Inhibitory effects of Cnidium officinale Makino and Tabanus fulvus Meigan on the high glucose-induced proliferation of glomerular mesangial cells.

This study describes a potent activity of Cnidium officinale Makino (Cnidii rhizoma) and Tabanus fulvus Meigan (Tabanus) as an inhibitor of high glucose-induced proliferation of glomerular mesangial cells (GMCs). Raising the ambient glucose concentration from 5.6 to 25 mM for 24 h caused a dramatic increase in [3H]thymidine incorporation, and these increases were attenuated by treatment of GMCs with the extracts of Cnidii rhizoma and Tabanus (2.5-20 microg/ml) in a dose-dependent manner. In contrast, extracts of Cnidii rhizoma or Tabanus (20 microg/ml) did not change the growth of GMCs cultured under normal glucose condition. To clarify the mechanism involved in anti-proliferative activity of these medicines, this study examined the effects of Cnidii rhizoma and Tabanus on high glucose-stimulated extracellular matrix (ECM) protein accumulation and transforming growth factor-beta1 (TGF-beta1) production. Exposure of GMCs to high glucose significantly stimulated the ECM protein, collagen and fibronectin, accumulation and TGF-beta1 secretion, and these changes were dramatically diminished by treatment of GMCs with extracts of Cnidii rhizoma or Tabanus (10 microg/ml). Taken together, these results indicate that Cnidii rhizoma and Tabanus inhibit the high glucose-induced GMC proliferation partially through suppressing the ECM accumulation and TGF-beta1 production, suggesting that these medicines may be a promising agent for treating the development and progression of diabetic glomerulopathy.

Seungnoidan increases cerebrocortical ATP and acetylcholine contents in ovariectomized rats.

This study investigated the effects of Seungnoidan (SND), which has been widely used as a remedy for cerebroneuronal diseases in Korean folk medicine, on the cerebrocortical adenosine triphosphate (ATP) and acetylcholine (ACh) contents in ovariectomized (OVX) rats. Female Sprague-Dawley rats were ovariectomized and maintained for 12 weeks to deplete ovarian steroid hormones, followed by oral administration of SND at 500 mg/kg/day for 14 weeks. SND markedly attenuated the high rate of body weight increase in OVX rats, and also reduced the decline of cerebral weight caused by ovariectomy (p < 0.05). Superfusion of SND at 50 mg/kg significantly increased the rate of cerebral blood fl ow, but did not change the mean arterial blood pressure. Deprivation of ovarian steroid hormones significantly decreased the cerebral ATP, choline and ACh contents, and these reductions were reduced by treatment of OVX rats with SND (p < 0.01). Additionally, SND also significantly elevated the cerebral choline acetyltransferase activities reduced by OVX (p < 0.01). Taken together, these results suggest that the pharmacological properties of SND may be implicated in the improvement of metabolic pathways of cerebral energy and cholinergic neurotransmitter function induced by deprivation of ovarian steroid hormones, and SND may be a promising herbal remedy for treatment of cerebral dysfunctions including dementia.

Effects of hwangryunjihwang-tang on in vitro ertilization and ovulation in mice fed a high-fat diet.

It has been generally accepted that hwangryunjihwang-tang (h-tang) is a useful prescription for treating polydipsia and to prevent obesity induced by a high-fat diet. The aim of this study was to clarify whether h-tang improved reproductive dysfunction caused by obesity in mice. Mice were fed a high density protein and lipid diet for 4 weeks, followed by administration of h-tang at 480 mg/kg body weight per day for 4 days. Thereafter, changes of body weight, ovulation rate, in vitro and in vivo fertilization, embryonic development and implantation rate were measured. H-tang markedly reduced the body weight of obese mice fed a high-fat diet, but not mice fed a normal diet. H-tang significantly improved ovulation rates, in vitro and in vivo fertilization rates and embryonic development. These results indicate pharmacological reversal of reproductive dysfunction caused by obesity, perhaps by adjusting internal secretions and metabolic functions.

Inhibitory activity of lignan components from the flower buds of Magnoliae fargesii on the expression of cell adhesion molecules.

Inhibitory activity of lignans isolated from Magnoliae fargesii Cheng on cell adhesion molecules on the surface of THP-1 human monocytic cell lines were investigated. Among 16 lignan components tested, six displayed relatively potent inhibitory activity on the expression of both intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1).

Radish extract stimulates motility of the intestine via the muscarinic receptors.

