Acid Saponins Research Articles

Two new compounds from Semen celosiae and their protective effects against CCl4-induced hepatotoxicity

Two new oleanolic acid saponins, namely celosin A (1) and celosin B (2), together with six known compounds, stigmasterol (3), β-sitosterol (4), β-daucosterol (5), hexacosoic acid (6), palmitic acid (7) and stearic acid (8), were isolated from the ethanolic extract of Semen celosiae. The structures of celosin A (1) and celosin B (2) were determined by spectral analysis (including 1D- and 2D-NMR). The hepatoprotective activity of 1 and 2 with oral doses 1.0, 2.0 and 4.0 mg kg−1 were investigated by carbon tetrachloride (CCl4)-induced hepatotoxicity in mice. The results indicate that they have significant hepatoprotective effects, and that these hepatoprotective effects may be due to the antioxidant capability.

Synthesis and cytotoxic activity of the N-acetylglucosamine-bearing triterpenoid saponins

Fourteen ursolic acid and oleanolic acid saponins with N-acetyl-β- d-glucosamine, and (1→4)-linked and (1→6)-linked N-acetyl-β- d-glucosamine oligosaccharide residues were synthesized in a convergent manner. The structures of all compounds were confirmed by 1H NMR and 13C NMR spectroscopy and by mass spectrometry, and their cytotoxic activities were assayed in three cancer cell lines. Only oleanolic acid-3-yl β- d-GluNAc showed significant cytotoxicity against HL-60 and BGC-823.

Triterpene glycosides from Agrostemma gracilis

Four triterpene saponins, agrostemmosides A-D were isolated from the methanol extract of Agrostemma gracilis. The structures of the compounds were determined as 3-O-beta-D-xylopyranosyloleanolic acid 28-O-beta-D-glucopyranosyl-(1-->2)-[beta-D-xylopyranosyl-(1-->6)]-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl ester, 3-O-alpha-L-rhamnopyranosyl-(1-->2)-beta-D-xylopyranosyloleanolic acid 28-O-beta-D-glucopyranosyl-(1-->2)-[beta-D-xylopyranosyl-(1-->6)]-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl ester, 3-O-beta-D-xylopyranosylechinocystic acid 28-O-beta-D-glucopyranosyl-(1-->2)-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl ester, 3-O-beta-D-xylopyranosylechinocystic acid 28-O-beta-D-glucopyranosyl-(1-->2)-[beta-D-xylopyranosyl-(1-->6)]-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl ester by a combination of one- and two-dimensional NMR techniques, and mass spectrometry. To the best of our knowledge this is the first phytochemical report on A. gracilis, and echinocystic acid saponins were encountered for the first time in Caryophyllaceae family.

Two new hepaprotective saponins from Semen celosiae

Two new oleanolic acid saponins, namely celosin C ( 1 ) and celosin D ( 2 ), were isolated from the ethanol extract of Semen celosiae. Their structures were identified as celosin C ( 1) and celosin D ( 2) by spectroscopic and chemical analyses. The hepatoprotective activity of 1 and 2 with oral dose 1.0, 2.0 and 4.0 mg/kg, respectively, were investigated by carbon tetrachloride (CCl 4)-induced hepatotoxicity in mice. The results indicate that they have significant hepatoprotective effects ( p < 0.01).

Chemoporation using saponins or cholates: an alternative method for transformation of bacterial cells

A new method for fast transformation of competent bacterial cells has been developed. The transformation is induced with cholic acid analogues or saponins which cause reversible disruption of the bacterial membrane. This method shortens the time of transformation without significant loss of transformation efficiency in comparison to heat shock method and is the first reported chemically-induced transformation. New data about interactions between cholates and biomembranes is revealed that may contribute to better understanding of bacterial transformation.

The Interleukin-18 Inhibitory Activities of Echinocystic Acid and its Saponins from Impatiens pritzellii var. hupehensis

Echinocystic acid (1), an echinocystic acid saponin, 2, and four of its ester saponins, 3-6, obtained from the active fraction of Impatiens pritzellii var. hupehensis, an traditional Chinese medicine for rheumatoid arthritis, were investigated for their effects on lipopolysaccharide (LPS)-induced interleukin (IL)-18 in human peripheral blood mononuclear cells. Three of them, 1, 2 and 6, showed obvious activity to inhibit the production of IL-18, especially the ester saponins with a sugar chain at C-28, 6. Structure-activity relationships are discussed in brief.

Facile synthesis of three bidesmosidic oleanolic acid saponins with strong inhibitory activity on pancreatic lipase

The first synthesis of scabiosaponins E ( 1), F ( 2), and G ( 3), three new oleanolic acid saponins with strong inhibitory activity on pancreatic lipase isolated from the Chinese traditional medicinal herb Scabiosa tschiliensis, was efficiently achieved in an one-pot strategy under the combined use of glycosyl trichloroacetimidates and p-toluene 1-thioglycosides (STol) as donors.

