Isolation of Symlandine from the Roots of Common Comfrey (<i>Symphytum officinale</i>) Using Countercurrent Chromatography

Kim, Nam-Cheol; Oberlies, Nicholas H.; Brine, Dolores R.; Handy, Robert W.; Wani, Mansukh C.; Wall, Monroe E.

doi:10.1021/np0004653

Cited by 27 publications

(26 citation statements)

References 16 publications

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“…Their PAs have been identified (Larson et al 1984;Kim et al 2001;Wiedenfeld and Andrade-Cetto 2001;Wiedenfeld et al 2006) and these species have also been part of nematode host studies and/or studies concerning nematicidal effects of plant extracts made from them (Moreno et al 1992;McSorley and Frederick 1994;Walker et al 1994;Brinkmann et al 1996;Lordello and Lordello 1996;Bernard and Jennings 1997;Dias et al 2000;Costa et al 2001).…”

Section: Introductionmentioning

confidence: 99%

Effects of plants containing pyrrolizidine alkaloids on the northern root-knot nematode Meloidogyne hapla

2008

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1,2-Dehydropyrrolizidine alkaloids (PAs), known to be nematotoxic in vitro, represent a class of secondary plant metabolites from hundreds of plant species worldwide. Pot experiments with the commercially available PA-containing plants Ageratum houstonianum, Borago officinalis, Senecio bicolor, and Symphytum officinalis demonstrate that Meloidogyne hapla is not per se repelled by these plants as all species were infested with nematodes. However, the development of M. hapla juveniles was completely suppressed on A. houstonianum and S. bicolor. Soil in which A. houstonianum and S. bicolor were cultivated and incorporated contained 200-400 times less nematodes than soil treated with Lycopersicon esculentum.Depending on their qualitative composition of PAs at least some of these plants thus appear to be valuable tools for integrated root-knot nematode management.

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Section: Introductionmentioning

confidence: 99%

Effects of plants containing pyrrolizidine alkaloids on the northern root-knot nematode Meloidogyne hapla

2008

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“…Fortuitously, methods have been developed to isolate and purify gram quantities of each flavonolignan from milk thistle extract, permitting delineation of the disposition and action of single constituents (Kim et al, 2001;Graf et al, 2007).…”

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Two Flavonolignans from Milk Thistle (Silybum marianum) Inhibit CYP2C9-Mediated Warfarin Metabolism at Clinically Achievable Concentrations

Brantley¹,

Oberlies²,

Kroll³

et al. 2009

J Pharmacol Exp Ther

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Milk thistle (Silybum marianum) is a popular herbal product used for hepatoprotection and chemoprevention. Two commercially available formulations are the crude extract, silymarin, and the semipurified product, silibinin. Silymarin consists of at least seven flavonolignans, of which the most prevalent are the diastereoisomers silybin A and silybin B; silibinin consists only of silybin A and silybin B. Based on a recent clinical study showing an interaction between a silymarin product and the CYP2C9 substrate losartan, the CYP2C9 inhibition properties of silybin A and silybin B and corresponding regioisomers, isosilybin A and isosilybin B, were evaluated using human liver microsomes (HLMs), recombinant CYP2C9 (rCYP2C9) enzymes, and the clinically relevant probe, (S)-warfarin. Silybin B was the most potent inhibitor in HLMs, followed by silybin A, isosilybin B, and isosilybin A (IC 50 of 8.2, 18, 74, and Ͼ100 M, respectively). Next, silybin A and silybin B were selected for further characterization. As with HLMs, silybin B was more potent than silybin A toward rCYP2C9*1 (6.7 versus 12 M), rCYP2C9*2 (9.3 versus 19 M), and rCYP2C9*3 (2.4 versus 9.3 M). Using a matrix of five substrate (1-15 M) and six inhibitor (1-80 M) concentrations and HLMs, both diastereoisomers inhibited (S)-warfarin 7-hydroxylation in a manner described best by a mixed-type inhibition model (K i values of 4.8 and 10 M for silybin B and silybin A, respectively). These observations, combined with the high systemic silibinin concentrations (Ͼ5-75 M) achieved in a phase I study involving prostate cancer patients, prompt clinical evaluation of a potential warfarin-milk thistle interaction.Milk thistle [Silybum marianum (L.) Gaertn.] is a resilient and sometimes noxious plant that has been valued for its medicinal qualities for more than 2000 years Post-White et al., 2007). In modern herbal compendia, milk thistle is used to self-treat hepatic disorders, including hepatitis C and cirrhosis, and as a hepatoprotectant, particularly for mushroom poisoning. Milk thistle is available mainly as an extract prepared from the seeds of the plant. The two most common commercial preparations are termed silymarin and silibinin. Silymarin, a crude extract, is a complex mixture of at least seven flavonolignans and one flavonoid (taxifolin) (Davis-Searles et al., 2005;Kroll et al., 2007). The most abundant flavonolignans are the diastereoisomers silybin A and silybin B (Fig. 1). The diastereoisomers isosilybin A and isosilybin B (Fig. 1) also are present and are regioisomers of silybin A and silybin B. The remaining three flavonolignans are silychristin, isosilychristin, and silydianin, all of which are constitutional isomers of the aforementioned compounds (Davis-Searles et al., 2005). Silibinin is a semipurified extract, representing approximately a 1:1 mixture of silybin A and silybin B. Because silymarin and silibinin are mixtures of compounds derived from a natural source, batch-to-batch variation in bioactive ingredient composition occurs, which can c...

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“…This suggests that the liver tumours in comfrey-treated rats might be induced by the PAs present in comfrey. Indeed, comfrey contains up to nine PAs (Stickel and Seitz, 2000;Kim et al, 2001;Schaneberg et al, 2004), at least two of which, symphytine and lasiocarpine, are carcinogenic when administered as pure compounds (Svoboda and Reddy, 1974;Hirono et al, 1979).…”

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Mutagenicity of comfrey (Symphytum Officinale) in rat liver

Mei

Guo

et al. 2005

Br J Cancer

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Comfrey is a rat liver toxin and carcinogen that has been used as a vegetable and herbal remedy by humans. In order to evaluate the mechanisms underlying its carcinogenicity, we examined the mutagenicity of comfrey in the transgenic Big Blue rat model. Our results indicate that comfrey is mutagenic in rat liver and the types of mutations induced by comfrey suggest that its tumorigenicity results from the genotoxicity of pyrrolizidine alkaloids in the plant.

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Isolation of Symlandine from the Roots of Common Comfrey (Symphytum officinale) Using Countercurrent Chromatography

Cited by 27 publications

References 16 publications

Effects of plants containing pyrrolizidine alkaloids on the northern root-knot nematode Meloidogyne hapla

Effects of plants containing pyrrolizidine alkaloids on the northern root-knot nematode Meloidogyne hapla

Two Flavonolignans from Milk Thistle (Silybum marianum) Inhibit CYP2C9-Mediated Warfarin Metabolism at Clinically Achievable Concentrations

Mutagenicity of comfrey (Symphytum Officinale) in rat liver

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