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Cytotoxic effects of substances in Indigo Plant (Polygonum tinctorium Lour.) on malignant tumor cells
Abstract
From the plant commonly known as Indigo Plant (Polygonum tinctorium Lour., Shimane, Japan), Tryptanthrin was isolated which had cytotoxic effects on malignant tumor cells. The cytotoxic effects on human solid cancer cells, leukemia cells, murine glioblastoma cell, colon cancer and malignant melanoma cells in vitro were assayed. Tryptanthrin induced remarkable necrotic and apoptotic changes in the malignant tumor cells.
... 4) Anticancer effect: the results showed the inhibition proliferation of HT-29 cell line (43). Other Pharmacological effects including: 5) Antioxidant effect, 6) Effect on respiratory system, 7) Protective effects, 8) Anti-inflammatory effect, 9) Effect in gastric duodenal ulcers, and 10) Effect on smooth muscles. ...
... Tryptanthrin was found to inhibit the growth of human gastric cancer (HGC), lung cancer (HLC), and promyelocytic leukemia HL-60 cells with IC50 values of 1.5-4.2 µg/mL [87]. It showed significant cytotoxicity against non-small cell lung cancer NCI-H460, human glioblastoma SF-268, and human breast cancer MCF-7 cell lines with IC50 values of 8.5-22.6 µM [88]. ...
Isatis tinctoria L. (Brassicaceae), which is commonly known as woad, is a species with an ancient and well-documented history as an indigo dye and medicinal plant. Currently, I. tinctoria is utilized more often as medicinal remedy and also as a cosmetic ingredient. In 2011, I. tinctoria root was accepted in the official European phytotherapy by introducing its monograph in the European Pharmacopoeia. The biological properties of raw material have been known from Traditional Chinese Medicine (TCM). Over recent decades, I. tinctoria has been investigated both from a phytochemical and a biological point of view. The modern in vitro and in vivo scientific studies proved anti-inflammatory, anti-tumour, antimicrobial, antiviral, analgesic, and antioxidant activities. The phytochemical composition of I. tinctoria has been thoroughly investigated and the plant was proven to contain many valuable biologically active compounds, including several alkaloids, among which tryptanthrin, indirubin, indolinone, phenolic compounds, and polysaccharides as well as glucosinolates, carotenoids, volatile constituents, and fatty acids. This article provides a general botanical and ethnobotanical overview that summarizes the up-to-date knowledge on the phytochemistry and biological properties of this valuable plant in order to support its therapeutic potential. Moreover, the biotechnological studies on I. tinctoria, which mainly focused on hairy root cultures for the enhanced production of flavonoids and alkaloids as well as on the establishment of shoot cultures and micropropagation protocols, were reviewed. They provide input for future research prospects.
... Tryptanthrin (3) is an already known AhR inducer which possesses also significant anti-inflammatory, antimicrobial and cytostatic activity. [24][25][26][27][28][29][30] It has been isolated from many plants as well as the yeast Candida (Yarrowia) lipolytica [31][32][33] and has also been detected and isolated in Malassezia furfur yeasts. 3,4 Additionally, the spectroscopic analysis of the mixture showed the formation of indolo[3,2-b]carbazole (4), another known Malassezia metabolite, in traces ( Figure 2). ...
