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The influence of traditional Chinese herbal drugs on serum 1, 5-anhydroglucitol levels.

The serum concentration of 1,5-anhydroglucitol (1,5-AG), a polyol which originates mainly in the diet, is used in Japan as a new marker for glycemia. To evaluate the potential interference of 1, 5-AG measurements by traditional Chinese medicines (Kampo), we examined the 1,5-AG content in 32 types of concentrated dosage forms of Kampo using high performance liquid chromatography (HPLC). The 32 types of Kampo were the most frequently used in Japan, two of which, Ninjin-yoei-to (7030 microg/g dry weight) and Kami-kihi-to (6700 microg/g dry weight), contained large amounts of 1,5-AG. Six others contained small amounts of 1,5-AG. Both Ninjin-yoei-to and Kami-kihi-to contain the same ingredient, Polygalae radix, which is a crude form of polygalitol (1,5-AG). To confirm the effects of these Kampo medicines on the serum levels of 1,5-AG, we administered Ninjin-yoei-to (7.5 g/day) for 8 weeks to 18 patients with Type 2 diabetes mellitus (Type 2 DM). The serum level of 1,5-AG increased from 9.8+/-8.9 to 28.1+/-17.5 microg/ml by week 8. Hemoglobin A1c (HbA1c) had not changed by week 8. Thus, an abnormal serum 1,5-AG level may be present in patients taking Kampo which contains Polygalae radix.

Aged↗

In vitro inhibition of drug-resistant and drug-sensitive strains of Mycobacterium tuberculosis by ethnobotanically selected South African plants.

Twenty South African medicinal plants used to treat pulmonary diseases were screened for activity against drug-resistant and drug-sensitive strains of Mycobacterium tuberculosis. A preliminary screening of acetone and water plant extracts against a drug-sensitive strain of Mycobacterium tuberculosis, H37Rv, was done by the agar plate method. Fourteen of the 20 acetone extracts showed inhibitory activity at a concentration of 0.5 mg/ml against this strain. Acetone as well as water extracts of Cryptocarya latifolia, Euclea natalensis, Helichrysum melanacme, Nidorella anomala and Thymus vulgaris inhibited the growth of M. tuberculosis. Given the activity of 14 acetone extracts at 0.5 mg/ml against the drug-sensitive strain by the agar plate method, a further study was done employing a rapid radiometric method to confirm the inhibitory activity. These active acetone extracts were screened against the H37Rv strain as well as a strain resistant to the drugs isoniazid and rifampin. The minimal inhibitory concentration of Croton pseudopulchellus, Ekebergia capensis, Euclea natalensis, Nidorella anomala and Polygala myrtifolia was 0.1 mg/ml against the H37Rv strain by the radiometric method. Extracts of Chenopodium ambrosioides, Ekebergia capensis, Euclea natalensis, Helichrysum melanacme, Nidorella anomala and Polygala myrtifolia were active against the resistant strain at 0.1 mg/ml. Eight plants showed activity against both strains at a concentration of 1.0 mg/ml.

Acetone↗

Screening of the wormicidal Chinese raw drugs on Clonorchis sinensis.

The wormicidal effect on Clonorchis sinensis in boiled water extracts of 223 species (vegetable origin 206, animal origin 10, mineral origin 7) of raw drugs prescribed in Oriental medicine was observed in vitro. The wormicidal substances were detected from 31 of the above-mentioned species. The wormicidal substances extracted from Platycodon grandiflorum (radix), Schizandra chinensis (fruit), Polygala tenuifolia (herb) and Aster tataricus (radix) were most effective. Those from Smilax glabra (radix), Pueraria thunbergiana (flower, radix), Polygala tenuifolia (radix), Scutellaria baicalensis (radix), Prunus mume (fruit), Glycyrrhiza uralensis (radix), Angelica koreana (radix), Phytolacca esculenta (radix) and Cyrtomium fortunei (rhizoma) were effective. The rest of the raw drugs were less effective.

Animals↗

[False-positive increase in 1,5-anhydro-D-glucitol due to Kampo (Japanese herbal) medicine].

