iridoids and catalpol

Rehmannia glutinosa, the fresh or dried root of Rehmannia glutinosa (Gaertn.) Libosch. ex Fisch. & Mey., and Gardenia, the fruit of Gardenia jasminoides Ellis from Rubiaceae, both are famous traditional Chinese medicines that have been traditionally used in China. Catalpol and geniposide, as two kinds of iridoid glycosides with high activities, are the main bioactive components in Rehmannia glutinosa and Gardenia jasminoides Ellis, respectively. Over the past few decades, catalpol and geniposide have been widely studied for their therapeutic effects. The preclinical experiments demonstrated that they possessed significant neuroprotective activities against Alzheimer's disease, Parkinson's disease, stroke, and depression, etc. In this paper, the pharmacological effects and mechanisms of catalpol and geniposide on Alzheimer's disease and Parkinson's disease from 2005 to now were systematically summarized and comprehensively analyzed. At the same time, the pharmacokinetic characteristics of the analyzed compounds were also described, hoping to provide some enlightenment for the design, research, and development of iridoid glycosides.

Topics: Alzheimer Disease; Animals; Antiparkinson Agents; Drugs, Chinese Herbal; Gardenia; Humans; Iridoid Glucosides; Iridoids; Medicine, Chinese Traditional; Parkinson Disease; Rehmannia

Catalpol is a effective components of rehmannia root, it have many pharmacological actions, such as anti-brain ischemia, anti-senile dementia, promoting neuro-remodeling and reducing capillary permeability and so on.

Topics: Animals; Brain Diseases; Drugs, Chinese Herbal; Gene Expression; Glucosides; Humans; Iridoid Glucosides; Iridoids; Rehmannia

Catalpol is a active component in Rehmannia Root, and its pharmacological effects are extensive. In this paper its effects and chemical changes were summarized. This will offer the reference for further research work catalpol.

Topics: Animals; Antineoplastic Agents, Phytogenic; Drugs, Chinese Herbal; Glucosides; Humans; Hypoglycemic Agents; Iridoid Glucosides; Iridoids; Neuroprotective Agents; Plants, Medicinal; Rehmannia; Technology, Pharmaceutical

Rehmanniae Radix (RR) and Cornus officinalis (CO) are a typical herbal pair used to treat diabetic nephropathy (DN) in clinical practice. DN can be effectively treated by catalpol (Cat) and loganin (Log), the main active components of RR and CO respectively, through combating apoptosis, oxidative stress and inflammation. Herein, a spontaneous DN and podocyte injury model induced by advanced glycation end products (AGEs), i.e. KK-Ay mice, was used to explore the cooperative effects of Log and Cat on DN and the mechanism targeting the AGEs-RAGE (receptor for AGE) pathway.. Log and Cat alone or in combination mitigated diabetic symptoms, decreased the level of fasting blood glucose, and increased that of serum insulin. The two drugs alone or in combination protected renal function from damage, prevented extracellular matrix hyperplasia and glycogen deposition, as well as alleviated the loss of podocytes detected by histological assay and immunohistochemistry. Flow cytometry revealed that Log and Cat alone or in combination relieved the apoptosis of AGEs-induced podocytes in vitro. Silencing RAGE by RNA interference played a protective role in podocyte apoptosis, whereas overexpression of it worked oppositely. Western blot exhibited that Log and Cat alone or in combination inhibited the activation of RAGE/p38 MAPK/p65 NF-κB and RAGE/Nox4/p65 NF-κB pathways in podocytes. The inhibitory effects of drug combination were more evident than those of individual treatments.. Log and Cat cooperatively resisted the apoptosis of podocytes upon DN by targeting AGEs-RAGE and its downstream pathways p38 MAPK and Nox4.

Topics: Animals; Apoptosis; Diabetic Nephropathies; Drug Therapy, Combination; Glycation End Products, Advanced; Iridoid Glucosides; Iridoids; Male; Mice; Mice, Inbred C57BL; NADPH Oxidase 4; Oxidative Stress; p38 Mitogen-Activated Protein Kinases; Podocytes; Receptor for Advanced Glycation End Products; Signal Transduction

Catalpol is an iridoid glycoside extracted from the root of Rehmannia glutinosa. It has been reported to have antioxidant stress effects. Adenosine 5' monophosphate-activated protein kinase( AMPK) plays an important role in inhibiting oxidative stress. This study was designed to investigate the protective effects of catalpol on TNF-α-exposed human aorta epithelial cells( HAECs) via inhibit oxidative stress,and the relationship between catalpol and AMPK was detected by RNA interference technique. Levels of superoxide dismutase( SOD),malonaldehyde( MDA),glutathione( GSH) and lactate dehydrogenase( LDH) were measured with a colorimetric assay kit. The level of ROS was measured with FACS calibur. Western blot was employed to detect the protein expression of AMPK,phosphorylated-AMPK and NOX4. Finally,RNA interference technique was used to investigate the role of AMPK in catalpol-induced protective effects. TNF-α treatment decreased the expression of phosphorylated-AMPK protein level,however,catalpol could reverse the decreased phosphorylated-AMPK level. Catalpol could inhibit NOX4 protein expression and decrease ROS overproduction. After using AMPK siRNA that effects of catalpol on ROS overproduction and NOX4 protein expression inhibition were attenuated. The above results suggest that catalpol inhibits oxidative stress in TNF-α-exposed HAECs by activating AMPK.

Topics: Humans; Iridoid Glucosides; Iridoids; Oxidative Stress; Reactive Oxygen Species; Tumor Necrosis Factor-alpha

Topics: Aedes; Animals; Buddleja; Female; Flavonoids; Glycosides; Insecticides; Iridoid Glucosides; Iridoids; Male; Plant Components, Aerial; Plant Extracts

Cornus officinalis-Rehmannia glutinosa herb couple is widely used herb medicine in clinical practice to treat chronic kidney disease (CKD). However, the in vivo integrated metabolism of its main bioactive components in CKD rats remains unknown. In this study, UPLC-Q-TOF/MS technique combined with Metabolynx

Topics: Administration, Oral; Animals; Case-Control Studies; Chromatography, High Pressure Liquid; Cornus; Feces; Glucosides; Glycosides; Iridoid Glucosides; Iridoids; Male; Phenols; Plant Extracts; Rats; Rehmannia; Renal Insufficiency, Chronic; Tandem Mass Spectrometry

Ten new glycosides, 6,10-O-di-trans-feruloyl catalpol (1), 6,6'-O-di-trans-feruloyl catalpol (2), 3,4-dihydro-6-O-di-trans-feruloyl catalpol (10), (8R,7'S,8'R)-lariciresinol 9'-O-β-d-(6-O-trans-feruloyl)glucopyranoside (17), and ovatosides A-F (18-22, 24), were isolated from the stem bark of Catalpa ovata along with 19 known compounds. All isolates, except 6 (catalposide) and 9 (6-O-veratroyl catalpol), were found to scavenge peroxynitrite (ONOO

Topics: Bignoniaceae; Furans; Glucosides; Glycosides; Inhibitory Concentration 50; Iridoid Glucosides; Iridoids; Lignans; Molecular Structure; Peroxynitrous Acid; Plant Stems

A sensitive and rapid method for determination of loganin, morroniside, catalpol and acteoside in rat plasma after oral administration of Rehmannia glutinosa Libosch and Cornus officinalis Sieb drug pair based on ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS). Chromatographic separation was achieved using an Acquity UPLC BEH C18 column (100mm×2.1mm, 1.7μm) at a flow rate of 0.4mL/min, using gradient mode containing 0.1% formic acid in water and acetonitrile were used as the mobile phase A and B. Loganin, morroniside, catalpol, acteoside and the internal standard (chloramphenicol) were detected by selected reaction monitoring in the negative ion mode with the mass transition of m/z 451.0→179.0 (morroniside), m/z 435.0→227.0 (loganin), m/z 407.1→199.1 (catalpol), m/z 623.2→161.0 (acteoside) and m/z 320.8→151.9 (chloramphenicol), respectively. All calibration curves showed good linearity (r>0.991). The precision was evaluated by intra-day and inter-day assays and the RSD% were all within 9.58%. The recovery ranged from 67.62 to 80.14%. The method was successfully applied to pharmacokinetic study of the analytes in normal and doxorubicin-induced chronic kidney disease rat plasma.

Topics: Administration, Oral; Animals; Chromatography, High Pressure Liquid; Cornus; Drugs, Chinese Herbal; Glucosides; Glycosides; Iridoid Glucosides; Iridoids; Limit of Detection; Male; Mass Spectrometry; Phenols; Rats; Rats, Sprague-Dawley; Rehmannia; Renal Insufficiency, Chronic

We recently discovered that the activation of the spinal glucagon-like peptide-1 receptors (GLP-1Rs) by the peptidic agonist exenatide produced antinociception in chronic pain. We suggested that the spinal GLP-1Rs are a potential target molecule for the management of chronic pain. This study evaluated the antinociceptive activities of geniposide, a presumed small molecule GLP-1R agonist. Geniposide produced concentration-dependent, complete protection against hydrogen peroxide-induced oxidative damage in PC12 and HEK293 cells expressing rat and human GLP-1Rs, but not in HEK293T cells that do not express GLP-1Rs. The orthosteric GLP-1R antagonist exendin(9-39) right-shifted the concentration-response curve of geniposide without changing the maximal protection, with identical pA2 values in both cell lines. Subcutaneous and oral geniposide dose-dependently blocked the formalin-induced tonic response but not the acute flinching response. Subcutaneous and oral geniposide had maximum inhibition of 72% and 68%, and ED50s of 13.1 and 52.7 mg/kg, respectively. Seven days of multidaily subcutaneous geniposide and exenatide injections did not induce antinociceptive tolerance. Intrathecal geniposide induced dose-dependent antinociception, which was completely prevented by spinal exendin(9-39), siRNA/GLP-1R and cyclic AMP/PKA pathway inhibitors. The geniposide iridoid analogs geniposidic acid, genipin methyl ether, 1,10-anhydrogenipin, loganin and catalpol effectively inhibited hydrogen peroxide-induced oxidative damage and formalin pain in an exendin(9-39)-reversible manner. Our results suggest that geniposide and its iridoid analogs produce antinociception during persistent pain by activating the spinal GLP-1Rs and that the iridoids represented by geniposide are orthosteric agonists of GLP-1Rs that function similarly in humans and rats and presumably act at the same binding site as exendin(9-39).

