sapogenins and sarsasapogenin

A four-step synthesis of five- and six-membered E/F ring spiroethers from tigogenin has been developed. An efficient strategy that features bis-Grignard reaction of dinorcholanic lactone with appropriate bis(bromomagnesio)alkanes followed by acid-mediated spirocyclization was employed to construct a new class of steroid compounds having E and F ring junction as an oxa-carbacyclic system. The synthesized carbaanalogs interact with liposomes and albumin, and also exhibit antibacterial and antifungal activity, demonstrating their pharmacological potential.

Topics: Sapogenins; Spirostans; Steroids

Two unnatural steroid sapogenins bearing a furospirostane side chain were prepared starting from the readily available spirostane sapogenins, tigogenin and diosgenin following a synthetic protocol that included: (i) introduction of a carbonyl group at position C-23, (ii) diacetoxyiodobenzene-induced F-ring contraction and (iii) LiAlH4 reduction of the newly emerged methoxycarbonyl moiety. The structures of the new compounds were corroborated by NMR and X-ray studies.

Topics: Acetates; Crystallography, X-Ray; Diosgenin; Hydrolysis; Iodobenzenes; Magnetic Resonance Spectroscopy; Molecular Conformation; Sapogenins; Spirostans

The regioselective opening of the F ring of 22-oxo-23-spiroketals using a saturated solution of HCl in acetic anhydride yielded novel cholestanic frameworks with pyranone or cyclopentenone E rings. The structures of the new derivatives of sarsasapogenin, diosgenin and hecogenin thus obtained were established using one and two dimensional (1)H, (13)C experiments (DEPT, COSY, HETCOR, HMBC, ROESY, and NOESY). The X-ray analysis for compound 11b confirmed the 23R configuration for the new stereogenic center.

Topics: Acetic Anhydrides; Cholestanes; Crystallography, X-Ray; Cyclopentanes; Diosgenin; Furans; Hydrochloric Acid; Magnetic Resonance Spectroscopy; Models, Chemical; Molecular Structure; Pyrones; Sapogenins; Spiro Compounds; Spirostans; Stereoisomerism

We report the deacylation of (20R)-20-acetyl-23,24-dinorcholanic lactones by hydrazine hydrate, under microwave irradiation in high yields. The elimination of the 20-acetyl group proceeded with retention of configuration which contrast with other proved deacylation methods that yield a mixture of diastereoisomers. In this way, unnatural (20R)-23,24-dinorcholanic lactones can be produced rapidly on a large scale. Both (20R)- and (20S)-lactones were prepared starting from diosgenin, hecogenin and sarsasapogenin, in 72-80% overall yields.

Topics: Acylation; Antineoplastic Agents; Diacetyl; Diosgenin; Hydrazines; Lactones; Microwaves; Models, Molecular; Molecular Structure; Sapogenins; Spirostans; Stereoisomerism; X-Ray Diffraction

An improved fast method for extraction of steroidal saponins in Tribulus terrestris based on the use of focus microwave-assisted extraction (FMAE) is proposed. Under optimized conditions, four steroidal saponins were extracted from Tribulus terrestris and identified by GC-MS, which are Tigogenin (TG), Gitogenin (GG), Hecogenin (HG) and Neohecogenin (NG). One of the most important steroidal saponins, namely TG was quantified finally. The recovery of TG was in the range of 86.7-91.9% with RSD<5.2%. The convention heating reflux extraction was also conducted in order to validate the reliability of this new FMAE method. The yield of total steroidal saponins was 90.3% in a one-step FMAE, while the yield of 65.0% was achieved during heating reflux extraction, and the extraction time was reduced from 3 h to 5 min by using less solvent. The method was successfully applied to analyze the steroidal saponins of Tribulus terrestris from different areas of occurrence. The difference in chromatographic characteristics of steroidal saponins was proved to be related to the different areas of occurrence. The results showed that FMAE-GC-MS is a simple, rapid, solvent-saving method for the extraction and determination of steroidal saponins in Tribulus terrestris.

Topics: Drugs, Chinese Herbal; Gas Chromatography-Mass Spectrometry; Microwaves; Phytosterols; Plants, Medicinal; Sapogenins; Saponins; Spirostans; Tribulus

