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Biomedical subjects

Adolf Nahrstedt

Publications and source records attributed to Adolf Nahrstedt.

13 recordsLinked to original sources
PubMed2006

Antioxidant oligomeric proanthocyanidins from Cistus salvifolius.

The purified proanthocyanidin oligomers of Cistus salvifolius herb extract accounted for 78% of the total proanthocyanidins and 73% of the total antioxidant activity of this extract. To elucidate the structure of the oligomer, it was depolymerized by acid catalysis in the presence of phloroglucinol. The structures of the resulting flavan-3-ols and phloroglucinol adducts were determined on the basis of 1D- and reverse 2D-NMR (HSQC, HMBC) experiments of their peracetylated derivatives, MALDI-TOF-MS and CD spectroscopy. These observations resulting from the degradation with phloroglucinol were confirmed by 13C NMR spectroscopy of the oligomer. The mean molecular weight of the higher oligomeric fraction was estimated to be 5-6 flavan-3-ol-units.

Antioxidants↗
PubMed2005

Phenolic esters from the rhizomes of Cimicifuga racemosa do not cause proliferation effects in MCF-7 cells.

Five phenylpropanoid esters, caffeoylglycolic acid, 2-caffeoylpiscidic acid (cimicifugic acid D), 3,4-dihydroxyphenacyl caffeate (petasiphenone), 3,4-dihydroxyphenyl-2-oxopropyl isoferulate (cimiciphenol) and 3,4-dihydroxyphenacyl isoferulate (cimiciphenone) were isolated from a commercially available extract of the rhizomes of Cimicifuga racemosa (L.) Nutt. (syn. Actaea racemosa L.) for the first time; the known cimicifugic acids A, B, E, F, fukinolic acid, fukiic acid and caffeic acid were also obtained. Cimiciphenone and caffeoylglycolic acid are new natural products. The structures were elucidated by means of spectroscopic data (ESI-MS, 1H-, 13C-NMR, COSY, HMQC, HMBC and NOE experiments). Ferulic acid and isoferulic acid were detected by HPLC analysis in comparison to standards. The estrogenic activity of the isolated compounds was tested in an estrogen-dependent MCF-7 mamma carcinoma cell line; 17beta-estradiol (10(-11) M) and the phytoestrogen coumestrol (10(-7) - 10(-5) M) were used as references. The results suggest that, in contrast to an earlier report, the phenolic esters do not exert a proliferative (estrogenic) effect in this test system.

Antineoplastic Agents, Phytogenic↗
PubMed2004

Pharmacokinetic herb-drug interactions: are preventive screenings necessary and appropriate?

Pharmacokinetic interactions often occur as a result of activity changes of drug-metabolizing and transporting proteins, especially cytochrome P450 (CYP) isoenzymes and P-glycoprotein (P-gp). The activity of these enzymes and drug transporters can be enhanced or inhibited by synthetic drugs as well as by natural products. Since the number of herb-drug interactions has increased in recent years, systematic in vitro screenings and more clinical studies to identify such interactions were proposed for herbal medicinal products. However, previous results regarding this issue are not only contradictory but also of less predictability. One reason for the discrepancies could be the lack of validation of the recommended in vitro tests. Furthermore, it has to be considered that pharmacokinetic drug interactions are not only mediated by herbal medicines but also by several foods, beverages and life-style products. Since herbal medicines are considered to have a broad therapeutic range, a preventive risk assessment for pharmacokinetic drug interactions should first be realized for synthetic drugs with a narrow therapeutic index. Efforts to identify all possible interactions will lead to limitless investigations and to inconsistent decisions.

Cytochrome P-450 Enzyme System↗
PubMed2004

New fatty acid esters originate during storage by the interaction of components in prasaplai, a Thai traditional medicine.

Prasaplai is a Thai traditional preparation composed of twelve ingredients; during storage three newly emerging compounds were detected by HPLC. Their structures were established as the new (E)-4-(3,4-dimethoxyphenyl)but-3-en-1-yl linoleate, (E)-4-(3,4-dimethoxyphenyl)but-3-en-1-yl oleate and the known (E)-4-(3,4-dimethoxyphenyl)but-3-en-1-yl palmitate on the basis of spectral data and chemical evidence. The artificial esters were already observable after one day of storage of the freshly prepared dry mixture, and steadily increased during a storage period of 30 days and more. A systematic search indicated that the three esters arose from the interaction of compounds contained in the rhizomes of Zingiber cassumunar and the seeds of Nigella sativa.

Drug Interactions↗
PubMed2003

Step by step removal of hyperforin and hypericin: activity profile of different Hypericum preparations in behavioral models.

