Celandine,Swallowwort:Celandine is named after the Greek word for the swallow, because it starts flowering when the birds arrive and stops when they leave.
Contents
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- Basic Botanical Info:Celandine,Swallowwort.
- Chelidonium majus Botanical Description.
- Historical or traditional use:Chelidonium majus.
- Chelidonium majus Phytochemicals and Constituents.
- Medicinal Action and Uses:Chelidonium majus.
- Chelidonium majus Therapeutics and Pharmacology.
- Dosage and Administrations:Chelidonium majus.
- Research Update:Chelidonium majus.
Research Update:Chelidonium majus.:
Apoptogenic activity of two benzophenanthridine alkaloids from Chelidonium majus L. does not correlate with their DNA damaging effects.:Toxicol In Vitro. 2007 Sep 21; Philchenkov A, Kaminskyy V, Zavelevich M, Stoika R.R.E. Kavetsky Institute of Experimental Oncology, Pathology and Radiobiology, National Academy of Sciences of Ukraine, Vasyl’kivska Str. 45, 03022 Kyiv, Ukraine.
Apoptogenic and DNA damaging effects of chelidonine (CHE) and sanguinarine (SAN), two structurally related benzophenanthridine alkaloids isolated from Chelidonium majus L. (Papaveraceae), were compared. Both alkaloids induced apoptosis in human acute T-lymphoblastic leukaemia MT-4 cells. Apoptosis induction by CHE and SAN in these cells was accompanied by caspase-9 and -3 activation and an increase in the pro-apoptotic Bax protein. An elevation in the percentage of MT-4 cells possessing caspase-3 in active form after their treatment with CHE or SAN was in parallel to a corresponding increase in the fraction of apoptotic cells. The involvement of mitochondria in apoptosis induction by both alkaloids was supported by cytochrome C elevation in cytosol, with an accompanying decrease in cytochrome C content in the mitochondrial fraction. At the same time, two alkaloids under study differed drastically in their cell cycle phase-specific effects, since only CHE arrested MT-4 cells in G(2)/M phase. It was shown earlier, that CHE, in contrast to SAN, does not interact directly with DNA. This fact is in line with DNA damaging effects of the alkaloids detected in the COMET assay. Nevertheless, apoptosis-inducing activity of CHE even slightly exceeded that of SAN.
A novel extracellular peroxidase and nucleases from a milky sap of Chelidonium majus.:Fitoterapia. 2007 Dec;78(7-8):496-501. Epub 2007 May 25.Nawrot R, Lesniewicz K, Pienkowska J, Gozdzicka-Jozefiak A.Department of Molecular Virology, Institute of Experimental Biology, Adam Mickiewicz University, Umultowska 89, 61-614 Poznan, Poland.
Using affinity chromatography, SDS-PAGE, peroxidase activity assay and mass spectrometry data, a new extracellular peroxidase (CMP) from Chelidonium majus milky sap was isolated and characterized. The protein has a molecular weight of about 40 kDa and belongs to secretory class III plant peroxidases. The peroxidase activity is also accompanied by DN-ase activities. A novel CMP combined with other proteins is probably involved in development and differentiation of the plant and defence against different pathogens. It suggests that the biological activity of C. majus whole plants and extracts may depend not only on its alkaloidal content but also on the presence of biologically active proteins.
Characterization of polyphenoloxidase from the latex of greater celandine (Chelidonium majus L.).:Ceska Slov Farm. 2007 Apr;56(2):90-4. Slovak. Bilka F, Vanko M, Balazová A, Bilková A, Holková I.Univerzita Komenského v Bratislave, Farmaceutická fakulta, Katedra bunkovej a molekulárnej biológie lieciv. bilka@fpharm.uniba.sk
Greater celandine, similarly as other plants of the family Papaveraceae, produces benzylisoquinoline alkaloids, primarily benzophenanthridines. Polyphenoloxidase (PPO) is most probably involved in the formation of dopamine, which is one of the precursors of norcoclaurine, the first intermediate with the benzylisoquinoline structure. This study has revealed that PPO present in the latex of greater celandine is localized in the organelles, which serve to store alkaloids (the so-called 1000 g organelles). The enzyme was purified by means of affinity chromatography into electrophoretic homogeneity. It possesses a relative molecular mass of approximately 65 kDa and exerts two activities, the monophenolase and diphenolase ones. With the use of a polymerase chain reaction, it was possible to amplify a part of the PPO gene from the region of the active site.
Effect of Chelerythrine on cell surface hydrophobicity and adherence of Streptococcus mutans.:Shanghai Kou Qiang Yi Xue. 2007 Feb;16(1):68-72. Chinese. Cheng RB, Chen X, Liu SJ, Zhang XF.School of Stomatology, China Medical University, Shenyang 110002, Liaoning Province, China.
PURPOSE: To detect the effect of Chelidonium majus L. extractive Chelerythrine on the cell surface hydrophobicity and adherence of Streptococcus mutans, and to investigate the mechanism of adherence. METHODS: The Chelerythrine was doubly diluted to different concentration from 24.4 microg/ml to 781.3 microg/ml. The method of microbial adhesion to hydrophobicity(MATH) was used to measure the cell surface hydrophobicity of Streptococcus mutans; The effect of the Chelerythrine on Streptococcus mutans adhesion to glass surface was also measured. SPSS13.0 software package was used for statistical analysis, and one-way ANOVA was used to compare the difference of means among sample groups. RESULTS: The cell surface hydrophobicity of Streptococcus mutans decreased gradually with the descent of each concentration of Chelerythrine. There was significant difference between each experimental group and control group (P<0.01). There was no significant difference among groups of 195.3 microg/ml, 97.7 microg/ml, 48.8 microg/ml and 24.4 microg/ml (P>0.05). The inhibition rate of adherence increased significantly with the increase of the concentration of Chelerythrine. There was highly significant difference between group of 195.3 microg/ml or 390.6 microg/ml and control group, and the same between the two experimental groups and other experimental groups (P<0.01). CONCLUSION: There is some degree of inhibitory effect of Chelerythrine on the cell surface hydrophobicity and adherence of Streptococcus mutans. Chelerythrine possesses powerful anticariogenic potential.
Suppressive effects of Chelidonium majus methanol extract in knee joint, regional lymph nodes, and spleen on collagen-induced arthritis in mice.:J Ethnopharmacol. 2007 May 30;112(1):40-8. Epub 2007 Feb 2.
Chelidonium majus L. has multiple applications in Korean traditional medicine because of its anti-tumoral, cytotoxic, anti-inflammatory and anti-microbial activities and has long been known to have anti-inflammatory effects. However, no study on the anti-arthritic activity of Chelidonium majus has been reported in vivo. Rheumatoid arthritis (RA) is a systemic autoimmune disease with chronic inflammation characterized by hyperplasia of synovial cells in affected joints, which ultimately leads to the destruction of cartilage and bone. Cytokine production and gene expression were assessed during CIA (collagen-induced arthritis) model mice in knee joint, lymph node (LN), and spleen, using ELISA and competitive RT-PCR. DBA/1J mice were immunized with bovine type II collagen. After a second collagen immunization, mice were treated with CME orally at 400, 40mg/kg once a day for 4 weeks. The severity of arthritis within the knee joints was evaluated by histological assessment of cartilage destruction and pannus formation. Administration of CME significantly suppressed the progression of CIA and inhibited the production of TNF-alpha and IL-6 in spleen and lymph node. The erosion of cartilage was dramatically reduced in mouse knees after treatment with CME. In conclusion, our results demonstrates that CME significantly suppressed the progression of CIA and that this action was characterized by the decreased production of TNF-alpha, IL-6, IFN-gamma, B cells, gammadelta T cells (in spleen) and increased proportion of CD4+CD25+ regulatory T cells in vivo. In the serum of CME-treated mice, the levels of IgG and IgM RA factor were decreased.
Modified alkaloids from Chelidonium majus L. induce G2/M arrest, caspase-3 activation, and apoptosis in human acute lymphoblastic leukemia MT-4 cells.:Ukr Biokhim Zh. 2006 Sep-Oct;78(5):81-7. Ukrainian.Fil'chenkov OO, Zavelevych MP, Khranovs'ka NM, Za?ka LA, Potopal's'ky? AI.
