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Axonal and dendritic extension by protopanaxadiol-type saponins from ginseng drugs in SK-N-SH cells.

Extension of axons and dendrites in neurons may compensate for and repair damaged neuronal networks in the dementia brain. To find out drugs capable of regenerating the neuronal network, we focused on several herbal drugs belonging to the genus Panax, kinds of Ginseng, and investigated neurite outgrowth activity of their extracts and compounds. We found that the methanol extracts of Ginseng (root of P. ginseng), Notoginseng (root of P. notoginseng) and Ye-Sanchi in Chinese (rhizome of a relative to P. vietnamensis) increased neurite outgrowth in SK-N-SH cells. The protopanaxadiol-type saponins, ginsenosides Rb(1) and Rb(3), and notoginsenosides R(4) and Fa isolated from Ye-Sanchi extract extended neurites, while protopanaxatriol-, ocotillol- and oleanane-type saponins had no effect on the neurite outgrowth. The percentage of cells with multipolar neurites and number of varicosities were intensely high in cells treated with the methanol extract of Ye-Sanchi as well as ginsenosides Rb(1) and Rb(3), and notoginsenosides R(4) and Fa. Both phosphorylated NF-H-expressing neurites and MAP2-expressing ones were extended by treatment with those saponins and the extract. Especially, longer neurites were mainly positive for phosphorylated NF-H. These results suggest that protopanaxadiol-type saponins enhance axonal and dendritic formation activity.

Axons↗

Effects of soybean saponin on protease hydrolyses of beta-lactoglobulin and alpha-lactalbumin.

Effects of Soybean Saponin on Protease Hydrolyses of beta-Lactoglobulin and alpha-Lactalbumin The effects of soybean saponin on tryptic and chymotryptic hydrolyses of whey proteins were evaluated. beta-lactoglobulin and alpha-lactalbumin became more sensitive to both trypsin and chymotrypsin by interacting with saponin in contrast to serum albumin. Soybean saponin was shown to have different effects on various proteins according to their nature.

Chymotrypsin↗

Mitogen-activated protein kinases mediate the oxidative burst and saponin synthesis induced by chitosan in cell cultures of Panax ginseng.

Chitosan (CHN) specially induced the activities of 39 kD and 42 kD protein kinases in ginseng cells, which could be suppressed by an inhibitor of mitogen-activated protein kinase (MAPK) pathway, PD98059. The immunoprecipitation (IP) using MAPK antibody or kinase assay in vitro also showed that CHN-induced 42 kD and 39 kD protein kinases belonged to the MAPK family. PD98059 suppressed CHN-induced transcriptions of ginseng squalene synthase and ginseng squalene epoxidase genes (gss and gse), CHN-induced accumulation of beta-Amyrin synthase (beta-AS) and synthesis of saponin. These results showed that CHN-induced activities of MAPKs were necessary for the CHN-induced saponin synthesis. EGTA and LaCl3 suppressed CHN-induced 39 kD and 42 kD MAPK activities. Ruthenium red (RR) could suppress CHN-induced 39 kD activity. All of them suppressed CHN-induced saponin synthesis. These results indicated that CHN-induced increment of cytosolic calcium was necessary for CHN-induced saponin synthesis. PD98059 also suppressed CHN-induced oxidative burst (including the increment of activity of plasma membrane NADPH oxidase and production of H2O2), but diphenylene iodonium (DPI), dimethylthiourea (DMTU) and 2,5-dihydroxycinnamic acid methyl ester (DHC) could not suppress CHN-induced MAPK activities, which indicated that MAPK was possibly function upstream of CHN-induced oxidative burst.

Cell Line↗

Features of ginseng saponin-induced corticosterone secretion.