We conducted our study to assess the antiproliferative and proapoptotic potential of hecogenin and tigogenin, two saponins which are structurally similar to diosgenin. We particularly focused our attention on mitogen-activated protein kinase (MAPK) activation in relation to apoptosis but also with the COX-2 expression and activity. Rheumatoid arthritis (RA) synoviocytes were isolated from fresh synovial biopsies obtained from five RA patients undergoing hip arthroplasty. Measurement of cell proliferation was determined using the MTT assay. Apoptosis was evaluated by studying caspase-8, caspase-9 and caspase-3 activities but also by quantification of DNA fragmentation. Quantification of human phospho-MAPKs was realized by ELISA. COX-2 expression was demonstrated by Western blot analysis and COX-2 activity by assay of endogenous prostaglandin E2 (PGE2) production. Tigogenin was more effective than hecogenin in inducing apoptosis in human RA fibroblast-like synoviocytes (FLS) which was caspase dependent but poly(ADP-ribose) polymerase independent and characterized by DNA fragmentation. Our results demonstrated hecogenin- and tigogenin-induced apoptosis through activation of p38 without affecting the JNK and ERK pathways. Indeed, pretreatment with a p38 inhibitor decreased saponin-induced apoptosis with a significant decrease in DNA fragmentation. Furthermore, the rate of apoptosis induced by hecogenin or tigogenin was associated with overexpression of COX-2 correlated with overproduction of endogenous PGE2. These new results provide strong evidence that a family of structurally similar plant steroids is capable of inducing apoptosis in human RA FLS with different rates and different signalling pathways. This study also confirms the discussed appearance of the downregulation or upregulation of COX-2 in cell apoptosis as a function of cell type.

Topics: Apoptosis; Arthritis, Rheumatoid; Caspase 8; Caspase 9; Cell Death; Cell Proliferation; Cell Shape; Cell Survival; Cyclooxygenase 2; Extracellular Signal-Regulated MAP Kinases; Fibroblasts; Humans; JNK Mitogen-Activated Protein Kinases; Middle Aged; p38 Mitogen-Activated Protein Kinases; Poly(ADP-ribose) Polymerases; Sapogenins; Saponins; Spirostans; Synovial Fluid; Up-Regulation

Regulation of growth arrest and apoptosis are, in part, controlled by the tumor suppressor p53 after its phosphorylation which causes a determinant role in its functional activation. Moreover, PPAR regulate many functions such as proliferation and apoptosis. We compared the biological activity of diosgenin with hecogenin and tigogenin, plant steroids structurally close to diosgenin, on proliferation rate, cell cycle distribution and apoptosis in human 1547 osteosarcoma cells. We found that all three molecules have an antiproliferative effect but gel shift analysis demonstrated that none of the plant steroids transactivated PPAR in human 1547 osteosarcoma cells whereas these molecules induced NF-kappaB binding to DNA. Although these plant steroids have a very close structure, only diosgenin caused a cell cycle arrest associated with strong apoptosis. This biological action seems correlated with a large increase of p53 protein expression. This fact was showed by immunofluorescence analysis which confirmed that diosgenin strongly enhanced the activation of p53 in contrast to hecogenin and tigogenin actions.

Topics: Antineoplastic Agents; Apoptosis; Blotting, Western; Cell Cycle; Cell Division; Cell Line, Tumor; Cell Nucleus; Cyclin-Dependent Kinase Inhibitor p21; Cyclins; Diosgenin; Drugs, Chinese Herbal; Electrophoresis, Polyacrylamide Gel; Humans; Luciferases; Microscopy, Fluorescence; Models, Chemical; Osteosarcoma; Receptors, Cytoplasmic and Nuclear; Reverse Transcriptase Polymerase Chain Reaction; Sapogenins; Spirostans; Time Factors; Transcription Factors; Transcriptional Activation; Transfection; Tumor Suppressor Protein p53

With the combination of high performance liquid chromatography-electrospray ionization mass spectrometry (HPLC/ESI-MS) and electron impact mass spectrometry (EI-MS), two steroidal saponins, one compound containing three glycosyls and tigogenin and the other one containing three glycosyls and diosgenin, from the bulbs of Lilium brownii var. calchesteri in China have been screened. In the method, on-line HPLC/ESI-MS allows us to obtain rapidly useful information about the molecular weight and the glycosyl chain of glycoside without the necessity of isolating individual compounds, but little information about steroidal sapogenins. Just with 1 mg to 2 mg of pure sample, off-line EI-MS allows us to acquire useful information about a steroidal sapogenin of saponins, but it is difficult to obtain the molecular ion peak. The combination of HPLC/ESI-MS and EI-MS is well suitable for rapidly screening steroidal saponins from plants.

Topics: Chromatography, High Pressure Liquid; Drugs, Chinese Herbal; Lilium; Sapogenins; Spectrometry, Mass, Electrospray Ionization; Spirostans

As part of an experimental study, crystal-associated cholangiopathy was induced in 9 sheep by grazing pure pastures of Brachiaria decumbens in Brazil. One of these sheep showed characteristic lesions of photosensitization. The analysis of the B decumbens samples by acidic hydrolysis followed by TLC and infrared spectrum revealed diosgenin as the principal sapogenin present in the plant. In the rumen contents samples from the B decumbens-grazing group were identified by TLC, 1H and 13C NMR and EIMS as epismilagenin, episarsasapogenin, and a mixture of smilagenin and sarsasapogenin. In the bile samples from the B decumbens-grazing group, TLC analysis demonstrated 2 compounds similar to epismilagenin and episarsasapogenin. However, by this same method, those compounds were not observed in the rumen contents and bile from 2 sheep which served as control animals. The P chartarum spore counts remained very low during the experimental period.