Topics: Analgesics; Animals; Central Nervous System Agents; Exenatide; Formaldehyde; Glucagon-Like Peptide-1 Receptor; HEK293 Cells; Heterocyclic Compounds, 3-Ring; Humans; Iridoid Glucosides; Iridoids; Male; Mice; Nociception; PC12 Cells; Peptide Fragments; Peptides; Rats; Rats, Wistar; Receptors, Glucagon; Spinal Cord; Venoms

Iridoid glycosides were the main active ingredient of Rehmannia glutinosa, of which catalpol has the highest content. This work will provide theoretical basis for metabolic study and cultivation of iridoids on the basis of the dynamic accumulation of catalpol and total iridoids in the growth of R. glutinosa. The samples of rehmannia 85-5 were gathered in the same filed from July to October. The contents of catalpol and total iridoid glycosides were measured by HPLC and specteophotometric, respectively. The results showed that youngest leaves had the higher content of catalpol and total iridoid glyosides than that of the other two leaf ages in the same growth stage from July to September, while their content of catalpol and total iridoid glycosides were all decreased as the growth of leaves of R. glutinosa. The content of catalpol didn't differ significantly from July to September, whereas it has significantly increased in October in the three leaf stage. In the same stage, the wider the root diameter is, the higher content of the effective components are. In August and September, the total iridoid glycosides have the fastest accumulation. The content of catalpol was increased as the accumulation of total iridoid glycosides.

Topics: Iridoid Glucosides; Iridoids; Plant Roots; Rehmannia; Seasons; Water

Diabetes mellitus can cause dysfunction of the central nervous system called "diabetic encephalopathy." Although insulin and various oral drugs are used to treat diabetes, they do not completely prevent the development of diabetic encephalopathy, and novel strategies for the prevention and treatment are urgently needed. Catalpol, an iridoid glycoside, has properties of anti-inflammation, antioxidant and decreasing blood glucose level and thus has the possibility of treating diabetic encephalopathy. Therefore, the study was designed to investigate the effects of catalpol on diabetic encephalopathy in rats. A single dose of 65 mg/kg streptozotocin was injected intraperitoneally to induce diabetes. Intragastric infusion of catalpol was performed for 6 weeks with the doses of 10, 50 and 100 mg/kg, respectively. The Y-type maze test, biochemical measurement, Nissl staining and the terminal deoxynucleotidyl transferase-mediated UTP nick end labeling methods were used to evaluate the neuropathological changes and the effects of catalpol on diabetic rats. The results showed that streptozotocin-induced diabetes produced obvious neuron damage and cognitive dysfunction coupling with markedly increased oxidative stress in the brain. Long-term oral supplementation of catalpol improved neuronal injury and cognitive dysfunction by attenuating oxidative stress. The effects that catalpol could both increase the nerve growth factor concentration and decrease the blood glucose level were related with the function of defending against oxidative stress of catalpol. The study suggested that oral supplementation of catalpol might be a potential therapeutic strategy for the treatment and/or prevention of diabetic encephalopathy.

Topics: Administration, Oral; Animals; Behavior, Animal; Blood Glucose; Body Weight; Catalase; Diabetes Mellitus, Experimental; Diabetic Neuropathies; Dietary Supplements; Disease Models, Animal; Dose-Response Relationship, Drug; Enzyme-Linked Immunosorbent Assay; Glucosides; Glutathione Peroxidase; In Situ Nick-End Labeling; Iridoid Glucosides; Iridoids; Lipid Peroxidation; Male; Malondialdehyde; Maze Learning; Nerve Growth Factor; Oxidative Stress; Rats; Rats, Sprague-Dawley; Superoxide Dismutase; Time Factors

The protective effect of an iridoid catalpol extracted and purified from the traditional Chinese medicinal herb Rehmannia glutinosa on the neuronal degeneration of nigral-striatal dopaminergic pathway was studied in a chronic 1-methyl-4-phenyl-1,2,3,4-tetrahydropyridine (MPTP)/probenecid C57BL/6 mouse model and in 1-methyl-4-phenylpyridimium (MPP(+)) intoxicated cultured mesencephalic neurons. Rotarod performance revealed that the locomotor ability of mice was significantly impaired after completion of model production and maintained thereafter for at least 4 weeks. Catalpol orally administered for 8 weeks (starting from the second week of model production) dose dependently improved the locomotor ability. HPLC revealed that catalpol significantly elevated striatal dopamine levels without changing the metabolite/dopamine ratios. Nor did it bind to dopamine receptors. Therefore it is unlikely that catalpol resembles any of the known compounds for treating Parkinsonism. Instead, catalpol dose dependently raised the tyrosine hydroxylase (TH) neuron number in substantia nigra pars compacta (SNpc), the striatal dopamine transporter (DAT) density and the striatal glial cell derived neurotrophic factor (GDNF) protein level. Linear regression revealed that both the TH neuron number and DAT density were positively correlated to the GDNF level. In the cultured mesencephalic neurons, MPP(+) decreased the dopaminergic neuron number and shortened the neurite length, whereas catalpol showed protective effect dose dependently. Furthermore, the expression of GDNF mRNA was up-regulated by catalpol to a peak nearly double of normal control in neurons intoxicated with MPP(+) for 24 h but not in normal neurons. The GDNF receptor tyrosine kinase RET inhibitor 4-amino-5-(4-methyphenyl)-7-(t-butyl)-pyrazolo-[3,4-d]pyrimidine (PP1) abolished the protective effect of catalpol either partially (TH positive neuron number) or completely (neurite length). Taken together, catalpol improves locomotor ability by attenuating the neuronal degeneration of nigral-striatal dopaminergic pathway, and this attenuation is at least partially through elevating the striatal GDNF expression.

Topics: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Animals; Brain; Cells, Cultured; Chronic Disease; Corpus Striatum; Disease Models, Animal; Dopamine; Dose-Response Relationship, Drug; Glial Cell Line-Derived Neurotrophic Factor; Glucosides; Iridoid Glucosides; Iridoids; Male; Mesencephalon; Mice; Mice, Inbred C57BL; Motor Activity; Nerve Degeneration; Neural Pathways; Neurons; Neuroprotective Agents; Probenecid; Substantia Nigra

The aim of this work was to evaluate the mechanisms involved in the effects of catalpol on mitochondrial function through the measurements of nitric oxide synthase (NOS) activity, reactive oxygen species (ROS) production, respiratory complex activities and mitochondrial membrane potential (MMP) in the brain cortex and hippocampus mitochondria of senescent mice induced by d-galactose. Except control group, mice were subcutaneously injected with d-galactose (150 mg/kg body weight) for 6 weeks. Meanwhile, drug group mice were treated with catalpol (2.5, 5, 10mg/kg body weight) and piracetam (300 mg/kg body weight) for the last 2 weeks. The results indicated that respiratory complex activities decreased while NOS activities increased in d-galactose treated mice brain. The production of ROS increased remarkably and MMP collapsed in the brain of senescent mice induced by d-galactose. Administration of catalpol for 2 weeks significantly decreased ROS production and NOS activities, in accordance with its increase on complex activities and MMP level. Our results suggest that in vivo effects of catalpol on mitochondrial function can occur through different mechanisms, involving inhibiting NOS activity and ROS production, increasing respiratory complex activities and MMP level.

Topics: Animals; Cerebral Cortex; Electron Transport Complex I; Electron Transport Complex IV; Female; Galactose; Glucosides; Hippocampus; Iridoid Glucosides; Iridoids; Male; Membrane Potential, Mitochondrial; Mice; Mitochondria; Neuroprotective Agents; Nitric Oxide Synthase; Reactive Oxygen Species

Two iridoid scaffolds were synthesized enantioselectively using as key step an l-proline-catalyzed alpha-formyl oxidation. The in vitro antiproliferative activities were evaluated against a representative panel of human solid tumor cell lines. Both iridoids induced considerably growth inhibition in the range 0.38-1.86muM. Cell cycle studies for these compounds showed the induction of cell cycle arrest at the G(1) phase. This result was consistent with a decrease in the expression of cyclin D1. Damaged cells underwent apoptosis as indicated by specific Annexin V staining.

Topics: Annexin A5; Antineoplastic Agents; Blotting, Western; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Enzyme Inhibitors; Glucosides; Humans; Iridoid Glucosides; Iridoids; Models, Molecular; Molecular Conformation; Structure-Activity Relationship

The antihyperglycemic effect of catalpol (1) purified from the roots of Rehmannia glutinosa was investigated in streptozotocin-induced diabetic rats (STZ-diabetic rats) representing insulin-dependent diabetes mellitus. Bolus intravenous injection of 1 showed antihyperglycemic activity in a dose-dependent manner in STZ-diabetic rats. An effective dose of 0.1 mg/kg 1 significantly attenuated the increase of plasma glucose induced by an intravenous glucose challenge test in normal rats. Catalpol enhanced the uptake of radioactive glucose in the isolated soleus muscle of STZ-diabetic rats in a concentration-related manner. Moreover, an effect by 1 was established on glycogen incorporation in hepatocytes isolated from STZ-diabetic rats. Catalpol was found to increase glycogen synthesis in STZ-diabetic rats. These results suggest that 1 can increase glucose utilization to lower plasma glucose in diabetic rats lacking insulin.

