Antiplatelet actions of panaxynol and ginsenosides isolated from ginseng.

The antiplatelet effect of panaxynol isolated from the diethyl ether layer was compared with those of ginsenosides from the butanol layer of Panax ginseng. Panaxynol (0.1 mg/ml) inhibited markedly the aggregation of washed platelets induced by collagen, arachidonic acid, ADP, ionophore A23187, PAF and thrombin while ginsenosides had no significant effect on the aggregation but ginsenoside Ro (1 mg/ml) inhibited the ATP release of platelets. Less inhibitory effect of panaxynol was observed in the aggregation of platelet-rich plasma. Thromboxane B2 formation of platelets was inhibited by panaxynol but not by ginsenosides. The antiplatelet effect of panaxynol was dependent on the incubation time and the aggregability of platelets inhibited by panaxynol could not easily be recovered after washing the platelets. In human platelet-rich plasma, panaxynol prevented secondary aggregation and completely blocked ATP release from platelets induced by epinephrine and ADP. Both panaxynol and ginsenoside Rg2 inhibited the rise of intracellular calcium caused by collagen. It is concluded that panaxynol is the most potent antiplatelet agent in ginseng and its mechanism of action is chiefly due to the inhibition of thromboxane formation.

Studies on the biochemical action of ginseng saponin. I. Purification from ginseng extract of the active component stimulating serum protein biosynthesis.

Systematic isolation and purification of the biologically active component of ginseng extract were followed by observing the incorporation of labeled leucine into serum protein at 6 hr after a single intraperitoneal injection in a mouse. Ginseng saponin mixture (fraction 5) exhibited high activity for such incorporation. Seven saponins were isolated from fraction 5 by means of preparative TLC, and assayed. Administration of all these saponins (ginsenoside-Rb2, Rc, Rc2, Rd, Re, and Rg1)except for ginsenoside-Rb1, caused an increase of leucine incorporation over that in control animals. The incorporation rate was directly proportional to the dose in the case of ginsenoside-Rd, which had the highest activity. The increase specific radio-activity of serum protein was not due to a decrease in the pool size of free amino acids in the liver. It was conclusively shown that the active component stimulating serum protein biosynthesis is saponin.

Two-dimensional TLC analysis of ginsenosides from root of dwarf ginseng (Panax trifolius L.) Araliaceae.

A procedure is reported for the two-dimensional TLC separation of ginsenosides from the root of Panax trifolius L. The solvent systems and spray reagents described are useful for the identification of ginsenosides in various species of Panax. The results of the separation and identification with controls of at least four ginsenosides from the root of P. trifolius L. are reported. The total percentage of ginsenosides was 0.0061%.

Evaluation of commercial ginseng products.

The variation in panaxoside content of roots and commercial products of Panax ginseng and P. quinquefolium was evaluated by a new spectrodensitometric TLC method. The method is rapid and applicable to all commercial products, and it has a relative standard deviation of 6.4%. Panaxoside patterns of slurry-filled capsules and root extracts most closely resembled those of whole roots. Tablets did not contain detectable panaxosides while teas and granules for infusion yielded only low concentrations. The wide variation among these products indicates the need for more rigid control.

Further structural studies of anti-complementary acidic heteroglycans from the leaves of Panax ginseng C.A. Meyer.