Herbal extracts of Hypericum perforatum L. (St. John's wort, SJW) are now successfully competing for status as a standard antidepressant therapy. Because of this, great effort has been devoted to identifying the antidepressive active compounds. In the present study we used the following strategy to evaluate the relative pharmacological importance of various extract components: 1. preparation of an hydroalcoholic SJW extract containing both hyperforin (3.2%) and hypericin (0.15%) (extract A); 2. step by step removal of hyperforin and hypericin led to the following extracts: Extract B, devoid of hyperforin but still containing hypericin (0.14%) and Extract C, free of hypericin and hyperforin but enriched in flavonoids ( approximately 12%). We characterized the in vivo activity profile of all three preparations using the tail suspension test (TST) in mice and the forced swimming test (FST) in rats as screening models. We further investigated the activity of pure hyperforin. Extract B and C (500 mg/kg each) as well as pure hyperforin (8 mg/kg) significantly shortened immobility time in the TST after acute pre-treatment whereas extract A was inactive. In the FST all three extracts decreased immobility time in a dosage of 500 mg/kg after acute as well as after repeated treatment. The present results clearly show that an SJW extract free of hyperforin and hypericin exerts antidepressant activity in behavioral models, supporting our working hypothesis that flavonoids are part of the constituents responsible for the therapeutic efficacy of SJW extracts. We also could show that hyperforin contributes to the beneficial properties of SJW extract, confirming the hypothesis that the crude SJW extract contains several constituents with antidepressant activity.

Administration, Oral↗
PubMed2003

New and known iridoid- and phenylethanoid glycosides from Harpagophytum procumbens and their in vitro inhibition of human leukocyte elastase.

Ten compounds, harpagoside (1), 8- p-coumaroylharpagide (2), 8-feruloylharpagide (3), 8-cinnamoylmyoporoside (4), pagoside (5), acteoside (6), isoacteoside (7), 6'- O-acetylacteoside (8), cinnamic acid (9) and caffeic acid (10) were isolated from the storage roots of Harpagophytum procumbens, Pedaliaceae. Compounds 1, 2, 6, 7 and 9 are known for H. procumbens; 3 and 10 were isolated the first time from H. procumbens; compounds 4, 5 and 8 are new natural products. Their structures were elucidated using spectroscopic data (NMR, with NOE, COSY and HMBC experiments, UV, [alpha]). The inhibitory activity of aqueous extracts of the roots of H. procumbens and H. zeyheri as well as the main compounds isolated from H. procumbens was tested on human neutrophile elastase. Although inhibition was comparatively weak a dose-dependence was observed. An IC (50) of 542 microg/mL was determined for the aqueous extract of H. procumbens, but 1012 microg/mL for that of H. zeyheri. 6'- O-Acetylacteoside (8), that is not present in H. zeyheri, inhibited the enzyme with an IC (50) of 47 microg/mL (70 microM), compound 7 with 179 microg/mL (286 microM), 2 with 179 microg/mL (331 microM), 5 with 154 microg/mL (260 microM) and 10, which was also used as reference compound, with an IC (50) of 86 microg/mL (475 microM). The IC (50) values of acteoside, harpagoside, cinnamic acid and stachyose were higher than 300 microg/mL and thus not further determined.

Chromatography, High Pressure Liquid↗
PubMed2003

In vitro studies indicate that miquelianin (quercetin 3-O-beta-D-glucuronopyranoside) is able to reach the CNS from the small intestine.

Miquelianin (quercetin 3-O-beta-D-glucuronopyranoside) is one of the flavonoids of St. John's wort (Hypericum perforatum L.) whose antidepressant activity has been shown by the forced swimming test, an in vivo pharmacological model with rats. However, nothing is known about its ability to reach the CNS after oral administration. We examined the pathway of miquelianin from the small intestine to the central nervous system using three in vitro membrane barrier cell systems. In the Caco-2 cell line, miquelianin showed a higher uptake (1.93 +/- 0.9 pmol x min(-1) x cm(-2)) than hyperoside (quercetin 3-O-beta-D-galactopyranoside; 0.55 +/- 0.18 pmol x min(-1) x cm(-2)) and quercitrin (quercetin 3-O-alpha-L-rhamnopyranoside; 0.22 +/- 0.08 pmol x min(-1) x cm(-2)). The permeability coefficient of miquelianin (Pc = 0.4 +/- 0.19 x 10(-6) cm/sec) was in the range of orally available drugs assuming sufficient absorption from the small intestine. Uptake and permeability of the examined compounds was increased by the MRP-2 inhibitor MK-571 indicating a backwards transport by this membrane protein. Porcine cell cultures of brain capillary endothelial cells were used as a model of the blood-brain barrier (bbb) and epithelial cells of the plexus chorioidei as a model of the blood-CSF barrier (bcb). Results indicate no active transport in one direction. Although moderate, the permeability coefficients (bbb: Pc = 1.34 +/- 0.05 x 10(-6) cm/sec; bcb: Pc = 2.0 +/- 0.33 x 10(-6) cm/sec) indicate the ability of miquelianin to cross both barriers to finally reach the CNS.

Administration, Oral↗
PubMed2002

In vitro receptor screening of pure constituents of St. John's wort reveals novel interactions with a number of GPCRs.