Ginseng saponin administered intraperitoneally to rats induced a significant rise in plasma corticosterone, while it tended to increase plasma glucose and to decrease plasma immunoreactive insulin. Oral or intraperitoneal administration of ginseng saponin increased plasma corticosterone in unanesthetized, pentobarbital-anesthetized or alloxan-diabetes rats. The histamine-induced rise in plasma corticosterone was suppressed by pretreatment with diphenhydramine, whereas the ginseng-induced rise was not. Ginseng saponin decreased rectal temperature while it increased plasma corticosterone. Ginseng-induced corticosterone secretion was superimposed on the basal levels of plasma corticosterone due to fasting and circadian rhythm. Thus ginseng saponin would be a kind of stressful agent and have different features associated with the stimulation of the pituitary-adrenocortical system from several other chemical agents.

Animals↗

Chemistry and cancer preventing activities of ginseng saponins and some related triterpenoid compounds.

More than 25 dammarane-type tetracyclic triterpenoid saponins have been isolated from ginseng, the root and rhizome of Panax ginseng C.A. Meyer (Araliaceae). The genuine sapogenins of those saponins, 20(S)-protopanaxa-diol and -triol, were identified as 20(S) 12beta-hydroxy-and 20(S) 6alpha,12beta-dihydroxy-dammarenediol-II, respectively. There are two types of preparations from ginseng: white ginseng prepared by drying after peelling off and red ginseng prepared by steaming and drying. Some partly deglycosylated saponins such as ginsenoside Rh-1, Rh-2, and Rg-3 are obtained from red ginseng as artifacts produced during steaming. Several workers studied the metabolic transformation by human intestinal bacteria after oral administration of ginsenoside Rb-1 and Rb-2 and found that the stepwise deglyco-sylation yielded compound K and finally 20(S)-protopanaxadiol. Ginsenoside Rg-1 was converted into 20(S)-protopanaxatriol via ginsenoside Rh-1. Yun et al. in Korea conducted the epidemiological case-control studies of ginseng and suggested its cancer preventing activities. Kitagawa et al. demonstrated in vitro that ginsenosides, especially 20(R)-ginsenoside Rg-3, specifically inhibited cancer cell invasion and metastasis. Azuma et al. found that ginsenoside Rb-2 inhibited tumor angiogenesis, and Kikuchi et al. reported that ginsenoside Rh-2 inhibited the human ovarian cancer growth in nude mice. Recently, ginsenoside Rg-3 was produced as an anti-angiogenic anti-cancer drug in China. The aforementioned reports suggest that less glycosylated protopanaxadiol derivatives are effective in cancer prevention. Apart from Ginseng tetracyclic triterpenoid saponins, some oleanane-type pentacyclic triterpenoid compounds showed the anti-carcinogenic activity in the two-stage anti-cancer-promotion experiments in vitro and in vivo.

Animals↗

Comparison of synthetic saponin cholesterol absorption inhibitors in rabbits: evidence for a non-stoichiometric, intestinal mechanism of action.

The hypocholesterolemic activities of pamaqueside and tiqueside, two structurally similar saponins, were evaluated in cholesterol-fed rabbits. The pharmacological profiles of the saponins were virtually identical: both dose-dependently decreased the intestinal absorption of labeled cholesterol 25-75%, increased fecal neutral sterol excretion up to 2.5-fold, and decreased hepatic cholesterol content 10-55%. High doses of pamaqueside (>5 mg/kg) or tiqueside (>125 mg/kg) completely prevented hypercholesterolemia. Decreases in plasma and hepatic cholesterol levels were strongly correlated with increased neutral sterol excretion. Ratios of neutral sterol excreted to pamaqueside administered were greater than 1:1 at all doses, in opposition to the formation of a stoichiometric complex previously suggested for tiqueside and other saponins. Ratios in tiqueside-treated rabbits were less than unity, a reflection of its lower potency. Pamaqueside-treated rabbits exhibited a more rapid decline in plasma cholesterol concentrations than control animals fed a cholesterol-free diet, indicating that the compound also inhibited the absorption of biliary cholesterol. Intravenous administration of pamaqueside had no effect on plasma cholesterol levels despite plasma levels twice those observed in rabbits given pamaqueside orally. These data indicate that pamaqueside and tiqueside induce hypocholesterolemia by blocking lumenal cholesterol absorption via a mechanism that apparently differs from the stoichiometric complexation of cholesterol hypothesized for other saponins.