The effects of radish (Brassica oleraceae, Cruciferae) on gastrointestinal motility were examined using rat intestinal segments with myenteric plexus in-vitro and measuring the intestinal transit of charcoal in-vivo. Radish extract (10 microg mL(-1) to 2 mg mL(-1)) caused a dose-dependent increase in contractions of the duodenum, jejunum and ileum, and 1 mg mL(-1) was the maximum effective dose. The largest contraction by the extract was found in ileal segments. The extract-induced (0.5 mg mL(-1)) ileal contraction was remarkably inhibited by pretreatment of segments with atropine (10(-7) M) for 10 min, but not by hexamethonium (0.5 mM). Moreover, antagonists of the muscarinic receptor reduced the radish-induced ileal contraction by a different ratio. The rank order of inhibitory effects was 4-diphenylacetoxy-N-methyl-(2-chloroethyl)-piperidine methiodide (90.5% of control) > tropicamide (67.4%) > pirenzepine (42.8%) > methoctramine (16.7%). Oral administration of radish extract (300-500 mg kg(-1) body weight) to mice remarkably improved the intestinal transit of charcoal, and this was significantly attenuated by co-administration of atropine (50 mg kg(-1)). Taken together, these results suggest that radish extract stimulates gastrointestinal motility through activation of muscarinic pathways.

Shibimijihwang-tang elevates intracellular ATP and choline content in the cerebral cortex of ovariectomized rats.

Shibimijihwang-tang (SJT) has been used traditionally to improve systemic blood circulation and biological energy production in patients with circulatory and neuronal diseases. The object of this study is to determine the effect of SJT extract on the intracellular adenosine triphosphate (ATP) and choline content in the cerebral cortex of ovariectomized (OVX) rats. Bilateral ovaries of 8-week-old rats were removed. Rats were maintained for 12 weeks to deplete ovarian steroid hormones, followed by treatment with SJT at 500 mg/kg body weight per day for 12 weeks. High rate of body weight increase in the OVX rats was markedly reduced by treatment with SJT, but the change in body weight of normal rats was not affected by it. SJT also significantly reduced the decline of cerebral weight in the OVX rats (P<0.05). Tissue glucose content in the cerebral cortex of OVX rats was significantly increased by SJT treatment (P<0.05). A decline in cerebral ATP content in OVX rats was dramatically restored by SJT administration (P<0.01), but SJT did not change the cerebral ATP content in normal rats. Cerebral choline content also declined following ovariectomy. This reduction was significantly elevated by SJT treatment (P<0.05), but SJT did not affect the change in cerebral choline in normal rats. Taken together, these results demonstrate that SJT can reduce the decrease in brain weight, cerebral ATP and choline content caused by deprivation of ovarian steroid hormones. This suggests that pharmacological properties of SJT may play a role in improvement of reduced cerebral energy production and cholinergic neurotransmitter synthesis caused by deficiency of ovarian steroid hormones in the cerebroneuronal cells of postmenopausal women.

Acylated flavonol glycosides with anti-complement activity from Persicaria lapathifolia.

During a search for biologically active compounds from traditional medicines, a crude extract of Persicaria lapathifolia was found to have anti-complement activity. Bioassay-guided chromatographic separation of the active constituents led to the isolation of a new acylated kaempferol glycoside (1) and three known acylated quercetin glycosides (2-4). The structures of compounds 1-4 were characterized as kaempferol 3-O-beta-D-(6"-p-hydroxybenzoyl)-galactopyranoside, quercetin 3-O-beta-D-(6"-feruloyl)-galactopyranoside, quercetin 3-O-beta-D-(2"-galloyl)-rhamnopyranoside and quercetin 3-O-beta-D-(2"-galloyl)-glucopyranoside, respectively. Compounds 1-4 showed strong anti-complement activity (IC50 values of 4.3, 9.7, 3.9 and 7.6 x 10(-5) M, respectively) on the classical pathway of the complement. On the other hand, six isolated flavonol glycosides (5-10) did not show any activity on this system.

Anticomplement activities of oleanolic acid monodesmosides and bisdesmosides isolated from Tiarella polyphylla.

Seven known oleanolic acid glycosides (1-7) were isolated from the MeOH extract of Tiarella polyphylla. The structures were identified to be 3-O-(beta-D-glucopyranosyl) oleanolic acid (1), 3-O-[beta-D-glucopyranosyl-(1-->3)-beta-D-glucopyranosyl] oleanolic acid (2), 3-O-[beta-D-glucopyranosyl-(1-->2)-beta-D-glucopyranosyl] oleanolic acid (3), 3-O-[beta-D-glucopyranosyl-(1-->3)-beta-D-glucopyranosyl] oleanolic acid 28-O-beta-D-glucopyranosyl ester (4), 3-O-[beta-D-glucopyranosyl-(1-->2)-beta-D-glucopyranosyl] oleanolic acid 28-O-beta-D-glucopyranosyl ester (5), 3-O-[a-L-rhamnopyranosyl-(1-->3)-beta-D-glucuronopyranosyl] oleanolic acid (6), and 3-O-[alpha-L-rhamnopyranosyl-(1-->3)-beta-D-glucuronopyranosyl] oleanolic acid 28-O-beta-D-glucopyranosyl ester (7) on the basis of physicochemical and spectral data. These triterpene glycosides were tested for the anticomplement activity and hemolytic activity. Bisdesmosidic saponins, 4, 5, and 7, showed anticomplement activity; in contrast, monodesmosidic saponins, 1-3, and 6, showed direct hemolytic activity. Methyl esterified monodesmosidic saponins showed anticomplement activity at a low concentration and hemolytic activity at a high concentration.