Malassezia furfur isolates from diseased skin preferentially biosynthesize compounds which are among the most active known Aryl-hydrocarbon Receptor (AhR) inducers, such as indirubin, tryptanthrin, indolo[3,2-b]carbazole and 6-formylindolo[3,2-b]carbazole. In our effort to study their production from Malassezia spp., we investigated the role of indole-3-carbaldehyde (I3A), the most abundant metabolite of Malassezia when grown on tryptophan agar, as a possible starting material for the biosynthesis of the alkaloids. Treatment of I3A with H2O2 and use of catalysts like diphenyldiselenide resulted in the simultaneous one-step transformation of I3A to indirubin and tryptanthrin in good yields. The same reaction was first applied on simple indole and then on substituted indoles and indole-3-carbaldehydes, leading to a series of mono- and bi-substituted indirubins and tryptanthrins bearing halogens, alkyl or carbomethoxy groups. Afterwards, they were evaluated for their AhR agonist activity in recombinant human and mouse hepatoma cell lines containing a stably transfected AhR-response luciferase reporter gene. Among them, 3,9-dibromotryptanthrin was found to be equipotent to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) as an AhR agonist and 3-bromotryptanthrin was 10-times more potent than TCDD in the human HG2L7.5c1 cell line. In contrast, 3,9-dibromotryptanthrin and 3-bromotryptanthrin were ~4,000- and >10,000-times less potent than TCDD in the mouse H1L7.5c3 cell line, respectively, demonstrating that they are species-specific AhR agonists. Involvement of the AhR in the action of 3-bromotryptanthrin was confirmed by the ability of the AhR antagonists CH223191 and SR1 to inhibit 3-bromotryptanthrin-dependent reporter gene induction in human HG2L7.5c1 cells. In conclusion, I3A can be the starting material used by Malassezia for the production of both indirubin and tryptanthrin through an oxidation mechanism and modification of these compounds can produce some highly potent, efficacious and species-selective AhR agonists.
... With the aid of HPLC-based activity profiling (Potterat and Hamburger, 2006) we then identified several pharmacologically active metabolites in the extracts, such as tryptanthrin (13), a-linolenic acid (22) and (E)-3-(3 0 ,5 0 -dimethoxy-4 0 -hydroxy-benzylidene)-2-indolinone (9) as inhibitors of cyclooxygenase-2, 5-lipoxygenase, expression of inducible nitric oxide synthase (iNOS), human neutrophil elastase, and release of histamine from mast cells (Danz et al., 2001(Danz et al., , 2002Hamburger et al., 2006;Oberthür et al., 2005;Rüster et al., 2004). These findings were corroborated by pharmacological studies on tryptanthrin (13) and indirubin (15) performed by other groups (Hoessel et al., 1999;Honda et al., 1980;Ishihara et al., 2000;Kimoto et al., 1999). The potential of lipophilic I. tinctoria extracts was substantiated by in vivo studies in models of acute and chronic inflammation, contact allergy, and rheumatoid arthritis (Recio et al., 2006a,b), and by a clinical pilot study in experimentally induced skin erythema (Heinemann et al., 2004). ...
... Although some of these compounds have been used for lead optimization studies aimed at improving their pharmacokinetic and pharmacodynamic profiles, none of natural product derivatives has yet progressed into clinical trials. Remarkably, the use of tryptanthrin (22) from the medicinal plants Polygonumtinctorium and Isatistinctoria has been described in the traditional Chinese medicine for its inhibitory activities against a variety of micro-organisms and parasites [116], along with its immunomodulatory, anti-inflammatory and antitumor activities [117][118][119][120]. ...
Inhibition of IDO1 is a strategy pursued to develop novel therapeutic treatments for cancer. Recent years have witnessed growing evidence that the enzyme plays a pivotal role in viral, bacterial and fungal infections. These studies have underscored the Janus-faced nature of IDO1 in the regulation of host-pathogen interactions and commensalism. Starting with an outlook on the advances in the structural features of IDO1, herein we report recent findings that pinpoint the involvement of IDO1 in infectious diseases. Then, we present an overview of IDO1 inhibitors that have been enrolled in clinical trials as well as other distinct modulators of the enzyme that may enable further investigations of IDO1 and its role in infectious disease.
... It has been reported that tryptanthrin has various biological activities, such as inhibitory activities against a variety of microorganisms and parasites, 28,29 immunomodulatory 30 and anti-inflammatory activity, 31 and antitumor activity. 32 Tryptanthrin has two characteristic reduction potentials (−0.75 and −1.40 V vs SCE) for the reduction of two carbonyl groups of the fiveand the six-membered rings, 33 thus having potentials for antileishmanial activity and photoelectronic reception abilities. 33,34 In recent years, tryptanthrin has attracted much attention as an anticancer agent. ...