Administration, Oral↗

An evaluation of the hemostatic effect of externally applied notoginseng and notoginseng total saponins.

No effective hemostatic agents are available for external use. This project was conducted to evaluate the hemostatic effects of notoginseng using a hemorrhagic rat model. Rats (n = 40) were divided into four groups, and their tails were transected 5 mm from the tip. Group 1 received no treatment (control), while the other groups received external powder applied to the wound. Group 2 received placebo (flour), group 3 received ground notoginseng, and group 4 received a saponin extract of notoginseng. The total bleeding time was determined and compared between groups. The notoginseng group had lower bleeding times (9.60 +/- 1.50 min) than the control group (19.23 +/- 4.09 min, p < 0.001) or the placebo group (15.18 +/- 2.24 min, p < 0.001). Likewise, the saponin extract group had significantly lower bleeding times (11.70 +/- 2.53 min) than the control and placebo groups (p < 0.001 for both comparisons). No differences were found between the notoginseng and the saponin extract groups (p = 0.35). Notoginseng and a saponin extract from notoginseng provide hemostatic effects when applied externally.

Analysis of Variance↗

Monodesmosidic saponins from Herniaria hirsuta.

Two new monodesmosidic saponins, herniaria saponins E and F, were isolated from the aerial parts of Herniaria hirsuta. On the basis of chemical and spectral evidence, their structures were established to be 2-O-acetyl medicagenic acid 28-O-beta-D-xylopyranosyl- (1-->4)-alpha-L-rhamnopyranosyl(1-->2)-[beta-D-glucopyranosyl(1-->6)]-be ta- D-glucopyranoside (herniaria saponin E, 1) and medicagenic acid 28-O-beta-D-xylopyranosyl(1-->4)-alpha-L- rhamnopyranosyl(1-->2)-[alpha-L-rhamnopyranosyl-(1-->4)-beta-D- glucopyranosyl-(1-->6)]-beta-D-glucopyranoside (herniaria saponin F, compound 2).

Carbohydrate Sequence↗

Hyperosmotic hemolysis and antihemolytic activity of the saponin fraction and triterpene glycosides from Panax ginseng C. A. Meyer.

A saponin fraction and triterpene glycosides Rb1, Rb2 and Rg1 from Panax ginseng C. A. Meyer (saponins) were shown to inhibit the hyperosmotic hemolysis of erythrocytes. Using scanning electron microscopy and light scattering, saponins were found to restore the shape of the cells by inhibiting their contraction and the formation of echinocytes and microspherocytes. Scanning microcalorimetry demonstrated that an increase in osmomolarity and ionic strength of the medium eliminated structural transitions of erythrocyte ghost membranes. The hyperosmotic conditions were shown to cause the destruction of the erythrocyte membrane skeleton, except for the cytoplasmic and membrane domains of band 3 proteins. Saponins changed the parameters of all membrane structural transitions, induced new reversible transitions in the membranes and eliminated the ripple phase of dipalmitoylphosphatidylcholine. The mechanism of the antihemolytic action is discussed based on the bilayer couple model hypothesis.

Erythrocytes↗

Erythrocyte folate analysis: saponin added during lysis of whole blood can increase apparent folate concentrations, depending on hemolysate pH.

BACKGROUND: The analysis of red cell folate (RCF) depends on complete hemolysis of erythrocytes, and it is assumed that complete hemolysis is achieved by 10-fold dilution of whole blood with hypotonic solutions of 10 g/L ascorbic acid/ascorbate. This report challenges this assumption. METHODS: The conventional method of erythrocyte lysis was modified to include saponin, a known effective hemolyzing agent. The influence of saponin was determined at various lysate pHs, using the microbiological (Lactobacillus rhamnosus) folate assay. The effect of saponin during lysate preparation was subsequently compared with either the effect of 30 s of sonication or a single 1-h freeze-thaw cycle. RESULTS: Saponin addition was found to increase assayable RCF up to ninefold, depending on lysate pH. Sonication of lysates had no effect, and freezing-thawing lysates once did not always guarantee complete hemolysis. Lysates created with 10 g/L ascorbic acid (a historically widely used diluent) without pH adjustment produced assayable folate concentrations significantly lower than optimal. CONCLUSIONS: A lysing agent should be incorporated into RCF assays to guarantee complete hemolysis. Ten-fold dilution of blood with 10 g/L ascorbic acid, without pH adjustment, produces lysates with pHs (pH 4.0) below the point (pH 4.7) at which hemoglobin can denature irreversibly. The optimum pH for hemolysates is approximately 5.0.

