Natural Saponins Research Articles

ChemInform Abstract: Facile Synthesis of Four Natural Triterpene Saponins with Important Antitumor Activity.

AbstractThe first synthesis of four natural triterpene saponins (I) and (II) is described, which exhibit significant antitumor activities.

Unraveling the response of plant cells to cytotoxic saponins

A wide range of pharmacological properties are ascribed to natural saponins, in addition to their biological activities against herbivores, plant soil-borne pathogens and pests. As for animal cells, the cytotoxicity and the chemopreventive role of saponins are mediated by a complex network of signal transduction pathways which include reactive oxygen species (ROS) and nitric oxide (NO). The involvement of other relevant components of the saponin-related signaling routes, such as the Tumor Necrosis Factor(TNF)-α, the interleukin(IL)-6 and the Nuclear Transcription Factor-kB (NF-κB), has been highlighted in animal cells. By contrast, information concerning the response of plant cells to saponins and the related signal transduction pathways is almost missing. To date, there are only a few common features which link plant and animal cells in their response to saponins, such as the early burst in ROS and NO production and the induction of metallothioneins (MTs), small cysteine-rich, metal-binding proteins. This aspect is discussed in the present paper in view of the recent hypothesis that MTs and NO are part of a novel signal transduction pathway participating in the cell response to oxidative stress.

Facile Synthesis of Four Natural Triterpene Saponins with Important Antitumor Activity

The first synthesis of four natural triterpene saponins, which exhibit significant antitumor activities, was concisely achieved by adopting a stepwise glycosylation. The key intermediate 13 was afforded via Bu2SnO-mediated regioseletive benzoylation. During the preparation of the target compounds, it was found that the α-L-arabinopyranosyl unit in intermediates 17 and 20 existed in the unusual 1 C 4 conformation, and after removing the benzoyl groups, the α-L-arabinopyranosyl unit was normal in a typical 4 C 1 form.

ChemInform Abstract: Synthesis of a Group of Diosgenyl Saponins by a One-Pot Sequential Glycosylation.

Abstract A group of natural diosgenyl saponins was synthesized in a highly efficient manner employing the ‘one-pot sequential glycosylation’ protocol with the combined use of glycosyl trichloroacetimidates and thioglycosides.

ChemInform Abstract: Synthesis of a Group of Diosgenyl Saponins with Combined Use of Glycosyl Trichloroacetimidate and Thioglycoside Donors.

With the combined use of glycosyl trichloroacetimidates and thioglycosides, a group of natural diosgenyl saponins (1–6) are efficiently synthesized, in either a stepwise or a ‘one-pot’ manner. The trichloroacetimidate is employed as an efficient temporary hydroxy protecting group in glycosylation with the glycosyl trichloroacetimidate. The intermolecular alkylthio-group transfer is demonstrated to be a common side-reaction during glycosylation with thioglycosides.

Advances in the synthesis and pharmacological activity of lupane-type triterpenoid saponins

Lupeol, betulin and betulinic acid are members of the so-called lupane-type triterpenoids. These natural products found worldwide in quite of lot of vegetables, fruits and plant species exhibit promising pharmacological activities including anti-inflammatory, anti-HIV and antitumor activities. Nevertheless, the poor pharmacokinetic properties of these cholesterol-like triterpenoids hampered further pharmaceutical developments. The synthesis of lupane-type saponins, i.e., sugar-derived lupanes, seems to be a good avenue to improve both their water solubility and pharmacological activity. The aims of this review are twofold: first, to describe the biological activity of naturally occurring lupane-type saponins, and second, report the different methodologies employed for the elaboration of glycosidic linkages at the C-3 and/or C-28 positions on the lupane core. The synthesis of both natural and unnatural lupane-type saponins is discussed with an emphasis on molecules exhibiting relevant biological activities.

Concise synthesis of two natural triterpenoid saponins, oleanolic acid derivatives isolated from the roots of Pulsatilla chinensis

The first synthesis of two natural triterpenoid saponins, which were isolated from the roots of Pulsatilla chinensis and exhibited excellent in vitro cytotoxic activity against HL-60 cells, was concisely achieved in a convergent approach. We employed an odourless 2-methyl-5- tert-butylphenyl (Mbp) thioglycoside and trichloroacetimidate donors in one-pot reaction as a key step.

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.

Wood Fluorescence of Commercial Timbers Marketed in Mexico

A market survey conducted in Mexico yielded 579 wood specimens attributed to 92 genera belonging to 40 families. The fluorescence characteristics of these timbers and their extracts were determined. Additional tests were conducted for the presence of natural saponins and aluminium. The combustion behavior (burning splinter test) was also studied. The results obtained largely concur with information on wood fluorescence and other physical characteristics published earlier. The families Fabaceae, Anacardiaceae and Rubiaceae showed positive fluorescence for a large number of genera or species. Vochysia was the only genus with a positive reaction to the test for aluminium. The froth test for natural saponins can contribute to wood identification in specific cases. The results of the burning splinter test are unambiguous only as regards the difference between charcoal and ash; ash characteristics (consistency, color) are difficult to interpret and their successful application in wood identification considered doubtful. The use of fluorescence and other physical features can be a very useful adjunct to the classical methods of wood identification in specific cases arising from the market situation and may be applied as rapid and easy tests to verify certain identifications.

