Peucedanol

Regioselective Olefination and Arylation of Arene-Tethered Diols Using the Easily Foldable Directing Groups.[Pubmed:38349252]

Org Lett. 2024 Feb 23;26(7):1463-1467.

Arene-tethered diols constitute a valuable class of structural motifs of drug and bioactive natural product molecules. In this study, a regioselective protocol for olefination and arylation of arene-tethered 1,2-diols and 1,3-diols has been developed using easily foldable acetal structures for attaching pyridine and nitrile directing groups. The method overcomes the steric hindrance effect of the short-chain diols and affords products in high yield and regioselectivity. This efficient cascaded catalysis has been successfully utilized in the syntheses of natural products such as Peucedanol, decursinol, and marmesin.

Regional Variations in Peucedanum japonicum Antioxidants and Phytochemicals.[Pubmed:38337910]

Plants (Basel). 2024 Jan 27;13(3):377.

Peucedanum japonicum has long been a staple in East Asian cuisine. In the context of traditional medicine, various members of the Peucedanum genus have been investigated for potential medicinal properties. In laboratory settings, some compounds derived from this plant have shown antioxidant and anti-inflammatory properties-characteristics often associated with potential medicinal applications. This study aimed to determine which part of the P. japonicum plants cultivated on two Korean islands contains the most antioxidant compounds. This determination was made through assessments of total polyphenol content and total flavonoid content, coupled with evaluation of antioxidant activity via DPPH and ABTS assays. The results showed that the aerial parts contain a richer array of bioactive compounds and demonstrate superior antioxidant activity compared to their root counterparts in the plants from both islands. To characterize the phytochemicals underpinning this bioactivity, LC-MS/MS and HPLC analyses were carried out. These methods detected varying amounts of chlorogenic acid, Peucedanol 7-O-glucoside, rutin, and Peucedanol, with good separation and retention times. This study addresses the lack of research on the antioxidant activity of different parts of P. japonicum. The findings hold significance for traditional medicine, dietary supplements, and the development of functional foods. Understanding antioxidant distribution aids in the development of medicinal and nutritional applications, influences agricultural practices, and contributes to regional biodiversity-conservation efforts. The study's geographical scope provides insights into how location impacts the concentration of bioactive compounds in plants. Overall, the results contribute valuable data for future research in plant biology, biochemistry, and related fields.

Chemical Constituents from Ficus sagittifolia Stem Bark and Their Antimicrobial Activities.[Pubmed:37570957]

Plants (Basel). 2023 Jul 28;12(15):2801.

The phytochemical investigation of the ethylacetate fraction of an ethanolic extract obtained from the stem bark of Ficus sagittifolia (Moraceae) led to the isolation of four flavonoids: (2R)-eriodictyol (1), 2'- hydroxygenistein (2), erycibenin A (3), and genistein (4); a dihydrobenzofuran: moracin P (5); a coumarin: Peucedanol (6); and an apocarotenoid terpenoid: dihydrophaseic acid (7). These were identified via 1D and 2D nuclear magnetic resonance spectroscopy (NMR) and ultra-high-resolution liquid chromatography-quadrupole time-of-flight mass spectroscopy (UHPLC-QTOF MS). Moracin P (5) is being reported for the first time in the genus Ficus, while the others are known compounds (1-4 and 6-7) isolated previously from the genus but being reported for the first time from the species F. sagittifolia. Their antimicrobial activity against various pathogens (five bacteria: Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, and Salmonella typhi; two fungi: Aspergillus niger and Candida albicans) was tested. The mixture of genistein and moracin P (4+5) exhibited strong activity against K. pneumoniae (MIC < 0.0039 mg/mL), whereas dihydrophaseic acid (7) was the most active against P. aeruginosa and A. niger (MIC = 0.0078 and <0.0039 mg/mL, respectively). These compounds might be considered potential antimicrobial agents with the potential to be starting points for the development of antimicrobial drugs.

In vitro study on the effect of peucedanol on the activity of cytochrome P450 enzymes.[Pubmed:35294326]

Pharm Biol. 2021 Dec;59(1):935-940.