Blood Chemical Analysis↗

Influence of simulated microgravity environmental factor on ginseng cell growth and ginseng saponin content.

When ginseng (Panax ginseng C.A. Meyer) cells were subjected horizontal rotation on a clinostat, their growth and ginseng saponin content differed from those cultured in normal gravitational environments (control). Both fresh and dry weights of ginseng cells rotating on clinostat were higher than those of the control, and the difference in dry weight was particularly obvious. After 3 weeks of cultivation, saponin content in ginseng was 10% higher under the horizontal rotation treatment on the clinostat than that of the control. When ginseng cells were cultured on Ca2(+)-deprived medium and clinostatted for 3 weeks, their ginseng saponin content was almost twice of that of the control. Besides, in our experiments, the higher the Ca2+ concentration in medium, the lower the ginseng saponin content in the ginseng cells cultured.

Biomass↗

[Determination of oleanolic acid and total saponins in Aralia L].

OBJECTIVE: To search for higher contents of olenolic acid and saponins in Aralia for medicinal use. METHOD: A HPLC method was developed for the determination of olenolic acid in Aralia. An YWG C-18 column was used and the mobile phase was methanol-water(90:10). The detection wavelength was UV 210 nm. The total saponins were determined by colorimetry. RESULT: Olenolic acid in root or stems of 13 species and total saponins in whole roots and root barks of 14 species of Aralia were determined. The contents of olenolic acid and total saponins in woody Aralia were higher than those in herbaceous. CONCLUSION: The contents of olenolic acid in A. decaisneana, A. elata, A. chinocaulis, A. chinensis and A. chinensis var. dasyphylloides are higher than those in other species. Furthermore, A. decaisneana and A. elata are rich in wild resources and thus of importance to the development and utilization of wild plants containing olenolic acid.

Aralia↗

[Studies on saponin accumulative in regularities Panax notoginseng (Burk) F. H. Chen].

OBJECTIVE: To determine the optimal harvest time for P. notoginseng through studying the changes of saponin contents with growth periods. METHODS: P. notoginseng samples were collected from the experimental plot regularly, and then the contents of total saponin and some main single saponins were analyzed by HPLC. RESULTS: Total saponin contents decreased from April through July, and increased from August through December. CONCLUSION: The optimal harvest time is determined as from October through December, which corresponds to the traditional harvest time.

Ginsenosides↗

[Hypoglycemic effect of saponin from Tribulus terrestris].

OBJECTIVE: To study the hypoglycemic effect of saponin from Tribulus terrestris L. METHOD: Alloxan was used to establish the diabetic model in mice. Phenformin Hydrochlride Tables was used as the positive control. The level of glucose, triglyceride, cholesterol and SOD in serum were determined. RESULTS: The level of serum glucose could be significantly reduced by saponin from Tribulus terrestris, which was the rate of 26.25% and 40.67% in normal mice and diabetic mice in respectively. The level of serum triglyceride could be reduced 23.35%. The saporin could also decrease the content of serum cholesterol. Serum SOD activity of the mice was increased by the saponin. CONCLUSION: Saponin from Tribulue terrestris could significantly reduce the level of serum glucose.

Animals↗

[Antimicrobial activity of saponins from Hedera taurica C a r r].

The antibacterial and antifungal action of saponins Sx1, taurozide H2, taurozide I and their effect on bioluminescent system of photobacteria Photobacterium phosphoreum (Cohn) Ford were investigated. Saponins H2 and I had no antimicrobial effect. Saponin Sx1 possessed antifungal activity in vitro with respect to Candida albicans, C. krusei, C. tropicalis. Saponin Sx1 is less toxic to P. phosphoreum than well-known antiseptics--chlorhexedin and miramistin.