Synthesis of oleanolic acid saponins mimicking components of Chinese folk medicine Di Wu

3,28-Di- O-rhamnosylated oleanolic acid saponins, mimicking components of Chinese folk medicine Di Wu, have been designed and synthesized. One-pot glycosylation and ‘inverse procedure’ technologies have been applied thus significantly simplifying the preparation of desired saponins. The cytotoxic activity of compounds 3- O-[α- l-rhamnopyranosyl-(1→2)-β- d-xylopyranosyl]oleanolic acid 28- O-[α- l-rhamnopyranosyl-(1→4)-β- d-glucopyranosyl-(1→6)-β- d-glucopyranosyl] ester ( 3), 3- O-[α- l-rhamnopyranosyl]oleanolic acid 28- O-[α- l-rhamnopyranosyl- (1→4)-β- d-glucopyranosyl-(1→6)-β- d-glucopyranosyl] ester ( 4), 3- O-[α- l-rhamnopyranosyl]oleanolic acid 28- O-[α- l-rhamnopyranosyl] ester ( 5), and 3- O-[α- l-rhamnopyranosyl]oleanolic acid 28- O-[6- O-(α- l-rhamnopyranosyl)hexyl] ester ( 6) was preliminarily evaluated against HL-60 human promyelocytic leukemia cells. The natural saponin 3 and designed saponin 4 exhibited comparable moderate cytotoxic activity under our testing conditions.

Achyranthoside H methyl ester, a novel oleanolic acid saponin derivative from Achyranthes fauriei roots, induces apoptosis in human breast cancer MCF-7 and MDA-MB-453 cells via a caspase activation pathway

Achyranthoside H methyl ester (AH-Me) is an oleanolic acid saponin derivative isolated from the roots of Achyranthes fauriei through diazomethane treatment. AH-Me exhibited significant cytotoxicity against human breast cancer MCF-7 and MDA-MB-453 cells, with respective ID(50) values of 4.0 and 6.5 muM: in the MTT assay. AH-Me is a unique saponin containing three methoxycarbonyl groups in the sugar moiety linked to the C-3 position of oleanolic acid. The demethylation of these methoxycarbonyl groups by alkaline hydrolysis caused a marked reduction of the cytotoxicity of AH-Me, suggesting that the methoxycarbonyl groups of AH-Me are key groups for the acquisition of cytotoxicity against human cancer cells. The staining of cancer cells with 4',6'-diamidino-2-phenylindole (DAPI) showed that the population of cells with altered nuclear morphology, for example chromatin condensation and fragmentation, increased markedly after AH-Me treatment. Exposure of MCF-7 and MDA-MB-453 cells to AH-Me resulted in a dose-dependent and time-dependent increase in the sub-G1 population, and in the cleavage of poly-ADP-ribose polymerase (PARP) followed by the formation of an 89 kD peptide. Pretreatment of the cells with the pan-caspase inhibitor z-VAD-fmk abolished the cleavage of PARP by AH-Me treatment and suppressed the antiproliferative effect of AH-Me on tumor cell growth. These results together led to the suggestion that AH-Me induces apoptosis via the caspase activation pathway in human breast cancer cells, and apoptosis is the major mode of the cytotoxic effect triggered by AH-Me.

Synthesis and Cytotoxicity of Bidesmosidic Betulin and Betulinic Acid Saponins

The naturally occurring cytotoxic saponin 28-O-beta-d-glucopyranosylbetulinic acid 3beta-O-alpha-l-arabinopyranoside (3) was easily synthesized along with seven bidesmosidic saponins starting from the lupane-type triterpenoids betulin (1) and betulinic acid (2). As highlighted by the preliminary cytotoxicity evaluation against A549, DLD-1, MCF7, and PC-3 human cancer cell lines, the bidesmosidic betulin saponin 22a, bearing alpha-l-rhamnopyranoside moieties at both C-3 and C-28 positions, was determined to be a potent cytotoxic agent (IC(50) 1.8-1.9 microM).

Facile Synthesis of Oleanolic Acid Monoglycosides and Diglycosides

Oleanolic acid and its glycosides are important natural products, possessing various attractive biological activities such as antitumor, antivirus and anti-inflammatory properties. In the present work, fifteen oleanolic acid saponins bearing various saccharide moieties, including 3-monoglycoside, 28-monoglycoside and 3,28-diglycoside, were easily synthesized in high yields. Benzyl was chosen as the protective group for the COOH(28) group, instead of commonly used methyl and allyl, to avoid difficulties in the final deprotection. Alkali-promoted condensation of the carboxylic acid with bromo-glycosides was found to be more efficient in the synthesis of 28-glycosides. Two approaches were investigated and proved practicable in the preparation of 3,28-diglycosides. This method is suitable for preparing oleanolic acid glycosides with structural diversity for extensive biological evaluation and structure-activity relationship study, and it also apply new idea for the corresponding synthetic methods to the glycoside derivatives of other triterpenoid.