Topics: Animals; Ascomycota; Bile; Brazil; Cholangitis; Chromatography, Thin Layer; Colony Count, Microbial; Diosgenin; Histocytochemistry; Liver; Liver Diseases; Magnetic Resonance Spectroscopy; Mass Spectrometry; Photosensitivity Disorders; Poaceae; Rumen; Sapogenins; Sheep; Sheep Diseases; Spectrophotometry, Infrared; Spirostans; Spores, Fungal

A relationship between the 1H NMR chemical shifts of the ring F resonances and orientation of the H3-27 group has been derived for the establishment of 25R- and 25S-stereochemistry in spirostane type of steroidal sapogenins.

Topics: Drugs, Chinese Herbal; Molecular Conformation; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Phytosterols; Sapogenins; Saponins; Spirostans; Stereoisomerism

Lyophilized aqueous extracts obtained from Agave americana L (Agavaceae) collected in the north of Sardinia were characterized with regard to their steroidal sapogenin content. Extracts of A. americana and genins isolated from them were evaluated for anti-inflammatory properties by testing their effects on carrageenin-induced edema. The effect of orally administered genins on gastric mucous membranes was also assessed. Lyophilized extracts administered by the intraperitoneal route at doses equivalent to 200 and 300 mg/kg of fresh plant starting material, showed good anti-inflammatory activity. Doses of genins (total steroidal sapogenins, hecogenin and tigogenin) equivalent to the amount in the lyophilized extracts produced an antiedentatous effect which was much stronger and more efficacious than that obtained with an i.p. administration of 5 mg/kg of indomethacin or dexamethasone 21-phosphate at a dose equivalent to the molar content of hecogenin administered. At the doses used to evaluate the anti-inflammatory activity, the genins did not have any harmful effect on the gastric mucous membranes. Lesions occurred when significantly higher doses of hecogenin were given, but gastric damage was still less than that caused by the drugs used for comparative purposes.

Topics: Animals; Anti-Inflammatory Agents; Carrageenan; Edema; Gastric Mucosa; Inflammation; Italy; Male; Plant Extracts; Plant Leaves; Plants, Medicinal; Rats; Rats, Wistar; Sapogenins; Spirostans; Stomach Ulcer; Water

The experimental results have shown that except the stem and leaves all kinds of Rhizoma Anemarrhenae and all parts of the herb contain sarsasapogenin, but the contents are different. Furthermore, the root and peel of Rhizoma Anemarrhenae may be used as drug instead of Rhizoma Anemarrhenae.

Topics: Drugs, Chinese Herbal; Plants, Medicinal; Sapogenins; Seasons; Spirostans

Spectroscopic examination of purified extracts of the rumen content of sheep intoxicated by Brachiaria decumbens revealed the presence of two spirostanes, identified as epi-sarsasapogenin and epi-smilagenin. Sarsasapogenone was obtained by the oxidation of sarsasapogenin. The reduction of sarsasapogenone using lithium aluminum hydride yielded isomeric products, sarsasapogenin (20%) and epi-sarsasapogenin (80%).

Topics: Animals; Magnetic Resonance Spectroscopy; Mass Spectrometry; Molecular Structure; Poaceae; Rumen; Sapogenins; Sheep; Sheep Diseases; Spirostans

The reactions of beta- and alpha-pyranose peracetates with PCl5 gave products regioselectively chlorinated. The reactions of 1,2,3,4,6-penta-O-acetyl-beta-D-glucopyranose (5) and -beta-D-galactopyranose (6) with PCl5 in CCl4 and that of methyl 2,3,4-tri-O-acetyl-beta-D-glucuronatopyranose (7) with PCl5 in toluene gave 2-O-trichloroacetyl-beta-D-pyranosyl chlorides 4, 12 and 14, respectively, as major products, and alpha-D-pyranosyl chlorides 11, 13 and 15, respectively, as minor products. On the other hand, the reactions of compounds 8 and 9 which were alpha-anomers of 5 and 6, respectively, with PCl5 gave as major products transformed acetyl groups at C-6 to -C(Cl) = CCl2 or -C(Cl)2-CCl3 group (16 and 17 from 8 and 18 from 9). The same reaction of 10, which was alpha-anomer of 7, gave alpha-chloride 15 as a major product. The glycosidation of sugar derivative 4 with sarsasapogenin 23 gave beta-glycoside 24 (29.1%) and alpha-glycoside 25 (46.9%), and that of 12 with 23 gave beta-glycoside 26 (24.0%) and alpha-glycoside 27 (40.8%). The improvement of the yields of beta-glycosides 24 and 26 (66.9 and 62.1% for 24 and 26, respectively) in the glycosidations were accomplished by the employment of alpha-bromides 28 and 29 obtained from 4 and 6, respectively. The glycosidations of monoglycosides 30 and 31 obtained by the treatment 24 and 26, respectively, with ammonia-saturated ether with sugar acetate bromides 32 and 34 gave diglycoside derivatives 35 and 33, respectively.