Carbohydrate Chemistry in the Total Synthesis of Saponins

AbstractSignificant examples relating to the total synthesis of natural saponins with potent biological activities are discussed, with major emphasis on the applicability of contemporary glycosylation and protecting group manipulation protocols to the sophisticated scaffolds of steroids/triterpenes. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

Macrostemonoside A Promotes Visfatin Expression in 3T3-L1 Cells

The newly identified fat cell-secreted factor, visfatin, is insulin-mimetic and play a positive role in attenuating insulin resistance and diabetes. Natural steroidal saponins including tigogenin saponins have been reported to provide anti-diabetic activity and modulate glucose metabolism, but the mechanism remains unknown. In this study, we examined the effect of macrostemonoside A, a tigogenin steroidal saponin isolated from the bulbs of Allium macrostemon Bung on the expression of visfatin in differentiated 3T3-L1 adipocytes. It was found that macrostemonoside A markedly enhanced the synthesis and secretion of visfatin protein in 3T3-L1 adipocytes, and increased visfatin mRNA in a dose and time dependent manner as well. Moreover, visfatin promoter-driven luciferase expression in cells was elevated by macrostemonoside A, which was blocked by SB-203580, a specific inhibitor of p38 MAPK pathway. Lastly, we found that macrostemonoside A did not affect the expression of PPARgamma and its DNA-binding ability to visfatin promoter. These results indicate that macrostemonoside A could potently stimulate visfatin expression in 3T3-L1 adipocytes, which occurs at the transcriptional level and is mediated at least partially via p38 MAPK signaling pathway. Its regulation on visfatin in adipocytes may constitute an important element in its improvement of insulin resistance and diabetes.

Avicins, natural anticancer saponins, permeabilize mitochondrial membranes

Avicins are a class of natural saponins with selective pro-apoptotic activity in cancer cells. In this work, we studied the influence of avicins on metabolic state of rat liver mitochondria. Avicin-treated mitochondria underwent a significant decrease in oxygen consumption rate that was completely restored by addition of exogenous cytochrome c. On the other hand, avicins increased the rotenone-insensitive oxidation of external NADH in the presence of exogenous cytochrome c, long before high amplitude swelling of mitochondria was observed. The increase in external NADH oxidation was cyclosporin A-insensitive. Avicin G significantly accelerated hydroperoxide-induced oxidation of mitochondrial endogenous NAD(P)H, the drop of the inner membrane potential and the high amplitude swelling of mitochondria. The obtained data might explain selective induction of apoptosis in tumor cells by avicins. Based on other studies showing that tumor cells generate hydroperoxides with a very high rate, avicins could provide a new strategy of anticancer therapy by sensitizing cells with high levels of reactive oxygen species to apoptosis.

Synthesis and antitumor activity of two natural N-acetylglucosamine-bearing triterpenoid saponins: Lotoidoside D and E

Two natural triterpenoid saponins bearing N-acetylglucosamine, lotoidoside D and lotoidoside E, which had been available only from Glinus lotoides growing in Egyptian desert, were facilely synthesized from readily available oleanolic acid. Preliminary pharmacological research showed their antitumor activity against HeLa cell.

Facile Synthesis of Saponins Containing 2,3‐Branched Oligosaccharides by Using Partially Protected Glycosyl Donors.

Two natural saponins 1 and 2, isolated from Solanum indicum L., and containing 2,3-branched sugar moieties, have been efficiently synthesized. Partially protected monosaccharide and disaccharide donors were used to facilitate target synthesis. Stereo factors were critical in incorporating 2,3-branched sugars on steroid aglycones. Saponin 1 was synthesized in five steps and 30% overall yield, while saponin 2 was obtained using six straightforward sequential reactions in 31% overall yield. Saponin 2 shows promising cytotoxic activity toward human hepatocellular carcinoma BEL-7402 with an IC50 of <6 μg/mL.

Facile synthesis of saponins containing 2,3-branched oligosaccharides by using partially protected glycosyl donors.

Two natural saponins 1 and 2, isolated from Solanum indicum L., and containing 2,3-branched sugar moieties, have been efficiently synthesized. Partially protected monosaccharide and disaccharide donors were used to facilitate target synthesis. Stereo factors were critical in incorporating 2,3-branched sugars on steroid aglycones. Saponin 1 was synthesized in five steps and 30% overall yield, while saponin 2 was obtained using six straightforward sequential reactions in 31% overall yield. Saponin 2 shows promising cytotoxic activity toward human hepatocellular carcinoma BEL-7402 with an IC50 of <6 microg/mL.