RATIONALE: Hypericum perforatum L. (St. John's wort; SJW) is one of the leading psychotherapeutic phytomedicines and great effort has been devoted to clarifying its mechanism of action. OBJECTIVE: We have undertaken a comprehensive analysis of several pure compounds isolated from the crude extract to gain further insight into the molecular actions of various substituents of SJW. METHODS: We characterized the in vitro pharmacology of the naphthodianthrones hypericin and pseudohypericin, the phloroglucinol derivative hyperforin, and several flavonoids at 42 biogenic amine receptors and transporters using the resources of the National Institute of Mental Health Psychoactive Drug Screening Program. RESULTS: The biflavonoid amentoflavone significantly inhibited binding at serotonin (5-HT(1D), 5-HT(2C)), D(3)-dopamine, delta-opiate, and benzodiazepine receptors. The naphthodianthrone hypericin had significant activity at D(3)- and D(4)-dopamine receptors and beta-adrenergic receptors. With the exception of the D(1)-dopamine receptor, the phloroglucinol derivative hyperforin was less active than other SJW constituents tested on all screened receptors. CONCLUSION: Our present in vitro data clearly show that several pure substances in SJW are potential CNS psychoactive agents and may contribute to the antidepressant efficacy of the plant in a complex manner. Our data also reveal novel and heretofore unexpected interactions of pure compounds in SJW at a number of GPCRs, transporters, and ion channels. We hypothesize that additive or synergistic actions of different single compounds may be responsible for the antidepressant efficacy of SJW. These results and this general approach may impact our understanding of phytomedicines in general and H. perforatum specifically.

Antidepressive Agents↗
PubMed2002

Cyanogenic allosides and glucosides from Passiflora edulis and Carica papaya.

Leaf and stem material of Passiflora edulis (Passifloraceae) contains the new cyanogenic glycosides (2R)-beta-D-allopyranosyloxy-2-phenylacetonitrile (1a) and (2S)-beta-D-allopyranosyloxy-2-phenylacetonitrile (1b), along with smaller amounts of (2R)-prunasin (2a), sambunigrin (2b), and the alloside of benzyl alcohol (4); the major cyanogens of the fruits are (2R)-prunasin (2a) and (2S)-sambunigrin (2b). The major cyanogenic glycoside of Carica papaya (Caricaceae) is 2a; only small amounts of 2b also are present. We were not able to confirm the presence of a cyclopentenoid cyanogenic glycoside, tetraphyllin B, in Carica papaya leaf and stem materials. In detailed 1H NMR studies of 1a/b and 2a/b, differences in higher order effects in glucosides and allosides proved to be valuable for assignment of structures in this series. The diagnostic chemical shifts of cyanogenic methine and anomeric protons in 1a/b are sensitive to anisotropic environmental effects. The assignment of C-2 stereochemistry of 1a/b was made in analogy to previous assignments in the glucoside series and was supported by GLC analysis of the TMS ethers.

Caricaceae↗
PubMed2002

Phenolic compounds from Hypericum perforatum.

During a re-investigation of phenolic compounds from the dried crude drug material of St. John's wort (Hypericum perforatum L.) 22 phenolic compounds were detected by HPLC; 14 of them were quantified using the same system. Twelve phenolic compounds were isolated from the plant material and their structures identified mainly by spectroscopic methods, among them quercetin-3-O-(2"-O-acetyl)-beta-D-galactoside as a new natural product. Cryptochlorogenic acid, protocatechuic acid, 3-O-[Z]-p-coumaroylquinic acid, isoorientin, cyanidin-3-O-alpha-L-rhamnoside, and astilbin were obtained for the first time from this source; the earlier suspected neochlorogenic acid, 3-O-[E]-p-coumaroylquinic acid, mangiferin, miquelianin and guaijaverin were confirmed.

Calibration↗
PubMedDate not supplied

Quantitative determination of curcuminoids in Curcuma rhizomes and rapid differentiation of Curcuma domestica Val. and Curcuma xanthorrhiza Roxb. by capillary electrophoresis.

The three major curcuminoids, curcumin, demethoxycurcumin and bis-demethoxycurcumin, from Curcuma domestica Val. (Curcuma longa L.) and Curcuma xanthorrhiza Roxb. (Zingiberaceae) were fully separated and quantified in less than 5 min using a capillary zone electrophoresis method with standard fused-silica capillaries and photodiode array detection. An electrolyte solution of 20 mM phosphate, 50 mM sodium hydroxide and 14 mM beta-cyclodextrin was found to be appropriate. Quantification was performed with 3,4-dimethoxy-trans-cinnamic acid as internal standard, and the limit of detection was 0.01 mg/mL. Extraction, stabilisation during sample storage and quantification procedures were optimised and carried out with drugs and commercial curry powder from different provenances. The results were compared with the photometric method of the monograph Curcumae xanthorrhizae rhizoma of the European Pharmacopoeia.

Curcuma↗