The novel anticancer drug amitosine representing the mixture of thiophosphamide-modified alkaloids from Chelidonium majus L. has been reported to inhibit growth of various solid tumors in vivo. However, its antileukemic activity as well as the mechanisms of anticancer action have not been yet extensively examined. In this study, amitosine treatment at a dose of 100-250 microg/mL for 24 h resulted in dose-dependent inhibition of MT-4 cell proliferation in vitro with apoptosis induction in the setting of the significant G2/M phase arrest (up to 70% of cells). While amitosine induced caspase-3 activation in MT-4 cells, the increase in the number of cells containing the active caspase-3 did not correlate with the increase of apoptotic cell percentage. Western blotting data revealed the accumulation of cytochrome c in cytosolic fraction of MT-4 cells within 6 h after treatment with 100 microg/mL amitosine. To sum up, amitosine has been shown to possess strong antiproliferative and apoptosis-inducing activities in MT-4 cells in vitro, which seem to be mediated partially through caspase-dependent mitochondrial death pathways.
Effect of alkaloids from celandine on calcium accumulation and oxidative phosphorylation in mitochondria depending on their DNA intercalating properties.:Ukr Biokhim Zh. 2006 Mar-Apr;78(2):73-8. Ukrainian. Kamins'ky? VO, Kryv'iak NV, Lutsyk MD, Sto?ka RS.
The effect of principal alkaloids (sanguinarine, chelerythrine, coptisine, chelidonine) of greater celandine Chelidonium majus L., as well as the alkaloids from Colchicum autumnale L. (colchicine and colchamine) on calcium accumulation and oxidative phosphorylation in rat liver mitochondria has been studied. The obtained data were compared with DNA intercalating properties of alkaloids detected by the method of thermodenaturation (DNA melting curve plots). It was found that chelerythrine and sanguinarine blocked absorption and accumulation of calcium cations and inhibited oxidative phosphorylation, while the coptisine significantly diminished those indices. Chelidonine, colchicines and colchamine had no influence on the studied characteristics. The effect of alkaloids upon mitochondria functional state correlated tightly with their DNA intercalating properties: chelerythrine and sanguinarine were strong intercalators, while coptisine was a weak one, and chelidonine, colchicine and colchamine did not interact with DNA and caused no changes in its melting point. Correlation coefficient between the intercalating properties of alkaloids and their inhibition of calcium accumulation was 0.89, and with their oxidative phosphorylation inhibition - 0.93. It is suggested that the effect of studied alkaloids upon functional properties of mitochondria can be mediated by mtDNA.
8-hydroxydihydrochelerythrine and 8-hydroxydihydrosanguinarine with a potent acetylcholinesterase inhibitory activity from Chelidonium majus L.:Biol Pharm Bull. 2006 Nov;29(11):2317-20.
Ethanol extract of the aerial portion of Chelidonium majus L. inhibited acetylcholinesterase (AChE) activity without a significant inhibition of butyrylcholinesterase (BuChE). Using mass spectrometry and NMR studies, three active constituents were isolated and identified: 8-hydroxydihydrochelerythrine (1), 8-hydroxydihydrosanguinarine (2), and berberine (3). Compounds 1-3 showed potent inhibitory activity against AChE, with IC50 (microM) values of 0.61-1.85. Compound 1 exhibited competitive and selective inhibition for AChE.
Experimental study of the inhibitory effects of Chelidonium majus L. extractive on Streptococcus mutans in vitro.:Shanghai Kou Qiang Yi Xue. 2006 Jun;15(3):318-20. Chinese.Cheng RB, Chen X, Liu SJ, Zhang XF, Zhang GH.School of Stomatology, China Medical University, Shenyang 110002, Liaoning Province, China. chengruibo@sohu.com
PURPOSE: To study the inhibitory effects of Chelidonium majus L. extractive on the growth of Streptococcus mutans in vitro, and to explore its mechanism in caries prevention. METHODS: Streptococcus mutans 25175 was chosen as the experimental bacterium. The Chelidonium majus L. extractives chelidonine and chelerythrine were double diluted to different concentrations by two-fold dilution. The inhibitory effect of Streptococcus mutans was measured by slip diffusion method. The minimal inhibitory concentration(MIC) was also determined. 0.16% liquor hibitane was used as positive control. Spearman correlation was used for statistical analysis. RESULTS: Inhibition zone of Streptococcus mutans appeared in some concentration of chelerythrine, but no inhibition zone in each concentration of chelidonine. The MIC of chelerythrine was 0.78 mg/ml which determined by liquid culture medium. The concentration of chelerythrine was highly related to the inhibitory zone of Streptococcus mutans (r=0.99, P<0.01). CONCLUSION: The antibacterial activity of Chelidonium majus L. extractive chelerythrine on Streptococcus mutans was significant,and the antibacterial activity of the concentration 100 mg/ml was higher than that of 0.16% liquor hibitane (19.4 mm), indicating that chelerythrine can be used as an agent for prevention of dental caries.
In vitro and in vivo anti-retroviral activity of the substance purified from the aqueous extract of Chelidonium majus L.:Antiviral Res. 2006 Nov;72(2):153-6. Epub 2006 Apr 18.Gerencer M, Turecek PL, Kistner O, Mitterer A, Savidis-Dacho H, Barrett NP.Biomedical Research Center, Baxter AG, Uferstrasse 15, A-2304 Orth/D., Austria. gerencm@baxter.com
We have isolated a substance with anti-retroviral activity from the freshly prepared crude extract of Chelidonium majus L. (greater celandine) by 9-aminoacridine precipitation method and ion exchange chromatography using Dowex-50W/H+ resin followed by the gel filtration on Sephadex-75 column. Elemental and phenol/sulfuric acid method analyses as well as the mass spectrometry of the purified substance indicated that it may represent a low-sulfated poly-glycosaminoglycan moiety with molecular weight of approximately 3800 Da. The substance prevented infection of human CD4+ T-cell lines AA2 and H9 with HIV-1 at concentration of 25 microg/mL as well as the cell-to-cell virus spread in H9 cells continuously infected with HIV-1, as determined by the measurement of reverse transcriptase activity and p24 content in cell cultures. Furthermore, we have shown in a murine AIDS model that the treatment with purified substance significantly prevented splenomegaly and the enlargement of cervical lymph nodes in C57Bl/6 mice chronically infected with the pool of murine leukemia retroviruses. The mechanism(s) of anti-retroviral activity of this substance have to be elucidated.
Proapoptotic activity of Ukrain is based on Chelidonium majus L. alkaloids and mediated via a mitochondrial death pathway.:BMC Cancer. 2006 Jan 17;6:14. Habermehl D, Kammerer B, Handrick R, Eldh T, Gruber C, Cordes N, Daniel PT, Plasswilm L, Bamberg M, Belka C, Jendrossek V.Department of Radiation Oncology, University Hospital of Tuebingen, Hoppe-Seyler-Str. 3, D-72076 Tuebingen, Germany. daniel.habermehl@med.uni-tuebingen.de
BACKGROUND: The anticancer drug Ukrain (NSC-631570) which has been specified by the manufacturer as semisynthetic derivative of the Chelidonium majus L. alkaloid chelidonine and the alkylans thiotepa was reported to exert selective cytotoxic effects on human tumour cell lines in vitro. Few clinical trials suggest beneficial effects in the treatment of human cancer. Aim of the present study was to elucidate the importance of apoptosis induction for the antineoplastic activity of Ukrain, to define the molecular mechanism of its cytotoxic effects and to identify its active constituents by mass spectrometry. METHODS: Apoptosis induction was analysed in a Jurkat T-lymphoma cell model by fluorescence microscopy (chromatin condensation and nuclear fragmentation), flow cytometry (cellular shrinkage, depolarisation of the mitochondrial membrane potential, caspase-activation) and Western blot analysis (caspase-activation). Composition of Ukrain was analysed by mass spectrometry and LC-MS coupling. RESULTS: Ukrain turned out to be a potent inducer of apoptosis. Mechanistic analyses revealed that Ukrain induced depolarisation of the mitochondrial membrane potential and activation of caspases. Lack of caspase-8, expression of cFLIP-L and resistance to death receptor ligand-induced apoptosis failed to inhibit Ukrain-induced apoptosis while lack of FADD caused a delay but not abrogation of Ukrain-induced apoptosis pointing to a death receptor independent signalling pathway. In contrast, the broad spectrum caspase-inhibitor zVAD-fmk blocked Ukrain-induced cell death. Moreover, over-expression of Bcl-2 or Bcl-xL and expression of dominant negative caspase-9 partially reduced Ukrain-induced apoptosis pointing to Bcl-2 controlled mitochondrial signalling events. However, mass spectrometric analysis of Ukrain failed to detect the suggested trimeric chelidonine thiophosphortriamide or putative dimeric or monomeric chelidonine thiophosphortriamide intermediates from chemical synthesis. Instead, the Chelidonium majus L. alkaloids chelidonine, sanguinarine, chelerythrine, protopine and allocryptopine were identified as major components of Ukrain. Apart from sanguinarine and chelerythrine, chelidonine turned out to be a potent inducer of apoptosis triggering cell death at concentrations of 0.001 mM, while protopine and allocryptopine were less effective. Similar to Ukrain, apoptosis signalling of chelidonine involved Bcl-2 controlled mitochondrial alterations and caspase-activation. CONCLUSION: The potent proapoptotic effects of Ukrain are not due to the suggested "Ukrain-molecule" but to the cytotoxic efficacy of Chelidonium majus L. alkaloids including chelidonine.
