tectorigenin and tectoridin

Iris tectorum Maxim, a well-known herb medicine, is commonly used for treatment of inflammation, cough, and pharyngitis for a long time in China. Tectoridin, main active ingredient of Iris tectorum Maxim, is often used for its quality control. This study was aimed to analyze the pharmacokinetic profile of tectorigenin (the metabolite of tectoridin) after oral administration of I. tectorum Maxim extract, and to compare the pharmacokinetic characterization of tectorigenin after oral administration of I. tectorum Maxim extract (ITME) and pure tectoridin (PT) in rats. In addition, a simple, reliable and sensitive UPLC-MS/MS method was developed for determination of tectorigenin in rat plasma, using kaempferol as internal standard. The processed samples were separated on a Poroshell 120 SB-C₁₈ column and detected by positive electrospray ionization in multiple reaction monitoring (MRM) mode. The method validation results indicated that the established method was simple, specific and reliable. The pharmacokinetic results showed that the plasma concentration of tectorigenin in ITME group was much higher than that of the PT group (p<0.01). Moreover, compared to PT group, t₁/₂ value and AUC(0-∞) value were also notably increased in ITME group (p<0.01). In conclusion, potential interaction exists between those chemical components in ITME, and the co-existing components in ITME could notably promote the absorption of tectoridin in rats, however, the exact compound(s) which enhance the absorption of tectoridin should be investigated in future study.

Topics: Administration, Oral; Animals; Area Under Curve; Calibration; Chromatography, High Pressure Liquid; Drugs, Chinese Herbal; Hydrolysis; Iris; Isoflavones; Kaempferols; Limit of Detection; Male; Plant Extracts; Quality Control; Rats; Rats, Sprague-Dawley; Reproducibility of Results; Spectrometry, Mass, Electrospray Ionization; Tandem Mass Spectrometry

A callus culture of Iris pseudacorus L. (Iridaceae) was established from plant leaves using a modified Murashige and Skoog medium. A derivative of cinnamic acid (lavandoside) (1), a neolignan (dehydrodiconiferyl alcohol-4-O-beta-D-glucopyranoside) (2) as well as three isoflavonoids, tectoridin (3), tectorigenin (4), and iristectorigenin A (5) were isolated from the callus culture. Under normal conditions, the calli accumulated 0.4% DW of polyphenols. The addition of phenylalanine to a concentration of 1 mM resulted in a 1.5-fold increase in isoflavonoid production, allowing the accumulation of 0.69% of polyphenols in the callus dry weight. Tectorigenin, a promising chemotherapeutic and chemopreventive agent for the treatment of carcinomas, was produced in I. pseudacorus calli in high quantities (0.3% DW).

Topics: Cells, Cultured; Culture Techniques; Iris Plant; Isoflavones; Lignans; Polyphenols

In this study, an efficient strategy based on bioassay-guided fractionation, high-performance liquid chromatography/electrospray ionization quadrupole time-of-flight mass spectrometry (HPLC-ESI-Q/TOF-MS) and high-speed counter-current chromatography (HSCCC) was established to screen and purify bioactive compounds from Chinese herbal medicines (CHMs). This screening system was efficient and successfully applied to reveal anti-prostate cancer candidates from Puerariae thomsonii Flos. As a result, an active fraction with strong in vitro anti-prostate cancer activity was obtained, and the main compounds in the fraction were purified by HSCCC, giving 82 mg of tectoridin, 36 mg of tectorigenin-7-O-[β-D-xylopyranosyl-(1→6)-β-D-glucopyranoside and 64 mg of tectorigenin. Among them, tectorigenin, possessing the highest anti-prostate cancer activity with IC₅₀ value of 0.08 μM, has priority to be lead compound. The results of this work demonstrated that the developed method was efficient and could be employed for the rapid screening, identification and purification of active components from CHMs.