Topics: Animals; Blood Glucose; Diabetes Mellitus, Experimental; Glucosides; Glycogen; Hepatocytes; Hypoglycemic Agents; Insulin; Iridoid Glucosides; Iridoids; Male; Molecular Structure; Muscle, Skeletal; Plant Roots; Plants, Medicinal; Rats; Rats, Wistar; Rehmannia; Taiwan

Topics: Chromatography, Liquid; Iridoid Glucosides; Iridoids; Spectrometry, Mass, Electrospray Ionization; Veronica

The aim of this study was to investigate whether catalpol could facilitate recovery from lipopolysaccharide (LPS)-induced cognitive deficits and protect brain mitochondrial function from LPS-induced acute systemic inflammation. In the study, except control group, mice were challenged with a single dose of LPS (100 microg/mouse, i.p.) to mimic an acute peripheral infection. The results showed that LPS enhanced nuclear factor kappa B (NF-kappaB) activation and induced a loss in mitochondrial integrity as shown by a significant decrease in membrane potential and increase in mitochondrial permeability transition pore opening. Pretreatment with catalpol (10 mg/kg d, i.p.) for 10d before injection of LPS reversed the memory deficits induced by LPS, protected brain mitochondrial function, and attenuated LPS-induced NF-kappaB activation. Taken together, these data indicate that catalpol may possess therapeutic potential against LPS-induced acute systemic inflammation by attenuating NF-kappaB activation and protecting mitochondrial function in cerebral cortex and hippocampus.

Topics: Animals; Anti-Inflammatory Agents; Brain; Glucosides; Inflammation; Iridoid Glucosides; Iridoids; Lipopolysaccharides; Maze Learning; Memory; Mice; Mitochondria; NF-kappa B

Verproside, isovanilloylcatalpol, catalposide and 6-O-veratroyl catalpol are bioactive iridoid glucosides isolated from in a number of folk medicinal plants. A rapid, sensitive and selective liquid chromatography/mass spectrometric (LC/MS) method for the simultaneous determination of verproside, isovanilloylcatalpol, catalposide and 6-O-veratroyl catalpol in rat plasma was developed. The analytes were extracted from 50 microL of rat plasma with ethyl acetate using 7-carboxymethyloxy-3',4',5-trimethoxyflavone as internal standard and analyzed on an X-Bridge C(18) column within 6.5 min with 40% methanol in 10 mm ammonium formate (pH 3.0). The analytes were quantified using an electrospray ionization mass spectrometry in the selected ion monitoring mode. The standard curves were linear over the concentration ranges of 10-2000 ng/mL for verproside, isovanilloylcatalpol and catalposide and 20-2000 ng/mL for 6-O-veratroyl catalpol. The coefficients of variation and relative errors of verproside, isovanilloylcatalpol, catalposide and 6-O-veratroyl catalpol for intra- and inter-assay at four quality control levels were 2.5-8.0 and-4.0-6.6%, respectively. This method was successfully applied to the pharmacokinetic study of verproside and its possible metabolite isovanilloylcatalpol after intravenous administration of verproside, a candidate anti-asthma drug, in male Sprague-Dawley rats.

Topics: Animals; Area Under Curve; Calibration; Chromatography, Liquid; Glucosides; Iridoid Glucosides; Iridoids; Least-Squares Analysis; Male; Rats; Rats, Sprague-Dawley; Reproducibility of Results; Sensitivity and Specificity; Spectrometry, Mass, Electrospray Ionization

In a greenhouse experiment using Plantago lanceolata, plants grown with different arbuscular mycorrhizal (AM) fungal species differed in constitutive levels of chemical defense depending on the species of AM fungi with which they were associated. AM fungal inoculation also modified the induced chemical response following herbivory by the specialist lepidopoteran herbivore Junonia coenia, and fungal species varied in how they affected induced responses. On average, inoculation with AM fungi substantially reduced the induced chemical response as compared with sterile controls, and inoculation with a mixture of AM fungi suppressed the induced response of P. lanceolata to herbivory. These results suggest that AM fungi can exert controlling influence over plant defensive phenotypes, and a portion of the substantial variation among experimental tests of induced chemical responses may be attributable to AM fungi.

Topics: Analysis of Variance; Animals; Butterflies; Feeding Behavior; Glomeromycota; Glucosides; Iridoid Glucosides; Iridoids; Larva; Mycorrhizae; North Carolina; Plantago

Arbuscular mycorrhizal fungi can strongly influence the metabolism of their host plant, but their effect on plant defense mechanisms has not yet been thoroughly investigated. We studied how the principal direct defenses (iridoid glycosides) and indirect defenses (volatile organic compounds) of Plantago lanceolata L. are affected by insect herbivory and mechanical wounding. Volatile compounds were collected and quantified from mycorrhizal and non-mycorrhizal P. lanceolata plants that underwent three different treatments: 1) insect herbivory, 2) mechanical wounding, or 3) no damage. The iridoids aucubin and catalpol were extracted and quantified from the same plants. Emission of terpenoid volatiles was significantly higher after insect herbivory than after the other treatments. However, herbivore-damaged mycorrhizal plants emitted lower amounts of sesquiterpenes, but not monoterpenes, than herbivore-damaged non-mycorrhizal plants. In contrast, mycorrhizal infection increased the emission of the green leaf volatile (Z)-3-hexenyl acetate in untreated control plants, making it comparable to emission from mechanically wounded or herbivore-damaged plants whether or not they had mycorrhizal associates. Neither mycorrhization nor treatment had any influence on the levels of iridoid glycosides. Thus, mycorrhizal infection did not have any effect on the levels of direct defense compounds measured in P. lanceolata. However, the large decline in herbivore-induced sesquiterpene emission may have important implications for the indirect defense potential of this species.

Topics: Acetates; Animals; Glucosides; Host-Parasite Interactions; Iridoid Glucosides; Iridoids; Mycorrhizae; Plantago; Sesquiterpenes; Spodoptera; Symbiosis; Volatile Organic Compounds

The purpose of this work is to study the effect of catalpol, an iridoid from Rehmannia glutinosa on neurodegenerative changes induced by beta-amyloid peptide Abeta(25-35) or Abeta(25-35)+ibotenic acid and the underlying mechanism. Results showed that catalpol significantly improved the memory deficits in the neurodegenerative mouse model produced by injection of Abeta(25-35)+ibotenic acid to the nucleus magnocellularis basalis, yet it is neither a cholinesterase inhibitor nor a muscarinic (M) receptor agonist. Instead, the choline acetyl transferase (ChAT) activity and the M receptor density in brain were significantly decreased in the model mice and catalpol could significantly elevate their levels. Furthermore, the brain-derived neurotrophic factor (BDNF) content in brain was significantly decreased in the model mice and catalpol elevated it to normal level (83%+/-3% and 102%+/-2% of normal respectively). There is a significant positive correlation between BDNF content and memory. Primary culture of forebrain neurons revealed that aggregated Abeta(25-35) induced significant decrease of ChAT positive neuron number, neurite outgrowth length, and M receptor density, while catalpol added to the culture medium 2 h prior to Abeta addition showed significant dose dependent protective effect. Notably, 24 h and 48 h after the addition of Abeta to the cultured cells, the BDNF mRNA level in the neurons decreased to 76%+/-7% and 66%+/-3% of control without catalpol treatment, but became 128%+/-17% and 131%+/-23% of control with catalpol treatment. When the action of BDNF was inhibited by k252a in the cultured neurons, the protective effect of catalpol was completely (neurite outgrowth length) or partially (ChAT positive neuron number and the M receptor density) abolished. Taken together, catalpol improves memory and protects the forebrain neurons from neurodegeneration through increasing BDNF expression. Whether catalpol could reverse the neurodegenerative changes already present before its application remains to be further studied.

Topics: Amyloid beta-Peptides; Animals; Brain; Brain-Derived Neurotrophic Factor; Cells, Cultured; Choline O-Acetyltransferase; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Glucosides; Iridoid Glucosides; Iridoids; Learning; Memory; Mice; Mice, Inbred ICR; Neurites; Neurodegenerative Diseases; Neurons; Neuroprotective Agents; Peptide Fragments; Rats; Rats, Sprague-Dawley; Receptors, Muscarinic

A sensitive, rapid and specific liquid chromatography/tandem mass spectrometry (LC/MS/MS) assay has been established for the quantitation of catalpol in rat plasma. Plasma samples were treated by precipitating protein with methanol and were chromatographed by a Diamonsil C(18) column (150 mm x 4.6 mm I.D., 5 microm) with the mobile phase consisting of methanol and 10 mM ammonium formate (30:70, v/v). The selected reaction monitoring (SRM) transitions were performed at m/z 380.1-->183.0 for catalpol and m/z 364.3-->167.0 for aucubin (IS) in the positive ion mode with electrospray ionization (ESI) source. Calibration curve was linear over the concentration range of 10-20,000 ng/mL. The mean recovery was 76.5+/-5.2% and the matrix effect ranged from -5.1 to 13.0%. The intra- and inter-day precisions were less than 6.3 and 14.6%, respectively, and the accuracy was within +/-5.6%. Catalpol was stable in possible conditions of storing and handling. The validated method has been successfully applied to determine the plasma concentration of catalpol for a pharmacokinetic study of catalpol after oral administration of 50 mg/kg to rats.

Topics: Animals; Chromatography, Liquid; Glucosides; Iridoid Glucosides; Iridoids; Rats; Reproducibility of Results; Spectrometry, Mass, Electrospray Ionization; Tandem Mass Spectrometry

To establish an HPLC method for determination of catalpol in CSF (cerebrospinal fluid) of rats.. Rats were intravenously injected 1.0 g x L(-1) catalpol physiological saline, and the sample of CSF from subarachnoid space of the cerebrum 40 minutes of injection. The sample of CSF from normal rats was used for blank control, the all samples were preserved in a refrigerator of - 20 degrees C, and use HPLC was employed to determine the catalpol content. The separation of catalpol was performed on Hypersil C18 reversion phase chromatographic column. The mobile phase consisted of water-acetonitrile (99.5: 0.5) with a flow rate of 1.0 mL x min(-1) and detection wavelength of 210 nm.. The linear range of catalpol in CSF was 0.5-40 mg x L(-1) (r = 0.999 7). The absolute recoveries were (90.2 +/- 1.71)%, (89.1 +/- 1.17)% and (86.9 +/- 0.98)%; and the methodological recoveries were (99.8 +/- 1.98)%, (101.1 +/- 3.04)%, (100.1 +/- 2.30)% respectively. The within-day and between-day derivation RSD were less than 4%. Catalpol was stable in a refrigerator of -20 degrees C for 15 days.. The method is simple and accurate for the determination of the content of catalpol in CSF.