Stylopine from Chelidonium majus inhibits LPS-induced inflammatory mediators in RAW 264.7 cells.:Arch Pharm Res. 2004 Sep;27(9):923-9.
Stylopine is a major component of the leaf of Chelidonium majus L. (Papaveraceae), which has been used for the removal of warts, papillomas and condylomas, as well as the treatment of liver disease, in oriental countries. Stylopine per se had no cytotoxic effect in unstimulated RAW 264.7 cells, but concentration-dependently reduced nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta), and the IL-6 production and cyclooxygenase-2 (COX-2) activity caused by the LPS stimulation. The levels of inducible nitric oxide synthase (iNOS) and COX-2 protein expressions were markedly suppressed by stylopine in a concentration dependent manner. These results suggest that stylopine suppress the NO and PGE2 production in macrophages by inhibiting the iNOS and COX-2 expressions. These biological activities of stylopine may contribute to the anti-inflammatory activity of Chelidonium majus.
Evaluation of protective potentials of a potentized homeopathic drug, Chelidonium majus, during azo dye induced hepatocarcinogenesis in mice.:Indian J Exp Biol. 2004 Jul;42(7):698-714.Biswas SJ, Khuda-Bukhsh AR.Department of Zoology, University of Kalyani, Kalyani 741 235, India.
Several cytogenetical and enzymatic protocols were used to test if two microdoses of Chelidonium majus, namely Chelidonium-30 (Ch-30) and Chelidonium-200 (Ch-200), used as homeopathic drugs, showed anti-tumor activity and also favorably modulated genotoxic damages produced by an azo dye in mice at several intervals of fixation. Different sets of healthy mice were fed: (i) hepatocarcinogen, p-dimethylaminoazobenzene (p-DAB, initiator) + phenobarbital (PB, promoter), (ii) only p-DAB, (iii) only PB, and (iv) neither p-DAB nor PB (normal control). Mice fed with p-DAB + PB were divided into different sets that were also fed either Ch-30 (v) or Ch-200 (vi) or diluted alcohol (vii), the "vehicle" of the microdoses of Chelidonium. All mice of group (i), a few of group (ii) and group (vii) and none of groups (iii) and (iv) developed tumors in liver at the longer intervals of fixation. The frequencies of chromosome aberrations (CA), micronucleated erythrocytes (MN), mitotic index (MI) and sperm head abnormality (SHA) were much higher in groups (i) and (vii) mice than in groups (ii), (iii) and (iv) mice at all fixation intervals. However, in mice of both groups (v) and (vi), the frequencies of CA, MN, SHA were strikingly less than those of groups (i) and (vii), and moderately less than those of groups (ii) and (iii). Both Ch-30 and Ch-200 also modulated favourably some toxicity marker enzymes like acid and alkaline phosphatases, peroxidases, glutamate oxaloacetate and glutamate pyruvate transaminases in liver, kidney and spleen tissues of the carcinogen fed mice. The microdoses of Chelidonium having no visible ill effects of their own, may be strong candidates for use in delaying/protecting liver cancer.
Water extract isolated from Chelidonium majus enhances nitric oxide and tumour necrosis factor-alpha production via nuclear factor-kappaB activation in mouse peritoneal macrophages.:J Pharm Pharmacol. 2004 Jan;56(1):129-34.
Chelidonium majus is used to treat several inflammatory diseases and tumours. We have examined the effect of C. majus on nitric oxide (NO) production using mouse peritoneal macrophages. When C. majus was used in combination with recombinant interferon-gamma (rIFN-gamma, 10 U mL(-1)), there was a marked cooperative induction of NO production. Treatment of rIFN-gamma plus C. majus (1 mgmL(-1)) in macrophages caused a significant increase in tumour necrosis factor-alpha (TNF-alpha) production. The increased production of NO and TNF-alpha from rIFN-gamma plus C. majus-stimulated cells was almost completely inhibited by nuclear factor-kappaB (NF-kappaB) inhibitor, pyrrolidine dithiocarbamate (100 microM). These findings demonstrated that C. majus increased the production of NO and TNF-alpha by rIFN-gamma-primed macrophages and suggested that NF-kappaB played a critical role in mediating the effects of C. majus.
Inhibition of mouse liver respiration by Chelidonium majus isoquinoline alkaloids.:Toxicol Lett. 2003 Dec 15;146(1):37-47. Barreto MC, Pinto RE, Arraba?a JD, Pav?o ML.Departamento de Ciências Tecnológicas e Desenvolvimento, Centro de Investiga??o de Recursos Naturais, Universidade dos A?ores, Rua da M?e de Deus, 9502 Ponta Delgada, Portugal. barreto@notes.uac.pt
The alkaloids from Chelidonium majus L. which had a significant inhibitory effect in mitochondrial respiration were those which contain a positive charge due to a quaternary nitrogen atom, i.e., chelerythrine, sanguinarine, berberine and coptisine, both with malate+glutamate or with succinate as substrates. When malate+glutamate was used as substrate, chelerythrine and berberine, which contain methoxy groups, were particularly more active, since they had a strong effect even at low concentrations. In submitochondrial particles, berberine and coptisine had a marked inhibitory effect on NADH dehydrogenase activity but practically no effect on succinate dehydrogenase activity, whereas chelerythrine and sanguinarine inhibited more strongly succinate dehydrogenase than NADH dehydrogenase, which is in agreement with the results found for mitochondrial respiration. Protopine and allocryptopine, which did not inhibit mitochondrial respiration, strongly inhibited NADH dehydrogenase in submitochondrial particles, but had no effect on succinate dehydrogenase activity.
Radiation protective effect of an extract from Chelidonium majus.:Int J Hematol. 2003 Oct;78(3):226-32.
We earlier reported that CM-AIa isolated from Chelidonium majus had mitogenic activity, generated lymphokine-activated killer cells, and increased the number of granulocyte-macrophage colony-forming cells (GM-CFC). In an extended effort to search for other immunostimulatory effects, we evaluated the protective effects of in vivo injected CM-AIa against irradiation. CM-AIa was found to increase the number of bone marrow cells, spleen cells, GM-CFC, and platelets in irradiated mice. In addition, this agent induced endogenous production of cytokines such as interleukin 1 and tumor necrosis factor alpha, which are required for hematopoietic recovery. We also demonstrated that CM-AIa treatment 24 hours before irradiation protected mice with 80% survival at lethal dose 100/15. These findings indicate that CM-AIa may be a useful agent for reducing the time needed for reconstitution of hematopoietic cells after irradiation treatment.
