A clinical study of CPH 82 vs methotrexate in early rheumatoid arthritis

Lerndal, Thomas; Svensson, Björn

doi:10.1093/rheumatology/39.3.316

Cited by 44 publications

(32 citation statements)

References 9 publications

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“…A crude resin extract of Podophyllum spp., podophyllin, was included in the US Pharmacopoeia in 1820, and this resin has been prescribed to treat venereal warts. Podophyllotoxin has been used as the starting compound for the production of the semi-synthetic drugs etoposide (VP-16-213), teniposide (VM-26) and etopophos, which are used to treat lung and testicular cancers [4], leukaemia and rheumatoid arthritis [5]. A recent review [6] stated that species containing podophyllotoxin were traditionally used as folk-remedies in China, Japan, India and the United States to treat several illnesses, including gout, tuberculosis, syphilis, warts and various tumors.…”

Section: Introductionmentioning

confidence: 99%

De novo transcriptome analysis using 454 pyrosequencing of the Himalayan Mayapple, Podophyllum hexandrum

et al. 2013

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BackgroundThe Himalayan or Indian Mayapple (Podophyllum hexandrum Royle) produces podophyllotoxin, which is used in the production of semisynthetic anticancer drugs. High throughput transcriptome sequences or genomic sequence data from the Indian Mayapple are essential for further understanding of the podophyllotoxin biosynthetic pathway.Results454 pyrosequencing of a P. hexandrum cell culture normalized cDNA library generated 2,667,207 raw reads and 1,503,232 high quality reads, with an average read length of 138 bp. The denovo assembly was performed by Newbler using default and optimized parameters. The optimized parameter generated 40, 380 assembled sequences, comprising 12,940 contigs and 27,440 singlets which resulted in better assembly as compared to default parameters. BLASTX analysis resulted in the annotation of 40,380 contigs/singlet using a cut-off value of ≤1E-03. High similarity to Medicago truncatula using optimized parameters and to Populus trichocarpa using default parameters was noted. The Kyoto encyclopedia of genes and genomes (KEGG) analysis using KEGG Automatic Annotation Server (KAAS) combined with domain analysis of the assembled transcripts revealed putative members of secondary metabolism pathways that may be involved in podophyllotoxin biosynthesis. A proposed schematic pathway for phenylpropanoids and podophyllotoxin biosynthesis was generated. Expression profiling was carried out based on fragments per kilobase of exon per million fragments (FPKM). 1036 simple sequence repeats were predicted in the P. hexandrum sequences. Sixty-nine transcripts were mapped to 99 mature and precursor microRNAs from the plant microRNA database. Around 961 transcripts containing transcription factor domains were noted. High performance liquid chromatography analysis showed the peak accumulation of podophyllotoxin in 12-day cell suspension cultures. A comparative qRT-PCR analysis of phenylpropanoid pathway genes identified in the present data was performed to analyze their expression patterns in 12-day cell culture, callus and rhizome.ConclusionsThe present data will help the identification of the potential genes and transcription factors involved in podophyllotoxin biosynthesis in P. hexandrum. The assembled transcripts could serve as potential candidates for marker discovery and conservation, which should form the foundations for future endeavors.

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Section: Introductionmentioning

confidence: 99%

De novo transcriptome analysis using 454 pyrosequencing of the Himalayan Mayapple, Podophyllum hexandrum

et al. 2013

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“…Roots and rhizomes of P. hexandrum contain lignans such as PTOX and other related aryltetralin lignans [2]. Till date, PTOX has been used as the starting compound for the production of the semi-synthetic drugs etoposide (VP-16-213), teniposide (VM-26) and ethophos, which are used in the treatment of lung and testicular cancers [3], leukaemia and rheumatoid arthritis [4]. The Indian species P. hexandrum (Figure 1) contains three times more PTOX than its American counterpart P. peltatum , which contains other lignans viz.…”