Topics: Animals; Chromatography, High Pressure Liquid; Glucosides; Iridoid Glucosides; Iridoids; Male; Random Allocation; Rats; Rats, Sprague-Dawley

To study the protective effects of catalpol against H2O2-induced oxidative damage in astrocytes.. Astrocytes were pretreated with 1, 10, 100 micromol x L(-1) catalpol and then exposed to H2O2. Effects of catalpol on cell morphous were observed by inverted microscope. Cell viability were detected by MTT assay. LDH content in the cell culture fluid, and intracellular T-SOD, GSH-Px activity and MDA content were assessed by colorimetric method.. The results showed that catalpol evidently ameliorated cell morphous, improved cell viability, and maintained integrality of cell membrane. Furthermore, catalpol could significantly inhibit the decrease of intracellullar T-SOD and GSH-Px activity, and the increase of MDA content.. Catalpol have protective effects against H2O2-induced oxidative damage in astrocytes.

Topics: Animals; Astrocytes; Cell Survival; Cells, Cultured; Glucosides; Hydrogen Peroxide; Iridoid Glucosides; Iridoids; Oxidative Stress; Protective Agents; Rats; Rats, Sprague-Dawley

The oxidative stress-induced changes and feasibility of prevention of these changes with an aid of vitamines E and C were investigated in cultured brain cortex of the newborn albino rats. Modeling the oxidative stress was achieved with addition of H(2)O(2) into the nutrient medium. In order to prevent an oxidative stress-induced cytotoxic effect, concomittantly with H(2)O(2), vitamines E and C were added into the nutrient medium. The data, obtained in our study revealed inhibition of the glial cells'- and axonal migration into the growth zone resulting from the oxidative stress. These changes were attenuated following action of vitamines E and C, which points at feasibility of their use against oxidative impact from the free radicals emerging during neurodegenerative disorders.

Topics: Animals; Ascorbic Acid; Brain; Brain Diseases; Drugs, Chinese Herbal; Glucosides; Iridoid Glucosides; Iridoids; Oxidative Stress; Rats; Vitamin E

The neuroprotective effects of catalpol, an iridoid glycoside isolated from the fresh rehmannia roots, on the behavior and brain energy metabolism in senescent mice induced by d-galactose were assessed. Except control group, mice were subcutaneously injected with d-galactose (150 mg/kg body weight) for 6 weeks. From the fifth week, drug group mice were treated with catalpol (2.5, 5, 10 mg/kg body weight) and piracetam (300 mg/kg body weight) for the last 2 weeks. Behavioral changes including open field test and passive avoidance were examined after drug administration. To determine the brain damage, pathological alterations were measured by hematoxylin and eosin (HE) staining. The activities of lactate dehydrogenase (LDH), glutathione S-transferase (GSH-ST), glutamine synthetase (GS), creatine kinase (CK) in brain cortex and hippocampus were determined using different biochemical methods. Consistent with the cognition deficits, the activities of GSH-ST, GS and CK decreased while the activity of LDH increased in aging mice brain. Administration of catalpol for 2-weeks not only ameliorated cognition deficit, but also reversed the biochemical markers mentioned above and reduced the histological lesions in mouse brain. These results suggest that catalpol has protective effects on memory damage and energy metabolism failure in aging model mice and is worth testing for further preclinical study aimed for senescence or neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD).

Topics: Aging; Animals; Avoidance Learning; Brain; Brain Chemistry; Cerebral Cortex; Cognition; Creatine Kinase; Energy Metabolism; Female; Galactose; Glucosides; Glutathione; Glutathione Transferase; Hippocampus; Indicators and Reagents; Iridoid Glucosides; Iridoids; L-Lactate Dehydrogenase; Male; Memory Disorders; Mice; Motor Activity; Plant Roots; Rehmannia

It has been proposed that ROS production, including H(2)O(2), may lead to neurodegenerative disorders such as Parkinson's disease and Alzheimer's disease. Catalpol, an iridoid glycoside, presents in the root of Rehmannia glutinosa, protects cells and mice from damage caused by a variety of toxic stimuli. In this study, we investigated whether catalpol could protect astrocytes from oxidant stress induced by H(2)O(2) because of the critical role of astrocytes in the brain and found the possible mechanism of protection. The results showed that catalpol could significantly increase the cell viability and reduce the intracellular ROS formation. Furthermore, catalpol attenuated H(2)O(2)-induced oxidative stress via preventing the decrease in the activities of antioxidant enzymes in glutathione redox cycling such as glutathione peroxidase, glutathione reductase and glutathione content. However, the catalase activity did not appear to be elevated by catalpol adequately. Together, the main mechanism underlying the protective effects of catalpol in H(2)O(2)-injured astrocytes might be related to the maintenance of glutathione metabolism balance and the decrease of ROS formation. Therefore, catalpol may be developed as a potential preventive or therapeutic drug for neurodegenerative diseases associated with oxidative stress.

Topics: Animals; Antioxidants; Astrocytes; Catalase; Cell Survival; Cells, Cultured; Glucosides; Glutathione; Glutathione Peroxidase; Glutathione Reductase; Hydrogen Peroxide; Iridoid Glucosides; Iridoids; Mice; Oxidants; Oxidative Stress; Reactive Oxygen Species

Catalpol, an iridoid glucoside, separated from the root of Rehmannia glutinosa Libosch, has been known to show various neuroprotective effects. In humans and rodents, MPTP is well known to produce clinical, biochemical and neurochemical changes similar to those which occur in Parkinson's disease (PD). Furthermore, the accumulated evidence suggests that MPP(+), conversed by monoamine oxidase type B (MAO-B) in astrocytes principally, is the active metabolite of MPTP and the major cause to PD associated with mitochondrial dysfunction. In this study, we treated mesencephalic neuron-astrocyte and astrocytes cultures with MPTP (0.05 mM) respectively to investigate the neuroprotective effects of catalpol and the underlying protective mechanisms. Our results showed that pre-treatment with catalpol (0.5mM) for 1h prior to MPTP treatment attenuated mitochondrial dysfunction not only by reversing the activity of mitochondrial complex I, mitochondrial membrane potential (MMP), intracellular Ca(2+) level, and ROS accumulation as well as mitochondrial permeability transition (MPT) pore opening in mesencephalic neuron-astrocyte cultures, but also inhibiting MAO-B activity to protect neurons from more MPP(+) toxicity produced in astrocytes. Together, all of these indicated that catalpol possesses potent neuroprotective activity and may be a potential anti-PD drug worthy for further study.

Topics: Animals; Astrocytes; Calcium; Cells, Cultured; Glucosides; Iridoid Glucosides; Iridoids; Membrane Potential, Mitochondrial; Mesencephalon; Mice; Mitochondrial Membrane Transport Proteins; Mitochondrial Permeability Transition Pore; Monoamine Oxidase; MPTP Poisoning; Neurons; Neuroprotective Agents; Neurotoxicity Syndromes; Reactive Oxygen Species; Rehmannia

To compare difference in character between wild germplasm and cultivar of Rehmannia glutinosa Libosch.. Field test and statistical analysis were applied.. The results showed that the plant height and leave weight of individual plant in cultivar were decreased significantly comparing to wild germplasm, and the output was increased significantly. The leave length was reduced. The leave width, the catalpol content in leave and polysaccharides and reducing sugar content in cultivar was increased not significantly. Whereas the catalpol content and the water extract content in cultivar were equal to wild germplasm.. The plant height and leave weight of individual plant of R. glutinosa was decreased significantly in cultivar, but the active compounds content not changed obviously.

Topics: Chromatography, High Pressure Liquid; Glucosides; Iridoid Glucosides; Iridoids; Plant Leaves; Plants, Medicinal; Rehmannia

Catalpol has been identified to have neuroprotective effect on gerbils subjected to transient global cerebral ischemia. However, the mechanism that catalpol prevents ischemia is still unclear. In the present study, PC12 cells, exposed to oxygen and glucose deprivation (OGD) followed by reperfusion, were used as an in vitro model of ischemia. The protective effects of catalpol were investigated in ischemic-induced apoptosis in PC12 cells.. After OGD for 3 hours and reoxygenation for 18 hours, cell survival was quantified by the reduction of 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). The activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) were determined using commercially available kits. Caspase-3 assay was performed using caspase-3 assay kit. Microplate reader was used to detect the intensities of rhodamine123 (Rh123) and reactive oxygen species (ROS). The level of Bcl-2 protein was measured by flow cytometry.. Catalpol attenuated ischemia-induced apoptotic death via preventing the decrease in the level of Bcl-2 protein and the activities of SOD and GSH-PX, inhibiting the reduction of mitochondrial membrane potential and suppressing activation of caspase-3.. The results suggest that the catalpol has the potential to prevent ischemic-induced apoptosis.