Acute hepatitis induced by Greater Celandine (Chelidonium majus).:Scand J Gastroenterol. 2003 May;38(5):565-8.Stickel F, P?schl G, Seitz HK, Waldherr R, Hahn EG, Schuppan D.Dept. of Medicine I, University of Erlangen-Nuremberg, Erlangen, Germany. felix.stickel@med1.imed.uni-erlangen.de
We report on two cases of acute liver injury along with the intake of Greater Celandine (Chelidonium majus), a well-known herbal remedy frequently used for irritable bowel syndrome. All other possible causes of acute liver damage were excluded in both patients. In one patient, cholestatic hepatitis recurred rapidly after involuntary re-exposition. Both patients fully recovered after the withdrawal of Greater Celandine. The two cases add to the existing database about the potential hepatotoxicity of drugs containing Greater Celandine and raise the question whether the approval of this drug should be re-evaluated in the light of lacking evidence for a therapeutic benefit.
Cytotoxic activity and quality control determinations on Chelidonium majus.:Fitoterapia. 2003 Feb;74(1-2):127-9.Saglam H, Arar G.Department of Pharmacognosy, Faculty of Pharmacy, University of Ege, Bornova, Izmir 35100, Turkey. saglamh@pharm.ege.edu.tr
The quality control determinations on herba and radix Chelidonii prepared from Chelidonium majus L., growing wildly in Bursa, Uluda? surroundings, have been conducted according to DAB 9. Ash, humidity and total alkaloidal content have been carried out. LC(50) value of chelidonine and protopine, the most important alkaloids, and the alcoholic and water extracts of herba Chelidonii were determined using brine shrimp (Artemia salina) lethality bioassay.
Genetic aspects of the relationship between isoquinoline alkaloids and mineral elements in greater celandine (Chelidonium majus L.).:Prikl Biokhim Mikrobiol. 2003 Jan-Feb;39(1):37-42. Russian.Buzuk GN, Lovkova MIa, Sokolova SM, Tiutekin IuV.Vitebsk Medical Institute, Vitebsk, 210026 Belarus. buzukg@mail.ru
Interrelations between the total content of isoquinoline alkaloids, concentrations of quaternary protoberberines and benzophenanthridines, and the amount of K, Cu, Co, Al, Ba, and Zn in aerial parts of individual celandine plants were revealed, within a single cenopopulation, using correlation analysis and regression analysis. Mathematical models describing the regulation of isoquinoline metabolism by some of the mineral elements were obtained in the analytical form. The results suggest that this process is genetically determined.
Immunomodulatory activity of protein-bound polysaccharide extracted from Chelidonium majus.:Arch Pharm Res. 2002 Apr;25(2):158-64.
In the course of searching immunomodulators from natural sources, the protein-bound polysaccharide, CM-Ala, has been isolated from the water extract of Chelidonium majus L. (Papaveraceae). The immunostimulatory characteristics have been investigated in several experiments such as generation of activated killer (AK) cells, proliferation of splenocytes, activation of macrophages and granulocyte macrophage-colony forming cell (GM-CFC) assay. Of the fractions obtained using Sephacryl S200 column chromatography, CM-Ala was the most effective fraction that augmented the cytotoxicity against Yac-1 tumor cells from 0.88% to 34.18% by culturing with splenocytes for 5 days. CM-Ala also enhanced nitric oxide production by two fold in peritoneal macrophages and exhibited antitumor activity. It showed mitogenic activity on both spleen cells and bone marrow cells. CM-Ala induced proliferation of splenocytes by 84 fold and increased GM-CFC numbers by 1.48 fold over than the non-treated. On the contrary, CM-Ala had cytotoxic activity to a diverse group of tumor cells. From the above results, we proposed that CM-Ala has a possibility of an effective antitumor immunostimulator.
Effect of a homeopathic drug, Chelidonium, in amelioration of p-DAB induced hepatocarcinogenesis in mice.:BMC Complement Altern Med. 2002 Apr 10;2:4.
BACKGROUND: Crude extracts of Chelidonium majus, and also purified compounds derived from crude extracts of this plant, have been reported to exhibit anti-viral, anti-inflammatory, anti-tumor and anti-microbial properties both in vitro and in vivo. Chelidonium is a homeopathic drug routinely used against various liver disorders including cancer in humans. Two potencies of Chelidonium (Ch-30, Ch-200) have been tested for their possible anti-tumor and enzyme modulating activities in liver and anti-clastogenic effects during p-DAB-induced hepatocarcinogenesis in mice compared to suitable controls. METHODS: Several cytogenetic and enzymatic protocols were used at three fixation intervals; at 60 days, 90 days and 120 days of treatment. Different sets of healthy mice were fed: i) hepatocarcinogen, p-DAB plus phenobarbital (PB), ii) only PB, iii) neither p-DAB nor PB (normal control). One set of mice fed with p-DAB plus PB was also fed Ch-30 (iv) and another set Ch-200 (v). All standard currently used methods were adopted for cytogenetical preparations and for the enzyme assays. RESULTS: All group (i) mice developed tumors in liver at all fixation intervals, while none of group (ii) and (iii) mice developed any tumors. About 40% mice in group (iv) and group (v) did not show tumor nodules in their liver. Feeding of Chelidonium to group (iv) and (v) mice reduced genotoxic effects to a significant extent (p < 0.05 to p < 0.001). CONCLUSION: The homeopathic drug Chelidonium exhibited anti-tumor and anti-genotoxic activities and also favorably modulated activities of some marker enzymes. Microdoses of Chelidonium may be effectively used in combating liver cancer.
The inhibition enzymatic hydrolysis of acetylthiocholine by acetylcholinesterase using principal alkaloids isolated from celandine and macleya and their derivatives.:Tsitologiia. 2001;43(11):1046-50. Russian.Kuznetsova LP, Nikol'skaia EB, Sochilina EE, Faddeeva MD.I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry RAS, St. Petersburg.
A study was made of a possible inhibitory action on the enzymatic hydrolysis of acetylthiocholine by human erythrocyte acetylcholinesterase of principal alkaloids isolated from Chelidonium majus L. and Macleaya (Bocconia) cordata and microcarpa (namely sanguinarine, chelidonine, berberine), and of drugs "Ukrain" (thiophosphoric acid derivative of a sum of the alkaloids isolated from Chelidonium majus L.) and "Sanguirythrine" (a mixture of unseparated closely related to benzo[c]phenanthridine alkaloids sanguinarine and chelerythrine, isolated from Chelidonium majus L. and other plants of Papaveraceae family). All agents under study have been shown to be reversible inhibitors of the enzymatic hydrolysis of acetylthiocholine. On the basis of the kinetic data it has been determined that chelidonine belonged to reversible inhibitors of a competitive type. All other examined agents have been demonstrated to be inhibitors of a mixed competitive-noncompetitive type, and a greater contribution to the inhibition was made by the competitive constituent. Among all examined agents berberine, sanguinarine and "Sanguirythrine" were the strongest inhibitors of this reaction (the values of generalized inhibitory constants being 0.23, 0.23 and 0.29 microM, respectively) and cheliodonine and "Ukrain" were much weaker (2.0 and 2.5 microM, respectively). Judging from the data obtained, sanguinarine and chelerythrine exert similar inhibitory effects on the reaction of enzymatic hydrolysis of acetylthiocholine, since sanguinarine and "Sanguirythrine" have nearly equal generalized inhibitory constants.
Acute hepatitis after use of a herbal preparation with greater celandine (Chelidonium majus).:Ned Tijdschr Geneeskd. 2002 Jan 19;146(3):124-8. Dutch. Erratum in: Ned Tijdschr Geneeskd 2002 Mar 16;146(11):544. Crijns AP, de Smet PA, van den Heuvel M, Schot BW, Haagsma EB.Afd. Maag-, Darm- en Leverziekten, Academisch Ziekenhuis, Hanzeplein 1, Postbus 30.001, 9700 RB Groningen.