Indoleamine 2,3-dioxygenase (IDO-1) is emerging as an important new therapeutic target for the treatment of cancer, neurological disorders and other diseases that are characterized by pathological tryptophan metabolism. However, only a few structural classes are known to be IDO-1 inhibitors. In this study, a natural compound tryptanthrin was discovered to be a novel potent IDO-1 inhibitor by screening of indole-based structures. Three series of thirteen tryptanthrin derivatives were synthesized, and the structure-activity analysis was undertaken. The optimization led to the identification of 5c, which exhibited the inhibitory activity at a nanomolar level. In vitro 5c dramatically augmented the proliferation of T cells. When administered to Lewis lung cancer (LLC) tumor-bearing mice, 5c significantly inhibited IDO-1 activity and suppressed tumor growth. In addition, 5c reduced the numbers of Foxp3+ regulatory T cells (Tregs), which are known to prevent the development of efficient antitumor immune responses.
... Indirubin inhibits cyclin dependent kinases and, hence, cell division (Hoessel et al., 1999). Cytoinhibitory activity was also reported for tryptanthrin (Kimoto et al., 1999). These findings are in disagreement with our own cytotoxicity studies in Mono Mac and RAW cells, where we found no inhibitory effects at concentrations up to 10 µg/ml and moderate inhibition only at 100 µg/ml (Danz et al., 2001). ...
An account on the reinvestigation of the old dye and medicinal plant Isatis tinctoria as an anti-inflammatory and current research on the active principles in woad is given. In a broad-based screening, a dichloromethane
extract from the leaves displayed significant activities on several clinically relevant targets of inflammation. The cyclooxygenase-2
inhibitory principle was identified with the aid of HPLC-based activity profiling as the alkaloid tryptanthrin. In cell based
assays, tryptanthrin strongly inhibited eicosanoid synthesis catalyzed by cyclooxygenase-2 and 5-lipoxygenase. A supercritical
carbon dioxide extraction process was developed to replace the dichloromethane extract. Dichloromethane and carbon dioxide
extracts showed in vivo anti-inflammatory activity in topical and oral application. With the aid of electrospray ionization liquid chromatography-mass
spectrometry coupled skin microdialysis, tryptanthrin was found to penetrate the skin. The penetration from the extract was
better than for the pure alkaloid. A screening of 67 woad samples of different geographic origin revealed up to 30-fold differences
in tryptanthrin content in leaves.
... With the aid of HPLC-based activity profiling (Potterat and Hamburger, 2006) we then identified several pharmacologically active metabolites in the extracts, such as tryptanthrin (13), a-linolenic acid (22) and (E)-3-(3 0 ,5 0 -dimethoxy-4 0 -hydroxy-benzylidene)-2-indolinone (9) as inhibitors of cyclooxygenase-2, 5-lipoxygenase, expression of inducible nitric oxide synthase (iNOS), human neutrophil elastase, and release of histamine from mast cells (Danz et al., 2001(Danz et al., , 2002Hamburger et al., 2006;Oberthür et al., 2005;Rüster et al., 2004). These findings were corroborated by pharmacological studies on tryptanthrin (13) and indirubin (15) performed by other groups (Hoessel et al., 1999;Honda et al., 1980;Ishihara et al., 2000;Kimoto et al., 1999). The potential of lipophilic I. tinctoria extracts was substantiated by in vivo studies in models of acute and chronic inflammation, contact allergy, and rheumatoid arthritis (Recio et al., 2006a,b), and by a clinical pilot study in experimentally induced skin erythema (Heinemann et al., 2004). ...
A broad-based characterisation of a pharmacologically active dichloromethane extract from Isatis tinctoria leaves was carried out. For a comprehensive picture we also included the polar constituents of I. tinctoria (MeOH extract) and for comparative purposes, the taxonomically closely related plant I. indigotica. Diode array detector, evaporative light scattering detector, atmospheric pressure chemical ionisation and electrospray ionisation mass spectrometry, and electrospray ionisation time-of-flight mass spectrometry detectors were used in parallel to ensure a wide coverage of secondary metabolites with highly diverging analytical properties. Off-line microprobe nuclear magnetic resonance spectroscopy after peak purification by semi-preparative high-pressure liquid chromatography served for structure elucidation of some minor constituents. More than 65 compounds belonging to various structural classes such as alkaloids, flavonoids, fatty acids, porphyrins, lignans, carotenoids, glucosinolates and cyclohexenones were unambiguously identified, and tentative structures were proposed for additional compounds. Numerous compounds were identified for the first time in the genus Isatis, and an indolic alkaloid was discovered.