The three potent anti-complementary polysaccharides, GL-PI, GL-PII, and GL-PIV, isolated from the leaves of Panax ginseng C. A. Meyer, were subjected to base-catalysed beta-elimination in the presence of sodium borodeuteride or enzymic digestion with endo-alpha-D-(1----4)-polygalacturonase. beta-Eliminative degradation of GL-PI and GL-PII each gave neutral (IN and IIN) and acidic (IA and IIA) fractions. Each fraction N consisted of Ara, Rha, Gal, and Glc, whereas each fraction A comprised a large proportion of GalA in addition to Rha, Gal, Glc, and GLcA. Methylation analysis and g.l.c.-m.s. showed that each fraction IN and IIN contained Rha-(1----2)-Rha-ol-1-d, Rha-(1----4)-Rha-ol-1-d, Ara-(1----4)-Rha-ol-1-d, Gal-(1----4)-Rha-ol-1-d, Gal-(1----6)-Gal-ol-1-d, and GlcA-(1----4)-Rha-ol-1-d, and that IA and IIA contained Rha----Rha-ol-1-d, HexA----Rha-ol-1-d, and HexA----Rha----Rha-ol-1-d. Methylation analysis indicated that IN and IIN also contained high-molecular-weight 6-linked galactan and 4-linked glucan, and that IA and IIA consisted mainly of 2-linked Rha, 4-linked GalA, and terminal and 6-linked Gal. IIA contained more 2-linked Rha than IA. Endo-alpha-D-(1----4)-polygalacturonase-mediated digestion of GL-PIV produced a high-molecular-weight fraction (PG-1) which was rich in neutral sugars, fragments of intermediate size (PG-2), and oligosaccharides (PG-3). PG-1 contained a rhamnogalacturonan core, galactan (which mainly comprised terminal, 6-linked, and 4,6-disubstituted Gal), and 4-linked glucans. PG-2 contained (1----4)-linked alpha-galacturonan partially branched at position 2 or 3 and a rhamnogalacturonan core in addition to small proportions of Gal and Glc. PG-3 contained large proportions of oligogalacturonides.

Effects of various ginseng saponins on 5-hydroxytryptamine release and aggregation in human platelets.

The effects of various ginseng saponins isolated from red ginseng roots, on aggregation and 5-hydroxytryptamine release (5-HT) human platelets have been investigated. Among the six saponins tested, only ginsenoside Rg1 inhibited adrenaline- and thrombin-induced platelet aggregation and 5-HT release dose-dependently, at concentrations of 5 to 500 micrograms ML-1. Ginsenoside Rg1 had no effect on adrenaline- and thrombin-induced arachidonic acid release and diacylglycerol production. But it did reduce the elevation of cytosolic free calcium concentration (Ca2+)i shown in the second phase induced by adrenaline and thrombin, at concentrations of 10 to 500 micrograms mL-1. Those data suggest that the inhibitory effects of ginsenoside Rg1 on 5-HT release from, and aggregation of, platelets might be due to the reduction of (Ca2+)i elevation at the second phase induced by adrenaline and thrombin. The results suggest that ginsenoside Rg1 in red ginseng roots may be active as a drug in the treatment of artheroscleorosis and thrombosis.

A double-blind, placebo-controlled clinical study on the effect of a standardized ginseng extract on psychomotor performance in healthy volunteers.

Various tests of psychomotor performance were carried out in a group of 16 healthy male volunteers given a standardized preparation of Korean ginseng (G 115; 100 mg twice a day for 12 weeks) and in a similar group given identical placebo capsules under double-blind conditions. A favourable effect of G 115 relative to baseline performance was observed in attention (cancellation test), processing (mental arithmetic, logical deduction), integrated sensory-motor function (choice reaction time) and auditory reaction time. However, end performance of the G 115 group was superior statistically to the placebo group only in mental arithmetic. No difference between G 115 and placebo was found in tests of pure motor function (tapping test), recognition (digit symbol substitution) and visual reaction time. No adverse effects were reported. It is concluded that G 115 may be superior to placebo in improving certain psychomotor functions in healthy subjects.

Isolation and hypoglycemic activity of panaxans I, J, K and L, glycans of Panax ginseng roots.

From an aqueous extract of the Oriental crude drug "ninjin" (ginseng), Panax ginseng roots from Korea, four glycans, panaxans I, J, K and L, have been isolated. These components remarkably reduced blood sugar levels in normal and alloxan-induced hyperglycemic mice.

Isolation and hypoglycemic activity of panaxans Q, R, S, T and U, glycans of Panax ginseng roots.