Topics: Animals; Antineoplastic Agents, Phytogenic; Cell Line, Tumor; Chromatography, High Pressure Liquid; Countercurrent Distribution; Drug Discovery; Drug Screening Assays, Antitumor; Drugs, Chinese Herbal; Ethnopharmacology; Glycosides; Inhibitory Concentration 50; Isoflavones; Male; Mice; Molecular Structure; Prostatic Neoplasms; Pueraria; Spectrometry, Mass, Electrospray Ionization; Tandem Mass Spectrometry

Tectoridin (4',5,7-thrihydroxy-6-methoxyisoflavone-7-O-β-d-glucopyranoside) isolated from the flowers of Pueraria thunbergiana is reported to have less hepatoprotective, hypoglycemic, antiallergic and anaphylaxis inhibitory activity than its aglycone form tectorigenin. To obtain tectorigenin, tectoridin was hydrolyzed in the current study. However, practical limitations of tectorigenin do exist due to its poor water-solubility. To increase its water-solubility, tectorigenin was sulfonated with sulfuric acid (98wt.%) and mixed with saturated salt water to produce tectorigenin sodium sulfonate. Tectoridin and the two transfer products were identified by UV, IR, HPLC-MS, (1)H NMR and (13)C NMR, and the solubility of tectorigenin sodium sulfonate was increased about 9-fold than tectorigenin. Antioxidant experiments of tectoridin, tectorigenin and modified tectorigenin in vitro including reducing power, superoxide anion radical scavenging activity, hydroxyl radical scavenging activity, 1,1-diphenyl-2-picryl-hydrazyl (DPPH) radical scavenging activity and anti-lipid peroxidation were carried on comparing with ascorbic acid (Vc) or butylated hydroxytoluene (BHT). The results suggested that the antioxidant activity in all the experimental systems exhibited the same order as follows: tectorigenin sodium sulfonate>tectorigenin>tectoridin. Due to the high water-solubility and good antioxidant properties with tectorigenin sodium sulfonate, appropriate chemical modifications could greatly improve the biological activities of the naturally occurring products.

Topics: Antioxidants; Biphenyl Compounds; Flowers; Isoflavones; Lipid Peroxidation; Molecular Structure; Picrates; Pueraria; Sulfonic Acids; Superoxides

To develop a HPLC method for the simultaneous determination of tectorigenin-7-O-xylosylglucosid, tectoridin and tectorigenin in flowers of Pueraria lobata.. The separation was performed on a Kromasil C18 column (4.6 mm x 250 mm, 5 microm), using a gradient elution with acetonitrile-water containing 0.2% phosphoric acid as the mobile phase. The flow rate was 1.0 mL x min(-1), the detection wavelength was 265 nm and the temperature of column was 35 degrees C.. The linear ranges of tectorigenin-7-O-xylosylglucosid, tectoridin and tectorigenin were 0.14-1.40 (r = 0.9994), 0.20-2.02 (r = 0.9993), and 0. 10-1.04 (r = 0.9991) , respectively. The average recoveries (n=6) of the three constituents were 99.5% (RSD 1.8%), 99.6% (RSD 1.7%), and 99.8% (RSD 1.9%), respectively.. The method is simple and accurate with a good eata and can be used as a quality control method for flowers of P. lobata of different sources.

Topics: Chromatography, High Pressure Liquid; Drugs, Chinese Herbal; Flowers; Glucosides; Isoflavones; Pueraria

To study the isoflavonoids of Iris tectorum.. The compounds were isolated by columm chromatography on silica gel and purified by Sephadex LH-20. Structures of these compounds were elucidated by spectral analysis and phytochemical properties.. Six isoflavonoids were isolated from Iris tectorum, which were tectoridin (I), tectorigenin (II), iristectorin A (III), iristectorigenin A (IV), iristectorin B (V), 5,7,4'-trihydroxy-6,3'-dimethoxy isoflvone (VI).. Compound VI is isolated from this plant for the first time.