Synthesis of a group of diosgenyl saponins with combined use of glycosyl trichloroacetimidate and thioglycoside donors

With the combined use of glycosyl trichloroacetimidates and thioglycosides, a group of natural diosgenyl saponins (1–6) are efficiently synthesized, in either a stepwise or a ‘one-pot’ manner. The trichloroacetimidate is employed as an efficient temporary hydroxy protecting group in glycosylation with the glycosyl trichloroacetimidate. The intermolecular alkylthio-group transfer is demonstrated to be a common side-reaction during glycosylation with thioglycosides.

Synthesis of a group of diosgenyl saponins by a one-pot sequential glycosylation

A group of natural diosgenyl saponins was synthesized in a highly efficient manner employing the ‘one-pot sequential glycosylation’ protocol with the combined use of glycosyl trichloroacetimidates and thioglycosides.

Indinavir crystallization and urolithiasis.

The crystallization of indinavir in synthetic urine at different pH values and indinavir concentrations was kinetically studied. It was found that precipitation time notably decreases at urinary pH values above 6.0. The effects of some products as potential crystallization inhibitors were studied. Some natural saponins such as escin and glycyrrhizic acid provoked a notable increase in the precipitation time of indinavir, this pointing out their possible use to prevent renal tubular solid deposition.

The Effect of Nutrition on Chemical Toxicity

The toxicity of chemicals, and of reactive oxygen species (ROS), are both affected by nutrition and diet. Calorific excess (continuous feeding), or deficiency (fasting), may increase production of ROS, which are also formed by interaction of toxic chemicals with cytochromes P450 (CYP2E or futile cycling). Both ROS (GSH reductase and peroxidase) and toxic chemicals (S-transferases) are detoxified by GSH enzymes; ROS are scavenged by a system comprising GSH, ascorbic acid and tocopherols, which may be regenerated by NADPH. Dietary protein is necessary for GSH or enzyme replacement, lipids are required for polyunsaturated fatty acids (PUFAs) and prostanoid biosynthesis, lipotropes and phospholipids for synthesis of endoplasmic reticulum, and folate is needed for dug metabolizing activity. Among required minerals, Se is necessary as the essential component of the antioxidant enzyme, glutathione peroxidase. Other dietary factors considered are the natural toxicants, gossypol, lathyrogens, glucosinolates, and saponins, and toxicants from food spoilage, food intoxication and food processing.

Pharmacologic consequences of cholesterol absorption inhibition: alteration in cholesterol metabolism and reduction in plasma cholesterol concentration induced by the synthetic saponin beta-tigogenin cellobioside (CP-88818; tiqueside).

Natural and synthetic saponins inhibit cholesterol absorption and reduce plasma cholesterol levels in experimental animals and are therefore of potential pharmacologic utility in the treatment of hypercholesterolemia. To determine the effects of this class of compounds on cholesterol absorption and metabolism, we evaluated the effects of the synthetic saponin, beta-tigogenin cellobioside (tiqueside; CP-88818), on male golden Syrian hamsters. When administered as either a single oral bolus or as a dietary supplement for up to 2 weeks, tiqueside inhibited cholesterol absorption in a dose-dependent manner in both the presence and absence of dietary cholesterol. Administration of tiqueside to chow-fed hamsters as a 0.2% dietary supplement (150 mg/kg per day) for 4 days resulted in a 68% decrease in intestinal cholesterol absorption with no change in either bile absorption or cholesterol 7 alpha-hydroxylase activity, suggesting that tiqueside inhibits cholesterol absorption without interfering with enterohepatic bile acid recirculation. Under these conditions, hepatic cholesterol levels were also reduced in a dose-dependent manner. Hepatic cholesterol reduction was highly correlated with cholesterol absorption inhibition, and induced compensatory increases in both hepatic HMG-CoA reductase activity and hepatic low density lipoprotein (LDL) receptor levels. Compensatory increases in intestinal HMG-CoA reductase activity were also noted after tiqueside administration, and are consistent with a luminal mechanism for tiqueside action. As a consequence of these changes to cholesterol metabolism, tiqueside administration induced plasma cholesterol reductions that were highly correlated with both hepatic cholesterol reduction and cholesterol absorption inhibition. Tiqueside also produced comparable plasma cholesterol lowering in a variety of other species fed either cholesterol-free diets (hamster, rat, mouse, dog) or cholesterol-containing diets (hamster, rat, rabbit, mouse, cynomolgus monkey, rhesus monkey, SEA quail) indicating the ubiquity of tiqueside action. For all species evaluated except the dog, the reduction in plasma cholesterol was due primarily to a reduction in circulating non-HDL cholesterol levels with little or no change in HDL cholesterol levels. Taken together, these results indicate that inhibition of cholesterol absorption by tiqueside produces profound effects on cholesterol metabolism without affecting bile acid metabolism, and that these changes lead to reductions primarily in plasma non-HDL cholesterol concentrations. The synthetic saponin, tiqueside, may thus represent a prototypical form of therapy for the treatment of hypercholesterolemia.