Topics: Acetates; Glucosides; Glycosides; Sapogenins; Spirostans

The transformation of fenugreek subfractions, rich in steroid saponins, was studied upon their passage through the digestive tract to determine the contribution of saponins and/or diosgenin and other steroid sapogenins to the hypocholesterolemic effect of fenugreek seeds. Feces of alloxan diabetic dogs fed fenugreek subfractions were analyzed, and diosgenin, smilagenin and gitogenin were identified and measured using capillary gas chromatography/mass spectrometry. Our results show that saponins are, in part (about 57%), hydrolyzed into sapogenins in the digestive tract. It appears that saponins may be implicated, alone or together with diosgenin, in the observed hypocholesterolemic effect of fenugreek seeds in diabetic dogs.

Topics: Alloxan; Animals; Cholesterol; Chromatography, Gas; Chromatography, Thin Layer; Diabetes Mellitus, Experimental; Diosgenin; Dogs; Feces; Gas Chromatography-Mass Spectrometry; Plant Extracts; Plants, Medicinal; Sapogenins; Saponins; Spirostans; Trigonella

Topics: Animal Feed; Animals; Bile; Chromatography, Thin Layer; Mass Spectrometry; Photosensitivity Disorders; Plant Poisoning; Sapogenins; Sheep; Sheep Diseases; Spirostans; Tissue Distribution

In four trials, steer calves were received in the feedlot, processed and fed diets supplemented with soybean meal (SBM), 1% urea (UR) or 1% urea plus sarsaponin (S) over a 28-d period. In trials 1 and 2, the feeding period was extended to approximately 62 d, in which steers were fed a common (SBM) diet the last 34 d. In trials 3 and 4, a SBM plus S diet treatment was included. During the first 28 d (four trial summary) daily gains of steers fed urea plus S (.74 kg) were intermediate to and significantly different from gains of steers fed SBM (.84 kg) or UR (.66 kg) diets. However, at the end of the 62-d feeding period (two trial summary) daily gains, feed intakes and feed efficiency did not differ (P greater than .05) among treatments. No significant improvements in performance were found in steers fed SBM diets supplemented with S. In swine trials, pigs were fed diets containing no additive, 63 mg S X kg-1, 55 mg chlortetracycline (C) X kg-1 or S plus C in a grower-finisher (GF) and grower (G) trial. In the GF trial, overall efficiency of feed conversion was improved (P less than .05) by feeding S or S plus C. In the G trial, daily gains and intakes were greatest for pigs fed S plus C and differed (P less than .1) from those of pigs fed S or C in the diet. Compared with feeding S or C alone, gain and intake of growing pigs were stimulated to a greater extent when S was fed in combination with C. Feeding S with or without C improved efficiency of feed conversion in finishing pigs.

Topics: Animal Feed; Animals; Body Weight; Cattle; Female; Male; Sapogenins; Saponins; Spirostans; Swine

Supplementation of dairy rations with steroidal sapogenins was evaluated in an in vitro, an in situ, and a production trial. Sixteen in vitro semicontinuous rumen cultures were supplied a 55:45 concentrate to roughage substrate with Sarsaponin concentrations of 0, 33, 55, and 77 ppm of air-dry feed for 22 d. Supplementation decreased protozoa numbers and increased bacterial numbers and acid detergent fiber digestion. Digestion of feed nitrogen tended to be lowest at the highest concentration of Sarsaponin, whereas microbial nitrogen output was similar for all concentrations. In rumen-cannulated animals fed a typical dairy ration, in situ rate of disappearance of organic matter, acid detergent fiber, and nitrogen of a complete ration substrate tended to be lower with 77 ppm added Sarsaponin. In a production trial, 16 primiparous dairy cows 6 to 10 wk postpartum were fed rations containing either 0 or 77 ppm Sarsaponin. Sarsaponin did not alter dry matter intake, digestibility, body weight change, or milk production and composition. Supplementation had no significant effect on ruminal fermentation in vivo as reflected by concentrations of ruminal ammonia nitrogen, blood urea, or molar ratios and concentrations of ruminal volatile fatty acids.

Topics: Animals; Cattle; Female; Fermentation; Lactation; Pregnancy; Rumen; Sapogenins; Spirostans

Topics: Plants, Medicinal; Sapogenins; Spirostans

Topics: Sapogenins; Spirostans; Steroids