Antifungal Agents↗

[Studies on saponin constituents in roots of Panax quinquefolium].

OBJECTIVE: To examine the saponins constituents in roots of Panax quinquefolium cultivated in China. METHOD: The methanol extract from roots of P. quinquefolium cultivated in Jiling province of China was extracted by chloroform and n-butanol successively. Ten pure saponins were isolated from the n-butanol extract by silica gel and RP-8 reversed-phase column chromatography. Their structures were identified by means of spectral methods and compared with known compounds. RESULT: Ten saponins were isolated from P. quinquefolium. They were identified as ginsenoside Rg1(2), Re(5), Rd(7), Rc(8), Rb1(9), Rb2(10), 24(R)-ginsenoside Rg3(3), 24(R)-pseudoginsenoside RT5(1), F11(4) and notoginsenoside K(6), respectively. CONCLUSION: This work has elucidated the saponins constituents of P. quinquefolium cultivated in Jilin province of China and has shown that compound 1 was isolated from this plant for the first time.

China↗

Structures of four new triterpenoid saponins from the leaves of Oplopanax elatus Nakai.

AIM: Isolation and structural elucidation of the triterpenoid saponins of Oplopanax elatus Nakai. METHODS: Solvent extraction and column chromatography were used to isolate the triterpenoid saponins, physico-chemical constants and spectroscopic analysis were employed for structural elucidation. RESULTS: Four newtriterpenoid saponins named cirenshenoside S (1), cirenshenoside T (2), cirenshenoside U (3) and cirenshenoside V (4) were isolated, and their structures were elucidated to be 3-O-beta-D-glucopyranosyl 3beta,23-dihydroxylup-20 (29)-en-28-oic acid 28-O-alpha-L-rhamnopyranosyl (1 --> 4)-beta-D-glucopyranosyl (1 --> 6)-beta-D-glucopyranoside (1), 3-O-beta-D-glucopyranosyl hederagenin 28-O-alpha-L-rhamnopyranosyl (1 --> 4)-beta-D-glucopyranosyl (1 --> 6)-beta-D-glucopyranoside (2), 3-O-beta-D-glucopyranosyl 3beta-hydroxyolean-9(11),12-dien-28-oic acid 28-O-alpha-L-rhamnopyranosyl (1 --> 4)-beta-D-glucopyranosyl (1 --> 6)-beta-D-glucopyranoside (3) and 3alpha-hydroxyolean-12-dien-23,28-dioic acid 28-O-alpha-L-rhamnopyranosyl (1 --> 4 )-beta-D-glucopyranosyl (1 --> 6)-beta-D-glucopyranoside (4), respectively. CONCLUSION: Compounds 1-4 are new triterpenoid saponins and isolated from the leaves of Oplopanax elatus Nakai for the first time.

Molecular Conformation↗

[Saponins in nutrition of swine, poultry and ruminants].

Saponins are glycosides found in many plants, which have soap character due to their surfactant properties. They work haemolytic and may cause symptoms of intoxication in high concentration. Among therapeutically relevant effects expectorative, anti-inflammatory and immune-stimulating effects have the highest ranking. Beyond that, saponins demonstrate antimicrobial properties particularly against fungi and additionally against bacteria and protozoa. In animal nutrition additions of saponins can suppress intestinal and ruminal ammonia production. The ammonia-reducing effect is primarily attributed to an inhibition of proteolytic microorganisms. Due to reduced NH3-concentrations metabolism is relieved, which offers benefits to animal welfare and animal performance. Accordingly improved feed convertion ratio can be registered in weanling and growing-finishing pigs with the employment of saponin-containing feed additives. With regard to ruminal fermentation in vitro and in vivo studies have shown that beside proteolytic protozoa also cellolytic and amylolytic bacterial species are restrained. To what extent antimicrobial activity supress digestion or whether the selective effects on microorganisms can be used purposefully to manipulate ruminal fermentation, must be clarified in further investigations.

Animal Feed↗