From a water extract of the Oriental crude drug "ninjin" (ginseng), Panax ginseng roots from Nagano, Japan, five glycans, panaxans Q, R, S, T and U, have been obtained. These constituents displayed marked hypoglycemic action in normal and alloxan-induced hyperglycemic mice.

Proliferative effect of ginseng saponin on neurite extension of primary cultured neurons of the rat cerebral cortex.

The effect of the crude saponins of Panax ginseng root on neurite extension of primary cultured neurons of the rat cerebral cortex was examined. Addition of the crude saponin extract to the culture medium showed a proliferative effect of neurite extension in 24-h and 48-h cultures. The looping phenomenon and disappearance of the growth cone due to the addition of cytochalasin-B to the culture medium were protected by the addition of the crude saponin. Addition of the crude saponin extract showed increases of about 1.5-fold in ganglioside content of cultured neurons. These results suggest that the crude saponin extract of the ginseng root has a promoting effect on neurite extension and also a protecting effect on distortion of neurites due to cytochalasin-B.

Quantitative analysis of ginsenosides in fresh Panax ginseng.

TLC, DCC and HPLC were used to study the ginsenoside composition of the main root, lateral root, rhizome, leaves and seeds of Panax ginseng cultivated in Jilin, China. Each of these methods has advantages of its own and the ensemble reveal the special features of Jilin ginseng. Total saponin content of various plant parts in Jilin ginseng showed a mid-range value as compared to those in ginsengs reported in literature. Fresh as well as sun-dried specimens from the same batch possessed a high percentage of Rg1 in the main root and this might account for the traditional preference of this plant part despite its lowest percentage of saponin in the whole plant. Large amounts of polar saponins were also observed in roots and rhizome of fresh Jilin ginseng, the nature and significance of which remained to be investigated.

Ginsenoside compositions of Panax ginseng C.A. Meyer tissue culture and juice.

By TLC, DCC and HPLC analysis, ginsenoside compositions of ginseng tissue culture and juice showed distinct features of fresh materials by a high proportion of "polar saponins" and low panaxadiol/panaxatriol ratio.

Effects of ginsenosides Rg1 and Rb1 of Panax ginseng on mitosis in root tip cells of Allium cepa.

The effects of ginsenosides Rg1 and Rb1 of Panax ginseng on mitosis in the onion root tip cells as well as on the rate of DNA synthesis in onion seedlings were studied. Results obtained from the concentration and time course study in bulb and seeding root tip cells indicate that Rg1 promotes and Rb1 inhibits mitosis, both being dose-dependent. The promoting effect of Rg1 on the rate of DNA synthesis was observed at the peak hour which occurs at the same time as that of the control. Rb1 was found to shift the peak hour of DNA synthesis to a later period of the experiment. These results are in agreement with the results obtained from the study of the cell cycle by pulse labeling and autoradiography, which show that Rg1 shortens the mitotic cell cycle and S period while Rb1 lengthens them. They in turn increase and decrease the mitotic indices respectively.

Immunopharmacology of Chinese medicine 1, ginseng induced immunosuppression in virus-infected mice.

Total saponins extracted from Panax ginseng, when injected into mice at a dose of approximately 10 mg/kg body weight, have no significant effect on the generation of cytotoxic T cell activity, induction of natural killer cell activity and humoral antibody production in mice infected subsequently with A/WSN influenza virus. The saponins, however, selectively suppressed the delayed-type hypersensitivity responses to the virus when administered to the animals before but not after virus sensitization. Thus, ginseng pretreatment can induce immunological unresponsiveness in one arm of the immune system. Such selective immunosuppression effect of the total saponins of ginseng may be related to their steroid-like structure.

Cardiovascular pharmacology of Panax notoginseng (Burk) F.H. Chen and Salvia miltiorrhiza.