... Various biological activities attributed to crude extracts and compounds isolated from P. tinctorium have been described. Anti-oxidative and anti-tumor activities in an ethyl acetate extract of this plant have been reported by Kimoto et al. 2,3) which were found to be caused by gallic acid and caŠeic acid, and tryptanthrin, respectively. We have recently reported that tryptanthrin exerted a potent anti-in‰ammatory eŠect on murine macrophages in an in vitro system by inhibiting the synthesis of NO and PGE2, 4) and this molecule was found to have a therapeutic eŠect in an in vivo model of in‰ammatory disease. ...
A number of agents have been reported to influence osteoblastic differentiation and to prevent and treat bone loss. We found that kaempferol, a flavonoid identified in extracts of the medicinal plant, Polygonum tinctorium. Lour, had stimulatory effects on the differentiation and mineralization of the murine pre-osteoblastic cell line, MC3T3-E1. After enhancing the alkaline phosphatase activity, significant augmentation of calcification by kaempferol was observed between concentrations of 10 and 20 μM, without any marked effect on cell proliferation. When kaempferol was combined with ipriflavone, which is clinically applied to treat bone loss, calcification was synergistically augmented, suggesting that these two flavonoids may have different mechanisms of action.
These results suggest that kaempferol may be a promising agent for the prevention or treatment of bone loss, especially when combined with ipriflavone.
This study was conducted to isolate the anti-neuroinflammatory component(s) in the 80% EtOH extract of P. tinctoria, and to investigate underlying molecular mechanism of the anti-neuroinflammatory component(s) in LPS-induced BV2 microglial cells. To isolate the active component(s) in the extract, various chromatographic methods were employed, and the structures of the isolated secondary metabolites were determined mainly by analysis of spectroscopic data such as NMR and MS data. Tryptanthrin (1), isolated from P. tinctoria extract, significantly inhibited the protein expression of iNOS and COX-2, and reduced the levels of their products (NO and PGE2) in LPS-stimulated BV2 microglial cells. Tryptanthrin (1) also downregulated the production of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1β. These anti-neuroinflammatory effects of tryptanthrin (1) was elucidated to be correlated with inactivating NF-κB pathway by interrupting the phosphorylation and degradation of the inhibitor of κB-α protein, and inhibiting the DNA binding activity of NF-κB. In addition, tryptanthrin (1) suppressed the activation of p38 MAPK pathway. Furthermore, tryptanthrin (1) inhibited the TLR4 and MyD88 protein expression in LPS-stimulated BV2 microglial cells. Taken together, it was suggested that tryptanthrin (1) have anti-neuroinflammatory effect by regulating TLR4-MyD88-mediated several inflammatory pathways including p38 and NF-κB pathways in LPS-induced BV2 microglial cells.
A crude extract of Polygonum tinctorium Lour. (P. tinctorium) has been demonstrated to have a variety of biological activities including anti- inflammatory effects. In this paper, we found that both methanol and ethyl acetate extracts of P. tinctorium inhibited the replication of viruses including vesicular stomatitis virus (VSV), influenza virus A/PR/8/34, vaccinia virus (VV), human herpes simplex virus type-1 (HSV-1) and mouse cytomegalo virus (MCMV). The methanol extract had the 50% inhibitory concentration of 6.25 μg/ml on VSV and the ethyl acetate had that of 25 μg/ml without any toxicity on the target cells. The water extract did not show any antiviral effects on these viruses. Addition of P. tinctorium extracts during the viral infection period apparently augmented the cell viability. These results suggest that P. tinctorium contains some antiviral substances inhibiting both the viral replication in infected cells and the viral infection of the target cells.