Topics: Chromatography, Liquid; Iris Plant; Isoflavones; Plants, Medicinal; Rhizome

Microglial activation plays an important role in alcohol-induced neuroinflammation. In search for natural medicines that may be of therapeutic potential for alcoholism, two new natural isoflavone glycosides, 6-hydroxybiochanin A-6,7-di-O-beta-d-glucopyranoside (1) and 6-hydroxygenistein-7-O-beta-d-glucopyranoside (2), were isolated from the ethanolic extract of the flowers of Pueraria thomsonii Benth., together with the seven known isoflavones, genistein (3), tectorigenin (4), irisolidone (5), genistin (7), tectoridin (8), tectorigenin-7-O-beta-d-xylosyl-(1 --> 6)-beta-d-glucopyranoside (9), and 6-hydroxygenistein-6,7-di-O-beta-d-glucopyranoside (11). Moreover, gehuain (6) and kakkalide (10) were obtained from the flowers of Pueraria lobata (Willd.) Ohwi. The structures of the new compounds were elucidated by UV, IR, HR-MS, and 1D and 2D NMR spectroscopic methods. Compounds 3-5 substantially inhibited the lipopolysaccharide-induced nitric oxide release from primary cultured rat cortical microglia (IC50: 1.3-9.3 microM). The inhibitory effects of compounds 6, 8, 9, and 11 (IC50: 38-62 microM) were significant but weaker than the above aglycones. However, compounds 1, 2, 7, and 10 showed little inhibitory activity. With regard to the structure-activity relationships of the isoflavonoids for the inhibition of microglial activation, the glycosylation at the C-7 hydroxyl group reduces the inhibitory activity. The methoxylation of 4'-hydroxyl group of 7-glycosylated isoflavonoids reduces the inhibitory activity, while the methoxyl group at the 6-position enhances the activity. The results suggest that isoflavonoids of Pueraria flowers may be of therapeutic potential in alcoholism related to microglial activation.

Topics: Animals; Drugs, Chinese Herbal; Flowers; Glucosides; Isoflavones; Lipopolysaccharides; Microglia; Molecular Structure; Nitric Oxide; Nuclear Magnetic Resonance, Biomolecular; Pueraria; Rats; Rats, Wistar; Stereoisomerism; Structure-Activity Relationship

Effects of compounds isolated from medicinal plants in Korea on prostaglandin E2 (PGE2) production in rat peritoneal macrophages were examined, and mechanism of action of the active constituents was analyzed. The active constituents were as follows; tectorigenin and tectoridin isolated from the rhizomes of Belamcanda chinensis, platycodin D isolated from the roots of Platycodon grandiflorum, imperatorin isolated from the roots of Angelica dahurica, and hyperin isolated from the roots of Acanthopanax chiisanensis. These compounds inhibit the induction of cyclooxygenase-2 (COX-2), thus inhibiting PGE2 production. The chemically synthesized chalcone derivative, 2'-hydroxy-4'-methoxychalcone, also inhibits PGE2 production by suppressing COX-2 induction. In contrast, taiwanin C isolated from the roots of Acanthopanax chiisanensis inhibited PGE2 production by direct inhibition of COX-1 and COX-2.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Cyclooxygenase Inhibitors; Dinoprostone; Drug Evaluation, Preclinical; Furocoumarins; Isoflavones; Korea; Lactones; Lignans; Macrophages, Peritoneal; Medicine, East Asian Traditional; Phytotherapy; Quercetin; Rats; Saponins; Triterpenes