Synthesis of two natural betulinic acid saponins containing α- l-rhamnopyranosyl-(1→2)-α- l-arabinopyranose and their analogues

A concise synthesis of naturally occurring betulinic acid saponins bearing an α- l-rhamnopyranosyl-(1→2)-α- l-arabinopyranoside moiety at the C-3 position is described. Betulinic acid 3β- O-α- l-rhamnopyranosyl-(1→2)-[β- d-glucopyranosyl-(1→4)]-α- l-arabinopyranoside isolated from Pulsatilla koreana and 28- O-β- d-glucopyranosyl betulinic acid 3β- O-α- l-rhamnopyranosyl-(1→2)-α- l-arabinopyranoside isolated from Schefflera rotundifolia were easily synthesized for the first time using a stepwise glycosidation approach. The overall syntheses involved eight linear steps starting from allyl betulinate and commercially available l-arabinose, l-rhamnose and d-glucose. The syntheses of betulin and betulinic acid O-glycoside analogues containing an α- l-arabinose moiety are also reported. These results open the way to the synthesis of various lupane-type saponin derivatives as potentially bioactive compounds.

Triterpenoid Saponins from the Seeds of Pharbitis nil

From the seeds of Pharbitis nil (Convolvulaceae), two new oleanene-type triterpene glycosides, pharbitosides A (1) and B (2), together with beta-sitosterol, beta-sitosterol glucoside (daucosterol), caffeic acid, and methyl caffeate were isolated. The structure of pharbitoside A (1) was elucidated to be queretaroic acid 3-O-alpha-L-rhamnopyranosyl-(1-->2)-O-beta-D-glucopyranosyl-(1-->2)-beta-D-glucopyranoside (1). Pharbitoside B (2) is a 21alpha-hydroxyoleanolic acid saponin carrying the same sugar moiety as that of pharbitoside A (1).

Two new glucuronide saponins, Achyranthosides G and H, from Achyranthes fauriei root

Two oleanolic acid saponins named achyranthosides G (1) and H (2) were newly isolated from Achyranthes fauriei root as methyl esters in addition to methyl esters of achyranthosides A - F and five oleanolic acid glucuronides (chikusetsusaponins IVa, V, 28-deglucosyl chikusetsusaponin V, pseudoginsenoside RT(1), and oleanolic acid 3-O-beta-D-glucuronopyranoside) as well as oleanolic acid 28-O-beta-D-glucopyranoside, beta-ecdysterone, and polypodine B. Their structures were characterized as follows on the basis of the chemical and spectroscopic evidences.

Synthesis and structure–activity relationship study of cytotoxic germanicane- and lupane-type 3β- O-monodesmosidic saponins starting from betulin

Germanicane-type triterpenes allobetulin ( 3) and 28-oxoallobetulin ( 4) can be obtained by the Wagner-Meerwein rearrangement of the more available lupane-type triterpenes betulin ( 1) and betulinic acid ( 2), respectively. The medical uses of betulinic acid ( 2) and its derivatives are limited because of their poor hydrosolubility and pharmacokinetics properties. In order to overcome this major problem, we synthesized and studied the in vitro anticancer activity of a series of 3β- O-monodesmosidic saponins derived from betulin ( 14– 16), betulinic acid ( 20– 22), allobetulin ( 23– 28) and 28-oxoallobetulin ( 29– 34) based on six different natural sugar residues ( d-glucose, l-rhamnose, d-arabinose, d-galactose, d-mannose and d-xylose). This structure–activity relationship study confirmed that betulinic acid saponins are generally better in vitro anticancer agents than those derived from betulin with the exception of betulin 3β- O-α- d-mannopyranoside ( 15) which exerted a potent cytotoxic activity against lung carcinoma (A-549) and colorectal adenocarcinoma (DLD-1) human cell lines with IC 50 ranging from 7.3 to 10.1 μmol/L. Furthermore, although the synthesis of novel germanicane-type saponins was carried out with success, the bioactivity measured for these glycosides was not as high as we anticipated since only the 3β- O-β- d-glucopyranoside and 3β- O-β- d-galactopyranoside of allobetulin ( 23, 24) showed moderate anticancer activity (IC 50 30–40 μmol/L).