We report a case presenting with a remarkable increase in blood 1,5-anhydro-D-glucitol (AG) upon taking a Kampo (Japanese Herbal) Medicine, Ninjin-Youei-To. The HPLC-analysis of the drug taken by the present case revealed 8.8 mg/g of AG in this Kampo (Japanese Herbal) Medicine. A similar increase in blood AG(maximum increase: 1.49 micrograms/mL/day) was observed when healthy normal volunteer's took Ninjin-Youei-To alone. Drug withdrawal led to a decrease in blood AG. No great change in diabetes-related items measured at the same time was noted, and glycosuria was always negative. These results led us to consider that the change in blood AG is not diabetic, but Ninjin-Youei-To-mediated. Ninjin-Youei-To is composed of 12 kinds of crude drugs, including Ginseng radix and Polygalae radix, and we made a search of the literature concerning these crude drugs. Polygalae radix, a component of Ninjin-Youei-To, was confirmed to contain AG. Where a change in blood AG does not accord with clinical symptoms and other laboratory findings, some influence or other of Kampo (Japanese Herbal) Medicine should be taken into account as a pre-analytical phase error.

Aged↗

Behavioural pharmacology of polygalasaponins indicates potential antipsychotic efficacy.

Polygalasaponins were extracted from a plant (Polygala tenuifolia Willdenow) that has been prescribed for hundreds of years to treat psychotic illnesses in Korean traditional medicine. Previous in vitro binding studies suggested a potential mechanism for its antipsychotic action, as polygalasaponin was shown to have an affinity for both dopamine and serotonin receptors [Psychopharmacol. Bull. 31 (1995) 139.]. In the present study we have investigated the functional in vivo actions of this material in tests that are predictive of dopamine and serotonin antagonist activities. Polygalasaponin (25-500 mg/kg) was shown to produce a dose-related reduction in the apomorphine-induced climbing behaviour (minimum effective dose [ED(min)] 25 mg/kg ip, 250 mg/kg sc and po), the 5-hydroxytryptamine (5-HTP)-induced serotonin syndrome (ED(min) 50 mg/kg ip) and the MK-801-induced hyperactivity (ED(min) 25 mg/kg ip) in mice. This compound also reduced the cocaine-induced hyperactivity (ED(min) 25 mg/kg ip) in rats. These results demonstrated that polygalasaponin has dopamine and serotonin receptor antagonist properties in vivo. This might suggest its possible utility as an antipsychotic agent.

Animals↗

Attenuating effect of a traditional korean formulation, Paeng-Jo-Yeon-Nyeon-Baek-Ja-In-Hwan (PJBH), on hydrogen peroxide-induced injury in PC12 cells.

The Paeng-Jo-Yeon-Nyeon-Baek-Ja-In-Hwan (PJBH) prescription is a dried decoctum consisting of a mixture of 18 medicinal herbs that include Semen Biotae, Fructus Torilis seu cnidii, Fructus Rubi, Herba Dendrobii, Radix Morindae officinalis, Cortex Eucommiae, Radix Aspragi, Radix Polygalae, Radix Dipsaci, Ramulus Cinnamomi, Rhizoma Acori graminei, Rhizoma Alismatis, Rhizoma Dioscoreae, Radix Ginseng, Radix Rehmanniae preparata, Fructus corni, Fructus Schisandrae and Herba Cistanches. The effect of PJBH extracts on H2O2-induced toxicity in the rat pheochromocytoma line PC12 was examined by measurements of cell lesion, level of lipid peroxidation and antioxidant enzyme activities, since free radicals are involved in neurodegeneration in Alzheimer's disease (AD). After a 30 min exposure of the cells to H2O2 (150 microM), a marked decrease in cell survival, activities of glutathione peroxidase and catalase as well as an increased production of malondialdehyde (MDA) were found. Pretreatment of the cells with PJBH (0.5-10 microg/ml) prior to H2O2 exposure significantly elevated cell survival, antioxidant enzyme activities and resulted in a decrease in the level of MDA. The effects of the PJBH on hydrogen peroxide-induced injury in PC12 cells were also examined. PJBH had a remarkable elevating effect on catalase and GSH-Px activities as well as cell survival, suggesting that cytoprotective effects of the PJBH are involved in stimulation against intermediate concentrations of H2O2-induced PC12 cell injury. The above-mentioned neuroprotective effects were also compared with the effect of tacrine. The results suggest that PJBH has potential for use as a novel neuronal therapeutic agent.

Alzheimer Disease↗

Involvement of protein kinase C and E2F-5 in euxanthone-induced neurite differentiation of neuroblastoma.