A 42-year-old woman developed jaundice due to acute hepatitis several weeks after ingestion of a herbal preparation containing greater celandine (Chelidonium majus) and curcuma root, which had been prescribed by an alternative therapist due to a skin complaint. After the medication had been withdrawn, clinical recovery was rapid and the hepatic functions returned to normal within 2 months. The hepatitis was ascribed to the known hepatotoxic effects of C. majus. In view of the increasing popularity of herbal remedies, greater awareness of side effects, such as hepatotoxicity, is needed. Quite a number of herbal preparations carry the risk of liver damage. The supposed clinical effectiveness of herbal remedies does not seem to always outweigh the potential risks. In the event of non-clarified liver function disturbances the ingestion of supposedly harmless, but potentially hepatotoxic, herbal products should be considered.
Effect of sample handling on alkaloid and mineral content of aqueous extracts of greater celandine (Chelidonium majus L.).:J Chromatogr A. 2000 Aug 11;889(1-2):69-74.Then M, Szentmihályi K, Sárk?zi A, Illés V, Forgács E.Semmelweis University of Medicine, Institute of Pharmacognosy, Budapest, Hungary.
The authors examined the extraction of alkaloids from the greater celandine (Chelidonium majus L.) by different methods (traditional pressing and tea making, microwave and supercritical fluid extraction). The extractants were water and propylene glycol. For comparison of the extraction methods, the yield was evaluated according to total alkaloid content measured by spectroscopy. The highest alkaloid yield was obtained by microwave extraction and by making tea. Distribution of the components was studied by thin-layer chromatography and densitometry. The concentration and the ratio of alkaloid components in extracts are significantly different depending on the extraction method. The solution obtained by supercritical fluid extraction contains coptisine and chelidonine, while berberine could be obtained by microwave extraction only. Extracts with high coptisine content were obtained by supercritical fluid extraction, followed by pressing and microwave extraction. Mineral element content of the drug and extracts was also determined by inductively coupled plasma atomic emission spectrometry. Element content (Na, Ca, Fe) was found to be highest in microwave extracts.
Chelidocystatin, a novel phytocystatin from Chelidonium majus.:Phytochemistry. 1998 Nov;49(6):1645-9.Rogelj B, Popovic T, Ritonja A, Strukelj B, Brzin J.Department of Biochemistry and Molecular Biology, Institute Jozef Stefan, Jamova, Ljubljana, Slovenia.
Greater celandine (Chelidonium majus L.) has traditional uses in European and Chinese herbal medicine. In the plant sap significant inhibitory activity against papain was observed. A cysteine proteinase inhibitor, named chelidocystatin, was isolated from the plant using papain Sepharose affinity chromatography followed by gel filtration and ion-exchange chromatography. Chelidocystatin showed a M(r) of 10,000 on SDS-PAGE with the pI of 9.3, and was a strong inhibitor of cathepsin L (Ki = 5.6 x 10(-11) M), papain (Ki = 1.1 x 10(-10) M) and cathepsin H (Ki = 7.5 x 10(-9) M). The complete amino acid sequence of the protein was obtained with N-terminal sequencing and sequencing of the peptides after digestion of the protein. Moreover, a major part of the sequence was verified by molecular cloning. The conserved glycine residue at the N-terminal region and the QVVAG motif, which are both believed to be involved in the inhibitory activity, indicate that it is a member of the cystatin superfamily. The amino acid sequence of chelidocystatin shows a high degree of homology with cysteine proteinase inhibitors belonging to the phytocystatin group, especially with the recently described carrot and sunflower phytocystatins with which it shares 57% and 54% homology, respectively.
The greater celandine (Chelidonium majus L.)--review of present knowledge.:Ceska Slov Farm. 1995 Apr;44(2):71-5. Review. Czech. Táborská E, Bochoráková H, Dostál J, Paulová H.Biochemicky ústav Lékarské fakulty, Masarykova Universita, Brno.
The greater celandine (Chelidonium majus L.) is a species of the Papaveraceae family. The principal secondary metabolites of the plant are isoquinoline alkaloids; more than 30 were found here. The richest organ is the root, the total content of alkaloids in it reaching 2-3%. The dominant alkaloids of the root are chelidonine and coptisine. The aerial parts contain about 0.5-1.5% alkaloids. The principal base for the whole period of vegetation is coptisine, the representation of other alkaloids substantially changing during the development of the plant. Of nonalkaloidal secondary metabolites, esters of caffeic acid have recently been demonstrated in the plant drug. In the past, the drug was used to treat tumours. At present, the extract of alkaloids from the plant is the base of the preparation Ukrain showing immunomodulating activity and being employed in the therapy of different types of carcinomata. Chelidonium majus is also a component of some preparations employed in the diseases of the biliary tract and liver. Biological effect of the principal constituents of the drug are different and often quite antagonistic. As their representation varies in the course of vegetation, the efficacy of the summary preparations changes in dependence on the prevailing substance in the preparation.
Hydroxycinnamic Acid Derivatives, Caffeoylmalic and New Caffeoylaldonic Acid Esters, from Chelidonium majus.:Planta Med. 1993 Feb;59(1):71-5.Hahn R, Nahrstedt A.Institut für Pharmazeutische Biologie and Phytochemie der Westf?lischen Wilhelms-Universit?t, D-4400 Münster, Federal Republic of Germany.
HPLC analysis of a hydrolyzed extract obtained from the aerial parts of CHELIDONIUM MAJUS yielded 0.4% caffeic, 0.06% P-coumaric, and 0.02% ferulic acids; gentisic and P-hydroxybenzoic acids were below 0.01%. The caffeic acid derivatives occur as esters of which four were isolated using gel permeation chromatography, centrifugal partition chromatography and HPLC; they were assigned on the basis of their spectroscopic data ( (1)H-, (13)C-NMR, UV, MS) as the new (-)-2-( E)-caffeoyl- D-glyceric acid, (-)-4-( E)-caffeoyl- L-threonic acid, (-)-2-( E)-caffeoyl- L-threonic acid lactone, and the known (+)-( E)-caffeoyl- L-malic acid.
Evaluation of thiophosphoric acid alkaloid derivatives from Chelidonium majus L. ("Ukrain") as an immunostimulant in patients with various carcinomas.:Drugs Exp Clin Res. 1991;17(2):139-43. Nowicky JW, Staniszewski A, Zbroja-Sontag W, Slesak B, Nowicky W, Hiesmayr W.Ukrainian Anti-Cancer Institute, Vienna, Austria.
This paper summarizes the preliminary results of two independent clinical trials conducted with the preparation "Ukrain", containing thiophosphoric acid alkaloid derivatives from the plant Chelidonium majus L. (greater celandine), in order to investigate whether it has immunopotentiating properties in cancer patients. A total of twenty-seven patients with various malignancies were treated with "Ukrain" given intravenously in a dose of 10 mg every three days. In all patients the cellular and humoral immune response was studied. There was an increase in both total T-cells and T-helper lymphocytes, a decrease in T-suppressor cells, and normalization of the helper/suppressor (HIS) ratio. A significant increase in erythrocyte-rosette-forming T-cells and NK cells was also demonstrated. Serum immunoglobulin levels, complement components (C3 and C4), and acute phase proteins were not significantly enhanced. Restoration of cellular immunity was accompanied by an improvement in the patients' performance status and in the clinical course of the disease. The treatment was generally well tolerated. The present study shows that some therapeutic benefit from the use of Chelidonium majus ("Ukrain") as an immunostimulant in cancer patients can be achieved.
Traditional plant treatments for diabetes. Studies in normal and streptozotocin diabetic mice.:Diabetologia. 1990 Aug;33(8):462-4.Swanston-Flatt SK, Day C, Bailey CJ, Flatt PR.Biomedical Sciences Research Centre, University of Ulster, Coleraine, UK.