Synthesis of an Ursolic Acid Saponin with N‐Acetylglucosamine‐containing Trisaccharide Residue

AbstractThe focus of this work is the synthesis of an ursolic acid saponin with an N‐acetylglucosamine‐containing trisaccharide residue. Therefore, ursolic acid 3‐yl α‐L‐arabinopyranosyl‐(1→2)‐α‐L‐arabinopyranosyl‐(1→6)‐2‐acetamido‐2‐deoxy‐β‐D‐glucopyranoside (1) was concisely synthesized in convergent synthesis with 48.0% overall yield. The structure of saponin 1 was confirmed by 1H NMR, 13C NMR and mass spectra.

Synthesis of two bidesmosidic ursolic acid saponins bearing a 2,3-branched trisaccharide residue

The focus of this work was on the synthesis of two bidesmosidic ursolic acid saponins bearing a 2,3-branched trisaccharide residue. Therefore, 3- O-{[β- d-glucopyranosyl-(1→2)]-[α- l-arabinopyranosyl-(1→3)]-α- l-arabinopyranosyl}ursolic acid-28- O-[β- d-glucopyranosyl] ester 1 was concisely synthesized by two strategies in 22% and 41% overall yield, respectively, and another congener 3- O-{[β- d-xylopyranosyl-(1→2)]-[β- d-glucopyranosyl-(1→3)]-α- l-arabinopyranosyl}ursolic acid-28- O-[β- d-glucopyranosyl] ester 2 was also efficiently prepared in 81% overall yield. The 1H NMR and 13C NMR signals of saponin 2 are all consistent with those reported for the natural product.

Metabolomic analysis of saponins in crude extracts of Quillaja saponaria by liquid chromatography/mass spectrometry for product authentication

Analysis of 50% aqueous methanolic extracts of bark of Quillaja saponaria Molina (quillaja) by liquid chromatography/mass spectrometry (LC/MS), using negative ion electrospray, revealed over 100 saponins. The majority could be assigned to known structures or generalised variations of these from the product ion spectra obtained by serial mass spectrometry in a quadrupole ion trap mass spectrometer. Ten saponins contained a fatty acid domain terminated with both a pentose and deoxyhexose unit, a feature thus far only reported in QS-III. Twenty saponins were based on a hydroxylated derivative of quillaic acid, whereas only six 22beta-hydroxyquillaic acid saponins have been described. The occurrence of pairs of saponins differing only by the presence of a rhamnose or xylose unit in the C-3-substituted saccharide was readily observed in two-dimensional mass maps, and these showed the presence of the unreported 'rhamnose partner' of QS-III. However, one sample labelled as Q. saponaria appeared to lack all saponins containing rhamnose in the C-3 saccharide. Methods to authenticate saponin extracts of quillaja by LC/MS are suggested based on the general metabolomic profile, the occurrence of specific major saponins covering known structural variations, or the presence of saponins containing the unusual fatty acid domain, revealed by neutral loss analysis.

Transformation of glycyrrhizinic acid. XV. Synthesis of triterpene saponins with monosaccharide residues, attached through complex ester bonds

Triterpene saponins, glycoside analogues of glycyrrhizic acid with a modified carbohydrate chain containing monosaccharide residues attached through ester bonds, were synthesized. To this end, peracetylated glycyrrhizic acid or its 30-methyl ester were glycosylated by 2,3,4,6-tetra-O-acetyl-alpha-D-gluco-or-alpha-D-galactopyranosyl bromide in dichloroethane in the presence of Ag2CO3. Glycerrhetinic acid saponin with D-Galp residues exhibited a higher antiulcer activity than glycyrrhizic acid in rats at a dose of 25 mg/kg. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2003, vol. 29, no. 6; see also http://www.maik.ru.

Three new saponins from the leaves of Ilex hylonoma

Three new triterpenoid saponins, hylonosides III–V (1–3) have been isolated, along with three known oleanolic acid saponins (4–6), from the methanol extract of leaves of Ilex hylonoma. The structures were elucidated using a combination of homo- and hetero-nuclear 2D NMR techniques (COSY, TOCSY, NOESY, HMQC and HMBC) and negative FAB-MS. The new compounds were characterized as 3-O-β-D-glucopyranosyl-(1→4)-β-D-glucuronopyranosyl siaresinolic acid-28-O-β-D-glucopyranosyl ester (1), 3-O-β-D-glucopyranosyl-(1→4)-β-D-glucopyranosyl-(1→2)-β-D-glucuronopyranosyl siaresinolic acid-28-O-β-D-glucopyranosyl ester (2), 3-O-β-D-glucopyranosyl-(1→4)-β-D-glucopyranosyl-(1→2)-β-D-glucuronopyranosyl oleanolic acid-28-O-β-D-glucopyranosyl ester (3).