Section: Introductionmentioning

confidence: 99%

Proteins differentially expressed in elicited cell suspension culture of Podophyllum hexandrum with enhanced podophyllotoxin content

et al. 2012

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BackgroundPodophyllotoxin (PTOX), the precursor for semi-synthesis of cancer therapeutics like etoposide, teniposide and etophos, is primarily obtained from an endangered medicinal herb, Podophyllum hexandrum Royle. PTOX, a lignan is biosynthetically derived from the phenylpropanoid pathway. The aim of this study is to investigate changes in the P. hexandrum cell proteome potentially related to PTOX accumulation in response to methyl jasmonate (MeJA) elicitation. High-resolution two-dimensional gel electrophoresis (2-DE) followed by colloidal Coomassie staining and mass spectrometric analysis was used to detect statistically significant changes in cell’s proteome.ResultThe HPLC analysis showed approximately 7–8 fold change in accumulation of PTOX, in the 12day old cell suspension culture (i.e. after 9days of elicitation) elicited with 100 μM MeJA as compared to the control. Using 2-DE a total of 233 spots was detected, out of which 105 spots were identified by MALDI TOF-TOF MS/MS. Data were subjected to functional annotation from a biological point of view through KEGG. The phenylpropanoid and monolignol pathway enzymes were identified, amongst these, chalcone synthase, polyphenol oxidase, caffeoyl CoA 3-O-methyltransferase, S-adenosyl-L-methionine-dependent methyltransferases, caffeic acid-O-methyl transferase etc. are noted as important. The relation of other differentially accumulated proteins with varied effects caused by elicitors on P. hexandrum cells namely stress and defense related protein, transcription and DNA replication and signaling are also discussed.ConclusionsElicitor-induced PTOX accumulation in P. hexandrum cell cultures provides a responsive model system to profile modulations in proteins related to phenylpropanoid/monolignol biosynthesis and other defense responses. Present findings form a baseline for future investigation on a non-sequenced medicinal herb P. hexandrum at molecular level.

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“…The lignan podophyllotoxin is the starting material for etoposide (VP- , teniposide (VM- 26), and etopophos that are used for the treatment of lung and testicular cancers [6], leukaemias, rheumatoid arthritis [7], psoriasis, and malaria [8][9][10]. However, the plants have become endangered because of intense collection and lack of organized cultivation practices [11,12].…”

Section: Introductionmentioning

confidence: 99%

An efficient method of propagation of Podophyllum hexandrum: an endangered medicinal plant of the Western Himalayas under ex situ conditions

et al. 2008

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This study shows an effective but simple method of conserving characterized populations and elite clones through vegetative propagation and genetic diversity through seeds in Podophyllum hexandrum (family Berberidaceae). Seed dormancy has been considered to be a major constraint in these seeds and most of the earlier reports recommended dormancy-breaking pretreatments such as chilling, gibberellic acid (GA(3)), etc. However, seeds of the 14 accessions that we tested exhibited no dormancy and hence did not require any pretreatments. Besides accession, collection of seeds with high moisture content could be one of the reasons for lack of dormancy. Thus, we propose germination of seeds (while they still retained moisture) in sand at 25 degrees C for high and reproducible results within a shorter period of time compared with earlier reports. Hypocotyl dormancy is known to considerably delay plant establishment and hence en masse propagation by preventing the emergence of functional leaves for up to 11-12 months. Manual removal of cotyledonary leaves, being labor and time intensive, is not a feasible method for large-scale seedling establishment. However, in this study, we showed that GA(3) at 200 ppm can alleviate hypocotyl dormancy besides reducing the time taken for true or functional leaf emergence. Treatment of cotyledonary leaves of 1 week-old-seedlings with 200 ppm GA(3 )resulted in true or functional leaf emergence within 7 days, and the resultant plants were also more vigorous than the ones obtained from manual removal of cotyledonary leaves. The study helped advance the establishment of seedlings by one growing season (almost 1 year).

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A clinical study of CPH 82 vs methotrexate in early rheumatoid arthritis

Abstract: The clinical effect of CPH 82 in this study was comparable to that of MTX at a dose of 10 mg/week. Both drugs reduced acute-phase reactants, MTX more effectively than CPH 82. The safety profile of CPH 82 was more favourable than that of MTX without folic acid supplementation.

Cited by 44 publications

References 9 publications

De novo transcriptome analysis using 454 pyrosequencing of the Himalayan Mayapple, Podophyllum hexandrum

De novo transcriptome analysis using 454 pyrosequencing of the Himalayan Mayapple, Podophyllum hexandrum

Proteins differentially expressed in elicited cell suspension culture of Podophyllum hexandrum with enhanced podophyllotoxin content

An efficient method of propagation of Podophyllum hexandrum: an endangered medicinal plant of the Western Himalayas under ex situ conditions

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