The effects on glucose homeostasis of eleven plants used as traditional treatments for diabetes mellitus were evaluated in normal and streptozotocin diabetic mice. Dried leaves of agrimony (Agrimonia eupatoria), alfalfa (Medicago sativa), blackberry (Rubus fructicosus), celandine (Chelidonium majus), eucalyptus (Eucalyptus globulus), lady's mantle (Alchemilla vulgaris), and lily of the valley (Convallaria majalis); seeds of coriander (Coriandrum sativum); dried berries of juniper (Juniperus communis); bulbs of garlic (Allium sativum) and roots of liquorice (Glycyrhizza glabra) were studied. Each plant material was supplied in the diet (6.25% by weight) and some plants were additionally supplied as decoctions or infusions (1 g/400 ml) in place of drinking water to coincide with the traditional method of preparation. Food and fluid intake, body weight gain, plasma glucose and insulin concentrations in normal mice were not altered by 12 days of treatment with any of the plants. After administration of streptozotocin (200 mg/kg i.p.) on day 12 the development of hyperphagia, polydipsia, body weight loss, hyperglycaemia and hypoinsulinaemia were not affected by blackberry, celandine, lady's mantle or lily of the valley. Garlic and liquorice reduced the hyperphagia and polydipsia but did not significantly alter the hyperglycaemia or hypoinsulinaemia. Treatment with agrimony, alfalfa, coriander, eucalyptus and juniper reduced the level of hyperglycaemia during the development of streptozotocin diabetes. This was associated with reduced polydipsia (except coriander) and a reduced rate of body weight loss (except agrimony). Alfalfa initially countered the hypoinsulinaemic effect of streptozotocin, but the other treatments did not affect the fall in plasma insulin. The results suggest that certain traditional plant treatments for diabetes, namely agrimony, alfalfa, coriander, eucalyptus and juniper, can retard the development of streptozotocin diabetes in mice.
Isolation and Partial Characterization of a New Lectin from Seeds of the Greater Celandine (Chelidonium majus).:Plant Physiol. 1985 Jun;78(2):379-383. Peumans WJ, De Ley M, Stinissen HM, Broekaert WF.Laboratorium voor Plantenbiochemie, KULeuven, Kardinaal Mercierlaan 92, B-3030 Leuven, Belgium.
Seeds of the greater celandine (Chelidonium majus L.) contain a lectin which could be isolated using a combination of affinity chromatography on chitin and ion exchange chromatography on sulphopropyl-Sephadex. The purified lectin was partially characterized with respect to its biochemical and physicochemical properties. It is a small dimeric protein composed of two different subunits of M(r) 9,500 and 11,500, respectively. Its amino acid composition is typified by high contents of glycine and cysteine. No covalently bound carbohydrate could be detected. Hapten inhibition experiments indicated that the lectin exhibits specificity towards oligomers of N-acetylglucosamine, the potency of inhibition increasing with chain length up to four residues. The greater celandine lectin is the first lectin to be isolated from a species belonging to the plant family Papaveraceae (poppy family). Although it represents a new type of plant lectin, resemblances to phytohemaglutinins from diverse taxonomic origin are obvious.
Biosynthesis of antitumoral and bactericidal sanguinarine.:
A simple, rapid, and reliable TLC method for the separation and determination of sanguinarine has been established. This intensively studied biologically active alkaloid has a wide range of potentially useful medicinal properties, such as antimicrobial, antiinflammatory, and antitumoral activities. Sanguinarine has also been incorporated into expectorant mixtures and has a strong bactericidal effect upon gram-positive bacteria, particularly Bacillus anthracis and staphylococci. These medicinal properties are due to the interaction of sanguinarine with DNA. A fibre-optic-based fluorescence instrument for in situ scanning was used for quantitative measurements. The sanguinarine was determined over the range 5-40 ng and a detection limit of 1.60 ng. The method was applied to the quantification of sanguinarine in tissue culture extracts of Chelidonium majus L.
Experimental study of the inhibitory effects of Chelidonium majus L. extractive on Streptococcus mutans in vitro.:
PURPOSE: To study the inhibitory effects of Chelidonium majus L. extractive on the growth of Streptococcus mutans in vitro, and to explore its mechanism in caries prevention. METHODS: Streptococcus mutans 25175 was chosen as the experimental bacterium. The Chelidonium majus L. extractives chelidonine and chelerythrine were double diluted to different concentrations by two-fold dilution. The inhibitory effect of Streptococcus mutans was measured by slip diffusion method. The minimal inhibitory concentration(MIC) was also determined. 0.16% liquor hibitane was used as positive control. Spearman correlation was used for statistical analysis. RESULTS: Inhibition zone of Streptococcus mutans appeared in some concentration of chelerythrine, but no inhibition zone in each concentration of chelidonine. The MIC of chelerythrine was 0.78mg/ml which determined by liquid culture medium. The concentration of chelerythrine was highly related to the inhibitory zone of Streptococcus mutans (r=0.99,P<0.01). CONCLUSION: The antibacterial activity of Chelidonium majus L. extractive chelerythrine on Streptococcus mutans was significant,and the antibacterial activity of the concentration 100mg/ml was higher than that of 0.16% liquor hibitane(19.4mm), indicating that chelerythrine can be used as an agent for prevention of dental caries.
In vitro and in vivo anti-retroviral activity of the substance purified from the aqueous extract of Chelidonium majus L.:
We have isolated a substance with anti-retroviral activity from the freshly prepared crude extract of Chelidonium majus L. (greater celandine) by 9-aminoacridine precipitation method and ion exchange chromatography using Dowex-50W/H+ resin followed by the gel filtration on Sephadex-75 column. Elemental and phenol/sulfuric acid method analyses as well as the mass spectrometry of the purified substance indicated that it may represent a low-sulfated poly-glycosaminoglycan moiety with molecular weight of approximately 3800Da. The substance prevented infection of human CD4+ T-cell lines AA2 and H9 with HIV-1 at concentration of 25mug/mL as well as the cell-to-cell virus spread in H9 cells continuously infected with HIV-1, as determined by the measurement of reverse transcriptase activity and p24 content in cell cultures. Furthermore, we have shown in a murine AIDS model that the treatment with purified substance significantly prevented splenomegaly and the enlargement of cervical lymph nodes in C57Bl/6 mice chronically infected with the pool of murine leukemia retroviruses. The mechanism(s) of anti-retroviral activity of this substance have to be elucidated.
Proapoptotic activity of Ukrain is based on Chelidonium majus L. alkaloids and mediated via a mitochondrial death pathway.:
BACKGROUND: The anticancer drug Ukrain (NSC-631570) which has been specified by the manufacturer as semisynthetic derivative of the Chelidonium majus L. alkaloid chelidonine and the alkylans thiotepa was reported to exert selective cytotoxic effects on human tumour cell lines in vitro. Few clinical trials suggest beneficial effects in the treatment of human cancer. Aim of the present study was to elucidate the importance of apoptosis induction for the antineoplastic activity of Ukrain, to define the molecular mechanism of its cytotoxic effects and to identify its active constituents by mass spectrometry. METHODS: Apoptosis induction was analysed in a Jurkat T-lymphoma cell model by fluorescence microscopy (chromatin condensation and nuclear fragmentation), flow cytometry (cellular shrinkage, depolarisation of the mitochondrial membrane potential, caspase-activation) and Western blot analysis (caspase-activation). Composition of Ukrain was analysed by mass spectrometry and LC-MS coupling. RESULTS: Ukrain turned out to be a potent inducer of apoptosis. Mechanistic analyses revealed that Ukrain induced depolarisation of the mitochondrial membrane potential and activation of caspases. Lack of caspase-8, expression of cFLIP-L and resistance to death receptor ligand-induced apoptosis failed to inhibit Ukrain-induced apoptosis while lack of FADD caused a delay but not abrogation of Ukrain-induced apoptosis pointing to a death receptor independent signalling pathway. In contrast, the broad spectrum caspase-inhibitor zVAD-fmk blocked Ukrain-induced cell death. Moreover, over-expression of Bcl-2 or Bcl-xL and expression of dominant negative caspase-9 partially reduced Ukrain-induced apoptosis pointing to Bcl-2 controlled mitochondrial signalling events. However, mass spectrometric analysis of Ukrain failed to detect the suggested trimeric chelidonine thiophosphortriamide or putative dimeric or monomeric chelidonine thiophosphortriamide intermediates from chemical synthesis. Instead, the Chelidonium majus L. alkaloids chelidonine, sanguinarine, chelerythrine, protopine and allocryptopine were identified as major components of Ukrain. Apart from sanguinarine and chelerythrine, chelidonine turned out to be a potent inducer of apoptosis triggering cell death at concentrations of 0.001 mM, while protopine and allocryptopine were less effective. Similar to Ukrain, apoptosis signalling of chelidonine involved Bcl-2 controlled mitochondrial alterations and caspase-activation. CONCLUSION: The potent proapoptotic effects of Ukrain are not due to the suggested "Ukrain-molecule" but to the cytotoxic efficacy of Chelidonium majus L. alkaloids including chelidonine.