Tectorigenin (Tg) and tectoridin (Td) are the major compounds isolated from the rhizomes of iridaceous plant Belamcanda chinensis which is well known as a chinese traditional medicine for the treatment of inflammatory diseases. In this study we investigated whether tectorigenin and tectoridin can be applied to the suppression of interferon-gamma and lipopolysaccharide (IFN-gamma/LPS)-induced inflammatory responses in macrophages. Anti-inflammatory activities of tectorigenin and tectoridin were compared with genistein (Ge), well known isoflavonoid as a phytoestrogen and regarded as an emerging anti-inflammatory agent. Both compounds showed low cytotoxic effect. In Raw 264.7 cells activated with IFN-gamma/LPS, pre-treated tectorigenin was found to inhibit the expression of inducible nitric oxide synthase (iNOS), the production of nitric oxide (NO) and the secretion of interleukin (IL)-1beta dose-dependently. Tectorigenin also decreased the expression of cyclooxigenase (COX)-2 and the production of prostaglandin E(2) (PGE(2)) in dose-dependent manner. These inhibitory effects of tectorigenin were found to be caused by the blocking of nuclear factor kappa-B (NF-kappaB) activation. Compared with genistein and tectoridin, tectorigenin showed significant inhibitory effect for almost anti-inflammatory tests in this study. All these results clearly demonstrated that tectorigenin appears to have the potential to prevent inflammation.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Blotting, Western; Cell Line; Cyclooxygenase 2; Dinoprostone; Enzyme-Linked Immunosorbent Assay; Genistein; I-kappa B Kinase; Indicators and Reagents; Interferon-gamma; Interleukin-1beta; Isoflavones; Lipopolysaccharides; Macrophages; Mice; Nitric Oxide; Nitric Oxide Synthase Type II; Phytoestrogens; Reverse Transcriptase Polymerase Chain Reaction; Tumor Necrosis Factor-alpha

To understand the relationship between the metabolism and estrogenic activity of kakkalide and tectoridin, main isoflavones in the flower of Pueraria thunbergiana (family Leguminosae), these isoflavones and their metabolites by human intestinal microflora as well as their estrogenic effects were investigated. All human fecal specimens metabolized kakkalide and tectoridin. All isolated kakkalide-hydrolyzing intestinal bacteria also hydrolyzed kakkalide and tectoridin to irisolidone and tectorigenin, respectively. When the estrogenic effects of kakkalide and tectoridin were compared with those of their metabolites irisolidone and tectorigenin, the metabolites more potently increased proliferation of MCF-7 cells than kakkalide and tectoridin. These metabolites also potently induced estrogen-response c-fos and pS2 mRNA expression. These results suggest that kakkalide and tectoridin may be metabolized mainly to irisolidone and tectorigenin, respectively, by intestinal microflora in the intestines, and which may be subsequently absorbed into the blood where they can express their estrogenic effect.

Topics: Adult; Bifidobacterium; Cell Line, Tumor; Cell Proliferation; Feces; Flavonoids; Flowers; Glycosides; Humans; Intestines; Isoflavones; Male; Phytoestrogens; Pueraria; Substrate Specificity; Xylosidases; Young Adult

To clarify the hepatoprotective effects of tectoridin and tectorigenin from Puerariae Flos, their effects on tert-butyl hyperoxide (t-BHP)-injured HepG2 cells and mice were investigated. When tectorigenin at a dose of 50 mg/kg was intraperitoneally administered to mice injured by t-BHP, it significantly inhibited the increase the activities of plasma ALT and AST by 39% and 41%, respectively, in the t-BHP-treated group. The inhibitory effect of tectorigenin is much more potent than that of a commercially available dimethyl diphenyl bicarboxylate. Orally administered tectoridin showed hepatoprotective activity. However, when tectoridin was intraperitoneally administrated to mice, no hepatoprotective activity was observed. Tectorigenin also protected against the cytotoxicity of HepG2 cells induced by t-BHP. This protection may have originated from the inhibition of apoptosis. Tectorigenin may be hepatoprotective and tectoridin should be a prodrug that is transformed to tectorigenin.

Topics: Administration, Oral; Alanine Transaminase; Animals; Aspartate Aminotransferases; Cell Line; Cytoprotection; Drugs, Chinese Herbal; Injections, Intraperitoneal; Isoflavones; Liver; Mice; tert-Butylhydroperoxide

In the present study, the antioxidative properties of tectorigenin, a metabolite formed by transformation of tectoridin by intestinal microflora, were investigated. Tectorigenin was found to scavenge intracellular reactive oxygen species, and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, and thus prevented lipid peroxidation. The radical scavenging activity of tectorigenin protected the viability of Chinese hamster lung fibroblast (V79-4) cells exposed to hydrogen peroxide (H2O2) via activation of extracellular signal regulated kinase (ERK) pathway. Furthermore, tectorigenin reduced the apoptotic cells formation and cell cycle arrest at G2/M phase induced by H2O2. Tectorigenin increased the activities of cellular antioxidant enzymes like superoxide dismutase, catalase, glutathione peroxidase, and also increased their protein level. Taken together, these findings suggest that tectorigenin protected V79-4 cells against H2O2 damage, by enhancing the antioxidative activity and by activating ERK pathway.

