Soyasaponin III

New triterpenoid saponins from the flowers of Pueraria thomsonii.[Pubmed:24168266]

J Asian Nat Prod Res. 2013;15(10):1065-72.

Two new oleanane-type triterpenoid saponins, kakkasaponin II (1) and kakkasaponin III (2), were isolated from the methanol extract of the flowers of Pueraria thomsonii (Leguminosae), together with seven known oleanane-type triterpenoid saponins, phaseoside IV (3), sophoradiol monoglucuronide (4), kakkasaponin I (5), kaikasaponin III (6), soyasaponin I (7), Soyasaponin III (8), and soyasaponin IV (9). The structures of 1 and 2 were elucidated by spectroscopic methods including IR, ESI-TOF-MS, and 1D and 2D NMR experiments.

Identification and characterization of glycosyltransferases involved in the biosynthesis of soyasaponin I in Glycine max.[Pubmed:20350545]

FEBS Lett. 2010 Jun 3;584(11):2258-64.

Triterpene saponins are a diverse group of compounds with a structure consisting of a triterpene aglycone and sugars. Identification of the sugar-transferase involved in triterpene saponin biosynthesis is difficult due to the structural complexity of triterpene saponin. Two glycosyltransferases from Glycine max, designated as GmSGT2 and GmSGT3, were identified and characterized. In vitro analysis revealed that GmSGT2 transfers a galactosyl group from UDP-galactose to soyasapogenol B monoglucuronide, and that GmSGT3 transfers a rhamnosyl group from UDP-rhamnose to Soyasaponin III. These results suggest that soyasaponin I is biosynthesized from soyasapogenol B by successive sugar transfer reactions.

Generation of group B soyasaponins I and III by hydrolysis.[Pubmed:19338335]

J Agric Food Chem. 2009 May 13;57(9):3620-5.

Soyasaponins are a group of oleanane triterpenoids found in soy and other legumes that have been associated with some of the benefits achieved by consuming plant-based diets. However, these groups of compounds are diverse and structurally complicated to chemically characterize, separate from the isoflavones, and isolate in sufficient quantities for bioactive testing. Therefore, the aim of this study was to maximize the extraction of soyasaponins from soy flour, remove isoflavones, separate group B soyasaponins from group A, and produce an extract that contained a majority of non-DDMP (2,3-dihydro-2,5-dihydroxy-6-methyl-4H-pyran-4-one)-conjugated group B soyasaponins I and III. Room temperature extraction in methanol for 24 or 48 h resulted in the maximum recovery of soyasaponins, and Soxhlet extraction resulted in the least. A solid-phase extraction using methanol (45%) was found to virtually eliminate the interfering isoflavones as compared to butanol-water liquid-liquid extraction and ammonium sulfate precipitation, while maximizing saponin recovery. Alkaline hydrolysis in anhydrous methanol produced the maximum amount of soyasaponins I and III as compared to aqueous methanol and acid hydrolysis in both aqueous and anhydrous methanol. The soyasaponin I amount was increased by 175%, and Soyasaponin III was increased by 211% after alkaline hydrolysis. Furthermore, after alkaline hydrolysis, a majority of DDMP-conjugated group B soyasaponins such as betag, betaa, gammag, and gammaa transformed into the non-DDMP-conjugated soyasaponins I and III without affecting the glycosidic bond at position C-3 of the ring structure. Therefore, we have developed a method that maximizes the recovery of DDMP-conjugated saponins and uses alkaline hydrolysis to produce an extract containing mainly soyasaponins I and III.

The isolation of soyasaponins by fractional precipitation, solid phase extraction, and low pressure liquid chromatography.[Pubmed:16503561]

Int J Food Sci Nutr. 2005 Nov;56(7):501-19.