The cardiovascular pharmacology of two Chinese herbs, Salvia miltiorrhiza (SM) and Panax notoginseng (Burk) F. H. Chen (PNG) were studied both in vivo and in vitro. Extracts of both herbs suppressed systemic blood pressure in albino rats and rabbits, an effect which was blocked or reversed by atropine, propranolol, and chlorpheniramine plus cimetidine. This reversed hypertension was blocked by phenoxybenzamine. These results indicate that these herbs have multiple effector sites in the cardiovascular system. This could be due to an increased utilization of extracellular calcium ions since the activity of SM on isolated blood vessels of rabbits was enhanced by 2 mM Ca++. The effects of aqueous extract of SM and purified active principles of SM (tanshinones) on rat and rabbit blood vessels in vitro were very similar both qualitatively and quantitatively. Both caused vasodilation of coronary arteries at all concentrations tested but induced vasodilation of renal, mesenteric and femoral arteries only at low concentrations. At higher concentrations, vasoconstriction was induced in these vessels. These results indicate that an economical decoction of SM is as efficacious as the more expensive isolated tanshinones. Both SM and PNG would be useful as antianginal agents since they dilate coronary vessels. Their use in hypertension is questionable since they induce both vasodilation and vasoconstriction depending on dose and target vessel.

Antioxidant action of certain simple phenolic compounds derived from Chinese herbs.

H2O2 and hydroxyl free radical active oxygen generation systems were utilized to define the antioxidant activities of simple phenolic compounds derived from Chinese herbs. Although the antioxidant activities of compounds differed when assessed in the two systems, all compounds tested were found to be effective at preventing red blood cell membrane lipid peroxidation, with the propyl and butyl esters of gallic acid being especially potent. No compound was able to prevent hemoglobin oxidation. All compounds but salicylic acid were found to interact dose-dependently with H2O2 and hydroxyl free radical as determined by a chemiluminescence method.

[A comparison between Chinese panax quinquefolius and imported Panax quinquefolius--analysis of composition of essential oil in Panax quinquefolius].

The content of essential oil of Panax quinquefolius from different producing area ranges from 0.04 to 0.097%. Twenty compounds were separated and identified from these essential oils by GC-MS. Chinese Panax quinquefolius is similar to imported Panax quinquefolius in the composition and content of essential oil.

[Isolation and elucidation of a new minor saponin from the leaves of Panax ginseng C.A. Meyer].

The structure of a new minor saponin isolated from the leaves of Panax ginseng C. A. Meyer was elucidated on the basis of chemical evidences and spectral data. The saponin was named as ginsenoside-La.

[Further study on dammarane saponins of leaves of Panax japonicus var. major collected in Quinling Mountains China].

In continuation of our studies on the leaves of Panax japonicus var. major (Burk.) Wu et Feng, two new dammarane saponins are isolated. By means of FAB-MS and 13CNMR, their structures were elucidated as dammar-22(23)-ene-3 beta, 6 alpha, 12 beta, 20(S), 24 section-pentaol- (20-O-beta-D-glucopyranosyl)-6-O-alpha-L-rhamnopyranosyl (1-2)-beta-D- glucopyranoside (majorosids F5) and dammar-23(24)-ene-3 beta, 6 alpha, 12 beta, 20(S), 25-pentaol-(20-O-beta-D- glucopyranosyl)-6-O-alpha-L-rhamnopyranosyl(1-2)-beta-D-glucopyranoside (majoroside F6).

[Chemical studies of minor triterpene compounds isolated from the stems and leaves of Panax ginseng C.A. Meyer].

Two new natural products were isolated from the stems and leaves of Panax ginseng C.A. Meyer cultivated in Liaoning, China. Their structures were characterized as 20(R)-dammaran-3 beta, 6 alpha, 12 beta, 20, 25-pentol and 20(R)-dammaran-3 beta, 6 alpha, 12 beta, 20, 25-pentol-6-O-alpha-L-rhampyranosyl(1----2)-O-beta-D-gluc opy ranoside.