Topics: Animals; Apoptosis; Bacteroides; Biotransformation; Blotting, Western; Catalase; Cell Cycle; Cell Line; Cell Survival; Culture Media, Serum-Free; Dose-Response Relationship, Drug; Enzyme Activation; Extracellular Signal-Regulated MAP Kinases; Free Radical Scavengers; Glutathione Peroxidase; Humans; Hydrogen Peroxide; Intestines; Isoflavones; Lipid Peroxidation; Oxidants; Oxidative Stress; Superoxide Dismutase; Transcription Factor AP-1

The present study was carried out to clarify whether tectorigenin and tectoridin isolated from the rhizomes of Belamcanda chinensis (Iridaceae) inhibit hepatic damage induced by carbon tetrachloride (CCl4)-intoxication in rats by the experimental methods in vitro and in vivo. Tectorigenin and tectoridin exhibited a significant decrease in serum transaminase activities elevated by hepatic damage induced by CCl4-intoxication in rats, as well as in a lipid peroxidation causing a significant decrease in malondialdehyde (MDA) production by thiobarbituric acid (TBA)-reactant assay. Both compounds also showed strong increase in the antioxidant enzymes such as hepatic cytosolic superoxide dismutase (SOD), catalase and glutathione peroxidase (GSH-px) activities in CCl4-intoxicated rats. These results suggested that tectorigenin and tectoridin isolated from the rhizomes of B. chinensis possess not only the antioxidative, but also the hepatoprotective activities in CCl4-intoxicated rats.

Topics: Alanine Transaminase; Animals; Antioxidants; Aspartate Aminotransferases; Carbon Tetrachloride Poisoning; Chemical and Drug Induced Liver Injury; Cytosol; Iridaceae; Isoflavones; Lipid Peroxidation; Liver; Male; Plant Extracts; Plant Roots; Rats; Rats, Sprague-Dawley; Superoxide Dismutase

Tectoridin isolated from the flowers of Pueraria thunbergiana (Leguminosae) are metabolized to tectorigenin by human intestinal microflora. When tectoridin was orally administered to rats, tectorigenin, but not tectoridin, was detected in urine after beta-glucuronidase hydrolysis. The main metabolite tectorigenin potently inhibited the passive cutaneous anaphylaxis reaction and inhibited in vitro the release of beta-hexosaminidase from RBL-2H3 cells induced by IgE. These results suggest that tectoridin is a prodrug, which can be transformed into the active agent tectorigenin by human intestinal bacteria and can be a candidate for antiallergic agent.

Topics: Animals; Cell Line; Feces; Flowers; Humans; Intestines; Isoflavones; Male; Mice; Mice, Inbred ICR; Passive Cutaneous Anaphylaxis; Plant Extracts; Pueraria; Rats; Rats, Sprague-Dawley

The present study was carried out to clarify whether tectorigenin and tectoridin isolated from the rhizomes of Belamcanda chinensis (Iridaceae) inhibit angiogenesis by the experimental methods in vitro and in vivo. Tectorigenin and tectoridin decreased angiogenesis of both chick embryos in the chorioallantoic membrane assay and basic fibroblast growth factor-induced vessel formation in the mouse Matrigel plug assay. Both compounds also reduced the proliferation of calf pulmonary arterial endothelial (CPAE) cells and found to possess relatively weak gelatinase/collagenase inhibitory activity in vitro. Tectorigenin exhibited a much stronger anti-proliferative activity than its glycoside, tectoridin and was almost equipotent to that of genistein, a reference drug. Tectorigenin, when administered subcutaneously at the dose of 30 mg/kg for 20 days to mice implanted with murine Lewis lung carcinoma (LLC), caused a significant inhibition of tumor volume by 30.8 %. Tectorigenin and tectoridin, when treated i. p. at the same dosage for 10 days to ICR mice bearing sarcoma 180, caused a significant suppression in tumor weight by 44.2 and 24.8 %, respectively.