Topics: Animals; Apoptosis; Caspase 3; Cell Count; Dose-Response Relationship, Drug; Drugs, Chinese Herbal; Glucose; Glucosides; Glutathione Peroxidase; Hypoxia; Iridoid Glucosides; Iridoids; Membrane Potential, Mitochondrial; PC12 Cells; Proto-Oncogene Proteins c-bcl-2; Rats; Reactive Oxygen Species; Superoxide Dismutase

We have previously evaluated the neuroprotective effect of catalpol on aging mice induced by d-galactose, in which catalpol treatment ameliorated cognition deficits and attenuated oxidative damage in mice brain. To thoroughly elucidate the anti-aging effects of catalpol, the liver and spleen antioxidative systems and energy metabolism in senescent mice induced by d-galactose have been studied. Except control group, mice were subcutaneously injected with d-galactose (150mgkg(-1)body weight) for 6 weeks. Meanwhile, drug group mice were treated with catalpol (2.5, 5, 10mgkg(-1)body weight) and piracetam (300mgkg(-1)body weight) for the last 2 weeks. The activities of endogenous antioxidants and the level of glutathione (GSH) and lipid peroxide in the liver and spleen were assayed. Compared to control group, model group mice had significantly lower spleen index (spleen weight/body weight), lower level of GSH, lower activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX), higher level of malondialdehyde (MDA) in the liver and spleen. However, catalpol administration markedly reversed these effects of senescence induced by d-galactose. Simultaneously, catalpol noticeably elevated the decreased activities of lactate dehydrogenase (LDH), glutamine synthetase (GS), Na(+)-K(+)-ATPase, Ca(2+)-Mg(2+)-ATPase and decreased the elevated activity of creatine kinase (CK) in mice liver or spleen. These results implied that the anti-aging effects of catalpol were achieved at least partly by promoting endogenous antioxidant enzyme activities and normalizing energy disturbance. Catalpol may be a potential anti-aging agent and worth testing for further preclinical study aimed for senescence or neurodegenerative diseases such as Alzheimer's and Parkinson's diseases.

Topics: Aging; Animals; Ca(2+) Mg(2+)-ATPase; Creatine Kinase; Energy Metabolism; Galactose; Glucosides; Glutamate-Ammonia Ligase; Glutathione; Iridoid Glucosides; Iridoids; Lipid Peroxidation; Liver; Malondialdehyde; Mice; Mitochondria, Liver; Neuroprotective Agents; Oxidative Stress; Oxidoreductases; Rehmannia; Sodium-Potassium-Exchanging ATPase; Spleen

Catalpol is an iridoid glycoside, distributed in the roots of Rehmannia glutinosa Libosch. In vitro results showed that preincubation with catalpol (0.5-0.5 mM) for 0.5 hours before and during 48 hour exposure to 0.2 mM MPP+ appeared to be significant protective effect while catalopl was considerably less effective at the doses of 0.001 to 0.01 mM. The addition of catalpol at the dose of 0.05-0.5 mM significantly increased DA and DOPAC to MPP+ treated group. C57bl/6 mice received administration of catalpol for 12 hours before and during the 7 day treatment with MPTP. Such treatment at doses of 15 mg/kg significantly and dramatically blocked tyrosine hydroxylase-positive cell loss in mice. DA turnover in MPTP mice was reversed in the nigrostriatal pathway. In conclusion, data obtained in the above study suggested that catalpol exerted neuroprotective action in vitro and in vivo PD model.

Topics: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; 3,4-Dihydroxyphenylacetic Acid; Analysis of Variance; Animals; Brain; Cell Survival; Dopamine; Dose-Response Relationship, Drug; Glucosides; Iridoid Glucosides; Iridoids; Male; Mice; Mice, Inbred C57BL; Neuroprotective Agents; Neurotoxicity Syndromes; Neurotoxins; PC12 Cells; Rats; Tetrazolium Salts; Thiazoles; Time Factors; Tyrosine 3-Monooxygenase

The neuroprotective effects of catalpol, an iridoid glycoside present in the roots of Rehmannia glutinosa, on 1-methyl-4-phenylpyridinium (MPP(+))-induced oxidative stress in cultured mesencephalic neurons, especially dopaminergic neurons, were investigated. Exposure of mesencephalic neurons to 10microM MPP(+) induced a leakage of lactate dehydrogenase (LDH) and decreased cell viability, measured with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Catalpol increased neuron viability and markedly attenuated MPP(+)-induced dopaminergic neuron death in a dose-dependent manner. In order to clarify the neuroprotective mechanism of catalpol, mitochondrial function, the activities of endogenous antioxidants and the lipid peroxide content were measured. The results indicated that catalpol prevented the MPP(+)-induced inhibition of complex I activity and the loss of mitochondrial membrane potential. In addition, catalpol reduced the content of lipid peroxide and increased the activity of glutathione peroxidase and superoxide dismutase. Taken together, the above results suggest that catalpol may be a candidate drug for the treatment of oxidative stress-induced neurodegenerative disease.

Topics: 1-Methyl-4-phenylpyridinium; Animals; Glucosides; Glutathione Peroxidase; Iridoid Glucosides; Iridoids; Membrane Potential, Mitochondrial; Mesencephalon; Mice; Neurons; Neuroprotective Agents; Oxidative Stress; Superoxide Dismutase

The neuroprotective effects of catalpol, an iridoid glycoside isolated from the fresh Rehmannia roots, on the senescent mice induced by D-galactose were assessed. The mice subcutaneously injected with catalpol (5 or 10 mg/kg, 2 weeks, from fifth week) showed significantly improved learning and memory ability in Morris water maze test compared with d-galactose treated mice (150 mg/kg, 6 weeks). We further investigated the mechanism involved in the neuroprotective effects of catalpol on the mice brain tissue. The results showed that catalpol increased the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), decreased the malondialdehyde (MDA) level, elevated the activities of Na+ -K+ ATPase and Ca2+ -Mg2+ ATPase on the cerebral cortex and hippocampus of d-galactose treated mouse. All the data suggested that catalpol had the potential to be a useful cognitive impairment treatment, and its beneficial effects may be partly mediated via enhancing endogenous antioxidant enzymatic activities and inhibiting free radical generation.

Topics: Aging; Animals; Brain Chemistry; Ca(2+) Mg(2+)-ATPase; Cerebral Cortex; Cognition Disorders; Female; Galactose; Glucosides; Glutathione Peroxidase; Indicators and Reagents; Iridoid Glucosides; Iridoids; Lipid Peroxidation; Male; Malondialdehyde; Maze Learning; Mice; Oxidative Stress; Plant Roots; Rehmannia; Sodium-Potassium-Exchanging ATPase; Superoxide Dismutase

To study on effect of concentration of catalpol and 5-hydroxy methyl-2-furaldehyde (5-HMF) from Rehmanniae Radix at various processing.. The Rehmanniae Radix was dried and prepared from the steaming process with 10% ethanol, 50% ethanol at 90 degrees C and 100 degrees C each other. And the changes of catalpol and 5-HMF was determinated. The extraction of 5-HMF and catalpol was sonicated in 30% methanol for 2 h. The analysis of 5-HMF and catalpol was conducted by HPLC with reversed-phase C-18 column and detected under UV 284 nm, 204 nm. Elution was carried out at 1.0 mL min(-1) with 3% acetonitrile.. From this analysis, we found out that the content of catalpol was decreased with the number of processing times, and content of 5-HMF was increased with the number of processing times at various processing. The temperature and concentration of ethanol can effect on content of catalpol and 5-HMF at processing. The Cooked Rehmanniae Radix processed at 100 degrees C, 10% ethanol is best. And the content of 5-HMF processed for more than 7 times was accorded with standard of Korea phamcopoetia.. Analyze the effect of concentration of catalpol and 5-HMF from Rehmanniae Radix at various processing, and provide the foundation for further study.

Topics: Chromatography, High Pressure Liquid; Ethanol; Furaldehyde; Glucosides; Hot Temperature; Iridoid Glucosides; Iridoids; Plant Tubers; Plants, Medicinal; Rehmannia; Technology, Pharmaceutical

To explore the effects of different concentration of catalpol on the cell survival and axonal growth of cortical neurons cultured in vitro from 24 h newly born rat.. Primary cultured cortical neurons from 24 h newly born rat were dissociated and cultured. The different concentration of catalpol and 1 mg mL(-1) citicoline were added to the culture plates for 48 h, and the final of catalpol concentration were 0.25, 0.5, 1, 2.5, 5 mg mL(-1), respectively. The cortical neuron was identified by NF-200 antigen and its survival activity detected by MTT assay. The axonal growth of cultured cortical neuron were observed by inverted microscopy with micrometer.. Immunocytochemistry demonstrated more than 95% of the primary cultured cortical neurons were positive for NF-200 antigen, which indicated the cultured cells were neurons. Neurons survived growing on the concentration of 0.25, 0.5, 1, 2.5, 5 mg mL(-1). Compared with blank and 1 mg mL(-1) citicoline group,neurons survival rates were not statistical significant difference. However, it demonstrated that catalpol significantly promoted axonal growth from 1-5 mg mL(-1) (P <0.05). Interestedly, compared with the dose of 2.5 mg mL(-1), axonal growth was shorter at the dose of 5 mg mL(-1), and 2.5 mg mL(-1) catalpol showed the strongest promotion effect.. The catalpol can enhance cortical neuron axonal growth, but not promote cortical neuron survival.

Topics: Animals; Animals, Newborn; Axons; Cell Survival; Cells, Cultured; Cerebral Cortex; Dose-Response Relationship, Drug; Drugs, Chinese Herbal; Glucosides; Iridoid Glucosides; Iridoids; Neurons; Neuroprotective Agents; Plants, Medicinal; Rats; Rats, Sprague-Dawley; Rehmannia

The methanol soluble fraction of the leaves of Buddleia scordioides after column chromatography resulted in the isolation of two known iridoid glucosides, catalpol and methylcatalpol. The structures were elucidated by extensive 1D-2D-NMR spectroscopy. The structure of methylcatalpol was confirmed by single-crystal x-ray diffraction. These compounds showed protective activity against increased (both chloroform and histamine) skin vascular permeability in rabbits. The protective effect was measured as the reduction in leakage of Evans blue. The results showed that the iridoids produced a significant inhibition of microvascular permeability. A comparison was made between the action of the iridoids and a known inhibitor of vascular permeability, troxerutin (50 mg/kg). Methylcatalpol and catalpol were found to be less effective than troxerutin.