Bioactive soyasaponins are present in soybean (Glycine max). In this study, the isolation of soyasaponins in relatively pure form (>80%) using precipitation, solid phase extraction and reverse phase low pressure liquid chromatography (RP-LPLC) is described. Soy flour soyasaponins were separated from non-saponins by methanol extraction and precipitation with ammonium sulphate. Acetylated group A soyasaponins were isolated first by solid phase extraction followed by RP-LPLC (solvent: ethanol-water). Soyasaponins, from a commercial preparation, were saponified and fractionated into deacetylated group A and group B soyasaponins by solid phase extraction (methanol-water). Partial hydrolysis of group B soyasaponins produced a mixture of Soyasaponin III and soyasapogenol B monoglucuronide. RP-LPLC of deacetylated group A soyasaponins separated soyasaponin A1 and A2 (38% methanol); of group B soyasaponins isolated soyasaponin I (50% ethanol); and of the partial hydrolysate separated Soyasaponin III from soyasapogenol B monoglucuronide (50% ethanol). This methodology provides soyasaponin fractions that are suitable for biological evaluation.

Human fecal metabolism of soyasaponin I.[Pubmed:15113177]

J Agric Food Chem. 2004 May 5;52(9):2689-96.

The metabolism of soyasaponin I (3-O-[alpha-L-rhamnopyranosyl-beta-D-galactopyranosyl-beta-D-glucuronopyranosyl]o lean-12-ene-3beta,22beta,24-triol) by human fecal microorganisms was investigated. Fresh feces were collected from 15 healthy women and incubated anaerobically with 10 mmol soyasaponin I/g feces at 37 degrees C for 48 h. The disappearance of soyasaponin I in this in vitro fermentation system displayed apparent first-order rate loss kinetics. Two distinct soyasaponin I degradation phenotypes were observed among the subjects: rapid soyasaponin degraders with a rate constant k = 0.24 +/- 0.04 h(-)(1) and slow degraders with a k = 0.07 +/- 0.02 h(-)(1). There were no significant differences in the body mass index, fecal moisture, gut transit time, and soy consumption frequency between the two soyasaponin degradation phenotypes. Two primary gut microbial metabolites of soyasaponin I were identified as Soyasaponin III (3-O-[beta-D-galactopyranosyl-beta-D-glucuronopyranosyl]olean-12-ene-3beta,22beta ,24-triol) and soyasapogenol B (olean-12-ene-3beta,22beta,24-triol) by NMR and electrospray ionized mass spectroscopy. Soyasaponin III appeared within the first 24 h and disappeared by 48 h. Soyasapogenol B seemed to be the final metabolic product during the 48 h anaerobic incubation. These results indicate that dietary soyasaponins can be metabolized by human gut microorganisms. The sugar moieties of soyasaponins seem to be hydrolyzed sequentially to yield smaller and more hydrophobic metabolites.

Soyasaponins: the relationship between chemical structure and colon anticarcinogenic activity.[Pubmed:14769534]

Nutr Cancer. 2003;47(1):24-33.

Soyasaponins are bioactive compounds found in many legumes. Although crude soyasaponins have been shown to have anti-colon carcinogenic activity, there have been no structure-activity studies. In this study, therefore, purified soyasaponins and soyasapogenins were tested for their ability to suppress the growth of HT-29 colon cancer cells, as determined by the WST-1 assay, over a concentration range of 0-50 ppm. Soyasaponin I and III, soyasapogenol B monoglucuronide, soyasapogenol B, soyasaponin A1, soyasaponin A2, and soyasapogenol A were evaluated. Also tested were mixtures comprising acetylated group A soyasaponins, deacetylated group A soyasaponins, and group B soyasaponins. The most potent compounds were the aglycones soyasapogenol A and B, which showed almost complete suppression of cell growth. The glycosidic soyasaponins by comparison were largely inactive. Soyasaponin A(1), A(2), and I, group B and deacetylated and acetylated group A fractions had no effect on cell growth. Soyasaponin III and soyasapogenol B monoglucuronide were marginally bioactive. These results suggested that the bioactivity of soyasaponins increased with increased lipophilicity. Results from in vitro fermentation suggested that colonic microflora readily hydrolyzed the soyasaponins to aglycones. These observations suggest that the soyasaponins may be an important dietary chemopreventive agent against colon cancer, after alteration by microflora.