CONTEXT: Peucedanol is a major extract of Peucedanum japonicum Thunb. (Apiaceae) roots, which is a commonly used herb in paediatrics. Its interaction with cytochrome P450 enzymes (CYP450s) would lead to adverse effects or even failure of therapy. OBJECTIVE: The interaction between Peucedanol and CYP450s was investigated. MATERIALS AND METHODS: Peucedanol (0, 2.5, 5, 10, 25, 50, and 100 muM) was incubated with eight human liver CYP isoforms (CYP1A2, 2A6, 3A4, 2C8, 2C9, 2C19, 2D6, and 2E1), in pooled human liver microsomes (HLMs) for 30 min with specific inhibitors as positive controls and untreated HLMs as negative controls. The enzyme kinetics and time-dependent study (0, 5, 10, 15, and 30 min) were performed to obtain corresponding parameters in vitro. RESULTS: Peucedanol significantly inhibited the activity of CYP1A2, 2D6, and 3A4 in a dose-dependent manner with IC(50) values of 6.03, 13.57, and 7.58 muM, respectively. Peucedanol served as a non-competitive inhibitor of CYP3A4 with a K(i) value of 4.07 muM and a competitive inhibitor of CYP1A2 and 2D6 with a K(i) values of 3.39 and 6.77 muM, respectively. Moreover, the inhibition of CYP3A4 was time-dependent with the K(i)/K(inact) value of 5.44/0.046 min/muM. DISCUSSION AND CONCLUSIONS: In vitro inhibitory effect of Peucedanol on the activity of CYP1A2, 2A6, and 3A4 was reported in this study. As these CYPs are involved in the metabolism of various drugs, these results implied potential drug-drug interactions between Peucedanol and drugs metabolized by CYP1A2, 2D6, and 3A4, which needs further in vivo validation.

Antimicrobial Activities of Extracts and Isolated Coumarins from the Roots of Four Ferulago Species Growing in Turkey.[Pubmed:32641960]

Iran J Pharm Res. 2019 Summer;18(3):1516-1529.

Ferulago species have been utilized since ancient times as digestive, sedative, aphrodisiac, along with in salads or as a spice due to their special odors. The study reports isolation and characterization of bioactive compounds of Ferulago pachyloba (F. pachyloba), Ferulago trachycarpa (F. trachycarpa), Ferulago bracteata (F. bracteata), and Ferulago blancheana (F. blancheana) via bioassay guided fractionation and isolation process. The structures of compounds were elucidated by detailed spectroscopic analyses. They were also assessed for their activities at 1000-31.25 microg/mL concentrations by microbroth-dilution methods. Antimicrobial activity of aqueous, methanol extracts and dichloromethane, ethyl acetate, n-butanol and aqueous residue fractions of methanol extracts from aerial parts and roots of species along with isolated compounds [osthole, imperatorin, bergapten, prantschimgin, Peucedanol-2'-benzoate, grandivitinol, suberosin, xanthotoxin, felamidin, marmesin, umbelliferone, ulopterol and a sterol mixture consisted of stigmasterol, beta-sitosterol] were evaluated. Antimicrobial effect has been seen against Gram-negative, Gram-positive bacteria, and a yeast C. albicans at a concentration between 31.25 and 62.5 mug/mL. Especially, C. albicans (MIC = 31.25 mug/mL) was the most inhibited microorganism. Moreover, growth of P. aeruginosa, B. subtilis, E. coli, and S. aureus were inhibited at 62.5 mug/mL MIC values. Among tested samples prantschimgin and dichloromethane fraction of aerial parts from F. pachyloba showed the best activity against C. albicans (MIC = 31.25 mug/mL). However, among aqueous extracts and residue fractions, only F. blancheana aerial parts, F. trachycarpa aerial parts, and roots and F. bracteata roots showed activity against C. albicans. Among microorganisms E. coli was found to be the least affected.