Topics: Animals; Buddleja; Capillaries; Glucosides; Hydroxyethylrutoside; Iridoid Glucosides; Iridoids; Male; Permeability; Rabbits; Skin; Vasoconstrictor Agents

Our previous study described the neuroprotective effects of catalpol in gerbil ischemic model, in which catalpol was shown to prevent hippocampal neurons from death and ameliorate the cognitive ability of the animals. In the study, we focused on investigating the neuroprotective mechanism of catalpol. Animals were randomly assigned three groups as sham-operated, ischemia-treated with saline and ischemia-treated with catalpol. Transient global ischemia was produced by a 5 min occlusion of the bilateral common carotid arteries. Catalpol was intraperitoneally injected at the dose of 5 mg/kg immediately after reperfusion and repeatedly at 12, 24, 48 and 72 h. Histology as well as immunohistochemistry and TUNEL (the terminal deoxynucleotidyl transferase-mediated UTP nick end label) analysis were performed on serial slices through the dorsal hippocampus after gerbils were sacrificed. The results showed that 5 min transient global ischemia followed by 4 days reperfusion caused significant increases in TUNEL-positive and Bax-positive cells in hippocampal CA1 subfield. Catalpol not only significantly reduced TUNEL-positive and Bax-positive cells but also significantly increased Bcl-2-positive cells. All these suggested that catalpol could effectively inhibit apoptosis by modulating the expressions of Bcl-2 and Bax genes.

Topics: Animals; Apoptosis; bcl-2-Associated X Protein; Brain Infarction; Brain Ischemia; Disease Models, Animal; Drug Administration Schedule; Drugs, Chinese Herbal; Female; Gene Expression Regulation, Enzymologic; Gerbillinae; Glucosides; Hippocampus; Immunohistochemistry; In Situ Nick-End Labeling; Iridoid Glucosides; Iridoids; Male; Nerve Degeneration; Neuroprotective Agents; Proto-Oncogene Proteins c-bcl-2; Reperfusion Injury; Treatment Outcome

Inflammation plays an important role in the pathogenesis of Parkinson's disease (PD). Microglia, the resident immune cells in the central nervous system, are pivotal in the inflammatory reaction. Activated microglia can induce expression of inducible nitric-oxide synthase (iNOS) and release significant amounts of nitric oxide (NO) and TNF-alpha, which can damage the dopaminergic neurons. Catalpol, an iridoid glycoside, contained richly in the roots of Rehmannia glutinosa, was found to be neuroprotective in gerbils subjected to transient global cerebral ischemia. But the effect of catalpol on inflammation-mediated neurodegeneration has not been examined. In this study, microglia in mesencephalic neuron-glia cultures were activated with lipopolysaccharide (LPS) and the aim of the study was to examine whether catalpol could protect dopaminergic neurons from LPS-induced neurotoxicity. The results showed that catalpol significantly reduced the release of reactive oxygen species (ROS), TNF-alpha and NO after LPS-induced microglial activation. Further, catalpol attenuated LPS-induced the expression of iNOS. As determined by immunocytochemical analysis, pretreatment by catalpol dose-dependently protected dopaminergic neurons against LPS-induced neurotoxicity. These results suggest that catalpol exerts its protective effect on dopaminergic neurons by inhibiting microglial activation and reducing the production of proinflammatory factors. Thus, catalpol may possess therapeutic potential against inflammation-related neurodegenerative diseases.

Topics: Animals; Cells, Cultured; Coculture Techniques; Dopamine; Dose-Response Relationship, Drug; Gene Expression Regulation, Enzymologic; Glucosides; Inflammation; Iridoid Glucosides; Iridoids; Lipopolysaccharides; Mesencephalon; Mice; Nerve Degeneration; Neurodegenerative Diseases; Neuroglia; Neurons; Neuroprotective Agents; Nitric Oxide; Nitric Oxide Synthase Type II; Reactive Oxygen Species; Tumor Necrosis Factor-alpha

Rehmannia, a traditional Chinese medical herb, has a long history in age-related disease therapy. Previous work has indicated that catalpol is a main active ingredient performing neuroprotective effect in rehmannia, while the mechanism underlying the effect remains poorly understood. In this study, we attempt to investigate the effect of catalpol on presynaptic proteins and explore a potential mechanism. The hippocampal levels of GAP-43 and synaptophysin in 3 groups of 4 months (young group), 22-24 months (aged group) and catalpol-treated 22-24 months (catalpol-treated group) rats were evaluated by western blotting. Results clearly showed a significant decrease in synaptophysin (46.6%) and GAP-43 (61.4%) levels in the aged group against the young animals and an increase (45.0% and 31.8% respectively) in the catalpol-treated aged rats in comparison with the untreated aged group. In particular, synaptophysin immunoreactivity (OD) in the dentate granule layer of the hippocampus was increased 0.0251 in the catalpol-treated group as compared with the aged group. The study also revealed a catalpol-associated increase of PKC and BDNF in the hippocampus of the catalpol-treated group in comparison with the aged rats and highly correlated with synaptophysin and GAP-43. Such positive correlations between presynaptic proteins and signaling molecules also existed in the young group. These results suggested that catalpol could increase presynaptic proteins and up-regulate relative signaling molecules in the hippocampus of the aged rats. Consequently, it seemed to indicate that catalpol might ameliorate age-related neuroplasticity loss by "normalizing" presynaptic proteins and their relative signaling pathways in the aged rats.

Topics: Aging; Analysis of Variance; Animals; Brain-Derived Neurotrophic Factor; Drugs, Chinese Herbal; GAP-43 Protein; Glucosides; Hippocampus; Iridoid Glucosides; Iridoids; Male; Neuronal Plasticity; Neuroprotective Agents; Protein Kinase C; Rats; Rats, Sprague-Dawley; Statistics, Nonparametric; Synaptophysin; Up-Regulation

Catalpol, an iridoid glycoside, contained richly in the roots of Rehmannia glutinosa, was found for the first time to be of neuroprotection in gerbils subjected to transient global cerebral ischemia. Catalpol (1 mg/kg ip) used immediately after reperfusion and repeatedly at 12, 24, 48 and 72 h significantly rescued neurons in hippocampal CA1 subfield and reduced working errors during behavioral testing. The neuroprotective efficacy of catalpol became more evident when the doses of catalpol were increased to 5 and 10mg/kg. In addition, it was exciting that the significant neuroprotection by catalpol was also evident when catalpol was applied up to 3 h after ischemia. But the neuroprotective efficacy of catalpol became weak when catalpol was given at 6h after ischemia. Of great encouragement was the finding that the neuroprotection of catalpol could be seen not only in a short post-ischemic period (12 days) but also in a long period (35 days). All these indicated that catalpol was truly neuroprotective rather than simply delayed the onset of neuronal damage and might be of therapeutic value for the treatment of global cerebral ischemia.

Topics: Analysis of Variance; Animals; Behavioral Symptoms; Dose-Response Relationship, Drug; Gerbillinae; Glucosides; Hippocampus; Iridoid Glucosides; Iridoids; Neurons; Neuroprotective Agents; Reperfusion Injury; Time Factors

In the present study, using a rat pheochromocytoma (PC12) cell line, the effect of catalpol on H2O2-induced apoptosis was studied. The apoptosis in H2O2-induced PC12 cells was accompanied by down-regulation of Bcl-2, up-regulation of Bax, the release of mitochondrial cytochrome c to cytosol and sequential activation of caspase-1 and caspase-3 then leading to cleavage of poly-ADP-ribose polymerase (PARP). Catalpol not only suppressed the down-regulation of Bcl-2, up-regulation of Bax and the release of mitochondrial cytochrome c to cytosol, but also attenuated caspase-3 activation, PARP cleavage, and eventually protected against H2O2-induced apoptosis. Taken together, these results suggest that treatment of PC12 cells with catalpol can block H2O2-induced apoptosis by the regulation of Bcl-2 family members, as well as suppression of cytochrome c release and caspase cascade activation.

Topics: Animals; Apoptosis; bcl-2-Associated X Protein; Caspases; Cytochromes c; Drugs, Chinese Herbal; Gene Expression Regulation; Genes, bcl-2; Glucosides; Hydrogen Peroxide; Iridoid Glucosides; Iridoids; PC12 Cells; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-bcl-2; Rats

Growth inhibitory activities and nutritional indices of catalpol (1), 8-O-acetylharpagide (2), and harpagide (3) were determinated in larvae and adults of Tribolium castaneum, respectively. Compound 1 produced a series of allelochemical effects probably related with the DNA synthesis. This iridoid possessed the highest inhibitory activity against DNA polymerase. Molecular orbital calculations suggest that a pi-pi charge transfer recognition model could explain the action of iridioids toward nucleic acid synthesis.

Topics: Animals; Enzyme Inhibitors; Glucosides; Insect Control; Iridoid Glucosides; Iridoid Glycosides; Iridoids; Larva; Models, Molecular; Molecular Structure; Nucleic Acid Synthesis Inhibitors; Pyrans; Tribolium

Plants are often attacked by multiple enemies, including pathogens and herbivores. While many plant secondary metabolites show specific effects toward either pathogens or herbivores, some can affect the performance of both these groups of natural enemies and are considered to be "generalized defense compounds". We tested whether aucubin and catalpol, two iridoid glycosides present in ribwort plantain (Plantago lanceolata), confer in vivo resistance to both the generalist insect herbivore Spodoptera exigua and the biotrophic fungal pathogen Diaporthe adunca using plants from P. lanceolata lines that had been selected for high- and low-leaf iridoid glycoside concentrations for four generations. The lines differed approximately three-fold in the levels of these compounds. Plants from the high-selection line showed enhanced resistance to both S. exigua and D. adunca, as evidenced by a smaller lesion size and a lower fungal growth rate and spore production, and a lower larval growth rate and herbivory under both choice and no-choice conditions. Gravimetric analysis revealed that the iridoid glycosides acted as feeding deterrents to S. exigua, thereby reducing its food intake rate, rather than having post-ingestive toxic effects as predicted from in vitro effects of hydrolysis products. We suggest that the bitter taste of iridoid glycosides deters feeding by S. exigua, whereas the hydrolysis products formed after tissue damage following fungal infection mediate pathogen resistance. We conclude that iridoid glycosides in P. lanceolata can serve as broad-spectrum defenses and that selection for pathogen resistance could potentially result in increased resistance to generalist insect herbivores and vice versa, resulting in diffuse rather than pairwise coevolution.