Hepatoprotective constituents in plants. 14. Effects of soyasapogenol B, sophoradiol, and their glucuronides on the cytotoxicity of tert-butyl hydroperoxide to HepG2 cells.[Pubmed:12951488]

Biol Pharm Bull. 2003 Sep;26(9):1357-60.

The effects of soyasapogenol B, sophoradiol, their glucuronides, and glycyrrhizin on the hepatotoxicity of tert-butyl hydroperoxide (t-BuOOH) in a human-liver-derived cell line (HepG2 cells) were investigated. Glycyrrhizin showed significant dose-dependent protective effects against the cytotoxicity of t-BuOOH. Among soyasapogenol B and its glucuronides, the monoglucuronide showed the most potent hepatoprotective activity, followed by soyasapogenol B itself. Soyasaponin III was weakly protective, while soyasaponin I increased the toxicity of t-BuOOH. Among sophoradiol and its glucuronides, sophoradiol itself showed the most potent hepatoprotective activity, which was equal to glycyrrhizin, while the monoglucuronide and kaikasaponin III showed an increase in cytotoxicity. These results were considerably different from those reported previously on the protective effects of these compounds using primary cultures of immunologically injured rat liver cells. Consequently, the hepatoprotective action of the triterpene derivatives investigated would be different in HepG2 cells and in rat primary hepatocyte cultures.

Relationship between adjuvant activity and amphipathic structure of soyasaponins.[Pubmed:12706705]

Vaccine. 2003 May 16;21(17-18):2145-51.

A correlation between adjuvant activity and amphipathic structure of saponin was first demonstrated on an experimental basis using structurally consecutive analogues. To clarify the physicochemical factors regulating the adjuvanticity of saponin, we compared the profile of the antibody response against chicken ovalbumin (OVA) in mice and hydrophile-lipophile balance (HLB) of eight purified soyasaponins. Soyasaponins bearing sugar chain(s) showed adjuvanticity stimulating anti-OVA total-IgG and IgG1 antibody responses, while their corresponding aglycones soyasapogenols A and B, did not. Among bisdesmosidic soyasaponins, soyasaponin A(1) (HLB: 26.9) with a long sugar side chain induced stronger total-IgG and IgG1 antibody responses than soyasaponin A(2) (HLB: 21.4). For monodesmosidic soyasaponins, the ranking in terms of antibody response was soyasaponin I (which has the highest HLB value (13.6) among the monodesmosidic soyasaponins) > soyasaponin II (HLB: 12.2) > Soyasaponin III (HLB: 10.0). The adjuvant activity increased with the HLB value. The length, the number, and the composition of sugar side chains affecting the HLB value would give the overall conformation of each saponin molecule, and the amphipathic structure may define the fundamental adjuvanticity of saponins.

Effects of triterpenoids from Pueraria lobata on immunohemolysis: beta-D-glucuronic acid plays an active role in anticomplementary activity in vitro.[Pubmed:10985074]

Planta Med. 2000 Aug;66(6):506-10.

The anticomplementary properties of kaikasaponin III (4) and soyasaponin I (8) from Pueraria lobata and their hydrolytic analogs were investigated in vitro. Diglycosidic saponins [kaikasaponin I (3), Soyasaponin III (7)] showed most potent anticomplementary activities, followed by monoglycosidic saponins [soyasapogenol B monoglucuronide (6), sophoradiol monoglucuronide (2)] and triglycosidic saponins [soyasaponin I (8), kaikasaponin III (4)], whereas sophoradiol (1) and soyasapogenol B (5) showed enhancement of hemolysis under the presence of serum on the classical pathway of complement system. But all of them showed very weak or no anticomplementary activities on the alternative pathway of complement system. The anticomplementary activity of the saponins was influenced by the nature of glucuronic acid, where the free acid forms (-COOH) showed much more potent activity than the sodium salt forms (-COO-Na+) or methyl ester forms (-COOCH3), and the reduced forms (-CH2OH) decreased the activity significantly.