Effect of some isoquinoline alkaloids on enzymatic activity of acetylcholinesterase and monoamine oxidase:
It has been shown, that some benzo[c]-phenanthridine and diisoquinoline alkaloids isolated from Chelidonium majus L. and Macleaya (Bocconia) cordata and M. microcarpa (berberine, sanguinarine, chelidonine) and of drugs ("Ukrain" and "Sanguirythrine") inhibited the enzyme activity of acetylcholinesterase from human erythrocyte and monoamine oxidase from the rat liver. All agents under study have been shown to be reversible inhibitors of the enzymatic hydrolysis of acetylthiocholine. It has been determined that chelidonine belonged to reversible inhibitors of a competitive type, all other examined agents have been demonstrated to be inhibitors of a mixed competitive-noncompetitive type, and a greater contribution to the inhibition was made by the competitive constituent. Among all examined agents berberine, sanguinarine and "Sanguirythrine" were the strongest inhibitors of this reaction and chelidonine and "Ukrain" were much weaker. All agents under study have been shown to be irreversible inhibitors of the oxidative deamination reaction of serotonine and tyramine and not to influence the oxidative deamination reaction of benzylamine as a substrate. Among the examined agents, alkaloid sanguinarine and drug "Ukrain" are the strongest inhibitors of the reaction, alkaloids berberine, sanguinarine and "Sanguirythrine" exhibit a weaker action.
Stylopine from Chelidonium majus inhibits LPS-induced inflammatory mediators in RAW 264.7 cells.:
Stylopine is a major component of the leaf of Chelidonium majus L. (Papaveraceae), which has been used for the removal of warts, papillomas and condylomas, as well as the treatment of liver disease, in oriental countries. Stylopine per se had no cytotoxic effect in unstimulated RAW 264.7 cells, but concentration-dependently reduced nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta), and the IL-6 production and cyclooxygenase-2 (COX-2) activity caused by the LPS stimulation. The levels of inducible nitric oxide synthase (iNOS) and COX-2 protein expressions were markedly suppressed by stylopine in a concentration dependent manner. These results suggest that stylopine suppress the NO and PGE2 production in macrophages by inhibiting the iNOS and COX-2 expressions. These biological activities of stylopine may contribute to the anti-inflammatory activity of Chelidonium majus.
Inhibition of liver mitochondrial monoamine oxidase activity by alkaloids isolated from Chelidonium and Macleaya and by their derivative drugs:
It has been shown that the major alkaloids from plants Chelidonium majus L. and Macleaya (Bocconia) cordata and microcarpa, namely, berberine, sanguinarine, chelidonine, and drugs "Ukrain" (thiophosphoric acid derivative of a sum of the alkaloids isolated from Ch. majus L.) and "Sanguirythrine" (a mixture of the alkaloids sanguinarine and chelerythrine, w/w 3:7, isolated from Macleaya), are irreversible inhibitors of oxidative deamination reaction of serotonin and tyramine as substrates, catalyzed by rat liver mitochondrial monoamine oxidase (MAO). At the same time these substances do not influence the oxidative deamination reaction of benzylamine as substrate (in concentration 1 mM or less). The substrate specificity of this inhibition manifests that mainly the oxidative deamination reactions catalyzed by MAO form A are inhibited by the agents studied. Among the examined agents, alkaloid chelidonine and drug "Ukrain" are the strongest inhibitors of the reaction. Alkaloids berberine and sanguinarine and drug "Sanguirythrine" exhibit a weaker action. Judging from the data obtained, sanguinarine and chelerythrine appear to exert similar inhibitory effects in this reaction, since sanguinarine and "Sanguirythrine" have similar values of bimolecular rate constants of their interaction with mitochondrial MAO. As it is well known, the MAO inhibitors appear to be, as a rule, pronounced antidepressants. The combination of malignotoxicity and antidepressive activity in drug "Ukrain" seems to be favourable for its clinical applications.
Radiation protective effect of an extract from Chelidonium majus.:
We earlier reported that CM-AIa isolated from Chelidonium majus had mitogenic activity, generated lymphokine-activated killer cells, and increased the number of granulocyte-macrophage colony-forming cells (GM-CFC). In an extended effort to search for other immunostimulatory effects, we evaluated the protective effects of in vivo injected CM-AIa against irradiation. CM-AIa was found to increase the number of bone marrow cells, spleen cells, GM-CFC, and platelets in irradiated mice. In addition, this agent induced endogenous production of cytokines such as interleukin 1 and tumor necrosis factor alpha, which are required for hematopoietic recovery. We also demonstrated that CM-AIa treatment 24 hours before irradiation protected mice with 80% survival at lethal dose 100/15. These findings indicate that CM-AIa may be a useful agent for reducing the time needed for reconstitution of hematopoietic cells after irradiation treatment.
Acute hepatitis induced by Greater Celandine (Chelidonium majus).:
We report on two cases of acute liver injury along with the intake of Greater Celandine (Chelidonium majus), a well-known herbal remedy frequently used for irritable bowel syndrome. All other possible causes of acute liver damage were excluded in both patients. In one patient, cholestatic hepatitis recurred rapidly after involuntary re-exposition. Both patients fully recovered after the withdrawal of Greater Celandine. The two cases add to the existing database about the potential hepatotoxicity of drugs containing Greater Celandine and raise the question whether the approval of this drug should be re-evaluated in the light of lacking evidence for a therapeutic benefit.
Genetic aspects of the relationship between isoquinoline alkaloids and mineral elements in greater celandine (Chelidonium majus L.):
Interrelations between the total content of isoquinoline alkaloids, concentrations of quaternary protoberberines and benzophenanthridines, and the amount of K, Cu, Co, Al, Ba, and Zn in aerial parts of individual celandine plants were revealed, within a single cenopopulation, using correlation analysis and regression analysis. Mathematical models describing the regulation of isoquinoline metabolism by some of the mineral elements were obtained in the analytical form. The results suggest that this process is genetically determined.
Immunomodulatory activity of protein-bound polysaccharide extracted from Chelidonium majus.:
In the course of searching immunomodulators from natural sources, the protein-bound polysaccharide, CM-Ala, has been isolated from the water extract of Chelidonium majus L. (Papaveraceae). The immunostimulatory characteristics have been investigated in several experiments such as generation of activated killer (AK) cells, proliferation of splenocytes, activation of macrophages and granulocyte macrophage-colony forming cell (GM-CFC) assay. Of the fractions obtained using Sephacryl S200 column chromatography, CM-Ala was the most effective fraction that augmented the cytotoxicity against Yac-1 tumor cells from 0.88% to 34.18% by culturing with splenocytes for 5 days. CM-Ala also enhanced nitric oxide production by two fold in peritoneal macrophages and exhibited antitumor activity. It showed mitogenic activity on both spleen cells and bone marrow cells. CM-Ala induced proliferation of splenocytes by 84 fold and increased GM-CFC numbers by 1.48 fold over than the non-treated. On the contrary, CM-Ala had cytotoxic activity to a diverse group of tumor cells. From the above results, we proposed that CM-Ala has a possibility of an effective antitumor immunostimulator.