Euxanthone, a neuritogenic agent isolated from the medicinal herb Polygala caudata, has been shown to induce morphological differentiation and neurite outgrowth in murine neuroblastoma Neuro 2a cells (BU-1 subclone). In order to elucidate the underlying mechanisms of euxanthone-induced neurite outgrowth, a proteomic approach was employed. In the present study, two dimensional (2-D) gel electrophoresis and matrix-assisted laser desorption/ionization-time of flight (MALDI-ToF) mass spectrometry were performed to investigate the alterations in protein expression profile of euxanthone-treated BU-1 cells. Fourteen identified proteins were changed in expression levels after induction of neurite growth. These proteins included participants in transcription and cell cycle regulation, calcium influx and calcium signaling, fatty acid metabolism, cytoskeleton reorganization, casein kinase signal transduction, putative transbilayer amphipath transport and protein biosynthesis. Among the 14 identified proteins, E2F transcription factor 5 (E2F-5) was significantly up-regulated after euxanthone treatment. Go6976, a protein kinase C (PKC) alpha/betaI inhibitor, was found to inhibit neuritogenesis and expression of E2F-5 in the euxanthone-treated BU-1 cells, while SH-6, the Akt/PKB inhibitor, had no inhibitory effect. The gene silencing of E2F-5 by small interfering RNA (siRNA) was found to abolish the euxanthone-induced neurite outgrowth. In conclusion, these results indicated that the transcription factor E2F-5 was actively involved in the regulation of euxanthone-induced neurite outgrowth via PKC pathway.

Animals↗

Uptake and accumulation of lead by plants from the Bo Ngam lead mine area in Thailand.

A field survey of terrestrial plants growing on Bo Ngam lead mine area, Thailand, was conducted to identify species accumulating exceptionally high concentrations of lead. Plant and soil samples were collected from five areas. Lead concentrations in surface soil ranged from 325 to 142,400 mg/kg. The highest lead concentration in soil was found at the ore dressing plant area and lowest at a natural pond area. In different areas, the concentrations of lead in plants were different when comparing various study sites. A total of 48 plant species belonging to 14 families were collected from five sampling sites. Twenty-six plant species had lead concentrations more than 1000 mg/kg in their shoots. Three species (Microstegium ciliatum, Polygala umbonata, Spermacoce mauritiana) showed extremely high lead concentrations in their shoots (12,200-28,370 mg/kg) and roots (14,580-128,830 mg/kg).

Biodegradation, Environmental↗

Tenuigenin treatment decreases secretion of the Alzheimer's disease amyloid beta-protein in cultured cells.

Amyloid beta-protein (A beta) is a pivotal pathological factor in Alzheimer's disease (AD). Tenuigenin, extracted from the Chinese herb Polygala tenuifolia, seems to ameliorate the reduction in cholinergic function on rat models induced by A beta. To examine this therapeutic effect, we tested whether Tenuigenin could inhibit secretion of A beta in neuroblastoma cells stably transfected with two amyloid precursor protein (APP) constructs: the APP695 cDNA (SH-SY5Y APP695) and the C-terminal 99 amino acid residues of APP plus the signal peptide (SH-SY5Y SPA4CT). Tenuigenin inhibited the secretion of A beta and the C-terminal 99 amino acids of APP (C99) in SH-SY5Y APP695 cells, but did not change the A beta and C99 levels in SH-SY5Y SPA4CT cells. Fluorescence Resonance Energy Transfer (FRET) assays showed that Tenuigenin inhibited the proteolytic activities of BACE1 (beta-secretase) on its substrate in vitro. In addition, Tenuigenin did not demonstrate any cytotoxic effects, nor did it affect APP mRNA expression, holoAPP synthesis or sAPP alpha secretion. Our data suggest that Tenuigenin can inhibit the secretion of A beta in SH-SY5Y APP 695 cells via BACE1 inhibition. Taken together, these results suggest that Tenuigenin may be worthy of future study as an anti-AD drug.

Amyloid Precursor Protein Secretases↗

Rhizoma acori graminei and its active principles protect PC-12 cells from the toxic effect of amyloid-beta peptide.

The effects of water extracts of six medicinal herbs (Radix polygalae tenuifoliae, Radix salviae miltiorrhizae, Rhizoma acori graminei, Rhizoma pinelliae ternatae, Tuber curcumae and Scletrotium poriae cocos) on the cytotoxic action of Abeta(1-40) were tested with PC-12 cells. Only the extract of R. acori graminei (RAG) significantly decreased Abeta(1-40)-induced cell death. Further, eugenol and beta-asarone were isolated and identified as the major active principles. Both purified eugenol and beta-asarone protected PC-12 cells from the toxic effect of Abeta(1-40). Eugenol was active between 1 and 100 microM, and 10 microM eugenol gave approximately a 50% response. beta-Asarone was less potent and exhibited little, if any, activity at this concentration. Both eugenol and beta-asarone inhibited Ca(2+) intake by PC-12 cells: beta-asarone mainly inhibited basal Ca(2+) intake, whereas eugenol inhibited Abeta-induced Ca(2+) intake preferentially. These results suggest that eugenol may act by blocking Abeta-induced-Ca(2+) intake and provide a strong case for further pursuit of the therapeutic and prophylactic potentials of RAG and its active principles for the management of Alzheimer's disease.