Topics: Angiogenesis Inhibitors; Animals; Antineoplastic Agents, Phytogenic; Carcinoma, Lewis Lung; Cattle; Cell Division; Cell Line; Chick Embryo; Collagenases; Gelatinases; Isoflavones; Mice; Mice, Inbred C57BL; Pulmonary Artery; Sarcoma 180; Tumor Cells, Cultured

Tectorigenin and tectoridin, isolated from the rhizomes of Korean Belamcanda chinensis (Iridaceae) which are used as Chinese traditional medicine for the treatment of inflammation, suppressed prostaglandin E2 production by rat peritoneal macrophages stimulated by the protein kinase C activator, 12-O-tetradecanoylphorbol 13-acetate (TPA), or the endomembrane Ca2+-ATPase inhibitor, thapsigargin. Tectorigenin inhibited prostaglandin E2 production more potently than tectoridin. Neither compound inhibited the release of radioactivity from [3H]arachidonic acid-labeled macrophages stimulated by TPA or thapsigargin. In addition, activities of isolated cyclooxygenase (COX)-1 and COX-2 were not inhibited by the two compounds. Western blot analysis revealed that the induction of COX-2 by TPA or thapsigargin was inhibited by the two compounds in parallel with the inhibition of prostaglandin E2 production. These findings suggest that one of the mechanisms of the anti-inflammatory activities of the rhizomes of Belamcanda chinensis is the inhibition of prostaglandin E2 production by tectorigenin and tectoridin due to the inhibition of the induction of COX-2 in the inflammatory cells.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Arachidonic Acid; Cyclooxygenase 1; Cyclooxygenase 2; Dinoprostone; Drugs, Chinese Herbal; Enzyme Induction; Isoenzymes; Isoflavones; Macrophages, Peritoneal; Male; Membrane Proteins; Prostaglandin-Endoperoxide Synthases; Rats; Rats, Sprague-Dawley; Tetradecanoylphorbol Acetate; Thapsigargin

Topics: Animals; Dinoprostone; Isoflavones; Macrophages, Peritoneal; Plants, Medicinal; Rats

6"-O-Xylosyltectoridin and tectoridin isolated from the flowers of Pueraria thunbergiana (Leguminosae), are metabolized to tectorigenin by human intestinal bacteria. Although tectoridin is metabolized to tectorigenin by most intestinal bacteria, 6"-O-xylosyltectoridin is metabolized to tectorigenin via tectoridin by only a few intestinal bacteria, such as Bifidobacterium breve K-110 and Eubacterium A-44. The metabolite, tectorigenin, had more potent hypoglycemic activity as well as in vitro cytotoxic activity against tumor cell lines than 6"-O-xylosyltectoridin and tectoridin. These results suggest that 6"-O-xylosyltectoridin and tectoridin are prodrugs which can be transformed to the active agents by human intestinal bacteria.

Topics: Animals; Antineoplastic Agents, Phytogenic; Bifidobacterium; Drug Screening Assays, Antitumor; Eubacterium; Fabaceae; Humans; Hyperglycemia; Hypoglycemic Agents; Intestines; Isoflavones; Male; Plants, Medicinal; Rats; Rats, Sprague-Dawley; Streptozocin; Time Factors; Tumor Cells, Cultured

In this paper, two compounds, isoflavone III and IV are isolated. On the bases of physical, chemical and spectral evidences, the structure of composition III is tectoridin, and composition IV is tectoriginin.

Topics: Iridaceae; Isoflavones; Magnetic Resonance Spectroscopy; Plants, Medicinal; Rhizome; Spectrophotometry, Infrared; Spectrophotometry, Ultraviolet