The alpha-amylase and alpha-glucosidase inhibitory activities of the dichloromethane extracts and constituents of Ferulago bracteata roots.[Pubmed:29233045]

Pharm Biol. 2018 Dec;56(1):18-24.

CONTEXT: Ferulago (Apiaceae) species have been used since ancient times for the treatment of intestinal worms, hemorrhoids, and as a tonic, digestive, aphrodisiac, or sedative, as well as in salads or as a spice due to their special odors. OBJECTIVES: This study reports the alpha-amylase and alpha-glucosidase inhibitory activities of dichloromethane extract and bioactive compounds isolated from Ferulago bracteata Boiss. & Hausskn. roots. MATERIALS AND METHODS: The isolated compounds obtained from dichloromethane extract of Ferulago bracteata roots through bioassay-guided fractionation and isolation process were evaluated for their in vitro alpha-amylase and alpha-glucosidase inhibitory activities at 5000-400 microg/mL concentrations. Compound structures were elucidated by detailed analyses (NMR and MS). RESULTS: A new coumarin, Peucedanol-2'-benzoate (1), along with nine known ones, osthole (2), imperatorin (3), bergapten (4), prantschimgin (5), grandivitinol (6), suberosin (7), xanthotoxin (8), felamidin (9), umbelliferone (10), and a sterol mixture consisted of stigmasterol (11), beta-sitosterol (12) was isolated from the roots of F. bracteata. Felamidin and suberosin showed significant alpha-glucosidase inhibitory activity (IC(50) 0.42 and 0.89 mg/mL, respectively) when compared to the reference standard acarbose (IC(50) 4.95 mg/mL). However, none of the tested extracts were found to be active on alpha-amylase inhibition. DISCUSSION AND CONCLUSIONS: The present study demonstrated that among the compounds isolated from CH(2)Cl(2) fraction of F. bracteata roots, coumarins were determined as the main chemical constituents of this fraction. This is the first report on isolation and characterization of the bioactive compounds from root extracts of F. bracteata and on their alpha-amylase and alpha-glucosidase inhibitory activities.

Simultaneous analysis of seven marker compounds from Saposhnikoviae Radix, Glehniae Radix and Peucedani Japonici Radix by HPLC/PDA.[Pubmed:27016947]

Arch Pharm Res. 2016 May;39(5):695-704.

A new combination of high performance liquid chromatography (HPLC) method coupled with photodiode array (PDA) analysis has been developed for the simultaneous quantitative determination of seven major components in Saposhnikoviae Radix (SR), Glehniae Radix (GR) and Peucedani Japonici Radix (PR), namely Peucedanol 7-O-beta-D-glucopyranoside (1), prim-O-glucosylcimifugin (2), cimifugin (3), 4'-O-beta-D-glucosyl-5-O-methylvisamminol (4), bergapten (5), sec-O-glucosylhamaudol (6), and imperatorin (7). Clear separation of these seven components were achieved on a Phenomenex Kinetex C18 (250 x 4.6 mm, 5 mum) column by gradient elution of water (A) and methanol (B) as mobile phase. The flow rate was 1.0 mL/min and the UV detector wavelength was set at 254 nm. The method was successfully used in the analysis of SR, GR, and PR with relatively simple conditions and procedures, and the results were satisfactory for linearity, recovery, precision, accuracy, stability and robustness. The results indicate that the established HPLC/PDA method is suitable for the classification of SR, GR, and PR.

Transport of Twelve Coumarins from Angelicae Pubescentis Radix across a MDCK-pHaMDR Cell Monolayer-An in Vitro Model for Blood-Brain Barrier Permeability.[Pubmed:26121397]

Molecules. 2015 Jun 25;20(7):11719-32.

