/kg) showed an antinociceptive effect in a dose-dependent manner as measured in the acetic acid-induced writhing test. Duration of antinociceptive action of coumarin maintained at least for 60 min. But, the cumulative response time of nociceptive behaviors induced by a subcutaneous (s.c.) formalin injection, intrathecal (i.t.) substance P (0.7 µg) or glutamate (20 µg) injection was not affected by coumarin. 1) Coumarins form a large group of plant polyphenols. Thus far about 1500 coumarin derivatives have been isolated from plants.2) They occur ubiquitously in the plant kingdom, and coumarin derivatives show a chemotaxonomical tendency to accumulate in large amounts in Rutaceae and Apiaceae. 3) Coumarin has been found to exhibit a wide range of bioactivities, such as hemoprevention against pathogens, 4) herbivores, 5) and abiotic stresses, 6) suggesting that physiological roles of coumarins for plants for the adaption to environmental stresses. Some coumarin derivatives are also known to act beneficially on human health due to their therapeutic effects such as inhibitory activities against various tumor cells, 7,8) mycobacteria, 9) antioxidant, 10,11) antihyperglycemic, 12) antifungal, 13) and antiasthmatic 14) which have been extensively studied in the medical and pharmaceutical fields for the treatment of diseases of human.Previous studies have demonstrated that some coumarins exert an antinociceptive action.15,16) However, exact antinociceptive profiles and mechanism of coumarin have not been well characterized. Thus, we, in the current study, tried to characterize antinociceptive profiles and mechanisms of coumarin in several pain models. Experimental Animals Male iCR mice (MJ Co., Seoul, Korea) weighing 20-25 g were used for all the experiments. Animals were housed 5 per cage in a room maintained at 22± 0.5°C with an alternating 12 h light-dark cycle. Food and water were available ad libitum. The animals were allowed to adapt to the laboratory for at least 2 h before testing and were only used once. experiments were performed during the light phase of the cycle (10:00-17:00). MATeRiALS And MeTHOdSDrug Administration Oral administration was performed with gage in a volume of 500 µL/25 g body weight. intraperitoneal (i.p.) injection was conducted to unanesthesized mice with volume of 250 µL. The intracerebroventricular (i.c.v.) administration followed the method described by Haley.17) The intrathecal (i.t.) administration was performed following the method of Hylden and Wilcox 18,19) using a 30-gauge needle connected to a 25 µL Hamilton syringe with polyethylene tubing. The i.c.v. and i.t. injection volumes were 5 µL and the injection sites were verified by injecting a similar volume of 1% methylene blue solution and determining the distribution of the injected dye in the ventricular space or in the spinal cord. The dye injected i.c.v. was found to be distributed through the v...

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Coumarins

Cited by 160 publications

References 84 publications

Genus Bupleurum: a review of its phytochemistry, pharmacology and modes of action

Genus Bupleurum: a review of its phytochemistry, pharmacology and modes of action

Molecular Cloning and Functional Characterization of Psoralen Synthase, the First Committed Monooxygenase of Furanocoumarin Biosynthesis

Antinociceptive Profiles and Mechanisms of Orally Administered Coumarin in Mice

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