Polygonum tinctorium Lour. has been used as a crude drug for pyrexia, food poisoning and inflammation. We investigated the effect of P. tinctorium on the serum cholesterol and triglyceride levels of hyperlipidemic mice induced by a high fat diet. After 20 weeks of a high fat diet feeding, the serum cholesterol and triglyceride levels were significantly increased, whereas the mice on the P. tinctorium-supplemented high fat diet had significantly decreased serum cholesterol and triglyceride levels. These results suggest that P. tinctorium improves hyperlipidemia induced by a high fat diet.
The idea and practice of developing or identifying compounds capable of eliminating the transformed cells or cancer cells without being nontoxic to their normal counterparts deserves much importance. Since ages, plants have been considered and proven to be repertoires of chemicals possessing immense therapeutic potential. A proportion of these plant-derived compounds or phytochemicals were shown to be highly competent anticancer agents besides being effective against many other diseases. Representative compounds of different classes of phytochemicals are in clinical use against cancer. In this chapter, we discuss the anticancer potential of two compounds: quercetin, a flavonoid and tryptanthrin, an indoloquinazoline alkaloid, and the mechanisms behind their cytotoxic effects on cancers of different origin. The chapter also gives a brief mention of their properties that make them effective against cancer.
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Various extracts prepared from the traditional dye and medicinal plant Isatis tinctoria L. were submitted to a broad in vitro screening against 16 anti-inflammatory targets. Dichloromethane (DCM) extracts from dried leaves showed a marked cyclooxygenase (COX) inhibitory activity with a preferential effect on COX-2 catalysed prostaglandin synthesis. A supercritical fluid extraction (SFE) procedure employing CO2-modifier mixtures was developed by which the bioactivity profile and chromatographic fingerprint of the DCM extract could be reproduced. High-resolution activity directed on-line identification of the COX-2 inhibitory principle, using a combination of LC-DAD-MS with a microtitre-based bioassay, led to the identification of tryptanthrin (1) as the constituent responsible for essentially all COX-2 inhibitory activity in the crude extract. Following on-line identification, 1 was isolated at preparative scale and its structure confirmed by comparison with synthetic tryptanthrin. In an assay with lipopolysaccharide stimulated Mono Mac 6 cells, tryptanthrin (1) was of comparable potency (IC50 = 64 nM) than the preferential COX-2 inhibitors nimesulide (IC50 = 39 nM) and NS 398 (IC50 = 2 nM). The SFE extract and 1 showed no cytotoxicity in Mono Mac 6 and RAW 264.7 cells when tested at 100 microg/ml and 10 microM, respectively.
Extract of the leaves of the indigo plant (Polygonum tinctorium Lour.) was examined for antimicrobial activity against oral pathogenic bacteria. The indigo plant extract at concentrations of 1.74–3.48mg/ml inhibited the growth of oral cariogenic and periodontopathic bacteria. Tryptanthrin, one of the components of indigo plant extract, showed the strongest antimicrobial effect at doses ranging from 3.13–25g/ml, indicating that this compound is one of the active ingredients. Furthermore, treatment of periodontopathic bacteria Porphyromonas gingivalis and Prevotella intermedia with the indigo plant extract for 3–8h resulted in death of the bacteria in a dose-dependent manner, whereas Streptococcus mutans was not affected by the extract. Thus, for its antimicrobial and bactericidal effects on oral pathogens, indigo plant extract would provide useful material for preventing and treating periodontal diseases and dental caries.