Angelicae Pubescentis Radix (APR), a widely used traditional Chinese medicine, is reported to have central nervous system activities. The purpose of this study was to characterize the blood-brain barrier permeability of twelve coumarins from APR including umbelliferone (1), osthol (2), scopoletin (3), Peucedanol (4), ulopterol (5), angepubebisin (6), psoralen (7), xanthotoxin (8), bergapten (9), isoimperatorin (10), columbianadin (11), and columbianetin acetate (12) with an in vitro model using a MDCK-pHaMDR cell monolayer. The cell monolayer was validated to be suitable for the permeation experiments. The samples' transports were analyzed by high performance liquid chromatography and their apparent permeability coefficients (Papp) were calculated. According to the Papp value, most coumarins could be characterized as well-absorbed compounds except for 4, 10 and 11 which were moderately absorbed ones, in concentration-dependent and time-dependent manners. The results of P-glycoprotein (P-gp) inhibitor (verapamil) experiments showed that the transport of coumarin 4 was affected by the transport protein P-gp. Sigmoid functions between permeability log(Papp AP-BL*MW0.5) and log D (at pH 7.4) were established to analyze the structure-activity relationship of coumarins. The results provide useful information for discovering the substance basis for the central nervous system activities of APR, and predicting the permeability of other coumarins through BBB.

[Study on the coumarin glucosides of Angelica dahurica].[Pubmed:23627089]

Zhong Yao Cai. 2012 Nov;35(11):1785-8.

OBJECTIVE: To study the coumarin glucosides of Angelica dahurica. METHODS: Fresh roots and rhizomes of Angelica dahurica were extracted with ethanol at room temperature. Repeated column chromatography and preparative HPLC were used to isolate and purify the compounds. Their structures were elucidated on the basis of chemical evidence and spectral analysis. RESULTS: Twenty-six coumarin glucosides were isolated from Angelica dahurica, while here we reported 7 of them: sec.-O-beta-D-Galactopyranosyl-(R)-byakangelicin (I);8-O-beta-D-Galactopyranosyl-xanthotoxol (II); 7-O-beta-D-Apiofuranosyl-(1-->6)-beta-D-Glucopyranosyl-Peucedanol (III); (R)-Peucedanol-7-O-beta-D-Glucopyranoside (IV); sec.-O-beta-D-Glucopyranosyl-(R)-Oxypeucedaninhydrate (V); 7-O-beta-D-Galactopyranosyl-Sco-poletin( VI); Aesculin (VII). CONCLUSION: Compound V is a new compound, Compound VII is isolated from Umbellifera for the first time, compounds III, IV are isolated from Angelica for the first time,while compound I, II and VI are isolated from this plant for the first time.

Novel coumarin and furan from the roots of Angelica pubescens f. biserrata.[Pubmed:20183310]

J Asian Nat Prod Res. 2009 Aug;11(8):698-703.

A new natural coumarin, angepubebisin (1), and a new furan, angepubefurin (2), together with the five known compounds, umbelliferone, angelol B (3), ulopterol (4), Peucedanol (5), and scopoletin, were isolated from the roots of Angelica pubescens Maxim. f. biserrata Shan et Yuan. The structures of angepubebisin (1) and known compounds were determined by spectroscopic methods, including IR, UV, EI-MS, HR-FTICR-MS, 1D-, and 2D-NMR spectral analyses, and angepubefurin (2) was determined by HR-FTICR-MS and X-ray diffraction analyses.

Neuroprotective coumarins from the root of Angelica gigas: structure-activity relationships.[Pubmed:18087802]

Arch Pharm Res. 2007 Nov;30(11):1368-73.

An n-butanol-soluble fraction of the root of Angelica gigas Nakai (Umbelliferae) exhibited significant protection against glutamate-induced toxicity in primary cultured rat cortical cells. Using neuroprotective activity-guided fractionation, nine coumarins; marmesinin (1), nodakenin (2), columbianetin-O-beta-D-glucopyranoside (3), (S)-Peucedanol-7-O-beta-D-glucopyranoside (4), (S)-Peucedanol-3'-O-beta-D-glucopyranoside (5), skimmin (6), apiosylskimmin (7), isoapiosylskimmin (8) and magnolioside (9), were isolated from the n-butanol fraction. Of these nine coumarins, three dihydrofuranocoumarins; 1, 2 and 3, exhibited significant neuroprotective activities against glutamate-induced toxicity, exhibiting cell viabilities of about 50% at concentrations ranging from 0.1 to 10 microM. To explore the structure-activity relationships of coumarins, sixteen previously isolated compounds; 10-25, were simultaneously evaluated in the same system. Our results revealed that cyclization of the isoprenyl group, such as dihydropyran or dihydrofuran, or the furan ring at the C-6 position of coumarin, as well as lipophilicity played an important role in the neuroprotective activity of coumarins.