Effect of a homeopathic drug, Chelidonium, in amelioration of p-DAB induced hepatocarcinogenesis in mice.:
BACKGROUND: Crude extracts of Chelidonium majus, and also purified compounds derived from crude extracts of this plant, have been reported to exhibit anti-viral, anti-inflammatory, anti-tumor and anti-microbial properties both in vitro and in vivo. Chelidonium is a homeopathic drug routinely used against various liver disorders including cancer in humans. Two potencies of Chelidonium (Ch-30, Ch-200) have been tested for their possible anti-tumor and enzyme modulating activities in liver and anti-clastogenic effects during p-DAB-induced hepatocarcinogenesis in mice compared to suitable controls. METHODS: Several cytogenetic and enzymatic protocols were used at three fixation intervals; at 60 days, 90 days and 120 days of treatment. Different sets of healthy mice were fed: i) hepatocarcinogen, p-DAB plus phenobarbital (PB), ii) only PB, iii) neither p-DAB nor PB (normal control). One set of mice fed with p-DAB plus PB was also fed Ch-30 (iv) and another set Ch-200 (v). All standard currently used methods were adopted for cytogenetical preparations and for the enzyme assays. RESULTS: All group (i) mice developed tumors in liver at all fixation intervals, while none of group (ii) and (iii) mice developed any tumors. About 40% mice in group (iv) and group (v) did not show tumor nodules in their liver. Feeding of Chelidonium to group (iv) and (v) mice reduced genotoxic effects to a significant extent (p < 0.05 to p < 0.001). CONCLUSION: The homeopathic drug Chelidonium exhibited anti-tumor and anti-genotoxic activities and also favorably modulated activities of some marker enzymes. Microdoses of Chelidonium may be effectively used in combating liver cancer.
Acute hepatitis after use of a herbal preparation with greater celandine (Chelidonium majus):
A 42-year-old woman developed jaundice due to acute hepatitis several weeks after ingestion of a herbal preparation containing greater celandine (Chelidonium majus) and curcuma root, which had been prescribed by an alternative therapist due to a skin complaint. After the medication had been withdrawn, clinical recovery was rapid and the hepatic functions returned to normal within 2 months. The hepatitis was ascribed to the known hepatotoxic effects of C. majus. In view of the increasing popularity of herbal remedies, greater awareness of side effects, such as hepatotoxicity, is needed. Quite a number of herbal preparations carry the risk of liver damage. The supposed clinical effectiveness of herbal remedies does not seem to always outweigh the potential risks. In the event of non-clarified liver function disturbances the ingestion of supposedly harmless, but potentially hepatotoxic, herbal products should be considered.
Ukrain, an alkaloid thiophosphoric acid derivative of Chelidonium majus L. protects human fibroblasts but not human tumour cells in vitro against ionizing radiation.:
PURPOSE: Ukrain, an alkaloid thiophosphoric acid derivative of Chelidonium majus L., has demonstrated a promising impact on chemotherapy in a variety of malignancies. The effects of the drug on cell survival, alteration of the cell cycle and induction of apoptosis were examined without and in combination with ionizing radiation (IR). The TP53 status of the cell lines used was also investigated. MATERIALS AND METHODS: Exponentially growing human tumour cell lines MDA-MB-231 (breast), PA-TU-8902 (pancreas), CCL-221 (colorectal), U-138MG (glioblastoma), and human skin and lung fibroblastic cells, HSF1, HSF2 and CCD32-LU were studied by colony assay, flow cytometry (cell-cycle, annexin-V staining for apoptosis) and Western blotting. Ukrain was used in concentrations from 0.1 to 50 microg ml(-1) for 1, 3 and 24 h and radiation as single doses of 1-10Gy. Combined drug-radiation exposure employed 1 microg ml(-1) Ukrain for 24h plus 2-8 Gy. RESULTS: Ukrain cytotoxicity was time- and dose-dependent. The combination of Ukrain plus IR gave enhanced toxicity in CCL-221 and U-138MG cells, but not in MDA-MB-231 and PA-TU-8902 cells. Most strikingly, a radioprotective effect was found in normal human skin and lung fibroblasts. Flow-cytometry analyses supported the differential and cell line-specific cytotoxicity of Ukrain. CCL-221 and U-138MG cells accumulated in G2 after 24-h Ukrain treatment, whereas no alterations were detected in the other tumour cells and normal fibroblasts tested. Western blotting of TP53 demonstrated non-functional overexpression in all tumour cell lines without affecting p21. HSF1 presented wild-type TP53 and a p21 response after IR. Flowcytometric analyses of annexin-V staining showed no induction of apoptosis after Ukrain treatment in comparison with untreated controls. CONCLUSIONS: Differential effects of Ukrain in modulating radiation toxicity of human cancer cell lines and its protective effect in normal human fibroblasts suggest that this alkaloid may have potential properties for clinical radiochemotherapy.
Chelidocystatin, a novel phytocystatin from Chelidonium majus.:
Greater celandine (Chelidonium majus L.) has traditional uses in European and Chinese herbal medicine. In the plant sap significant inhibitory activity against papain was observed. A cysteine proteinase inhibitor, named chelidocystatin, was isolated from the plant using papain Sepharose affinity chromatography followed by gel filtration and ion-exchange chromatography. Chelidocystatin showed a M(r) of 10,000 on SDS-PAGE with the pI of 9.3, and was a strong inhibitor of cathepsin L (Ki = 5.6 x 10(-11) M), papain (Ki = 1.1 x 10(-10) M) and cathepsin H (Ki = 7.5 x 10(-9) M). The complete amino acid sequence of the protein was obtained with N-terminal sequencing and sequencing of the peptides after digestion of the protein. Moreover, a major part of the sequence was verified by molecular cloning. The conserved glycine residue at the N-terminal region and the QVVAG motif, which are both believed to be involved in the inhibitory activity, indicate that it is a member of the cystatin superfamily. The amino acid sequence of chelidocystatin shows a high degree of homology with cysteine proteinase inhibitors belonging to the phytocystatin group, especially with the recently described carrot and sunflower phytocystatins with which it shares 57% and 54% homology, respectively.
Isolation and Partial Characterization of a New Lectin from Seeds of the Greater Celandine (Chelidonium majus).:
Seeds of the greater celandine (Chelidonium majus L.) contain a lectin which could be isolated using a combination of affinity chromatography on chitin and ion exchange chromatography on sulphopropyl-Sephadex. The purified lectin was partially characterized with respect to its biochemical and physicochemical properties. It is a small dimeric protein composed of two different subunits of M(r) 9,500 and 11,500, respectively. Its amino acid composition is typified by high contents of glycine and cysteine. No covalently bound carbohydrate could be detected. Hapten inhibition experiments indicated that the lectin exhibits specificity towards oligomers of N-acetylglucosamine, the potency of inhibition increasing with chain length up to four residues. The greater celandine lectin is the first lectin to be isolated from a species belonging to the plant family Papaveraceae (poppy family). Although it represents a new type of plant lectin, resemblances to phytohemaglutinins from diverse taxonomic origin are obvious.
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celandine is almost in flower now
celandine is right
celandine is very nice and i like her because she says ooh and ner a lot
celandine is also said to protect anyone who carries a sprig with them
celandine is normally thought of as a weed
celandine is flowering at the moment
celandine is a coarse yellow flowering plant which blooms in the early spring
celandine is also known as greater celandine
celandine is in flower in sheltered sunny places such as bradda glen
celandine is primarily used as a liver detoxifying herb for treatment of hepatitis
celandine is an herbal medicine that is used for cramping pain associated with the gall bladder or stomach
celandine is a relative of the buttercup which likes a damp woodland spot and flowers before the leaves emerge on the trees; the few
celandine is a common name for ranunculus
celandine is a variable biennial or perennial with a thick
celandine is common along roadsides
celandine is also popularly known as swallow
celandine is said to have powers of protection and escape
celandine is to cease trading
celandine is told to climb the hill and finds ballaw
celandine is primarily for residents who originate from edmonton and currently most people are transferred from the long stay hospitals
celandine is back at the old manhole cover
celandine is out in leaf
celandine is restricted to shaded sites in damp soils in the ph range of 4 to 8
celandine is the daughter of seredic and hilda
celandine is put into cold water and
celandine is for the eyes & pennyroyal soothes the roiled brow; ophelia's rue floats upon the tide
celandine is practically absent and is replaced by large patches of asarum canadense and the ferns dryopteris marginalis and polystichium aerostichoides
celandine is not recommended for prolonged usage
celandine is in full bloom in the churchyard
celandine is useful in matters of protection
celandine is all growing on a steeply sloped part of the property where newspapers and mulch refuse to stick
celandine is popular in russia
celandine is the rootstock of the plant chelidonium majus
celandine is starting to appear
celandine is in flower
celandine is an herb of protection
Reference:
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- 1.Celandine,Swallowwort:Celandine is named after the Greek word for the swallow, because it starts flowering when the birds arrive and stops when they leave.
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