Topics: Adaptation, Physiological; Animals; Biological Evolution; Feeding Behavior; Fungi; Glucosides; Iridoid Glucosides; Iridoids; Plantago; Plants, Edible; Spodoptera

Studies on plant-defensive chemistry have mainly focused on plants in direct interaction with aboveground and occasionally belowground herbivores and pathogens. Here we investigate whether decomposers and the spatial distribution of organic residues in soil affect plant-defensive chemistry. Litter concentrated in a patch (vs. homogeneously mixed into the soil) led to an increase in the aucubin content in shoots of Plantago lanceolata. Earthworms increased total phytosterol content of shoots, but only when the litter was mixed homogeneously into the soil. The phytosterol content increased and aphid reproduction decreased with increasing N concentration of the shoots. This study documents for the first time that earthworms and the spatial distribution of litter may change plant-defensive chemistry against herbivores.

Topics: Animals; Aphids; Glucosides; Iridoid Glucosides; Iridoids; Nitrogen; Nitrogen Radioisotopes; Oligochaeta; Phytosterols; Plant Leaves; Plant Shoots; Plantago; Soil

To determinate the catalpol contents in dried rehmannia root and Taohong Siwu Decoction containing rehmannia root with high performance liquid chromatography (HPLC).. Catalpol was separated on a YWG-C18 column using water-acetonitrile (99.4:0.6) as mobile phase and detective wavelength at 210 nm.. The linear curve of tested catalpol concentration within the range of 0.0536-5.3600 microg/microl was ideal (n=5, r=0.999 7). The average recovery rate of the dried rehmannia root and Taohong Siwu decoction was 98.7% (RSD=0.48%) and 98.2% (RSD=1.29%) respectively.. HPLC method is accurate and valuable for the quality control of Radix Rehmanniae and Taohong Siwu Decoction.

Topics: Chromatography, High Pressure Liquid; Glucosides; Iridoid Glucosides; Iridoids; Medicine, Chinese Traditional; Rehmannia

The neuroprotection of catalpol and its mechanism was evaluated in cerebral ischemic model in gerbils. Three groups were designed as sham-operated, ischemia-treated, respectively, with catalpol and saline. Catalpol was injected intraperitoneally immediately after reperfusion and repeatedly at 12, 24, 48 and 72 h with the dose of 5.0 mg/kg. The neuroprotection was estimated by the indexes of behavior and histology. Behavioral testing was performed in Y-maze and the survival neurons in CA1 subfield were counted under a microscope after behavioral testing. In addition, apoptosis induced by ischemia was also examined by using the terminal deoxynucleotidyl transferase-mediated UTP nick end labeling method. It was shown that catalpol significantly attenuated apoptosis, rescued hippocampal CA1 neurons and reduced cognitive impairment. In order to make clear the mechanism of catalpol's neuroprotection, the activities of endogenous antioxidants and nitric oxide synthase together with the content of lipid peroxide in cortex and hippocampus were assayed. The results proved that catalpol significantly reduced the content of lipid peroxide, increased the activity of glutathione peroxidase and decreased the activity of nitric oxide synthase. All these suggested that catalpol was a potential neuroprotective agent and its neuroprotective effects were achieved at least partly by promoting endogenous antioxidant enzymatic activities and reducing the formation of nitric oxide.

Topics: Animals; Apoptosis; Behavior, Animal; Brain Ischemia; Disease Models, Animal; Female; Gerbillinae; Glucosides; Glutathione Peroxidase; Hippocampus; In Situ Nick-End Labeling; Iridoid Glucosides; Iridoids; Lipid Peroxides; Male; Maze Learning; Neurons; Neuroprotective Agents; Nitric Oxide Synthase

Induction of allelochemicals is one way that plants efficiently deploy defenses against herbivory. In two separate experiments we investigated the time course of this inductive response and the importance of the timing of herbivory for Plantago lanceolata (Plantaginaceae). We found a localized induced response of catalpol and the ratio of catalpol to total iridoid glycosides in damaged leaves that was evident at d 6 after caterpillars of the specialist Junonia coenia were put onto the plants. On the whole plant level, we detected small, but significant changes in the iridoid glycoside metabolism of P. lanceolata on several different days following herbivory. We also found considerable change in the amounts of allelochemicals produced during P. lanceolata's ontogeny. This ontogenetic effect might help to explain some of the reasons why induction may be difficult to detect in P. lanceolata. We also investigated the importance of the timing of herbivory on P. lanceolata's inductive response, but neither herbivory after 5 wk of growth nor after 6 or 7 wk of growth induced an increase in aucubin or catalpol.

Topics: Glucosides; Iridoid Glucosides; Iridoids; Plant Leaves; Plantago; Time Factors

DNA polymerases have recently emerged as important cellular targets for chemical intervention in the development of anti-cancer agents. This report describes a PCR assay as a method to investigate the action mechanism of the inhibition of Taq DNA polymerase by catalpol. This inhibition was not primer or template specific, nor was it due to chelation of Mg2+ ions. In assays of hyperchromicity of double-stranded DNA, catalpol did not affect melting profile. The inhibitory effect of catalpol does not appear to depend on DNA concentration. In contrast, increasing dNTP concentration rescue the Taq DNA polymerase activity, suggestingthat catalpol acts in a competitive way with dNTPs at the binding site of the enzyme. Theoretical calculations reinforce the experimental data and the proposed mode of action of catalpol.

Topics: Binding Sites; DNA; Glucosides; Iridoid Glucosides; Iridoids; Molecular Structure; Nucleotides; Polymerase Chain Reaction; Taq Polymerase

A colorimetric method has been developed for the selective analysis of the total iridoid content of the rhizomes of Picrorhiza kurrooa in terms of catalpol. The method of analysis is based on the reaction between iridoid compounds and primary amine. The iridoid glycosides present in P. kurrooa are mainly the esters of catalpol, and can be easily converted into catalpol by saponification. Catalpol thus obtained by hydrolysis is treated with glycine in acidic medium to give a purple color with a maxmimum absorption of 542 nm. The method was validated as per the ICH guidelines for linearity, accuracy and precision. Several other rhizome samples of the plant were also assayed using this method. The method developed is precise, sensitive, reproducible and easy to perform and can be used for the standardization of crude drug.

Topics: Colorimetry; Glucosides; Glycine; India; Iridoid Glucosides; Iridoids; Picrorhiza; Plant Roots

To study the effect of chitosan clarification refining the decoction of Jiangtangtongmai by homogenous design method.. The content of catalpol in the refined decoction by the alcohol-precipitation method and chitosan clarification method was determined by RP-HPLC.. Catalpol can be well preserved by chitosan clarification method.. Chitosan clarification method can replace alcohol-precipitation method in refining of the decoction of Jiangtangtongmai.

Topics: Alcohols; Chitin; Chitosan; Drug Combinations; Drugs, Chinese Herbal; Glucosides; Hypoglycemic Agents; Iridoid Glucosides; Iridoids; Plants, Medicinal; Rehmannia; Rosa; Technology, Pharmaceutical

The growth and survival of the Catalpa sphinx, Ceratomia catalpae (Sphingidae), were measured on five different species of Catalpa: C. bignonioides, C. bungeii, C. fargeseii, C. ovata, and C. speciosa. Larval growth varied significantly among these host plant species; however, survival did not differ. Quantification of the iridoid glycoside content of larvae, pupae, adults, larval frass, and leaves of the larval host plant, C. bignonioides, by gas chromatography showed that leaves contained both catalpol and catalposide; larvae, pupae, and frass contained only catalpol; and the adults contained no detectable iridoid glycosides. Amounts were highest in the larvae and declined in the pupal stage. Very small amounts of catalpol were detected in adults of the parasitoid, Cotesia congregata, and in the silken cocoons. The hemolymph in which the parasitoid larvae grew contained over 50% dry weight catalpol. Larvae of C. catalpae often regurgitate when disturbed. This may serve as a defense against predators. A comparison of the growth of larvae pinched with forceps to induce regurgitation with those that were not so treated showed that larvae that were pinched, and usually regurgitated, grew significantly more slowly than those that were not.

Topics: Adaptation, Physiological; Age Factors; Animals; Chromatography, Gas; Glucosides; Hemolymph; Host-Parasite Interactions; Iridoid Glucosides; Iridoids; Larva; Moths; Plants, Edible; Predatory Behavior

The plantain is used in herbal medicines and for pasturage. Two cultivars of plantain (Plantago lanceolata L.), Grasslands Lancelot and Ceres Tonic, were sown in spring. Changes in catalpol, aucubin, and acteoside concentrations in the leaves during the growing season and by drying after harvesting were quantitatively determined by high-performance liquid chromatography. The concentration of catalpol was relatively low, fluctuating between 1 and 2% of dry matter during the growing season, and there was no clear-cut seasonal change. From spring to midfall, the aucubin concentration increased from 2.1 to 4.8% in Grasslands Lancelot and from 1.0 to 2.7% in Ceres Tonic. These increases were gradual over the season, except for during midsummer, when aucubin concentrations were relatively constant. The acteoside concentration increased from 3.4 to 7.1% in Grasslands Lancelot and from 1.5 to 4.1% in Ceres Tonic over the course of the growing season, although in the summer it declined steadily to lows of 2.5% in Grasslands Lancelot and 1.9% in Ceres Tonic. Our data suggested that midfall was the appropriate time for harvesting plantain for medicinal use. The concentrations of the bioactive compounds steadily decreased in the initial stages of drying both under natural climatic conditions and at 60 degrees C. The development of processing methods to minimize the loss of bioactive compounds is imperative.