Rehmannia glutinosa inhibits tumour necrosis factor-alpha and interleukin-1 secretion from mouse astrocytes.

We investigated whether an aqueous extract of Rehmannia glutinosa steamed root (RGAE) inhibits secretion of tumour necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1) from primary cultures of mouse astrocytes. RGAE dose-dependently inhibited the TNF-alpha secretion by astrocytes stimulated with substance P (SP) and lipopolysaccharide (LPS). IL-1 has been shown to elevate TNF-alpha secretion from LPS-stimulated astrocytes while having no effect on astrocytes in the absence of LPS. We therefore investigated whether IL-1 mediated inhibition of TNF-alpha secretion from astrocytes by RGAE. Treatment of RGAE to astrocytes stimulated with both LPS+SP decreased IL-1 secretion. Moreover, incubation of astrocytes with IL-1 antibody abolished the synergistic cooperative effect of LPS+SP. These results suggest that RGAE may inhibits TNF-alpha secretion by inhibiting IL-1 secretion and that RGAE has an anti-inflammatory activity in the central nervous system curing some pathological disease states.

In vitro anticomplementary activity of hederagenin saponins isolated from roots of Dipsacus asper.

Anticomplementary activity of hederagenin and related saponins isolated from Dipsacus asper was investigated in vitro. HN saponin F (3) was most potent with IC50 value of 3.7x10(-5) M followed by 3-O-beta-D-glucopyranosyl-(1->3)-alpha-L-rhamnopyranosyl-(1->2)-beta-L-+ ++arabi nopyranosyl hederagenin 28-O-beta-D-glucopyranosyl-(1->6)-beta-D-glucopyrano side (8), 3-O-beta-L-arabinopyranosyl hederagenin 28-O-beta-D-glucopyranosyl-(1->6)-beta-D-glucopyranoside (5), dipsacus saponin A (4), and hederagenin (1) on the classical pathway (CP) of complement system, while the saponins 3-5 did not show the inhibition of hemolysis and rather increase the hemolysis on the alternative pathway (AP). However, all of C-3 monodesmosides [prosapogenin CP (2), dipsacus saponin B (6), and dipsacus saponin C (7)] evoked hemolysis directly on the erythrocytes.

Structure-activity relationships of lignans from Schisandra chinensis as platelet activating factor antagonists.

We studied the structure-activity relationships of lignans from Schisandra chinensis and their derivatives as platelet activating factor (PAF) antagonists. Strong activity was shown in lignans without an ester group at C-6, a hydroxyl group at C-7 or a methylene dioxy moiety and with an R-biphenyl configuration. 6(7)-Dehydroschisandrol A, a derivative of schisandrol A, showed the highest activity (IC50, 2.1x10(-6) M) in this study.

Synthesis and biological activity of KCB-328 and its analogues: novel class III antiarrhythmic agents with little reverse frequency dependence.

A series of 3,4-dimethoxyphenethylamine derivatives was prepared, and their prolongation effects on effective refractory period of contractile response (ERPc) and action potential duration (APD) in isolated guinea-pig papillary muscles at 1 Hz and 3 Hz were examined. SAR studies led to the identification of KCB-328 (51) which is a novel class III antiarrhythmic agent with little reverse frequency dependence.

Improvement of cerebral ATP and choline deficiencies by Shao-Yin-Ren Shi-Quang-Da-Bu-Tang in senescence-accelerated mouse prone 8.

Shao-Yin-Ren Shi-Quang-Da-Bu-Tang (SDT) has been used traditionally to improve the systemic blood circulation and biological energy production in the body. The object of this study is to determine the effect of SDT extract on the decline of cerebral adenosine triphosphate (ATP) and choline content associated with learning and memory impairments in senescence-accelerated mice prone 8 (SAM P8). Twenty-four-week old mice were orally treated with SDT at 400 mg/kg body weight per day, and continued for 12 consecutive weeks. At the termination of the treatment, the body weight of SAM P8 was markedly lower than that of the equal aged senescence-resistant prone 1 (SAM R1), but this was conspicuously recovered to the level of SAM R1 by SDT treatment. SDT also significantly reduced the decline of cerebral weight (P < 0.05). By comparison with normal mice, a spontaneous decrease of cerebral ATP was observed in the SAM P8. Two- and 6-fold increases of cerebral ATP content were found in SAM R1 and SAM P8 by SDT administration, respectively. The cerebral choline content was significantly different between SAM R1 and SAM P8 aged 36-week old (P < 0.01). SDT remarkably restored the decrease of cerebral choline content in SAM P8 (P < 0.01). Taken together, these results demonstrate that SDT can reduce the decrease of cerebral weight, and restore the decline of cerebral ATP and choline content associated with an alteration of neuronal metabolism in SAM P8 brain. This suggests that pharmacological properties of SDT may participate in improvement of declined cerebral energy production and cholinergic neurotransmitter synthesis in senile dementia.