Allylbenzene Derivatives↗

Synthesis of lignan aryldihydronaphthalene lactones by cyclization of cinnamyl arylpropiolate esters: revised structure of beta-apopolygamatin.

Unlike arylpropargyl arylpropiolates (e.g., 3) which yield, on heating in xylene, arylnaphthalene type I and type II lactones (4 and 5, respectively) in 1:1 ratio, cinnamyl arylpropiolates (e.g., 7) on heating in DMF gave the aryldihydronaphthalene-2-carboxylic acid lactones (e.g., 8) in excellent yield and regioselectivity. It is suggested that the aryldihydronaphthalene lactone product isolated from the tumor-inhibiting extract of Polygala polygama and previously named beta-apopolygamatin [17] has in fact the structure 1-(3',4'-methylene-dioxyphenyl)-3-hydroxymethyl-7,8-dimethoxy-3,4- dihydro-2- naphthoic acid lactone [18].

Cinnamates↗

Hypoglycemic activity of some triterpenoid glycosides.

Four triterpenoid glycosides isolated from the rhizomes of Polygala senega var. latifolia, senegins II-IV (1-3) and desmethoxysenegin II (4), were tested for hypoglycemic activity in normal and KK-Ay mice. Compounds 1 and 2 reduced the blood glucose of normal mice 4 h after intraperitoneal administration and also significantly lowered the glucose level of KK-Ay mice under similar conditions. Compounds 3 and 4, as well as senegose A (5), an oligosaccharide ester, were inactive when tested against normal mice.

Animals↗

Expression of protein kinase C isoforms in euxanthone-induced differentiation of neuroblastoma cells.

Euxanthone, a potent neuritogenic compound isolated from the roots of the medicinal herb Polygala caudata, has recently been shown to induce the differentiation of murine neuroblastoma Neuro 2A (BU-1) cells. In this study, the role of protein kinase C (PKC) and the expression of various PKC isoforms in euxanthone-treated BU-1 cells were examined. mRNA phenotyping using the reverse-transcription polymerase chain reaction (RT-PCR) showed that BU-1 cells express six different PKC isoforms, namely PKC-alpha, -beta, -delta, -epsilon, -lambda, and -zeta. Differential regulation and expression of PKC isoforms was observed in BU-1 cells treated with 100 microM euxanthone. PKC-apha, -beta, -delta, -lambda and -zeta were all up-regulated, with 1.7- to 9.5-fold increase, at around 30 to 60 minutes after euxanthone treatment. The expression level of PKC-epsilon remained relatively constant during the treatment. PKC-gamma, -eta, and -theta were not detected in both untreated and euxanthone-treated BU-1 cells. Staurosporine, a broad spectrum PKC inhibitor, was found to inhibit both spontaneous and euxanthone-induced neuritogenesis in BU-1 cells. A significant reduction of the euxanthone-induced neuritogenic effect was also observed when the PKC isoform-specific inhibitor Go6976 was included in the culture. These results suggest that the euxanthone-induced differentiation of the neuroblastoma BU-1 cells may be mediated through the differential expression of PKC-alpha, -beta, -delta, -lambda and -zeta isoforms.

Animals↗

Trypanocidal activity of extracts from Brazilian Atlantic Rain Forest plant species.

The trypanocidal activity of crude hydro alcoholic extracts and several fractions of 13 plants from Brazilian Atlantic Rain Forest were tested in vitro against epimastigote and trypomastigote forms of Trypanosoma cruzi, the etiological agent of Chagas disease. Crude ethanol extracts with promising in vitro activity (DL50 between 5-10 microg/ml) against epimastigotes were fractionated by solvent partition and further tested against bloodstream form of the parasite. Activity against bloodstream parasites was observed in both dichloromethane and hexane fractions of Polygala sabulosa and P. paniculata.

Animals↗

The effect of a traditional Chinese prescription for a case of lung carcinoma.