Despite its beneficial role in host defense mechanisms, excessive nitric oxide (NO) production by activated macrophages has been implicated in several inflammatory diseases. To clarify the mechanisms of anti-inflammatory activities of Polygonum tinctorium, we evaluated whether extracts of P. tinctorium could modulate the production of NO by activated macrophages. An AcOEt extract of P. tinctorium markedly inhibited NO synthesis by interferon-gamma (IFN-gamma)/lipopolysaccharide (LPS)-stimulated murine peritoneal macrophages and the macrophage-like cell line RAW 264.7 in a dose-dependent manner. Inhibition of NO synthesis was achieved by reducing inducible NO synthase (iNOS) expression at protein and mRNA levels. However, the AcOEt extract of P. tinctorium failed to inhibit NO synthesis when iNOS was already expressed following stimulation with IFN-gamma and LPS. The AcOEt extract also exhibited inhibitory activity on iNOS expression in human lung epithelial A549 cells stimulated with a combination of IFN-gamma, TNF-alpha and IL-1 beta without affecting the expression of constitutive isoforms of NOS. Furthermore, in vivo injection of the AcOEt extract of P. tinctorium into LPS-treated mice significantly reduced NO synthesis by peritoneal exudate cells under ex vivo conditions. These results suggest that P. tinctorium extract may be a potential therapeutic modulator of NO synthesis in various pathological conditions.
Nitric oxide (NO) and prostaglandins have been implicated in the pathogenesis of several inflammatory diseases. In this study, we investigated the effect of tryptanthrin (6,12-dihydro-6, 12-dioxoindolo-(2,1-b)-quinazoline), an antimicrobial and antitumoral plant compound isolated from Porigonum tinctorium, on NO and prostaglandin E(2) production by interferon-gamma and lipopolysaccharide-stimulated murine macrophage-like RAW 264.7 cells. Tryptanthrin markedly inhibited both NO and prostaglandin E(2) production in a dose-dependent manner. Tryptanthrin at 20 microM fully inhibited expression of inducible NO synthase, suggesting that the inhibitory effect on NO synthesis was mediated by inhibited expression of the enzyme. On the other hand, tryptanthrin had no effect on the levels of cyclooxygenase-2 protein, but inhibited cyclooxygenase enzyme activity with a ICM(50) value of 1.5 microM. Thus, tryptanthrin has the dual functions of inhibiting both NO and prostaglandin E(2) production by activated macrophages, suggesting that tryptanthrin exhibits anti-inflammatory properties.
We evaluated the effect of tryptanthrin and kaempferol, both isolated from Polygonum tinctorium Lour., against Helicobacter pylori colony formation in vitro and in H. pylori-infected Mongolian gerbils. H. pylori suspension was mixed with solution of tryptanthrin and/or kaempferol and placed onto agar plates. These plates were incubated at 37 degrees C, under 10% CO2 for 5 days, and the H. pylori colonies were counted. For the in vivo experiment, Mongolian gerbils were inoculated with H. pylori ATCC 43504 orally. After 4 weeks, the infected gerbils were given tryptanthrin and/or kaempferol, administered orally, twice a day for 10 days. The animals were killed and the number of live H. pylori in their stomachs was determined. In vitro both tryptanthrin and kaempferol significantly decreased the numbers of H. pylori colonies a dose-dependent manner. An additive effect on colony formation was observed with the combined use. In the in vivo experiment, oral administration of tryptanthrin and/or kaempferol significantly decreased the numbers of colonies in the gerbils' stomachs. We concluded that tryptanthrin and kaempferol were effective against H. pylori in vivo.
Tryptanthrin, a bioactive ingredient of Polygonum tinctorium Lour., is a member of the Indigo plant family and has potent cytocidal effects on various human leukemia cells in vitro. At low concentrations, tryptanthrin enhanced the expression of cell differentiation (CD) markers in human monocytic (U-937) and promyelocytic (HL-60) leukemia cells indicative of differentiation to monocytes/macrophages. Furthermore, nitroblue tetrazolium (NBT) reductive and alpha-naphthyl butyrate esterase (NBE) activities were markedly increased after treatment. Tryptanthrin was more potent than dimethyl sulfoxide (DMSO) at inducing U-937 cell differentiation into monocytes/macrophages. After treatment with higher concentrations of tryptanthrin for 24 h, cytoplasmic vacuolation and destruction of mitochondria were observed. The leukemia cells died via apoptosis 48 h after treatment. Cytoplasmic vacuolation and apoptotic changes correlated with the dysfunction of mitochondria. Electron microscopic observations revealed marked swelling and destruction of mitochondria after exposure of the leukemia cells to tryptanthrin. Exposure to tryptanthrin enhanced Fas-induced apoptosis and increased caspase-3 activity before induction of apoptosis. These results show that low concentrations of tryptanthrin can induce differentiation of leukemia cells but higher concentrations will kill leukemia cells through apoptosis, possibly through a caspase-3/Fas antigen pathway.