Anticomplementary activity of stilbenes from medicinal plants.

The anticomplementary activity of stilbenes from medicinal plants in Korea was investigated in vitro. 3,5-Dihydroxy-4'-methoxystilbene (3) was most potent with IC50 value of 1.5 x 10(-4) M followed by rhapontigenin (4), oxyresverastrol (2), 2,3,4',5-tetrahydroxystilbene-2-O-beta-glucoside (9), rhaponticin (8), resverastrol (1), and piceid (7). The activity was found to be increased by a methylation on a hydroxy group of C-4' of 1, but decreased by further methylation on hydroxy groups of C-3 and C-5 and glucosylation on any hydroxy group of 1. Addition of hydroxy group on C-2' of 1 or C-3' of 3 was little affected on the anticomplementary activity but the activity was increased by O-glucosylation on C-2 of 1.

Anti-complement activity of tiliroside from the flower buds of Magnolia fargesii.

As part of the search for anticomplementary active components from natural products, the anticomplementary properties of methanolic extracts from the flower buds of Magnoliafargesii have been investigated. Bioassay-guided chromatographic separation of the active constituents led to the isolation of compound 1, whose structure was identified by spectroscopic methods to be kaempferol 3-O-beta-D-(6"-O-coumaroyl)glucopyranoside (tiliroside). Tiliroside showed very potent anti-complement activity (IC50=5.4 x 10(-5) M) on the classical pathway of the complement system, even higher than rosmarinic acid, which is a well-known inhibitor against the complement system. On the other hand, the hydrolysates of tiliroside, kaempferol, astragalin and p-coumaric acid showed very weak activity on this system.

Anticomplementary activity of constituents from the heartwood of Caesalpinia sappan.

The anticomplementary activity of compounds isolated from the heartwood of Caesalpinia sappan L. (Leguminosae) was investigated. The sterol mixture (campesterol 11.2%, stigmasterol 18.9% and beta-sitosterol 69.9%) was most potent and brazilin, brazilein, and protosappanin E showed a new anticomplementary activity on the complement system in vitro.

Magnone A and B, novel anti-PAF tetrahydrofuran lignans from the flower buds of Magnolia fargesii.

In a search for platelet-activating-factor (PAF) antagonists, two new lignan compounds were isolated from the Chinese crude drug shin-i, the flower buds of Magnolia fargesii. Their structures were elucidated as (2S,3R,4R)-tetrahydro-2-(3,4-dimethoxyphenyl)-4-(3, 4-dimethoxybenzoyl)-3-(hydroxymethyl)furan (magnone A, 1) and (2S,3R, 4R)-tetrahydro-2-(3,4,5-trimethoxyphenyl)-4-(3, 4-dimethoxybenzoyl)-3-(hydroxymethyl)furan (magnone B, 2). Magnones A and B showed antagonistic activity against PAF in the [3H]PAF receptor binding assay with the IC50 values of 3.8 x 10(-5) M and 2.7 x 10(-5) M, respectively.

Platelet activating factor antagonist activity of ginsenosides.

Ginseng saponins and their degradation products have been screened for antagonist activity towards [3H]PAF (platelet activating factor) in washed rabbit platelet receptor binding studies. 20(S)- and delta20-ginsenosides Rg3, protopanaxadiol-type saponins, were found to be relatively potent PAF antagonists (IC50 = 4.9 x 10(-5) M and 9.2 x 10(-5) M, respectively).

Anticomplementary activity of ginseng saponins and their degradation products.

The anticomplementary activity of ginseng saponins and their degradation products obtained by chemical treatment of Korean red ginseng saponins was investigated. The total saponin and its major components showed strong anticomplementary activity and their structure-activity relationship was evaluated.

Lignans with platelet activating factor antagonist activity from Schisandra chinensis (Turcz.) Baill.

Three lignans, which had antagonistic activities of [(3)H]PAF to washed rabbit platelet receptor binding, were isolated from the fruits of Schisandra chinensis. Schisandrin A showed most potent antagonistic activity against PAF in this group.