Antidiabetic coumarin and cyclitol compounds from Peucedanum japonicum.[Pubmed:15646792]

Arch Pharm Res. 2004 Dec;27(12):1207-10.

The antidiabetic activity-guided fractionation and isolation of the 80% EtOH extracts from Peucedani Radix (Peucedanum japonicum, Umbelliferae) led to the isolation and characterization of a coumarin and a cyclitol as active principles, that is, Peucedanol 7-O-beta-D-glucopyranoside (1) and myo-inositol (2). Their structures were identified by spectroscopic methods. Compound 1 showed 39% inhibition of postprandial hyperglycemia at 5.8 mg/kg dose, and compound 2 also significantly inhibited postprandial hyperglycemia by 34% (P<0.05).

Antioxidant compounds from the leaves of Peucedanum japonicum thunb.[Pubmed:12926867]

J Agric Food Chem. 2003 Aug 27;51(18):5255-61.

Seventeen compounds were isolated from the n-butanol soluble fraction of the leaves of Peucedanum japonicum Thunb. On the basis of MS and various NMR spectroscopic techniques, the structures of the isolated compounds were determined as isoquercitrin (1), rutin (2), 3-O-caffeoylquinic acid (3), 4-O-caffeoylquinic acid (4), 5-O-caffeoylquinic acid (5), cnidioside A (6), praeroside II (7), praeroside III (8), apterin (9), esculin (10), (R)-Peucedanol (11), (R)-Peucedanol 7-O-beta-d-glucopyranoside (12), l-tryptophan (13), uracil (14), guanosine (15), uridine (16), and thymidine (17). All compounds except 11 and 12 were isolated for the first time from P. japonicum. Several isolated compounds were quantified by high-performance liquid chromatography analysis. In addition, all isolated compounds were examined for radical scavenging on 1,1-diphenyl-2-picrylhydrazyl radical and for inhibition of oxidation of liposome induced by 2,2'-azobis(2-amidinopropane)dihydrochloride. Compounds 2-5 were found to be the major potent constituents, which contribute to the antioxidant activity of P. japonicum leaves.

Medicinal foodstuffs. XX. Vasorelaxant active constituents from the roots of Angelica furcijuga Kitagawa: structures of hyuganins A, B, C, and D.[Pubmed:11045445]

Chem Pharm Bull (Tokyo). 2000 Oct;48(10):1429-35.

From the methanolic extract with vasorelaxant activity obtained from Angelica furcijuga Kitagawa, four new khellactone-type coumarins, hyuganins A, B, C, and D, were isolated together with twelve known coumarins, two known acetylenic compounds, and a known lignan. The structures of hyuganins A, B, C, and D were determined on the basis of chemical and physicochemical evidence. Nine principal coumarins (hyuganin A, anomalin, pteryxin, isopteryxin, isoepoxypteryxin, praerosides II and IV, apiosylskimmin, (R)-Peucedanol 7-O-beta-D-glucopyranoside), two acetylenic compounds [(-)-falcarinol and falcarindioll, and related compounds were examined for inhibitory activities on high concentration of K+ (High K+)- and dl-norepinephrine (NE)-induced contractions. The results indicate that the 3'- and 4'-acyl groups of khellactone-type coumarins are essential for the inhibitory activity on the contractions by High K+. Hyuganin A and anomalin showed inhibitory effects on High K+-induced contraction, but not on NE-induced contraction. Other active coumarins (pteryxin, isopteryxin, isoepoxypteryxin) and an acetylenic compound (falcarindiol) non-selectively inhibited both contractions by High K+ and NE.