OBJECTIVE: To examine the effectiveness of Ninjin Yoei To (NYT; Ren-Shen-Yang-Rong-Tang in Chinese medicine; Kotaro Pharmaceutical Co., Ltd., Osaka, Japan), one of the traditional herbal medicines, against lung carcinoma. SETTING: The Nursing Center Himawari DESIGN, PATIENT, AND PREPARATION: The regular dosage of NYT (15 g/d) was prescribed for 7 weeks to one elderly patient with lung carcinoma. The daily standard dose of NYT is prepared from dried extract obtained from 12 crude natural substances, ginseng, cinnamon bark, Japanese angelica root, astragalus root, peony root, citrus unshiu peel, rehmannia root, polygala root, atractylodes rhizome, schisanda fruit, poria sclerotium, and glycyrrhiza. NYT is certified by the Japanese Ministry of Health and Welfare. RESULTS: The tumor marker levels (CEA and CA19-9) decreased and the scores of yin-yang and xu-shi inverted from negative and positive during 7 weeks. The patient's cough disappeared and her appetite recovered. CONCLUSION: NYT has a positive effect on life expectancy for patients with malignancy. The diagnostic scoring system in yin-yang and xu-shi and prescription of Chinese herb may be available to gain control over a patient's health.

Aged↗

Clinical and pharmacological studies on liver diseases treated with Kampo herbal medicine.

Hepatitis C virus (HCV) infection frequently causes chronic hepatitis, which is linked to the development of liver cirrhosis and hepatocellular carcinoma. Most physicians who practice Kampo medicine in Japan have observed that Kampo medicine can be as effective as interferon therapy in the treatment of chronic hepatitis C. In the present study, to evaluate the effect of Kampo medicine on chronic hepatitis C, clinical treatment was assessed in short-term and long-term study, and it was shown that ninjin-yoei-to (Formula ginseng compositae: TJ-108) was very effective. Therefore, to find the most active herbal component of TJ-108 in the treatment of HCV, Citrus Unshiu Peel, Schisandra Fruit, and Polygala Root, which are specific to TJ-108, were screened using an in vitro HCV infection model. Among the three herbs, Schisandra Fruit was found to be most active. In the next step, Gomisin A, an active component of Schisandra Fruit, was studied using an in vitro model with MOLT-4 cells and an animal model of immunologically induced acute hepatic failures. It is concluded that the therapeutic effect of TJ-108 on chronic hepatitis C is from the inhibitory effect on HCV infection, and also from the protective effect on immunological hepatopathy of Schisandra Fruit and its lignan component, Gomisin A.

Adult↗

Improving effects of DX-9386, a traditional Chinese medicinal prescription, on thymectomy-induced impairment of learning behaviors in mice.

The subject mice were thymectomized 4 weeks after birth. Ten months after the thymectomy, learning behaviors in passive and active avoidance performances and a spatial memory task, the contents of brain monoamines and brain choline acetyltransferase (ChAT) activity, as well as the immune response were evaluated. DX-9386, a traditional Chinese medicinal prescription consisting of ginseng, polygala, acorus and hoelen, was prepared in CE-2 mouse food (1%, w/w) and given to the thymectomized mice after the operation until all the experiments were finished. DX-9386 treatment significantly ameliorated the learning and memory ability impaired by thymectomy in passive avoidance performances and in a spatial memory task, and the mice tended to improve in the active avoidance performance of a lever press test. However, DX-9386 treatment did not improve the thymectomy-reduced immune response. The contents of hypothalamic norepinephrine, 3,4-dihydroxyphenylacetic acid and homovanillic acid, and hypothalamic ChAT activity were significantly increased in thymectomized mice, and DX-9386 restored them to the control levels. These results suggested that DX-9386 mainly affected the cognitive process of the central nervous system to ameliorate the learning and memory deficit induced by thymectomy.

Acetylcholinesterase↗

Effects of DX-9386, a traditional Chinese medicinal prescription, on long-term potentiation in the dentate gyrus in rats.

DX-9386, a traditional Chinese medicinal prescription consisting of ginseng, polygala, acorus and hoelen in the ratio of 1:1:25:50 (dry weight), was studied regarding the formation of long-term potentiation (LTP) in the dentate gyrus of anesthetized rats. Single oral administration of DX-9386 did not affect LTP formation evoked by suprathreshold tetanic stimulation; however, it significantly intensified the spike amplitude evoked by a subthreshold stimulation. LTP formation induced by suprathreshold tetanus was significantly inhibited by ethanol given either orally or intracerebroventricularly. DX-9386 significantly antagonized this inhibitory effect of ethanol. Basal spike amplitude was not influenced by DX-9386. These results indicate that DX-9386 potentiated LTP formation in the hippocampus and suggest that the ameliorative effect of this prescription on learning deficit model animals was, at least partly, due to its direct action on the hippocampus.

Administration, Oral↗