The effect of a crude ethyl acetate (AcOEt)-extract and tryptanthrin extracted from the Indigo plant (Polygonum tinctorium Lour.) on azoxymethane (AOM)-induced intestinal tumors was examined in F344 rats. The rats were given subcutaneous (s.c.) injections of either AOM (15 mg/kg body weight (b.w.)) once a week for 3 weeks to induce atypical crypt foci (ACF) as a known cancer precursor, or AOM (7.5 mg/kg b.w.) once a week for 10 weeks to induce intestinal tumors. The rats were also administered the AcOEt-extract (500 mg/kg b.w.) or tryptanthrin (50 mg/kg b.w.) orally, 5 days a week, for 7 or 30 weeks, starting two days before the first administration of AOM. All rats were killed 4 or 20 weeks after the last treatment. In the short-term experiment, the incidence of ACE and atypical crypts (AC) in the groups receiving the AcOEt-extract and tryptanthrin was significantly lower than in the control group. In the tumor-inducing experiment, intestinal tumor incidence in the tryptanthrin group was lower than in the AOM-control group (5% versus 26%), and small intestine tumor incidence in the AcOEt-extract and tryptanthrin groups were lower than in the AOM-control group (0% and 0% versus 23%). These results show that the AcOEt-extract of Indigo and tryptanthrin have cancer chemopreventive activity.
Tryptanthrin (1), indole-3-acetonitrile (2) and p-coumaric acid methylester (3) were isolated from the aerial parts of Isatis tinctoria L. The compounds show insecticidal and anti-feedant activity against termites (Reticulitermis santonensis), insect preventive and control activity against larvae of the house longhorn beetle (Hylotrupes bajulus) and fungicidal activity against the brown-rot fungus (Coniophora puteana).
A new flavonoid-glucoside, 3, 5, 4'-trihydroxy-6, 7-methylenedioxy-3-O-β-D-glucopyranoside, which has an anti-platelet activity, was isolated from Polygonum tinctorium LOUR. and its structure was elucidated by means of carbon-13 nuclear magnetic resonance, including long range selective-proton decoupling (LSPD), and other spectroscopic methods.
L-[5-3 H]Tryptophan was administered to young plants of Isatis tinctoria and Polygonum tinctorium. Labelled indoxyl derivatives could be isolated from stems and roots of both plant species. Stems of I. tinctoria are able to convert [3H]-labelled tryptophan into indican and isatan B. Root cultures of I. tinctoria synthesize indican and isatan B and incorporate biosynthetic precursors into indoxyl derivatives.
In order to clarify the role of spontaneous apoptosis of non-Hodgkin's lymphomas in the growth regulation system, apoptotic indices (AI) assessed by DNA nick end-labeling and proliferative activity, estimated in terms of KI-67 labeling indices (KI) and mitotic indices (MI), were compared. In addition, expression of bcl-2, p53 and c-myc was also examined in relation to these indicators. For this study, 103 lymphoma cases were used, comprising 72 of B cell and 31 of T cell origin (42 nodal and 62 extranodal). AI, KI and MI were significantly increased in line with bcl-2 negativity and p53 positivity, and there was no relation to the T, B cell classification or expression of c-myc. These indicators positively correlated overall. Positive correlation was stricter in groups believed to represent a good prognostic predictive factor, such as B cell origin, bcl-2(+), p53(-) and c-myc(-). Significant cross-correlation was noted only between bcl-2 versus T, B cell classification. However, no inverse correlation between bcl-2 and p53 was evident. These results suggest, in non-Hodgkin's lymphomas, that apoptosis plays an important role together with proliferative activity in counter-balancing tumor volume, and is strictly linked to bcl-2 expression, less so to p53 expression, but independent of T, B cell classification and c-myc expression. Apoptotic indices may be a predictive indicator for prognosis similar to proliferative activity.