Topics: Chromatography, High Pressure Liquid; Climate; Desiccation; Glucosides; Iridoid Glucosides; Iridoids; Phenols; Plant Leaves; Plantago; Pyrans; Seasons

To compare the economical characters, yield characters and content of catalpol on Rehmannia glutinosa Libosch. varieties.. To study characters by field randomized block test and analysis of variance. To analyse the content of catalpol by HPLC.. The results by analysis of variance were that the F value in plant width was 15.4 (F0.01 = 5.54), the F value in length of leaves was 12.2, the F value in width of leaves was 13.35, the F value in yield of single plant was 55.7 and the F value in content of catalpol was 8.03. The results by correlative analysis were that the linear correlation coefficient of signal plant yield with length of leaves was 0.9639, with width of leaves was 0.9073, with amount of earthnuts was 0.7060 and with plant fresh weight was 0.9950. The linear correlation coefficient of content of catalpol with plant width was 0.9169, with length of leaves was 0.7046 and with width of leaves was 0.7159.. There were significant differences in plant width, length of leaves width of leaves, and yield of single plant and content of catalpol of Rehmannia glutinosa Libnosch. varieties. There were significantly positive correlations in signal plant yield with plant fresh weight, length of leaves, width of leaves and amount of earthnuts. There were significantly positive correlations in content of catalpol with plant width, length of leaves and width of leaves.

Topics: Glucosides; Iridoid Glucosides; Iridoids; Plant Leaves; Plant Tubers; Rehmannia

A fast and easy method was sought for determination of the iridoid glycosides catalpol, ketologanin, verbenalin, loganin, 8-epi-loganic acid, geniposidic acid and 10-cinnamoyl catalpol in plant samples. The method involved micellar electrokinetic capillary chromatography (MEKC) coupled on-line to mass spectrometry. The partial filling technique and electrospray ionization were used. Seven iridoid glycosides could be separated with use of MEKC under basic conditions. However, 8-epi-loganic acid and geniposidic acid could not be detected simultaneously with the five neutral iridoid glycosides by mass spectrometry. Therefore, only the neutral iridoid glycosides were screened from plant samples. Catalpol, verbenalin, loganin and possibly 10-cinnamoyl catalpol were found in an examination of seven plant species in the genera Plantago, Veronica, Melampyrum, Succisa, and Valeriana. Aucubin, which was not included in the sample mixture used in method development because of overlapping with catalpol in MEKC, was also detected. The limits of detection for the iridoid glycosides, both at the UV and at the mass spectrometer, are given.

Topics: Chromatography, Micellar Electrokinetic Capillary; Glucosides; Hydrogen-Ion Concentration; Iridoid Glucosides; Iridoid Glycosides; Iridoids; Mass Spectrometry; Molecular Structure; Molecular Weight; Plantago; Plants, Medicinal; Pyrans; Scrophulariaceae; Species Specificity; Spectrophotometry, Ultraviolet; Valerianaceae

Caterpillars of the arctiid moth, Grammia geneura, are polyphagous, but species of Plantago are amongst their preferred food plants. A neuron in the medial styloconic sensillum on the galea has been shown to have a general phagostimulatory function. Experiments with binary mixtures and cross-adaptation have demonstrated that it responds to some sugars, to several amino acids, and also to catalpol. Catalpol is a plant secondary compound in Plantago and a phagostimulant for the caterpillars. The possible significance of combining sensitivity to nutrient compounds with sensitivity to a secondary compound is discussed.

Topics: Action Potentials; Amino Acids; Animals; Behavior, Animal; Carbohydrates; Electrophysiology; Feeding Behavior; Glucosides; Iridoid Glucosides; Iridoids; Moths; Neurons, Afferent; Pyrans; Serine; Taste

Several methods for the extraction of two iridoid glycosides, catalpol and aucubin, from the plant matrix (Veronica longifolia leaves) were compared. Pressurized hot water extraction and hot water extraction were the most efficient isolation techniques for both. Pressurized liquid extraction and maceration with various organic solvents were also tested. Relative to the amounts extracted with hot water, ethanol extracted only 22% of catalpol and 25% of aucubin and pressurized hot water extracted 83% of catalpol and 92% of aucubin. The lowest relative standard deviations, 22% for catalpol and 8% for aucubin, were achieved with hot water extraction (13 repetitions), and the highest relative standard deviations, 76% for catalpol and 73% for aucubin, with pressurized liquid extraction (five repetitions). A fast capillary electrophoretic method was developed for the quantitative determination of catalpol and aucubin.

Topics: Chromatography, Micellar Electrokinetic Capillary; Glucosides; Hot Temperature; Iridoid Glucosides; Iridoids; Plant Leaves; Pressure; Pyrans; Solvents

HPLC determination has shown that the content of catapol in Rehmannia glutinosa decreases markedly after being dried and processed. This change of content is related to acidic and alkaline conditions. But in boiling water or saccharide solution no marked changes have been observed.

Topics: Chromatography, High Pressure Liquid; Drugs, Chinese Herbal; Glucosides; Hot Temperature; Iridoid Glucosides; Iridoids; Magnoliopsida; Plants, Medicinal; Pyrans; Technology, Pharmaceutical

The relation between constituents and effects on hemorheology with processing of root of Rehmannia glutinosa was investigated. With the processing to dried or steamed root from crude root, the content of stachyose, which was the highest component in crude root, was decreased and the content of manninotriose was increased. Iridoid glycoside, catalpol, was gradually decreased with the processing. From these results, the content of carbohydrates and catalpol made it possible to estimate the quality of Rehmanniae Radix by processings. On the other hand, the change of pharmacological activities with the processing was investigated. The 50% ethanolic extract (BJ-ext) from steamed root of R. glutinosa increased erythrocyte deformability and erythrocyte ATP contents, inhibited polybrene-induced erythrocyte aggregation, and promoted an activity of fibrinolytic system. The extracts from crude or dried root had weak or no effect. The crude or dried root and steamed root of R. glutinosa showed the different pharmacological activities, and the quality of Rehamanniae Radix by processings may be estimated by investigation of correlation between the changes of constituents and improvable effects of hemorheology.

Topics: Adenosine Triphosphate; Animals; Carbohydrates; Drugs, Chinese Herbal; Erythrocyte Aggregation; Erythrocyte Deformability; Erythrocytes; Fibrinolysis; Glucosides; Iridoid Glucosides; Iridoids; Male; Pyrans; Rabbits; Rats; Rats, Wistar

We examined effect of iridoid glucosides, aucubin, catalpol, geniposide and gardenoside, and their enzymic hydrolysates on neurite outgrowth of PC12h cells. Except for aucubin, these glucosides induced neurite outgrowth at 0.1 microgram/ml and above in medium after 3 d of treatment. Hydrolysates of the four glucosides all caused neuritogenesis. Geniposide hydrolysate enhanced responses of cells to carbachol and KCl-induced depolarization in terms of cytoplasmic free-calcium concentration. The aglucone of geniposide, genipin, also promoted neurite outgrowth in a dose-dependent manner (ED50 = 0.7 microM). The neuritogenic effect of genipin was partially or considerably inhibited in the presence of H-89 and genistein. All the results presented suggest that certain iridoid compounds can induce neuronal differentiation in PC12h cells through activation of components of the intracellular signal transduction pathway.

Topics: Animals; beta-Glucosidase; Calcium; Glucosides; Hydrolysis; Iridoid Glucosides; Iridoid Glycosides; Iridoids; Neurites; Neurons; PC12 Cells; Protein Kinase Inhibitors; Pyrans; Rats; Signal Transduction

In vitro, the peracetates of penstemonoside, aucubin and catalpol, iridoids isolated from Parentucellia latifolia, antagonize the uterine muscular contractions induced by acetylcholine and calcium, in a similar way to papaverine. The antagonism is non-competitive against acetylcholine (pD2' values: 5.60 for the peracetates of penstemonoside, 5.74 for aucubin, 5.59 for catalpol, and 5.32 for papaverine) and competitive against calcium (pA2 values: 6.60 for the peracetates of penstemonoside, 6.34 for aucubin, 6.48 for catalpol, and 6.23 for papaverine). The two components, phasic and tonic, of the response of the vas deferens to potassium are reduced by the three iridoids. The reduction is similar for both phases. The antispasmodic activity of the three iridoids, similar to papaverine, is related to an inhibiting effect of extracellular calcium, intracellular or both.

Topics: Acetylation; Animals; Female; Glucosides; In Vitro Techniques; Iridoid Glucosides; Iridoids; Male; Parasympatholytics; Plants; Pyrans; Rats; Uterus; Vas Deferens

In this paper, the contents of catalpol, water-extract and alcohol-extract materials, ash, total reducing sugar and inorganic elements in Dihuang from different habitats have been measured. The result shows that Huai Dihuang, the genuine drug, excels all those from other habitats in quality. The quality of commercial dry Dihuang may be related closely to the production area, storage time, etc.

Topics: Calcium; Carbohydrates; Drugs, Chinese Herbal; Glucosides; Iridoid Glucosides; Iridoids; Phosphorus; Pyrans; Quality Control; Trace Elements

1. A glycoside of the aucubin type has been isolated in crystalline form from Plantago and Buddleia species, and has been shown to be identical with catalpol (Lunn, Edward & Edward, 1962). Catalpol has not been found in the free state before, but occurs as its p-hydroxybenzoyl ester, catalposide, in the genus Catalpa. 2. A second glycoside of this type has been obtained in crystalline form from Buddleia, and has been shown to be a mono-O-methyl derivative of catalpol, for which the name ;methylcatalpol' is proposed. 3. Both Plantago and Buddleia species are known to contain aucubin. The concentrations of this glycoside and catalpol are comparable in Plantago. In Buddleia methylcatalpol predominates somewhat over catalpol. Yields of the individual glycosides were about 0.1% of the fresh weight of the leaves. 4. Bobbitt, Spiggle, Mahboob, Philipsborn & Schmid (1962) have suggested structures for catalposide and catalpol based on chemical and physical evidence, in particular on n.m.r. spectra. Reappraisal of this evidence and additional measurements have now confirmed these structures and show that the Buddleia glycoside is the 6-O-methyl derivative of catalpol.

Topics: Buddleja; Chemistry, Pharmaceutical; Glucosides; Glycosides; Iridoid Glucosides; Iridoids; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Plant Leaves; Plantago; Plants, Medicinal; Research; Spectrum Analysis