Structure-hepatoprotective relationships study of soyasaponins I-IV having soyasapogenol B as aglycone.[Pubmed:9581521]

Planta Med. 1998 Apr;64(3):233-6.

As a part of our study on the leguminous plants, we investigated the constituents of the aerial parts of Glycine soya. We isolated and identified four known saponins, soyasaponins I, II, III, and IV which have the same aglycone, soyasapogenol B. As a part of our studies concerning hepatoprotective drugs, we also examined the hepatoprotective actions of these saponins towards immunologically induced liver injury on primary cultured rat hepatocytes. The action of soyasaponin II was almost comparable with that of soyasaponin I, whereas those of Soyasaponin III and IV were more effective than soyasaponins I and II. This means that the disaccharide group shows greater action than the trisaccharide group. Furthermore, the saponin having a hexosyl unit shows a slightly greater action than that of the pentosyl unit in each disaccharide group or trisaccharide group. Structure-activity relationships suggest that the sugar moiety linked at C-3 may play an important role in hepatoprotective actions of soybean saponins.

Partial hydrolysis of soyasaponin I and the hepatoprotective effects of the hydrolytic products. Study of the structure-hepatoprotective relationship of soyasapogenol B analogs.[Pubmed:9501471]

Chem Pharm Bull (Tokyo). 1998 Feb;46(2):359-61.

As a part of our studies of hepatoprotective drugs, we prepared some soyasapogenol B analogs from soyasaponin I. We examined the hepatoprotective effects of these analogs, using immunologically-induced liver injury, in primary cultured rat hepatocytes. Soyasaponin III and soyasapogenol B monoglucuronide were more effective than soyasaponin I. Both compounds were significantly effective even at 30 microM. The action of soyasapogenol B was almost equal to that of soyasaponin I, although glucuronic acid did not show any activity even at the highest dose (500 microM). When the two compounds were mixed, the hepatoprotective action did not change, compared with soyasapogenol B. Therefore, we concluded that the linkage between glucuronic acid and soyasapogenol B could enhance the hepato-protective activity.

An activator of calcium-dependent potassium channels isolated from a medicinal herb.[Pubmed:7685635]

Biochemistry. 1993 Jun 22;32(24):6128-33.

Large-conductance calcium-dependent potassium (maxi-K) channels play an important role in regulating the tone of airway smooth muscle and the release of bronchoconstrictive substances from nerves in the lung. Crude extracts of Desmodium adscendens, a medicinal herb used in Ghana as a treatment for asthma, inhibit binding of monoiodotyrosine charybdotoxin (125I-ChTX) to receptor sites in bovine tracheal smooth muscle membranes that have been shown to be associated with maxi-K channels. Using this assay, three active components have been purified and identified by NMR and MS. Comparison with authentic samples revealed the three active components as the known triterpenoid glycosides dehydrosoyasaponin I (DHS-I), soyasaponin I, and Soyasaponin III. The most potent of these compounds, DHS-I, is a partial inhibitor of 125I-ChTX binding (Ki = 120 nM, 62% maximum inhibition). Inhibition of 125I-ChTX binding is primarily due to a decrease in the observed maximum number of binding sites, with a smaller decrease in affinity. DHS-I increases the rate of toxin dissociation from its receptor, suggesting that modulation of ChTX binding occurs through an allosteric mechanism. DHS-I reversibly increases the open probability of maxi-K channels from bovine tracheal smooth muscle incorporated into planar lipid bilayers when applied to the intracellular, but not the extracellular, side of the membrane at concentrations as low as 10 nM. In contrast, DHS-I had no effect on several other types of potassium channels or membrane transporters. This natural product is the first example of a high-affinity activator of calcium-dependent potassium channels and is the most potent known potassium channel opener.